Clinical Review

Vaccination against human papillomavirus (HPV) infection and periodic cervical screening have significantly decreased the incidence of invasive cervical cancer. But cancers still exist despite the availability of these useful clinical tools, especially in women of reproductive age in developing regions of the world. In the 2016 update on cervical disease, I reviewed studies on 2 promising and novel immunotherapies for cervical cancer: HPV therapeutic vaccine and adoptive T-cell therapy. This year the focus is on remarkable advances in the field of genomics and related studies that are rapidly expanding our understanding of the molecular characteristics of cervical cancer. Rewards of this research already being explored include novel immunotherapeutic agents as well as the repurposed use of existing drugs.

But first, with regard to cervical screening and follow-up, 2 recent large studies have yielded findings that have important implications for patient management. One pertains to the monitoring of women who have persistent infection with high-risk HPV but cytology results that are negative. Its conclusion was unequivocal and very useful in the management of our patients. The other study tracked HPV screening performed every 3 years and reported on the diagnostic efficiency of this shorter interval screening strategy.

Read about persistent HPV infection and CIN

Persistent HPV infection has a higher risk than most clinicians might think

Elfgren K, Elfström KM, Naucler P, Arnheim-Dahlström L, Dillner J. Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial. Am J Obstet Gynecol. 2017;216(3):264.e1-e7.

It is well known that most cases of cervical cancer arise from persistent HPV infection, with the highest percentage of cancers caused by high-risk types 16 or 18. What has been uncertain, however, is the actual degree of risk that persistent infection confers over time for the development of cervical intraepithelial neoplasia (CIN) or worse when a woman's repeated cytology reports are negative. In an analysis of a long-term double-blind, randomized, controlled screening study, Elfgren and colleagues showed that all women whose HPV infection persisted up to 7 years developed CIN grade 2 (CIN2+), while those whose infection cleared in that period, or changed genotype, had no precancerous lesions out to 13 years of follow-up.

Related Article:
It is time for HPV vaccination to be considered part of routine preventive health care

Details of the study

Between 1997 and 2000, 12,527 Swedish women between the ages of 32 and 38 years who were undergoing organized cervical cancer screening agreed to participate in a 1:1-randomized prospective trial to determine the benefit of screening with HPV and cytology (intervention group) compared with cytology screening alone (control group). However, brush sampling for HPV was performed even on women in the control group, with the samples frozen for later testing. All participants were identified in the Swedish National Cervical Screening Registry.

Women in the intervention group who initially tested positive for HPV but whose cytology test results were negative (n = 341) were invited to return a year later for repeat HPV testing; 270 women returned and 119 had type-specific HPV persistence. Of those with persistent infection, 100 agreed to undergo colposcopy; 111 women from the control group were randomly selected to undergo sham HPV testing and colposcopy, and 95 attended. Women with evident cytologic abnormalities received treatment per protocol. Those with negative cytology results were offered annual HPV testing thereafter, and each follow-up with documented type-specific HPV persistence led to repeat colposcopy. A comparable number of women from the control group had repeat colposcopies.

Although some women were lost to clinical follow-up throughout the trial, all 195 who attended the first colposcopy were followed for at least 5 years in the Swedish registry, and 191 were followed in the registry for 13 years. Of 102 women with known HPV persistence at baseline (100 in the treatment group; 2 in the randomly selected control group), 31 became HPV negative, 4 evidenced a switch in HPV type but cleared the initial infection, 27 had unknown persistence status due to missed HPV tests, and 40 had continuously type-specific persistence. Of note, persistent HPV16 infection seemed to impart a higher risk of CIN development than did persistent HPV18 infection.

All 40 participants with clinically verified continuously persistent HPV infection developed CIN2+ within 7 years of baseline documentation of persistence (FIGURE 1). Among the 27 women with unknown persistence status, risk of CIN2+ occurrence within 7 years was 50%. None of the 35 women who cleared their infection or switched HPV type developed CIN2+.

Read about HPV-cytology cotesting

HPV−cytology cotesting every 3 years lowers population rates of cervical precancer and cancer

Silver MI, Schiffman M, Fetterman B, et al. The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: reduced cervical cancer risk and decreased yield of precancer per screen. Cancer. 2016;122(23):3682−3686.

Current guidelines on screening for cervical cancer in women 30 to 65 years of age advise the preferred strategy of using cytology alone every 3 years or combining HPV testing and cytology every 5 years.¹ These guidelines, based on data available at the time they were written, were meant to offer a reasonable balance between timely detection of abnormalities and avoidance of potential harms from screening too frequently. However, many patients are reluctant to postpone repeat testing to the extent recommended. Several authorities have in fact asked that screening intervals be revisited, perhaps allowing for a range of strategies, contending that the level of protection once provided by annual screening should be the benchmark by which evolving strategies are judged.² Today, they point out, the risk of cancer doubles in the 3 years following an initial negative cytology result, and it also increases by lengthening the cotesting interval from 3 to 5 years. They additionally question the validity of using frequency of colposcopies as a surrogate to measure harms of screening, and suggest that many women would willingly accept the procedure's minimal discomfort and inconvenience to gain peace of mind.

The study by Silver and colleagues gives credence to considering a shorter cotesting interval. Since 2003, Kaiser Permanente Northern California (KPNC) has implemented 3-year cotesting. To determine actual clinical outcomes of cotesting at this interval, KPNC analyzed data on more than 1 million women in its care between 2003 and 2012. Although investigators expected that they might see decreasing efficiency in cotesting over time, they instead found an increased detection rate of precancerous lesions per woman screened in the larger of 2 study cohorts.

Related Article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns

Details of the study

Included were all women 30 years of age or older enrolled in this study at KPNC between 2003 and 2012 who underwent HPV−cytology cotesting every 3 years. The population in its entirety (1,065,273 women) was deemed the "open cohort" and represented KPNC's total annual experience. A subset of this population, the "closed cohort," was designed to gauge the effect of repeated screening on a fixed population and comprised only those women enrolled and initially screened between 2003 and 2004 and then followed longitudinally until 2012.

For each cohort, investigators calculated the ratios of precancer and cancer diagnoses to the total number of cotests performed on the cohort's population. The 3-year testing periods were 2004−2006, 2007−2009, and 2010−2012. Also calculated in these periods were the ratios of colposcopic biopsies to cotests and the rates of precancer diagnoses (TABLE). 

In the open cohort, the biopsy rate nearly doubled over the course of the study. Precancer diagnoses per number of cotests rose by 71.5% between the first and second testing periods (P = .001) and then eased off by 10% in the third period (P<.001). These corresponding increases throughout the study yielded a stable number of biopsies (16 to 22) needed to detect precancer.

In the closed long-term cohort, the biopsy rate rose, but not as much as in the open cohort. Precancer diagnoses per number of cotests rose by 47% between the first and second periods (P≤.001), but in the third period fell back by 28% (P<.001) to a level just above the first period results. The number of biopsies needed to detect a precancerous lesion in the closed cohort rose from 19 to 33 over the course of the study, suggesting there may have been some loss of screening efficiency in the fixed group.

Read about molecular profiling of cervical cancer

Molecular profiling of cervical cancer is revolutionizing treatment

The Cancer Genome Atlas Research Network. Integratedgenomic and molecular characterization of cervical cancer. Nature. 2017;543(7645):378−384.

Effective treatments for cervical cancer could be close at hand, thanks to a recent explosion of knowledge at the molecular level about how specific cancers arise and what drives them other than HPV. The Cancer Genome Atlas Research Network (TCGA) recently published the results of its genomic and proteomic analyses, which yielded distinct profiles for 178 cervical cancers with important patterns common to other cancers, such as uterine and breast cancer. These recently published findings on cervical cancer highlight areas of gene and protein dysfunction it shares with these other cancers, which could open the doors for new targets for treatments already developed or in the pipeline.

Related Article:
2016 Update on cervical disease

How molecular profiling is paying off for cervical cancer

Cancers develop in any given tissue through the altered function of different genes and signaling pathways in the tissue's cells. The latest extensive investigation conducted by the TCGA network has identified significant mutations in 5 genes previously unrecognized in association with cervical cancer, bringing the total now to 14.

Several highlights are featured in the TCGA's recently published work. One discovery is the amplification of genes CD274 and PDCD1LG2, which are involved with the expression of 2 cytolytic effector genes and are therefore likely targets for immunotherapeutic strategies. Another line of exploration, whole-genome sequencing, has detected an aberration in some cervical cancer tissue with the potential for immediate application. Duplication and copy number gain of BCAR4, a noncoding RNA, facilitates cell proliferation through the HER2/HER3 pathway, a target of the tyrosine-kinase inhibitor, lapatinib, which is currently used to treat breast cancer.

The integration of data from multiple layers of analysis (FIGURE 2) is helping investigators identify variations in cancers. DNA methylation, for instance, is a means by which cells control gene expression. An analysis of this process in cervical tumor tissue has revealed additional cancer subgroups in which messenger RNA increases the transition of epithelial cells to invasive mesenchymal cells. Targeting that process in these subgroups would likely enhance the effectiveness of novel small-molecule inhibitors and some standard cytotoxic chemotherapy.  

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vaccination against human papillomavirus (HPV) infection and periodic cervical screening have significantly decreased the incidence of invasive cervical cancer. But cancers still exist despite the availability of these useful clinical tools, especially in women of reproductive age in developing regions of the world. In the 2016 update on cervical disease, I reviewed studies on 2 promising and novel immunotherapies for cervical cancer: HPV therapeutic vaccine and adoptive T-cell therapy. This year the focus is on remarkable advances in the field of genomics and related studies that are rapidly expanding our understanding of the molecular characteristics of cervical cancer. Rewards of this research already being explored include novel immunotherapeutic agents as well as the repurposed use of existing drugs.

But first, with regard to cervical screening and follow-up, 2 recent large studies have yielded findings that have important implications for patient management. One pertains to the monitoring of women who have persistent infection with high-risk HPV but cytology results that are negative. Its conclusion was unequivocal and very useful in the management of our patients. The other study tracked HPV screening performed every 3 years and reported on the diagnostic efficiency of this shorter interval screening strategy.

Read about persistent HPV infection and CIN

Persistent HPV infection has a higher risk than most clinicians might think

Elfgren K, Elfström KM, Naucler P, Arnheim-Dahlström L, Dillner J. Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial. Am J Obstet Gynecol. 2017;216(3):264.e1-e7.

It is well known that most cases of cervical cancer arise from persistent HPV infection, with the highest percentage of cancers caused by high-risk types 16 or 18. What has been uncertain, however, is the actual degree of risk that persistent infection confers over time for the development of cervical intraepithelial neoplasia (CIN) or worse when a woman's repeated cytology reports are negative. In an analysis of a long-term double-blind, randomized, controlled screening study, Elfgren and colleagues showed that all women whose HPV infection persisted up to 7 years developed CIN grade 2 (CIN2+), while those whose infection cleared in that period, or changed genotype, had no precancerous lesions out to 13 years of follow-up.

Related Article:
It is time for HPV vaccination to be considered part of routine preventive health care

Details of the study

Between 1997 and 2000, 12,527 Swedish women between the ages of 32 and 38 years who were undergoing organized cervical cancer screening agreed to participate in a 1:1-randomized prospective trial to determine the benefit of screening with HPV and cytology (intervention group) compared with cytology screening alone (control group). However, brush sampling for HPV was performed even on women in the control group, with the samples frozen for later testing. All participants were identified in the Swedish National Cervical Screening Registry.

Women in the intervention group who initially tested positive for HPV but whose cytology test results were negative (n = 341) were invited to return a year later for repeat HPV testing; 270 women returned and 119 had type-specific HPV persistence. Of those with persistent infection, 100 agreed to undergo colposcopy; 111 women from the control group were randomly selected to undergo sham HPV testing and colposcopy, and 95 attended. Women with evident cytologic abnormalities received treatment per protocol. Those with negative cytology results were offered annual HPV testing thereafter, and each follow-up with documented type-specific HPV persistence led to repeat colposcopy. A comparable number of women from the control group had repeat colposcopies.

Although some women were lost to clinical follow-up throughout the trial, all 195 who attended the first colposcopy were followed for at least 5 years in the Swedish registry, and 191 were followed in the registry for 13 years. Of 102 women with known HPV persistence at baseline (100 in the treatment group; 2 in the randomly selected control group), 31 became HPV negative, 4 evidenced a switch in HPV type but cleared the initial infection, 27 had unknown persistence status due to missed HPV tests, and 40 had continuously type-specific persistence. Of note, persistent HPV16 infection seemed to impart a higher risk of CIN development than did persistent HPV18 infection.

All 40 participants with clinically verified continuously persistent HPV infection developed CIN2+ within 7 years of baseline documentation of persistence (FIGURE 1). Among the 27 women with unknown persistence status, risk of CIN2+ occurrence within 7 years was 50%. None of the 35 women who cleared their infection or switched HPV type developed CIN2+.

Read about HPV-cytology cotesting

HPV−cytology cotesting every 3 years lowers population rates of cervical precancer and cancer

Silver MI, Schiffman M, Fetterman B, et al. The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: reduced cervical cancer risk and decreased yield of precancer per screen. Cancer. 2016;122(23):3682−3686.

Current guidelines on screening for cervical cancer in women 30 to 65 years of age advise the preferred strategy of using cytology alone every 3 years or combining HPV testing and cytology every 5 years.¹ These guidelines, based on data available at the time they were written, were meant to offer a reasonable balance between timely detection of abnormalities and avoidance of potential harms from screening too frequently. However, many patients are reluctant to postpone repeat testing to the extent recommended. Several authorities have in fact asked that screening intervals be revisited, perhaps allowing for a range of strategies, contending that the level of protection once provided by annual screening should be the benchmark by which evolving strategies are judged.² Today, they point out, the risk of cancer doubles in the 3 years following an initial negative cytology result, and it also increases by lengthening the cotesting interval from 3 to 5 years. They additionally question the validity of using frequency of colposcopies as a surrogate to measure harms of screening, and suggest that many women would willingly accept the procedure's minimal discomfort and inconvenience to gain peace of mind.

The study by Silver and colleagues gives credence to considering a shorter cotesting interval. Since 2003, Kaiser Permanente Northern California (KPNC) has implemented 3-year cotesting. To determine actual clinical outcomes of cotesting at this interval, KPNC analyzed data on more than 1 million women in its care between 2003 and 2012. Although investigators expected that they might see decreasing efficiency in cotesting over time, they instead found an increased detection rate of precancerous lesions per woman screened in the larger of 2 study cohorts.

Related Article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns

Details of the study

Included were all women 30 years of age or older enrolled in this study at KPNC between 2003 and 2012 who underwent HPV−cytology cotesting every 3 years. The population in its entirety (1,065,273 women) was deemed the "open cohort" and represented KPNC's total annual experience. A subset of this population, the "closed cohort," was designed to gauge the effect of repeated screening on a fixed population and comprised only those women enrolled and initially screened between 2003 and 2004 and then followed longitudinally until 2012.

For each cohort, investigators calculated the ratios of precancer and cancer diagnoses to the total number of cotests performed on the cohort's population. The 3-year testing periods were 2004−2006, 2007−2009, and 2010−2012. Also calculated in these periods were the ratios of colposcopic biopsies to cotests and the rates of precancer diagnoses (TABLE). 

In the open cohort, the biopsy rate nearly doubled over the course of the study. Precancer diagnoses per number of cotests rose by 71.5% between the first and second testing periods (P = .001) and then eased off by 10% in the third period (P<.001). These corresponding increases throughout the study yielded a stable number of biopsies (16 to 22) needed to detect precancer.

In the closed long-term cohort, the biopsy rate rose, but not as much as in the open cohort. Precancer diagnoses per number of cotests rose by 47% between the first and second periods (P≤.001), but in the third period fell back by 28% (P<.001) to a level just above the first period results. The number of biopsies needed to detect a precancerous lesion in the closed cohort rose from 19 to 33 over the course of the study, suggesting there may have been some loss of screening efficiency in the fixed group.

Read about molecular profiling of cervical cancer

Molecular profiling of cervical cancer is revolutionizing treatment

The Cancer Genome Atlas Research Network. Integratedgenomic and molecular characterization of cervical cancer. Nature. 2017;543(7645):378−384.

Effective treatments for cervical cancer could be close at hand, thanks to a recent explosion of knowledge at the molecular level about how specific cancers arise and what drives them other than HPV. The Cancer Genome Atlas Research Network (TCGA) recently published the results of its genomic and proteomic analyses, which yielded distinct profiles for 178 cervical cancers with important patterns common to other cancers, such as uterine and breast cancer. These recently published findings on cervical cancer highlight areas of gene and protein dysfunction it shares with these other cancers, which could open the doors for new targets for treatments already developed or in the pipeline.

Related Article:
2016 Update on cervical disease

How molecular profiling is paying off for cervical cancer

Cancers develop in any given tissue through the altered function of different genes and signaling pathways in the tissue's cells. The latest extensive investigation conducted by the TCGA network has identified significant mutations in 5 genes previously unrecognized in association with cervical cancer, bringing the total now to 14.

Several highlights are featured in the TCGA's recently published work. One discovery is the amplification of genes CD274 and PDCD1LG2, which are involved with the expression of 2 cytolytic effector genes and are therefore likely targets for immunotherapeutic strategies. Another line of exploration, whole-genome sequencing, has detected an aberration in some cervical cancer tissue with the potential for immediate application. Duplication and copy number gain of BCAR4, a noncoding RNA, facilitates cell proliferation through the HER2/HER3 pathway, a target of the tyrosine-kinase inhibitor, lapatinib, which is currently used to treat breast cancer.

The integration of data from multiple layers of analysis (FIGURE 2) is helping investigators identify variations in cancers. DNA methylation, for instance, is a means by which cells control gene expression. An analysis of this process in cervical tumor tissue has revealed additional cancer subgroups in which messenger RNA increases the transition of epithelial cells to invasive mesenchymal cells. Targeting that process in these subgroups would likely enhance the effectiveness of novel small-molecule inhibitors and some standard cytotoxic chemotherapy.  

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Vaccination against human papillomavirus (HPV) infection and periodic cervical screening have significantly decreased the incidence of invasive cervical cancer. But cancers still exist despite the availability of these useful clinical tools, especially in women of reproductive age in developing regions of the world. In the 2016 update on cervical disease, I reviewed studies on 2 promising and novel immunotherapies for cervical cancer: HPV therapeutic vaccine and adoptive T-cell therapy. This year the focus is on remarkable advances in the field of genomics and related studies that are rapidly expanding our understanding of the molecular characteristics of cervical cancer. Rewards of this research already being explored include novel immunotherapeutic agents as well as the repurposed use of existing drugs.

But first, with regard to cervical screening and follow-up, 2 recent large studies have yielded findings that have important implications for patient management. One pertains to the monitoring of women who have persistent infection with high-risk HPV but cytology results that are negative. Its conclusion was unequivocal and very useful in the management of our patients. The other study tracked HPV screening performed every 3 years and reported on the diagnostic efficiency of this shorter interval screening strategy.

Read about persistent HPV infection and CIN

Persistent HPV infection has a higher risk than most clinicians might think

Elfgren K, Elfström KM, Naucler P, Arnheim-Dahlström L, Dillner J. Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial. Am J Obstet Gynecol. 2017;216(3):264.e1-e7.

It is well known that most cases of cervical cancer arise from persistent HPV infection, with the highest percentage of cancers caused by high-risk types 16 or 18. What has been uncertain, however, is the actual degree of risk that persistent infection confers over time for the development of cervical intraepithelial neoplasia (CIN) or worse when a woman's repeated cytology reports are negative. In an analysis of a long-term double-blind, randomized, controlled screening study, Elfgren and colleagues showed that all women whose HPV infection persisted up to 7 years developed CIN grade 2 (CIN2+), while those whose infection cleared in that period, or changed genotype, had no precancerous lesions out to 13 years of follow-up.

Related Article:
It is time for HPV vaccination to be considered part of routine preventive health care

Details of the study

Between 1997 and 2000, 12,527 Swedish women between the ages of 32 and 38 years who were undergoing organized cervical cancer screening agreed to participate in a 1:1-randomized prospective trial to determine the benefit of screening with HPV and cytology (intervention group) compared with cytology screening alone (control group). However, brush sampling for HPV was performed even on women in the control group, with the samples frozen for later testing. All participants were identified in the Swedish National Cervical Screening Registry.

Women in the intervention group who initially tested positive for HPV but whose cytology test results were negative (n = 341) were invited to return a year later for repeat HPV testing; 270 women returned and 119 had type-specific HPV persistence. Of those with persistent infection, 100 agreed to undergo colposcopy; 111 women from the control group were randomly selected to undergo sham HPV testing and colposcopy, and 95 attended. Women with evident cytologic abnormalities received treatment per protocol. Those with negative cytology results were offered annual HPV testing thereafter, and each follow-up with documented type-specific HPV persistence led to repeat colposcopy. A comparable number of women from the control group had repeat colposcopies.

Although some women were lost to clinical follow-up throughout the trial, all 195 who attended the first colposcopy were followed for at least 5 years in the Swedish registry, and 191 were followed in the registry for 13 years. Of 102 women with known HPV persistence at baseline (100 in the treatment group; 2 in the randomly selected control group), 31 became HPV negative, 4 evidenced a switch in HPV type but cleared the initial infection, 27 had unknown persistence status due to missed HPV tests, and 40 had continuously type-specific persistence. Of note, persistent HPV16 infection seemed to impart a higher risk of CIN development than did persistent HPV18 infection.

All 40 participants with clinically verified continuously persistent HPV infection developed CIN2+ within 7 years of baseline documentation of persistence (FIGURE 1). Among the 27 women with unknown persistence status, risk of CIN2+ occurrence within 7 years was 50%. None of the 35 women who cleared their infection or switched HPV type developed CIN2+.

Read about HPV-cytology cotesting

HPV−cytology cotesting every 3 years lowers population rates of cervical precancer and cancer

Silver MI, Schiffman M, Fetterman B, et al. The population impact of human papillomavirus/cytology cervical cotesting at 3-year intervals: reduced cervical cancer risk and decreased yield of precancer per screen. Cancer. 2016;122(23):3682−3686.

Current guidelines on screening for cervical cancer in women 30 to 65 years of age advise the preferred strategy of using cytology alone every 3 years or combining HPV testing and cytology every 5 years.¹ These guidelines, based on data available at the time they were written, were meant to offer a reasonable balance between timely detection of abnormalities and avoidance of potential harms from screening too frequently. However, many patients are reluctant to postpone repeat testing to the extent recommended. Several authorities have in fact asked that screening intervals be revisited, perhaps allowing for a range of strategies, contending that the level of protection once provided by annual screening should be the benchmark by which evolving strategies are judged.² Today, they point out, the risk of cancer doubles in the 3 years following an initial negative cytology result, and it also increases by lengthening the cotesting interval from 3 to 5 years. They additionally question the validity of using frequency of colposcopies as a surrogate to measure harms of screening, and suggest that many women would willingly accept the procedure's minimal discomfort and inconvenience to gain peace of mind.

The study by Silver and colleagues gives credence to considering a shorter cotesting interval. Since 2003, Kaiser Permanente Northern California (KPNC) has implemented 3-year cotesting. To determine actual clinical outcomes of cotesting at this interval, KPNC analyzed data on more than 1 million women in its care between 2003 and 2012. Although investigators expected that they might see decreasing efficiency in cotesting over time, they instead found an increased detection rate of precancerous lesions per woman screened in the larger of 2 study cohorts.

Related Article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns

Details of the study

Included were all women 30 years of age or older enrolled in this study at KPNC between 2003 and 2012 who underwent HPV−cytology cotesting every 3 years. The population in its entirety (1,065,273 women) was deemed the "open cohort" and represented KPNC's total annual experience. A subset of this population, the "closed cohort," was designed to gauge the effect of repeated screening on a fixed population and comprised only those women enrolled and initially screened between 2003 and 2004 and then followed longitudinally until 2012.

For each cohort, investigators calculated the ratios of precancer and cancer diagnoses to the total number of cotests performed on the cohort's population. The 3-year testing periods were 2004−2006, 2007−2009, and 2010−2012. Also calculated in these periods were the ratios of colposcopic biopsies to cotests and the rates of precancer diagnoses (TABLE). 

In the open cohort, the biopsy rate nearly doubled over the course of the study. Precancer diagnoses per number of cotests rose by 71.5% between the first and second testing periods (P = .001) and then eased off by 10% in the third period (P<.001). These corresponding increases throughout the study yielded a stable number of biopsies (16 to 22) needed to detect precancer.

In the closed long-term cohort, the biopsy rate rose, but not as much as in the open cohort. Precancer diagnoses per number of cotests rose by 47% between the first and second periods (P≤.001), but in the third period fell back by 28% (P<.001) to a level just above the first period results. The number of biopsies needed to detect a precancerous lesion in the closed cohort rose from 19 to 33 over the course of the study, suggesting there may have been some loss of screening efficiency in the fixed group.

Read about molecular profiling of cervical cancer

Molecular profiling of cervical cancer is revolutionizing treatment

The Cancer Genome Atlas Research Network. Integratedgenomic and molecular characterization of cervical cancer. Nature. 2017;543(7645):378−384.

Effective treatments for cervical cancer could be close at hand, thanks to a recent explosion of knowledge at the molecular level about how specific cancers arise and what drives them other than HPV. The Cancer Genome Atlas Research Network (TCGA) recently published the results of its genomic and proteomic analyses, which yielded distinct profiles for 178 cervical cancers with important patterns common to other cancers, such as uterine and breast cancer. These recently published findings on cervical cancer highlight areas of gene and protein dysfunction it shares with these other cancers, which could open the doors for new targets for treatments already developed or in the pipeline.

Related Article:
2016 Update on cervical disease

How molecular profiling is paying off for cervical cancer

Cancers develop in any given tissue through the altered function of different genes and signaling pathways in the tissue's cells. The latest extensive investigation conducted by the TCGA network has identified significant mutations in 5 genes previously unrecognized in association with cervical cancer, bringing the total now to 14.

Several highlights are featured in the TCGA's recently published work. One discovery is the amplification of genes CD274 and PDCD1LG2, which are involved with the expression of 2 cytolytic effector genes and are therefore likely targets for immunotherapeutic strategies. Another line of exploration, whole-genome sequencing, has detected an aberration in some cervical cancer tissue with the potential for immediate application. Duplication and copy number gain of BCAR4, a noncoding RNA, facilitates cell proliferation through the HER2/HER3 pathway, a target of the tyrosine-kinase inhibitor, lapatinib, which is currently used to treat breast cancer.

The integration of data from multiple layers of analysis (FIGURE 2) is helping investigators identify variations in cancers. DNA methylation, for instance, is a means by which cells control gene expression. An analysis of this process in cervical tumor tissue has revealed additional cancer subgroups in which messenger RNA increases the transition of epithelial cells to invasive mesenchymal cells. Targeting that process in these subgroups would likely enhance the effectiveness of novel small-molecule inhibitors and some standard cytotoxic chemotherapy.  

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Case

An 85-year-old right-handed woman who recently had been diagnosed with mild cognitive impairment arrived at the ED via emergency medical services (EMS) for evaluation of a reported fall. She was accompanied by her daughter, who resided with the patient and was her primary caregiver. The patient stated that she had tripped on a wet rug in the bathroom of her home, striking her head and face on the edge of the sink without losing consciousness. Her daughter reported that she was not assisting her mother when the fall occurred, but had witnessed the fall from the hallway and called EMS. At the patient’s home, EMS found the patient to be alert, oriented, and ambulatory with normal vital signs that remained stable throughout prehospital transport.

The remainder of the patient’s history was provided almost entirely by her daughter, who constantly interrupted her mother whenever she attempted to directly answer a question or provide information. On physical examination, the patient had bilateral tenderness, edema, and periorbital ecchymoses, and a left eye that was nearly swollen shut. Extraocular movements were normal, visual acuity was intact, and sclerae were noninjected. The patient had tenderness over both maxillary sinuses, and edema and ecchymosis of her left cheek. There was also tenderness, ecchymoses, and edema on the lateral aspects of both forearms, and decreased range of motion of her right lower arm and wrist. With the exception of the patient not knowing the date during the orientation part of the thorough neurological examination, the remainder of the physical examination was unremarkable.

Radiological evaluation found no evidence of traumatic brain injury, but did reveal an acute fracture of the left zygomatic arch, an acute displaced nasal bone fracture, an age-indeterminate fracture of the right zygomatic arch, and an acute right ulnar fracture. Considering all of these findings, particularly the pattern of acute injuries, the emergency physician (EP) considered elder abuse as the possible etiology of the patient’s acute and chronic injuries.

Although the patient had initially agreed with her daughter’s description of the events—including her claim that she had fallen—when the EP questioned the patient alone, she related a history of frequent verbal and less frequent physical abuse by her daughter. The patient further noted that immediately before sustaining the injuries that brought her to the ED, her daughter had been insisting that she sign documents to give her control of her banking and finances. After refusing to sign the papers, the patient said that she and her daughter got into an argument, which she noted “they tended to do frequently.” The patient admitted that during this argument, her daughter struck her in the face repeatedly with the cane that the daughter had grabbed with her right hand.

The EP admitted the patient to the hospital for management of her orthopedic injuries and related pain, and to formulate a safe discharge plan. During admission, additional diagnostic testing revealed multiple old rib fractures, anemia, and a low-serum albumin, which suggested poor nutritional status.

Epidemiology

The term elder abuse refers to harm or the risk of harm to an older adult from either action or negligence committed by someone in a relationship of trust, or when a victim has been targeted because of age or disability. Elder abuse encompasses physical, sexual, or psychological abuse, neglect, and financial exploitation.^1-5 Identified victims of elder abuse typically suffer from multiple forms of abuse.^1-5

At present, elder abuse annually affects 5% to 10% of community-dwelling older adults,^1-6 and nursing-home residents are at increased risk of abuse.^7-10 Poor medical outcomes, including depression and dementia,¹¹ and much higher mortality^6,12,13 have been linked to victims of elder abuse.

Etiology

When treating older adults, it is critically important for EPs and the ED staff to consider and identify elder abuse in the differential diagnosis.^14,15 Presently, only an estimated 1 in 24 cases of abuse is recognized and reported to the authorities,² and much of the subsequent morbidity and mortality of elder abuse results from poor detection. A visit to the ED for an acute injury or illness may be the only time socially isolated older adults leave their homes.^15-17 Additionally, the ED setting is uniquely suited to identify mistreatment, as a patient typically may be evaluated for several hours by providers from multiple disciplines who are able to observe, interact with, and examine the patient.¹⁵ The ED already exercises a similar essential role in the identification and initial intervention for both child abuse^18,19 and intimate partner violence among younger adults.^20,21

Recognition

Unfortunately, at present, ED providers rarely recognize and report elder abuse.^22-24 Though the reasons for this are not entirely understood, inadequate training, lack of time and space to conduct complete evaluations, reluctance to become involved with the legal system, and challenges to distinguishing intentional from unintentional injuries may be contributing factors.^24,25 A focus on improving EP and ED staff approaches to elder abuse is relevant and timely given the growing elderly population.

Risk Factors

When evaluating elderly patients, providers should consider research suggesting that some older adults may be at particularly high risk for abuse.^4,26-29 Notably, individuals who have cognitive impairment are more likely to be victims of abuse.^30-32 Health-related demographic characteristics such as poor physical and mental health, substance abuse, low income/socioeconomic status, and social isolation all may increase the potential for mistreatment.

Family History

Similar to situations resulting in intimate partner violence, a family history of abuse and exposure to traumatic events may increase risk, and those responsible for elder abuse often turn out to be spouses, romantic partners, or an adult child living with the elderly parent—though paid caregivers also can be abusive.

Suspicion of abuse should be increased when individuals in caregiving roles have a history or show signs of mental illness, substance abuse, financial dependence on the victim, or caregiver stress. Considering that a caregiver may be overwhelmed is particularly relevant when an elderly patient exhibits behavioral issues.

Medical History

Obtaining a clear and thorough medical history from the patient and caregiver, both together and alone, is paramount to assessing the potential for abuse. Many indicators from the history may suggest the possibility of mistreatment (Table 1)^33-37 and although challenging in a busy ED, a comprehensive head-to-toe examination is crucial to adequately assess abuse. Suspicious physical findings and injury patterns of physical abuse, sexual abuse, and neglect are listed in Table 2.^33-37 Ongoing research is aimed at improving ED providers’ ability to differentiate accidental injuries, such as fall injuries, from injuries caused by physical elder abuse.

Injury Patterns

Preliminary studies have indicated that physical abuse injuries most commonly occur on the head, neck, and upper extremities.^38,39 A study comparing abuse victims to accidental injury sufferers found that abuse victims often had large bruises (>5 cm) on the face, lateral right arm, or posterior torso.⁴⁰ Preliminary results from a study in progress suggest that injuries to the left periorbital area, neck, and ulnar forearm may be much more common in abuse than in accident.

Imaging Studies

Emergency radiologists are contributing additional concerning findings indicative of elder abuse,^38,41,42 such as the concomitant presence of old and new fractures, high-energy fractures inconsistent with the purported mechanism, and distal ulnar diaphyseal fractures.^41,42 The ultimate goal is to identify pathognomonic injury patterns similar to those found in child abuse cases, to assist ED providers.

Laboratory Studies

Although there are no laboratory tests to definitively identify abuse or neglect, specific findings that may indicate abuse include anemia, dehydration, malnutrition, hypothermia/hyperthermia, and rhabdomyolysis.⁴³ In addition, inappropriately high- or low-medication levels and the presence of illicit drugs, which are not often checked in elderly patients in the ED, may be a sign of abuse.⁴³

Laboratory studies that reveal undetectable levels of a patient’s prescription medications may indicate a caregiver’s intentional or neglectful withholding of such medications—especially diversion of opioid medications prescribed for painful conditions.⁴³ Likewise, elevated levels of prescribed drugs may point to intentional or unintentional overdose, whereas the presence of nonprescribed drugs or toxins may suggest poisoning.⁴³

Screening Tools

To improve identification of elder abuse in the ED, universal or targeted screening tools are under consideration. Though several screening tools for elder abuse are already available, none have been validated in the ED.^15,44,45 Research sponsored by the National Institute of Justice to identify an ED-specific screening tool is ongoing.¹⁵

Elder Abuse Suspicion Index

The Elder Abuse Suspicion Index (EASI) is a short screening tool that has been validated for cognitively intact patients being treated in family practice and ambulatory care settings, and may be used in EDs.⁴⁴ The tool comprises six questions: five for patient response, and a sixth question for clinician response. This tool is available at http://www.nicenet.ca/tools-easi-elder-abuse-suspicion-index.⁴⁶

Interventional Measures

When elder mistreatment is suspected or confirmed, health care providers must first address any acute medical, traumatic, or psychological issues. Bleeding, orthopedic injuries, metabolic abnormalities, infections, and agitation must be treated and/or stabilized, while neglected or inappropriately managed chronic medical conditions may require treatment.

Hospitalization should be considered for an older adult who needs extended treatment or observation and, in cases of immediate or continued danger of abuse, separation from contact with the suspected abuser. These measures present several challenges, particularly if the suspected abuser is the patient’s health care proxy, in which case early involvement of the hospital’s legal department, social services, and administration may be necessary—especially in navigating the guardianship process.

Engaging security also may be necessary if the patient requires one-to-one patient watch or when the perpetrator must be removed from the ED. Social workers, patient services representatives, and law enforcement officials should be informed when such intervention is necessary.

In instances when a patient is not at risk of immediate harm, interventions can be more individualized. Coordination with primary care physicians (PCPs) must also be facilitated prior to discharge, to ensure consistent longitudinal follow-up care, and social workers should provide any needed out-of-hospital resources to the patient—and caregiver—such as Meals-on-Wheels, medical transportation services, adult day care/senior center participation, and substance abuse treatment.

Patient Decision-Making Capacity

When a patient experiencing abuse declines interventions or services, the EP must evaluate the patient’s decision-making capacity. In unclear cases, a psychiatric evaluation can help to assess decision-making capacity. If the victim is deemed to have capacity with regard to care and/or discharge, the patient’s choice of returning to an unsafe environment must be respected, as is true in instances of intimate partner violence among younger adults—but not in child abuse cases. In such situations, the EP should nevertheless discuss safety planning, offer psychoeducation about violence and abuse, suggest appropriate community referrals, and encourage abused patients to return or call a contact person whenever they desire or feel the need to talk further. For a victim who is deemed not to possess capacity, providers should proceed with treatment considered to be in the best interest of the patient.

Reporting Abuse

Emergency department providers should notify the appropriate authorities when elder abuse is suspected or identified. A report may be made to the local Adult Protective Services (APS), but this agency operates much differently than Child Protective Services. Case workers with APS will not open a case while a patient is in the ED or hospital, as it is deemed a safe environment and any investigation they undertake will only commence upon discharge. Because of this, contacting the local police department prior to discharge should be considered.

Mandatory elder abuse-reporting laws vary from state to state. Health care providers should therefore contact their respective state or city department of health to obtain local legislation.

Multidisciplinary Approach

Ideally, a multidisciplinary, ED-based intervention team modeled on child abuse teams^18,19 would help to optimize treatment and ensure the safety and treatment of vulnerable older adults. These teams could conduct thorough medical, forensic, and social work assessments, allowing ED providers to attend to other patients. The team could also assist in arranging for appropriate and safe dispositions. An innovative Vulnerable Elder Protection Team was recently launched at New York-Presbyterian Weill Cornell Medical Center to provide these services, and its impact is currently being evaluated.

Case Conclusion

The EP who treated the patient realized that blows from a blunt object held by a right-handed person would tend to land on the left side of the victim’s face and upper torso, and that a right-handed victim who successfully blocked the blows intended for her face would instead sustain an isolated right ulna or radius midshaft fracture. These findings, together with the concomitant presence of both old and new fractures, led the EP to question the patient alone and, after obtaining a different history of the events that led to the injuries, admit her for further evaluation, treatment, and interventions to prevent continuing abuse.

Summary

Elder abuse has the potential to affect an increasing number of older adults in this growing population, and an ED visit may offer the only opportunity to identify victims and provide intervention, in turn reducing morbidity and mortality. The results of ongoing research will improve the ability of EPs and ED staff to accurately assess the presence or risk of elder abuse and respond more effectively. It is essential that EPs always consider elder abuse and neglect as a possible etiology when evaluating injuries in this population. Moreover, when identified, addressing elder mistreatment may dramatically improve quality of life or save the lives of these vulnerable patients.


Case

An 85-year-old right-handed woman who recently had been diagnosed with mild cognitive impairment arrived at the ED via emergency medical services (EMS) for evaluation of a reported fall. She was accompanied by her daughter, who resided with the patient and was her primary caregiver. The patient stated that she had tripped on a wet rug in the bathroom of her home, striking her head and face on the edge of the sink without losing consciousness. Her daughter reported that she was not assisting her mother when the fall occurred, but had witnessed the fall from the hallway and called EMS. At the patient’s home, EMS found the patient to be alert, oriented, and ambulatory with normal vital signs that remained stable throughout prehospital transport.

The remainder of the patient’s history was provided almost entirely by her daughter, who constantly interrupted her mother whenever she attempted to directly answer a question or provide information. On physical examination, the patient had bilateral tenderness, edema, and periorbital ecchymoses, and a left eye that was nearly swollen shut. Extraocular movements were normal, visual acuity was intact, and sclerae were noninjected. The patient had tenderness over both maxillary sinuses, and edema and ecchymosis of her left cheek. There was also tenderness, ecchymoses, and edema on the lateral aspects of both forearms, and decreased range of motion of her right lower arm and wrist. With the exception of the patient not knowing the date during the orientation part of the thorough neurological examination, the remainder of the physical examination was unremarkable.

Radiological evaluation found no evidence of traumatic brain injury, but did reveal an acute fracture of the left zygomatic arch, an acute displaced nasal bone fracture, an age-indeterminate fracture of the right zygomatic arch, and an acute right ulnar fracture. Considering all of these findings, particularly the pattern of acute injuries, the emergency physician (EP) considered elder abuse as the possible etiology of the patient’s acute and chronic injuries.

Although the patient had initially agreed with her daughter’s description of the events—including her claim that she had fallen—when the EP questioned the patient alone, she related a history of frequent verbal and less frequent physical abuse by her daughter. The patient further noted that immediately before sustaining the injuries that brought her to the ED, her daughter had been insisting that she sign documents to give her control of her banking and finances. After refusing to sign the papers, the patient said that she and her daughter got into an argument, which she noted “they tended to do frequently.” The patient admitted that during this argument, her daughter struck her in the face repeatedly with the cane that the daughter had grabbed with her right hand.

The EP admitted the patient to the hospital for management of her orthopedic injuries and related pain, and to formulate a safe discharge plan. During admission, additional diagnostic testing revealed multiple old rib fractures, anemia, and a low-serum albumin, which suggested poor nutritional status.

Epidemiology

The term elder abuse refers to harm or the risk of harm to an older adult from either action or negligence committed by someone in a relationship of trust, or when a victim has been targeted because of age or disability. Elder abuse encompasses physical, sexual, or psychological abuse, neglect, and financial exploitation.^1-5 Identified victims of elder abuse typically suffer from multiple forms of abuse.^1-5

At present, elder abuse annually affects 5% to 10% of community-dwelling older adults,^1-6 and nursing-home residents are at increased risk of abuse.^7-10 Poor medical outcomes, including depression and dementia,¹¹ and much higher mortality^6,12,13 have been linked to victims of elder abuse.

Etiology

When treating older adults, it is critically important for EPs and the ED staff to consider and identify elder abuse in the differential diagnosis.^14,15 Presently, only an estimated 1 in 24 cases of abuse is recognized and reported to the authorities,² and much of the subsequent morbidity and mortality of elder abuse results from poor detection. A visit to the ED for an acute injury or illness may be the only time socially isolated older adults leave their homes.^15-17 Additionally, the ED setting is uniquely suited to identify mistreatment, as a patient typically may be evaluated for several hours by providers from multiple disciplines who are able to observe, interact with, and examine the patient.¹⁵ The ED already exercises a similar essential role in the identification and initial intervention for both child abuse^18,19 and intimate partner violence among younger adults.^20,21

Recognition

Unfortunately, at present, ED providers rarely recognize and report elder abuse.^22-24 Though the reasons for this are not entirely understood, inadequate training, lack of time and space to conduct complete evaluations, reluctance to become involved with the legal system, and challenges to distinguishing intentional from unintentional injuries may be contributing factors.^24,25 A focus on improving EP and ED staff approaches to elder abuse is relevant and timely given the growing elderly population.

Risk Factors

When evaluating elderly patients, providers should consider research suggesting that some older adults may be at particularly high risk for abuse.^4,26-29 Notably, individuals who have cognitive impairment are more likely to be victims of abuse.^30-32 Health-related demographic characteristics such as poor physical and mental health, substance abuse, low income/socioeconomic status, and social isolation all may increase the potential for mistreatment.

Family History

Similar to situations resulting in intimate partner violence, a family history of abuse and exposure to traumatic events may increase risk, and those responsible for elder abuse often turn out to be spouses, romantic partners, or an adult child living with the elderly parent—though paid caregivers also can be abusive.

Suspicion of abuse should be increased when individuals in caregiving roles have a history or show signs of mental illness, substance abuse, financial dependence on the victim, or caregiver stress. Considering that a caregiver may be overwhelmed is particularly relevant when an elderly patient exhibits behavioral issues.

Medical History

Obtaining a clear and thorough medical history from the patient and caregiver, both together and alone, is paramount to assessing the potential for abuse. Many indicators from the history may suggest the possibility of mistreatment (Table 1)^33-37 and although challenging in a busy ED, a comprehensive head-to-toe examination is crucial to adequately assess abuse. Suspicious physical findings and injury patterns of physical abuse, sexual abuse, and neglect are listed in Table 2.^33-37 Ongoing research is aimed at improving ED providers’ ability to differentiate accidental injuries, such as fall injuries, from injuries caused by physical elder abuse.

Injury Patterns

Preliminary studies have indicated that physical abuse injuries most commonly occur on the head, neck, and upper extremities.^38,39 A study comparing abuse victims to accidental injury sufferers found that abuse victims often had large bruises (>5 cm) on the face, lateral right arm, or posterior torso.⁴⁰ Preliminary results from a study in progress suggest that injuries to the left periorbital area, neck, and ulnar forearm may be much more common in abuse than in accident.

Imaging Studies

Emergency radiologists are contributing additional concerning findings indicative of elder abuse,^38,41,42 such as the concomitant presence of old and new fractures, high-energy fractures inconsistent with the purported mechanism, and distal ulnar diaphyseal fractures.^41,42 The ultimate goal is to identify pathognomonic injury patterns similar to those found in child abuse cases, to assist ED providers.

Laboratory Studies

Although there are no laboratory tests to definitively identify abuse or neglect, specific findings that may indicate abuse include anemia, dehydration, malnutrition, hypothermia/hyperthermia, and rhabdomyolysis.⁴³ In addition, inappropriately high- or low-medication levels and the presence of illicit drugs, which are not often checked in elderly patients in the ED, may be a sign of abuse.⁴³

Laboratory studies that reveal undetectable levels of a patient’s prescription medications may indicate a caregiver’s intentional or neglectful withholding of such medications—especially diversion of opioid medications prescribed for painful conditions.⁴³ Likewise, elevated levels of prescribed drugs may point to intentional or unintentional overdose, whereas the presence of nonprescribed drugs or toxins may suggest poisoning.⁴³

Screening Tools

To improve identification of elder abuse in the ED, universal or targeted screening tools are under consideration. Though several screening tools for elder abuse are already available, none have been validated in the ED.^15,44,45 Research sponsored by the National Institute of Justice to identify an ED-specific screening tool is ongoing.¹⁵

Elder Abuse Suspicion Index

The Elder Abuse Suspicion Index (EASI) is a short screening tool that has been validated for cognitively intact patients being treated in family practice and ambulatory care settings, and may be used in EDs.⁴⁴ The tool comprises six questions: five for patient response, and a sixth question for clinician response. This tool is available at http://www.nicenet.ca/tools-easi-elder-abuse-suspicion-index.⁴⁶

Interventional Measures

When elder mistreatment is suspected or confirmed, health care providers must first address any acute medical, traumatic, or psychological issues. Bleeding, orthopedic injuries, metabolic abnormalities, infections, and agitation must be treated and/or stabilized, while neglected or inappropriately managed chronic medical conditions may require treatment.

Hospitalization should be considered for an older adult who needs extended treatment or observation and, in cases of immediate or continued danger of abuse, separation from contact with the suspected abuser. These measures present several challenges, particularly if the suspected abuser is the patient’s health care proxy, in which case early involvement of the hospital’s legal department, social services, and administration may be necessary—especially in navigating the guardianship process.

Engaging security also may be necessary if the patient requires one-to-one patient watch or when the perpetrator must be removed from the ED. Social workers, patient services representatives, and law enforcement officials should be informed when such intervention is necessary.

In instances when a patient is not at risk of immediate harm, interventions can be more individualized. Coordination with primary care physicians (PCPs) must also be facilitated prior to discharge, to ensure consistent longitudinal follow-up care, and social workers should provide any needed out-of-hospital resources to the patient—and caregiver—such as Meals-on-Wheels, medical transportation services, adult day care/senior center participation, and substance abuse treatment.

Patient Decision-Making Capacity

When a patient experiencing abuse declines interventions or services, the EP must evaluate the patient’s decision-making capacity. In unclear cases, a psychiatric evaluation can help to assess decision-making capacity. If the victim is deemed to have capacity with regard to care and/or discharge, the patient’s choice of returning to an unsafe environment must be respected, as is true in instances of intimate partner violence among younger adults—but not in child abuse cases. In such situations, the EP should nevertheless discuss safety planning, offer psychoeducation about violence and abuse, suggest appropriate community referrals, and encourage abused patients to return or call a contact person whenever they desire or feel the need to talk further. For a victim who is deemed not to possess capacity, providers should proceed with treatment considered to be in the best interest of the patient.

Reporting Abuse

Emergency department providers should notify the appropriate authorities when elder abuse is suspected or identified. A report may be made to the local Adult Protective Services (APS), but this agency operates much differently than Child Protective Services. Case workers with APS will not open a case while a patient is in the ED or hospital, as it is deemed a safe environment and any investigation they undertake will only commence upon discharge. Because of this, contacting the local police department prior to discharge should be considered.

Mandatory elder abuse-reporting laws vary from state to state. Health care providers should therefore contact their respective state or city department of health to obtain local legislation.

Multidisciplinary Approach

Ideally, a multidisciplinary, ED-based intervention team modeled on child abuse teams^18,19 would help to optimize treatment and ensure the safety and treatment of vulnerable older adults. These teams could conduct thorough medical, forensic, and social work assessments, allowing ED providers to attend to other patients. The team could also assist in arranging for appropriate and safe dispositions. An innovative Vulnerable Elder Protection Team was recently launched at New York-Presbyterian Weill Cornell Medical Center to provide these services, and its impact is currently being evaluated.

Case Conclusion

The EP who treated the patient realized that blows from a blunt object held by a right-handed person would tend to land on the left side of the victim’s face and upper torso, and that a right-handed victim who successfully blocked the blows intended for her face would instead sustain an isolated right ulna or radius midshaft fracture. These findings, together with the concomitant presence of both old and new fractures, led the EP to question the patient alone and, after obtaining a different history of the events that led to the injuries, admit her for further evaluation, treatment, and interventions to prevent continuing abuse.

Summary

Elder abuse has the potential to affect an increasing number of older adults in this growing population, and an ED visit may offer the only opportunity to identify victims and provide intervention, in turn reducing morbidity and mortality. The results of ongoing research will improve the ability of EPs and ED staff to accurately assess the presence or risk of elder abuse and respond more effectively. It is essential that EPs always consider elder abuse and neglect as a possible etiology when evaluating injuries in this population. Moreover, when identified, addressing elder mistreatment may dramatically improve quality of life or save the lives of these vulnerable patients.


Case

An 85-year-old right-handed woman who recently had been diagnosed with mild cognitive impairment arrived at the ED via emergency medical services (EMS) for evaluation of a reported fall. She was accompanied by her daughter, who resided with the patient and was her primary caregiver. The patient stated that she had tripped on a wet rug in the bathroom of her home, striking her head and face on the edge of the sink without losing consciousness. Her daughter reported that she was not assisting her mother when the fall occurred, but had witnessed the fall from the hallway and called EMS. At the patient’s home, EMS found the patient to be alert, oriented, and ambulatory with normal vital signs that remained stable throughout prehospital transport.

The remainder of the patient’s history was provided almost entirely by her daughter, who constantly interrupted her mother whenever she attempted to directly answer a question or provide information. On physical examination, the patient had bilateral tenderness, edema, and periorbital ecchymoses, and a left eye that was nearly swollen shut. Extraocular movements were normal, visual acuity was intact, and sclerae were noninjected. The patient had tenderness over both maxillary sinuses, and edema and ecchymosis of her left cheek. There was also tenderness, ecchymoses, and edema on the lateral aspects of both forearms, and decreased range of motion of her right lower arm and wrist. With the exception of the patient not knowing the date during the orientation part of the thorough neurological examination, the remainder of the physical examination was unremarkable.

Radiological evaluation found no evidence of traumatic brain injury, but did reveal an acute fracture of the left zygomatic arch, an acute displaced nasal bone fracture, an age-indeterminate fracture of the right zygomatic arch, and an acute right ulnar fracture. Considering all of these findings, particularly the pattern of acute injuries, the emergency physician (EP) considered elder abuse as the possible etiology of the patient’s acute and chronic injuries.

Although the patient had initially agreed with her daughter’s description of the events—including her claim that she had fallen—when the EP questioned the patient alone, she related a history of frequent verbal and less frequent physical abuse by her daughter. The patient further noted that immediately before sustaining the injuries that brought her to the ED, her daughter had been insisting that she sign documents to give her control of her banking and finances. After refusing to sign the papers, the patient said that she and her daughter got into an argument, which she noted “they tended to do frequently.” The patient admitted that during this argument, her daughter struck her in the face repeatedly with the cane that the daughter had grabbed with her right hand.

The EP admitted the patient to the hospital for management of her orthopedic injuries and related pain, and to formulate a safe discharge plan. During admission, additional diagnostic testing revealed multiple old rib fractures, anemia, and a low-serum albumin, which suggested poor nutritional status.

Epidemiology

The term elder abuse refers to harm or the risk of harm to an older adult from either action or negligence committed by someone in a relationship of trust, or when a victim has been targeted because of age or disability. Elder abuse encompasses physical, sexual, or psychological abuse, neglect, and financial exploitation.^1-5 Identified victims of elder abuse typically suffer from multiple forms of abuse.^1-5

At present, elder abuse annually affects 5% to 10% of community-dwelling older adults,^1-6 and nursing-home residents are at increased risk of abuse.^7-10 Poor medical outcomes, including depression and dementia,¹¹ and much higher mortality^6,12,13 have been linked to victims of elder abuse.

Etiology

When treating older adults, it is critically important for EPs and the ED staff to consider and identify elder abuse in the differential diagnosis.^14,15 Presently, only an estimated 1 in 24 cases of abuse is recognized and reported to the authorities,² and much of the subsequent morbidity and mortality of elder abuse results from poor detection. A visit to the ED for an acute injury or illness may be the only time socially isolated older adults leave their homes.^15-17 Additionally, the ED setting is uniquely suited to identify mistreatment, as a patient typically may be evaluated for several hours by providers from multiple disciplines who are able to observe, interact with, and examine the patient.¹⁵ The ED already exercises a similar essential role in the identification and initial intervention for both child abuse^18,19 and intimate partner violence among younger adults.^20,21

Recognition

Unfortunately, at present, ED providers rarely recognize and report elder abuse.^22-24 Though the reasons for this are not entirely understood, inadequate training, lack of time and space to conduct complete evaluations, reluctance to become involved with the legal system, and challenges to distinguishing intentional from unintentional injuries may be contributing factors.^24,25 A focus on improving EP and ED staff approaches to elder abuse is relevant and timely given the growing elderly population.

Risk Factors

When evaluating elderly patients, providers should consider research suggesting that some older adults may be at particularly high risk for abuse.^4,26-29 Notably, individuals who have cognitive impairment are more likely to be victims of abuse.^30-32 Health-related demographic characteristics such as poor physical and mental health, substance abuse, low income/socioeconomic status, and social isolation all may increase the potential for mistreatment.

Family History

Similar to situations resulting in intimate partner violence, a family history of abuse and exposure to traumatic events may increase risk, and those responsible for elder abuse often turn out to be spouses, romantic partners, or an adult child living with the elderly parent—though paid caregivers also can be abusive.

Suspicion of abuse should be increased when individuals in caregiving roles have a history or show signs of mental illness, substance abuse, financial dependence on the victim, or caregiver stress. Considering that a caregiver may be overwhelmed is particularly relevant when an elderly patient exhibits behavioral issues.

Medical History

Obtaining a clear and thorough medical history from the patient and caregiver, both together and alone, is paramount to assessing the potential for abuse. Many indicators from the history may suggest the possibility of mistreatment (Table 1)^33-37 and although challenging in a busy ED, a comprehensive head-to-toe examination is crucial to adequately assess abuse. Suspicious physical findings and injury patterns of physical abuse, sexual abuse, and neglect are listed in Table 2.^33-37 Ongoing research is aimed at improving ED providers’ ability to differentiate accidental injuries, such as fall injuries, from injuries caused by physical elder abuse.

Injury Patterns

Preliminary studies have indicated that physical abuse injuries most commonly occur on the head, neck, and upper extremities.^38,39 A study comparing abuse victims to accidental injury sufferers found that abuse victims often had large bruises (>5 cm) on the face, lateral right arm, or posterior torso.⁴⁰ Preliminary results from a study in progress suggest that injuries to the left periorbital area, neck, and ulnar forearm may be much more common in abuse than in accident.

Imaging Studies

Emergency radiologists are contributing additional concerning findings indicative of elder abuse,^38,41,42 such as the concomitant presence of old and new fractures, high-energy fractures inconsistent with the purported mechanism, and distal ulnar diaphyseal fractures.^41,42 The ultimate goal is to identify pathognomonic injury patterns similar to those found in child abuse cases, to assist ED providers.

Laboratory Studies

Although there are no laboratory tests to definitively identify abuse or neglect, specific findings that may indicate abuse include anemia, dehydration, malnutrition, hypothermia/hyperthermia, and rhabdomyolysis.⁴³ In addition, inappropriately high- or low-medication levels and the presence of illicit drugs, which are not often checked in elderly patients in the ED, may be a sign of abuse.⁴³

Laboratory studies that reveal undetectable levels of a patient’s prescription medications may indicate a caregiver’s intentional or neglectful withholding of such medications—especially diversion of opioid medications prescribed for painful conditions.⁴³ Likewise, elevated levels of prescribed drugs may point to intentional or unintentional overdose, whereas the presence of nonprescribed drugs or toxins may suggest poisoning.⁴³

Screening Tools

To improve identification of elder abuse in the ED, universal or targeted screening tools are under consideration. Though several screening tools for elder abuse are already available, none have been validated in the ED.^15,44,45 Research sponsored by the National Institute of Justice to identify an ED-specific screening tool is ongoing.¹⁵

Elder Abuse Suspicion Index

The Elder Abuse Suspicion Index (EASI) is a short screening tool that has been validated for cognitively intact patients being treated in family practice and ambulatory care settings, and may be used in EDs.⁴⁴ The tool comprises six questions: five for patient response, and a sixth question for clinician response. This tool is available at http://www.nicenet.ca/tools-easi-elder-abuse-suspicion-index.⁴⁶

Interventional Measures

When elder mistreatment is suspected or confirmed, health care providers must first address any acute medical, traumatic, or psychological issues. Bleeding, orthopedic injuries, metabolic abnormalities, infections, and agitation must be treated and/or stabilized, while neglected or inappropriately managed chronic medical conditions may require treatment.

Hospitalization should be considered for an older adult who needs extended treatment or observation and, in cases of immediate or continued danger of abuse, separation from contact with the suspected abuser. These measures present several challenges, particularly if the suspected abuser is the patient’s health care proxy, in which case early involvement of the hospital’s legal department, social services, and administration may be necessary—especially in navigating the guardianship process.

Engaging security also may be necessary if the patient requires one-to-one patient watch or when the perpetrator must be removed from the ED. Social workers, patient services representatives, and law enforcement officials should be informed when such intervention is necessary.

In instances when a patient is not at risk of immediate harm, interventions can be more individualized. Coordination with primary care physicians (PCPs) must also be facilitated prior to discharge, to ensure consistent longitudinal follow-up care, and social workers should provide any needed out-of-hospital resources to the patient—and caregiver—such as Meals-on-Wheels, medical transportation services, adult day care/senior center participation, and substance abuse treatment.

Patient Decision-Making Capacity

When a patient experiencing abuse declines interventions or services, the EP must evaluate the patient’s decision-making capacity. In unclear cases, a psychiatric evaluation can help to assess decision-making capacity. If the victim is deemed to have capacity with regard to care and/or discharge, the patient’s choice of returning to an unsafe environment must be respected, as is true in instances of intimate partner violence among younger adults—but not in child abuse cases. In such situations, the EP should nevertheless discuss safety planning, offer psychoeducation about violence and abuse, suggest appropriate community referrals, and encourage abused patients to return or call a contact person whenever they desire or feel the need to talk further. For a victim who is deemed not to possess capacity, providers should proceed with treatment considered to be in the best interest of the patient.

Reporting Abuse

Emergency department providers should notify the appropriate authorities when elder abuse is suspected or identified. A report may be made to the local Adult Protective Services (APS), but this agency operates much differently than Child Protective Services. Case workers with APS will not open a case while a patient is in the ED or hospital, as it is deemed a safe environment and any investigation they undertake will only commence upon discharge. Because of this, contacting the local police department prior to discharge should be considered.

Mandatory elder abuse-reporting laws vary from state to state. Health care providers should therefore contact their respective state or city department of health to obtain local legislation.

Multidisciplinary Approach

Ideally, a multidisciplinary, ED-based intervention team modeled on child abuse teams^18,19 would help to optimize treatment and ensure the safety and treatment of vulnerable older adults. These teams could conduct thorough medical, forensic, and social work assessments, allowing ED providers to attend to other patients. The team could also assist in arranging for appropriate and safe dispositions. An innovative Vulnerable Elder Protection Team was recently launched at New York-Presbyterian Weill Cornell Medical Center to provide these services, and its impact is currently being evaluated.

Case Conclusion

The EP who treated the patient realized that blows from a blunt object held by a right-handed person would tend to land on the left side of the victim’s face and upper torso, and that a right-handed victim who successfully blocked the blows intended for her face would instead sustain an isolated right ulna or radius midshaft fracture. These findings, together with the concomitant presence of both old and new fractures, led the EP to question the patient alone and, after obtaining a different history of the events that led to the injuries, admit her for further evaluation, treatment, and interventions to prevent continuing abuse.

Summary

Elder abuse has the potential to affect an increasing number of older adults in this growing population, and an ED visit may offer the only opportunity to identify victims and provide intervention, in turn reducing morbidity and mortality. The results of ongoing research will improve the ability of EPs and ED staff to accurately assess the presence or risk of elder abuse and respond more effectively. It is essential that EPs always consider elder abuse and neglect as a possible etiology when evaluating injuries in this population. Moreover, when identified, addressing elder mistreatment may dramatically improve quality of life or save the lives of these vulnerable patients.


Artificial dermal fillers and autologous fat grafting have become increasingly popular in recent years, primarily because they augment existing soft tissue volumes, thus producing aesthetic improvements at a lower cost than traditional plastic surgery (ie, facelift), and with nearly no recovery time. According to the American Society for Aesthetic Plastic Surgery, more than 2 million hyaluronic acid (HA) dermal filler procedures were performed in 2016, an increase of 3% from 2015.¹ In addition, 80,000 autologous fat grafting procedures were performed in 2016, an increase of 13% from 2015. In total, there were 2.6 million soft tissue filler procedures in 2016, an increase of 2% from 2015.¹

With the increased demand and access to both artificial dermal fillers and autologous fat grafting, there has been a plethora of reported adverse events, ranging from expected erythema to acute blindness and stroke. Emergency physicians should have a thorough understanding of facial vascular anatomy, as well as the effects of available facial volumization products, including potential complications and treatment options. Through our review of two patient cases, we propose a simplified protocol for the treatment of patients with acute arterial occlusion secondary to facial volumization procedures.

Case 1

A 38-year-old white woman presented to the ED for evaluation of transient blurred vision and blanching of the left cheek and upper lip, which began approximately 40 minutes prior to presentation, immediately after her primary care physician (PCP) injected her left nasolabial fold with calcium hydroxyapatite (CaHA). The patient stated that her vision became blurry and her eyes began to tear within 1 minute of receiving the injection. She further noted that these visual changes were painless and lasted for approximately 30 seconds.

The patient’s PCP believed these symptoms were due to pain at the injection site. While the patient was at her PCP’s office, the reception clerk noticed the blanching of the patient’s left cheek and informed the PCP, who referred the patient to our ED for evaluation.

Workup

The patient’s vital signs at presentation were normal. Her medical history was unremarkable and negative for smoking, alcohol, or drug use. She was not taking any medications and had no known drug allergies. The patient’s history was negative for any prior cosmetic procedures, and she confirmed this was the first and only time had a facial revolumization.

Facial examination revealed a Fitzpatrick scale (FS; a numerical scoring system used to assess a patient’s reaction to ultraviolet radiation) score of type 3. She also had left-sided blanching that extended from the midpoint of the nose diagonally to the lateral midbuccal cheek to the level of the oral commissure, including the cutaneous upper lip, alar, and nasal side wall. There was minimal capillary refill with compression at the affected site, and sensation was diminished to fine touch and pinprick. The facial muscles were intact, and, with the exception of puncture marks along both nasolabial folds, the remainder of the facial examination was normal.

The ophthalmic examination revealed a reactive pupil at 2 mm, white sclera, pink conjunctiva, red reflex, and normal fundoscopic vessels. The patient’s bedside Snellen visual acuity and visual field assessments were normal. The neurological examination was likewise normal, and no other physical findings were noted.

Laboratory evaluation included complete blood count (CBC), Chem 7 panel (creatinine, blood urea nitrogen [BUN], carbon dioxide, chloride, glucose, sodium, and potassium), and international normalized ratio (INR), which were all within normal limits.

Diagnosis and Treatment

The patient was diagnosed with acute angular arterial occlusion and transient retinal artery embolism secondary to facial volumization with CaHA. She was treated with oral acetylsalicylic acid aspirin (ASA) 325 mg, prednisone 40 mg, and sildenafil 50 mg; and subcutaneous (SC) enoxaparin 60 mg (1 mg/kg). Topical nitroglycerin paste 2% was applied to the affected area.

Ophthalmology and plastic surgery services were contacted for consultation. Based on no acute findings on examination, the ophthalmologist provided no additional treatment recommendations. The patient was observed in the ED for 4 hours, during which time the facial blanching resolved and her capillary refill time returned to normal at 2 seconds.

After evaluating the patient, the plastic surgeon recommended discharge home with instructions to continue taking the oral ASA and sildenafil, as well as a methylprednisolone dose pack for 6 days. He also recommended the patient begin hyperbaric oxygen (HBO) therapy the day after discharge, since there was no HBO chamber available during her hospital stay.

The patient complied with all discharge instructions, including HBO therapy. At plastic surgery follow-up, the patient had no long-term adverse effects from the CaHA injection.

Case 2

A 54-year-old Asian woman presented to the ED for evaluation of a 24-hour history of progressive and persistent pain, swelling, and discoloration of the nasolabial and upper lip region. She stated her symptoms began within 1 hour of receiving a fat graft injection into the affected area by her cosmetic surgeon. After examining the patient, the cosmetic surgeon referred her to the ED for further evaluation. The patient stated that she had undergone six prior facial revolumization procedures, but noted the recent procedure was her first autologous fat graft.

Workup

The patient’s medical history was unremarkable. Her social history was positive for one glass of wine per day and negative for smoking. The patient was not taking any medications and had no known drug allergies.

The patient’s vital signs at presentation were normal. She was evaluated approximately 30 hours after the fat graft procedure. Facial examination revealed an FS of type 4 with right-sided ischemia along the cutaneous upper lip, alar, and cheek (Figure 1).

Capillary refill time with compression was 0 in the affected area. Sensation to fine touch and pinprick was 0. The facial muscles were intact and, with the exception of puncture marks along both nasolabial folds, the remainder of the facial examination was normal. The neurological examination was likewise normal, and no other physical findings were noted. Laboratory evaluation included CBC, Chem 7 panel, and INR, which were all within normal limits.

Diagnosis and Treatment

The patient was diagnosed with acute angular arterial occlusion with soft tissue ischemia secondary to facial revolumization with autologous fat grafting. She was given oral acyclovir 800 mg, ASA 325 mg, cephalexin 500 mg, prednisone 40 mg, and sildenafil 50 mg; and SC enoxaparin 60 mg (1 mg/kg). Topical nitroglycerin paste 2% was applied to the affected area.

Plastic surgery services were contacted for consultation. After evaluating the patient, the plastic surgeon recommended discharge home with instructions to continue taking the oral acyclovir, ASA, cephalexin, prednisone, and sildenafil for 6 days. He also recommended the patient start HBO therapy the day after discharge home.

The patient refused HBO therapy, but did visit a plastic surgeon for a follow-up examination 3 days after discharge from the ED. A photograph of the patient’s nasolabial and upper lip region taken during this visit is presented in Figure 2.

Five days after discharge from the ED, the patient presented to a plastic surgery clinic for evaluation; a photograph was also obtained at this visit (Figure 3). The plastic surgeon at this clinic referred the patient to a tertiary center for a second opinion regarding the need for HBO therapy. The plastic surgeon at the tertiary center affirmed the initial plastic surgeon’s diagnosis and recommendation for HBO therapy. Although the patient did not return for further evaluation, she underwent 10 HBO treatments at the tertiary center with an acceptable aesthetic result.

Noninvasive Injectable Cosmetic Facial Augmentation

Facial augmentation procedures include the use of autologous adipose bovine collagen, HA gels, CaHA, and plastic compounds to fill wrinkles, folds, or soft tissue defects due to normal aging or trauma. Plastic surgeons traditionally use adipose and manufactured products for scar revision, midfacial restoration of volume loss from aging or trauma, cheek and chin augmentation, tear-trough correction (the diagonal crease running from the inner eye canthus to the maxilla resulting in a groove that creates a tired appearance), nose reshaping, lip enhancement, and correction of facial asymmetry.

Today the use of manufactured soft tissue revolumization products (ie, fillers) is no longer solely in the purview of plastic surgeons, but rather has become ubiquitous with nonsurgeons and allied health care professionals. As the overall number of revolumization procedures increases, so too does the risk for local and distant vascular complications.

Dermal Fillers

Dermal fillers vary widely in their respective properties, solubility, injection-technique flow requirements, and inherent complication risks. Regardless of type, all dermal fillers have the potential to cause serious complications. Most adverse events are related to substance type, volume, and injection technique. Bruising and trauma-related edema following dermal filler procedures are considered normal.

Though complications from dermal filler injections are rarely lethal, serious adverse events can result in permanent functional and aesthetic deficits. With proper physician training, planning, and injection technique, most adverse events can be avoided.

Hyaluronic Acid. Hyaluronic acid (HA)-containing injectable gel fillers (eg, Belotero, Juvederm, Perlane, and Restylane) are one of the most commonly used volumization products—especially by nonplastic surgeons. These gel fillers, which vary in viscosity and elasticity, may be injected from the superficial dermis to the periosteum. Dilution, dispersion, and degradation may be achieved in vivo either by high arterial flow or hyaluronidase.

Calcium Hydroxylapatite. Calcium hydroxylapatite (Radiesse) microsphere fillers consist of a very viscous paste that is mixed with lidocaine prior to injection to increase its flowability. The CaHA solution is injected at the deep dermis to periosteum level. Since CaHA is not easily diluted, dispersed, or degraded by high arterial flow, it tends to retain its consistency. When this procedure is performed by a novice, it can result in complete occlusion at the injection site or through embolization via antegrade or retrograde flow.

Poly-L-lactic Acid. Poly-L-lactic acid (PLLA; Sculptra) is a low-viscosity fluid comprised of synthetic polymer beads. The PLLA microparticles are not dissolvable or degradable by high arterial flow, and are designed to induce an inflammatory response with neocollagenesis.

Polymethyl Methacrylate. Polymethyl methacrylate (PMMA; Bellafil) consists of a combination of microscopic synthetic polymer beads suspended in a variety of substances. For facial enhancement, PMMA is usually suspended in HA or bovine collagen. Off-label use of silicon oils and gels such as PMMA are gaining in popularity—often with disastrous consequences such as acute arterial occlusion, bone erosion, and skin ulcerations.^2,3

Autologous Adipose Tissue. Plastic surgeons primarily use autologous adipose tissue to volumize the face, breasts, buttocks, and scars. Autologous fat grafts are typically placed in fat, superficial and deep muscles, and deep fat pads through a 2- to 2.5-mm facial fat grafting cannula using a multichannel technique that leaves minute amounts of fat in each channel. Fat embolization may occur when a nonfacial fat graft cannula or needle used to transplant the fat graft enters an artery either through direct sharp puncture or traumatic tear cannulation.^4-9

Adverse Events

The first recorded manufactured adverse event from an injectable dermal filler was in 1991. At that time, the US Food and Drug Administration warned of adverse events secondary to collagen injections, including open sores, abscess formation associated with delayed healing of the skin, and partial blindness.¹⁰

Arterial Embolization and Cannulation. The most serious complications from dermal fillers are accidental injection and/or embolization of the filler into the arterial system. Since 1991, an increased number of cases of soft tissue necrosis, blindness, and stroke have been reported as a result of injection of fillers in the glabella, forehead creases, temple, crow’s feet, nose, cheeks, nasolabial folds, and lower lip.^11-15

Accidental cannulation and inadvertent injection of fillers into the arterial vessels can have catastrophic complications. The potential of such inadvertent complications occurs despite skill level of the practitioner or surgeon. Therefore, recognition and treatment of a vascular occlusion must be immediate and aggressive to avoid devastating and potentially irreversible complications including blindness, stroke, and death.^11-15

Acute Blindness and Stroke. The issues and concerns associated with local intra-arterial dermal filler injection and distal embolism are well described in the literature. However, the mechanism of retinal artery occlusion is much more complex given the need for deep placement of products and the force necessary to cause distention and elevation of the dermis. Hence, higher g-forces are applied via the plunger, forcing the intra-arterial filler proximally past the origin of the retinal artery. When the clinician stops the injection, the arterial systolic pressure immediately embolizes the filler into the distal branches of the ophthalmic artery. This causes acute pain and blindness (Figure 5). Depending on the g-force applied, filler can enter into the internal carotid artery and embolize resulting in cerebral ischemia. Signs of cerebral ischemia may be mild or overt.^4-9

Management

Patients with intra-arterial dermal filler injection constitute a medical emergency requiring immediate intervention. We recommend clinicians initiate the treatment protocols outlined in the Box and Table 1.

Hyaluronidase. Injection of hyaluronidase may assist in degrading the HA around the arterial puncture site, relieving compression, which may increase blood flow. There is a risk of distal embolization from a dislodged HA emboli.

Fat Graft Injections. There are no known degradation products for fat, CaHA, PLLA, or PMMA products. The use of normal saline or hyaluronidase has no proven efficacy and may increase the compression pressure in the artery and surrounding tissue, causing further ischemia.

Long-term Sequelae

Despite aggressive intervention, permanent complications of cerebral ischemia, blindness, and severe soft tissue necrosis may occur. In six cases in the literature, patients treated with ocular massage therapy,^7,14 carbon dioxide rebreathing,¹⁴ HBO therapy,^7,14 oral and IV corticosteroids,^6-9 antiplatelet drugs,⁶ and fibrinolytic agents,^7,16 or mechanical thrombolysis¹⁶ showed no clinical effects. Neither the treated nor the untreated patients in any of these case studies had any return of vision.^4-7,9,20-27

Conclusion

Although artificial dermal fillers such as HA, CaHA, PLLA, and PMMA, and autologous adipose tissue grafts offer a minimally invasive alternative to plastic surgical procedures, they are not without complication or adverse effects, such as the acute arterial occlusion experienced by both of our patients. Patients presenting to the ED with adverse effects from such procedures must be managed promptly, employing the suggested management and treatment protocol, including consultation with ophthalmology, plastic surgery, and neurological services as indicated, to avoid permanent sequela and damage.

Artificial dermal fillers and autologous fat grafting have become increasingly popular in recent years, primarily because they augment existing soft tissue volumes, thus producing aesthetic improvements at a lower cost than traditional plastic surgery (ie, facelift), and with nearly no recovery time. According to the American Society for Aesthetic Plastic Surgery, more than 2 million hyaluronic acid (HA) dermal filler procedures were performed in 2016, an increase of 3% from 2015.¹ In addition, 80,000 autologous fat grafting procedures were performed in 2016, an increase of 13% from 2015. In total, there were 2.6 million soft tissue filler procedures in 2016, an increase of 2% from 2015.¹

With the increased demand and access to both artificial dermal fillers and autologous fat grafting, there has been a plethora of reported adverse events, ranging from expected erythema to acute blindness and stroke. Emergency physicians should have a thorough understanding of facial vascular anatomy, as well as the effects of available facial volumization products, including potential complications and treatment options. Through our review of two patient cases, we propose a simplified protocol for the treatment of patients with acute arterial occlusion secondary to facial volumization procedures.

Case 1

A 38-year-old white woman presented to the ED for evaluation of transient blurred vision and blanching of the left cheek and upper lip, which began approximately 40 minutes prior to presentation, immediately after her primary care physician (PCP) injected her left nasolabial fold with calcium hydroxyapatite (CaHA). The patient stated that her vision became blurry and her eyes began to tear within 1 minute of receiving the injection. She further noted that these visual changes were painless and lasted for approximately 30 seconds.

The patient’s PCP believed these symptoms were due to pain at the injection site. While the patient was at her PCP’s office, the reception clerk noticed the blanching of the patient’s left cheek and informed the PCP, who referred the patient to our ED for evaluation.

Workup

The patient’s vital signs at presentation were normal. Her medical history was unremarkable and negative for smoking, alcohol, or drug use. She was not taking any medications and had no known drug allergies. The patient’s history was negative for any prior cosmetic procedures, and she confirmed this was the first and only time had a facial revolumization.

Facial examination revealed a Fitzpatrick scale (FS; a numerical scoring system used to assess a patient’s reaction to ultraviolet radiation) score of type 3. She also had left-sided blanching that extended from the midpoint of the nose diagonally to the lateral midbuccal cheek to the level of the oral commissure, including the cutaneous upper lip, alar, and nasal side wall. There was minimal capillary refill with compression at the affected site, and sensation was diminished to fine touch and pinprick. The facial muscles were intact, and, with the exception of puncture marks along both nasolabial folds, the remainder of the facial examination was normal.

The ophthalmic examination revealed a reactive pupil at 2 mm, white sclera, pink conjunctiva, red reflex, and normal fundoscopic vessels. The patient’s bedside Snellen visual acuity and visual field assessments were normal. The neurological examination was likewise normal, and no other physical findings were noted.

Laboratory evaluation included complete blood count (CBC), Chem 7 panel (creatinine, blood urea nitrogen [BUN], carbon dioxide, chloride, glucose, sodium, and potassium), and international normalized ratio (INR), which were all within normal limits.

Diagnosis and Treatment

The patient was diagnosed with acute angular arterial occlusion and transient retinal artery embolism secondary to facial volumization with CaHA. She was treated with oral acetylsalicylic acid aspirin (ASA) 325 mg, prednisone 40 mg, and sildenafil 50 mg; and subcutaneous (SC) enoxaparin 60 mg (1 mg/kg). Topical nitroglycerin paste 2% was applied to the affected area.

Ophthalmology and plastic surgery services were contacted for consultation. Based on no acute findings on examination, the ophthalmologist provided no additional treatment recommendations. The patient was observed in the ED for 4 hours, during which time the facial blanching resolved and her capillary refill time returned to normal at 2 seconds.

After evaluating the patient, the plastic surgeon recommended discharge home with instructions to continue taking the oral ASA and sildenafil, as well as a methylprednisolone dose pack for 6 days. He also recommended the patient begin hyperbaric oxygen (HBO) therapy the day after discharge, since there was no HBO chamber available during her hospital stay.

The patient complied with all discharge instructions, including HBO therapy. At plastic surgery follow-up, the patient had no long-term adverse effects from the CaHA injection.

Case 2

A 54-year-old Asian woman presented to the ED for evaluation of a 24-hour history of progressive and persistent pain, swelling, and discoloration of the nasolabial and upper lip region. She stated her symptoms began within 1 hour of receiving a fat graft injection into the affected area by her cosmetic surgeon. After examining the patient, the cosmetic surgeon referred her to the ED for further evaluation. The patient stated that she had undergone six prior facial revolumization procedures, but noted the recent procedure was her first autologous fat graft.

Workup

The patient’s medical history was unremarkable. Her social history was positive for one glass of wine per day and negative for smoking. The patient was not taking any medications and had no known drug allergies.

The patient’s vital signs at presentation were normal. She was evaluated approximately 30 hours after the fat graft procedure. Facial examination revealed an FS of type 4 with right-sided ischemia along the cutaneous upper lip, alar, and cheek (Figure 1).

Capillary refill time with compression was 0 in the affected area. Sensation to fine touch and pinprick was 0. The facial muscles were intact and, with the exception of puncture marks along both nasolabial folds, the remainder of the facial examination was normal. The neurological examination was likewise normal, and no other physical findings were noted. Laboratory evaluation included CBC, Chem 7 panel, and INR, which were all within normal limits.

Diagnosis and Treatment

The patient was diagnosed with acute angular arterial occlusion with soft tissue ischemia secondary to facial revolumization with autologous fat grafting. She was given oral acyclovir 800 mg, ASA 325 mg, cephalexin 500 mg, prednisone 40 mg, and sildenafil 50 mg; and SC enoxaparin 60 mg (1 mg/kg). Topical nitroglycerin paste 2% was applied to the affected area.

Plastic surgery services were contacted for consultation. After evaluating the patient, the plastic surgeon recommended discharge home with instructions to continue taking the oral acyclovir, ASA, cephalexin, prednisone, and sildenafil for 6 days. He also recommended the patient start HBO therapy the day after discharge home.

The patient refused HBO therapy, but did visit a plastic surgeon for a follow-up examination 3 days after discharge from the ED. A photograph of the patient’s nasolabial and upper lip region taken during this visit is presented in Figure 2.

Five days after discharge from the ED, the patient presented to a plastic surgery clinic for evaluation; a photograph was also obtained at this visit (Figure 3). The plastic surgeon at this clinic referred the patient to a tertiary center for a second opinion regarding the need for HBO therapy. The plastic surgeon at the tertiary center affirmed the initial plastic surgeon’s diagnosis and recommendation for HBO therapy. Although the patient did not return for further evaluation, she underwent 10 HBO treatments at the tertiary center with an acceptable aesthetic result.

Noninvasive Injectable Cosmetic Facial Augmentation

Facial augmentation procedures include the use of autologous adipose bovine collagen, HA gels, CaHA, and plastic compounds to fill wrinkles, folds, or soft tissue defects due to normal aging or trauma. Plastic surgeons traditionally use adipose and manufactured products for scar revision, midfacial restoration of volume loss from aging or trauma, cheek and chin augmentation, tear-trough correction (the diagonal crease running from the inner eye canthus to the maxilla resulting in a groove that creates a tired appearance), nose reshaping, lip enhancement, and correction of facial asymmetry.

Today the use of manufactured soft tissue revolumization products (ie, fillers) is no longer solely in the purview of plastic surgeons, but rather has become ubiquitous with nonsurgeons and allied health care professionals. As the overall number of revolumization procedures increases, so too does the risk for local and distant vascular complications.

Dermal Fillers

Dermal fillers vary widely in their respective properties, solubility, injection-technique flow requirements, and inherent complication risks. Regardless of type, all dermal fillers have the potential to cause serious complications. Most adverse events are related to substance type, volume, and injection technique. Bruising and trauma-related edema following dermal filler procedures are considered normal.

Though complications from dermal filler injections are rarely lethal, serious adverse events can result in permanent functional and aesthetic deficits. With proper physician training, planning, and injection technique, most adverse events can be avoided.

Hyaluronic Acid. Hyaluronic acid (HA)-containing injectable gel fillers (eg, Belotero, Juvederm, Perlane, and Restylane) are one of the most commonly used volumization products—especially by nonplastic surgeons. These gel fillers, which vary in viscosity and elasticity, may be injected from the superficial dermis to the periosteum. Dilution, dispersion, and degradation may be achieved in vivo either by high arterial flow or hyaluronidase.

Calcium Hydroxylapatite. Calcium hydroxylapatite (Radiesse) microsphere fillers consist of a very viscous paste that is mixed with lidocaine prior to injection to increase its flowability. The CaHA solution is injected at the deep dermis to periosteum level. Since CaHA is not easily diluted, dispersed, or degraded by high arterial flow, it tends to retain its consistency. When this procedure is performed by a novice, it can result in complete occlusion at the injection site or through embolization via antegrade or retrograde flow.

Poly-L-lactic Acid. Poly-L-lactic acid (PLLA; Sculptra) is a low-viscosity fluid comprised of synthetic polymer beads. The PLLA microparticles are not dissolvable or degradable by high arterial flow, and are designed to induce an inflammatory response with neocollagenesis.

Polymethyl Methacrylate. Polymethyl methacrylate (PMMA; Bellafil) consists of a combination of microscopic synthetic polymer beads suspended in a variety of substances. For facial enhancement, PMMA is usually suspended in HA or bovine collagen. Off-label use of silicon oils and gels such as PMMA are gaining in popularity—often with disastrous consequences such as acute arterial occlusion, bone erosion, and skin ulcerations.^2,3

Autologous Adipose Tissue. Plastic surgeons primarily use autologous adipose tissue to volumize the face, breasts, buttocks, and scars. Autologous fat grafts are typically placed in fat, superficial and deep muscles, and deep fat pads through a 2- to 2.5-mm facial fat grafting cannula using a multichannel technique that leaves minute amounts of fat in each channel. Fat embolization may occur when a nonfacial fat graft cannula or needle used to transplant the fat graft enters an artery either through direct sharp puncture or traumatic tear cannulation.^4-9

Adverse Events

The first recorded manufactured adverse event from an injectable dermal filler was in 1991. At that time, the US Food and Drug Administration warned of adverse events secondary to collagen injections, including open sores, abscess formation associated with delayed healing of the skin, and partial blindness.¹⁰

Arterial Embolization and Cannulation. The most serious complications from dermal fillers are accidental injection and/or embolization of the filler into the arterial system. Since 1991, an increased number of cases of soft tissue necrosis, blindness, and stroke have been reported as a result of injection of fillers in the glabella, forehead creases, temple, crow’s feet, nose, cheeks, nasolabial folds, and lower lip.^11-15

Accidental cannulation and inadvertent injection of fillers into the arterial vessels can have catastrophic complications. The potential of such inadvertent complications occurs despite skill level of the practitioner or surgeon. Therefore, recognition and treatment of a vascular occlusion must be immediate and aggressive to avoid devastating and potentially irreversible complications including blindness, stroke, and death.^11-15

Acute Blindness and Stroke. The issues and concerns associated with local intra-arterial dermal filler injection and distal embolism are well described in the literature. However, the mechanism of retinal artery occlusion is much more complex given the need for deep placement of products and the force necessary to cause distention and elevation of the dermis. Hence, higher g-forces are applied via the plunger, forcing the intra-arterial filler proximally past the origin of the retinal artery. When the clinician stops the injection, the arterial systolic pressure immediately embolizes the filler into the distal branches of the ophthalmic artery. This causes acute pain and blindness (Figure 5). Depending on the g-force applied, filler can enter into the internal carotid artery and embolize resulting in cerebral ischemia. Signs of cerebral ischemia may be mild or overt.^4-9

Management

Patients with intra-arterial dermal filler injection constitute a medical emergency requiring immediate intervention. We recommend clinicians initiate the treatment protocols outlined in the Box and Table 1.

Hyaluronidase. Injection of hyaluronidase may assist in degrading the HA around the arterial puncture site, relieving compression, which may increase blood flow. There is a risk of distal embolization from a dislodged HA emboli.

Fat Graft Injections. There are no known degradation products for fat, CaHA, PLLA, or PMMA products. The use of normal saline or hyaluronidase has no proven efficacy and may increase the compression pressure in the artery and surrounding tissue, causing further ischemia.

Long-term Sequelae

Despite aggressive intervention, permanent complications of cerebral ischemia, blindness, and severe soft tissue necrosis may occur. In six cases in the literature, patients treated with ocular massage therapy,^7,14 carbon dioxide rebreathing,¹⁴ HBO therapy,^7,14 oral and IV corticosteroids,^6-9 antiplatelet drugs,⁶ and fibrinolytic agents,^7,16 or mechanical thrombolysis¹⁶ showed no clinical effects. Neither the treated nor the untreated patients in any of these case studies had any return of vision.^4-7,9,20-27

Conclusion

Although artificial dermal fillers such as HA, CaHA, PLLA, and PMMA, and autologous adipose tissue grafts offer a minimally invasive alternative to plastic surgical procedures, they are not without complication or adverse effects, such as the acute arterial occlusion experienced by both of our patients. Patients presenting to the ED with adverse effects from such procedures must be managed promptly, employing the suggested management and treatment protocol, including consultation with ophthalmology, plastic surgery, and neurological services as indicated, to avoid permanent sequela and damage.

Artificial dermal fillers and autologous fat grafting have become increasingly popular in recent years, primarily because they augment existing soft tissue volumes, thus producing aesthetic improvements at a lower cost than traditional plastic surgery (ie, facelift), and with nearly no recovery time. According to the American Society for Aesthetic Plastic Surgery, more than 2 million hyaluronic acid (HA) dermal filler procedures were performed in 2016, an increase of 3% from 2015.¹ In addition, 80,000 autologous fat grafting procedures were performed in 2016, an increase of 13% from 2015. In total, there were 2.6 million soft tissue filler procedures in 2016, an increase of 2% from 2015.¹

With the increased demand and access to both artificial dermal fillers and autologous fat grafting, there has been a plethora of reported adverse events, ranging from expected erythema to acute blindness and stroke. Emergency physicians should have a thorough understanding of facial vascular anatomy, as well as the effects of available facial volumization products, including potential complications and treatment options. Through our review of two patient cases, we propose a simplified protocol for the treatment of patients with acute arterial occlusion secondary to facial volumization procedures.

Case 1

A 38-year-old white woman presented to the ED for evaluation of transient blurred vision and blanching of the left cheek and upper lip, which began approximately 40 minutes prior to presentation, immediately after her primary care physician (PCP) injected her left nasolabial fold with calcium hydroxyapatite (CaHA). The patient stated that her vision became blurry and her eyes began to tear within 1 minute of receiving the injection. She further noted that these visual changes were painless and lasted for approximately 30 seconds.

The patient’s PCP believed these symptoms were due to pain at the injection site. While the patient was at her PCP’s office, the reception clerk noticed the blanching of the patient’s left cheek and informed the PCP, who referred the patient to our ED for evaluation.

Workup

The patient’s vital signs at presentation were normal. Her medical history was unremarkable and negative for smoking, alcohol, or drug use. She was not taking any medications and had no known drug allergies. The patient’s history was negative for any prior cosmetic procedures, and she confirmed this was the first and only time had a facial revolumization.

Facial examination revealed a Fitzpatrick scale (FS; a numerical scoring system used to assess a patient’s reaction to ultraviolet radiation) score of type 3. She also had left-sided blanching that extended from the midpoint of the nose diagonally to the lateral midbuccal cheek to the level of the oral commissure, including the cutaneous upper lip, alar, and nasal side wall. There was minimal capillary refill with compression at the affected site, and sensation was diminished to fine touch and pinprick. The facial muscles were intact, and, with the exception of puncture marks along both nasolabial folds, the remainder of the facial examination was normal.

The ophthalmic examination revealed a reactive pupil at 2 mm, white sclera, pink conjunctiva, red reflex, and normal fundoscopic vessels. The patient’s bedside Snellen visual acuity and visual field assessments were normal. The neurological examination was likewise normal, and no other physical findings were noted.

Laboratory evaluation included complete blood count (CBC), Chem 7 panel (creatinine, blood urea nitrogen [BUN], carbon dioxide, chloride, glucose, sodium, and potassium), and international normalized ratio (INR), which were all within normal limits.

Diagnosis and Treatment

The patient was diagnosed with acute angular arterial occlusion and transient retinal artery embolism secondary to facial volumization with CaHA. She was treated with oral acetylsalicylic acid aspirin (ASA) 325 mg, prednisone 40 mg, and sildenafil 50 mg; and subcutaneous (SC) enoxaparin 60 mg (1 mg/kg). Topical nitroglycerin paste 2% was applied to the affected area.

Ophthalmology and plastic surgery services were contacted for consultation. Based on no acute findings on examination, the ophthalmologist provided no additional treatment recommendations. The patient was observed in the ED for 4 hours, during which time the facial blanching resolved and her capillary refill time returned to normal at 2 seconds.

After evaluating the patient, the plastic surgeon recommended discharge home with instructions to continue taking the oral ASA and sildenafil, as well as a methylprednisolone dose pack for 6 days. He also recommended the patient begin hyperbaric oxygen (HBO) therapy the day after discharge, since there was no HBO chamber available during her hospital stay.

The patient complied with all discharge instructions, including HBO therapy. At plastic surgery follow-up, the patient had no long-term adverse effects from the CaHA injection.

Case 2

A 54-year-old Asian woman presented to the ED for evaluation of a 24-hour history of progressive and persistent pain, swelling, and discoloration of the nasolabial and upper lip region. She stated her symptoms began within 1 hour of receiving a fat graft injection into the affected area by her cosmetic surgeon. After examining the patient, the cosmetic surgeon referred her to the ED for further evaluation. The patient stated that she had undergone six prior facial revolumization procedures, but noted the recent procedure was her first autologous fat graft.

Workup

The patient’s medical history was unremarkable. Her social history was positive for one glass of wine per day and negative for smoking. The patient was not taking any medications and had no known drug allergies.

The patient’s vital signs at presentation were normal. She was evaluated approximately 30 hours after the fat graft procedure. Facial examination revealed an FS of type 4 with right-sided ischemia along the cutaneous upper lip, alar, and cheek (Figure 1).

Capillary refill time with compression was 0 in the affected area. Sensation to fine touch and pinprick was 0. The facial muscles were intact and, with the exception of puncture marks along both nasolabial folds, the remainder of the facial examination was normal. The neurological examination was likewise normal, and no other physical findings were noted. Laboratory evaluation included CBC, Chem 7 panel, and INR, which were all within normal limits.

Diagnosis and Treatment

The patient was diagnosed with acute angular arterial occlusion with soft tissue ischemia secondary to facial revolumization with autologous fat grafting. She was given oral acyclovir 800 mg, ASA 325 mg, cephalexin 500 mg, prednisone 40 mg, and sildenafil 50 mg; and SC enoxaparin 60 mg (1 mg/kg). Topical nitroglycerin paste 2% was applied to the affected area.

Plastic surgery services were contacted for consultation. After evaluating the patient, the plastic surgeon recommended discharge home with instructions to continue taking the oral acyclovir, ASA, cephalexin, prednisone, and sildenafil for 6 days. He also recommended the patient start HBO therapy the day after discharge home.

The patient refused HBO therapy, but did visit a plastic surgeon for a follow-up examination 3 days after discharge from the ED. A photograph of the patient’s nasolabial and upper lip region taken during this visit is presented in Figure 2.

Five days after discharge from the ED, the patient presented to a plastic surgery clinic for evaluation; a photograph was also obtained at this visit (Figure 3). The plastic surgeon at this clinic referred the patient to a tertiary center for a second opinion regarding the need for HBO therapy. The plastic surgeon at the tertiary center affirmed the initial plastic surgeon’s diagnosis and recommendation for HBO therapy. Although the patient did not return for further evaluation, she underwent 10 HBO treatments at the tertiary center with an acceptable aesthetic result.

Noninvasive Injectable Cosmetic Facial Augmentation

Facial augmentation procedures include the use of autologous adipose bovine collagen, HA gels, CaHA, and plastic compounds to fill wrinkles, folds, or soft tissue defects due to normal aging or trauma. Plastic surgeons traditionally use adipose and manufactured products for scar revision, midfacial restoration of volume loss from aging or trauma, cheek and chin augmentation, tear-trough correction (the diagonal crease running from the inner eye canthus to the maxilla resulting in a groove that creates a tired appearance), nose reshaping, lip enhancement, and correction of facial asymmetry.

Today the use of manufactured soft tissue revolumization products (ie, fillers) is no longer solely in the purview of plastic surgeons, but rather has become ubiquitous with nonsurgeons and allied health care professionals. As the overall number of revolumization procedures increases, so too does the risk for local and distant vascular complications.

Dermal Fillers

Dermal fillers vary widely in their respective properties, solubility, injection-technique flow requirements, and inherent complication risks. Regardless of type, all dermal fillers have the potential to cause serious complications. Most adverse events are related to substance type, volume, and injection technique. Bruising and trauma-related edema following dermal filler procedures are considered normal.

Though complications from dermal filler injections are rarely lethal, serious adverse events can result in permanent functional and aesthetic deficits. With proper physician training, planning, and injection technique, most adverse events can be avoided.

Hyaluronic Acid. Hyaluronic acid (HA)-containing injectable gel fillers (eg, Belotero, Juvederm, Perlane, and Restylane) are one of the most commonly used volumization products—especially by nonplastic surgeons. These gel fillers, which vary in viscosity and elasticity, may be injected from the superficial dermis to the periosteum. Dilution, dispersion, and degradation may be achieved in vivo either by high arterial flow or hyaluronidase.

Calcium Hydroxylapatite. Calcium hydroxylapatite (Radiesse) microsphere fillers consist of a very viscous paste that is mixed with lidocaine prior to injection to increase its flowability. The CaHA solution is injected at the deep dermis to periosteum level. Since CaHA is not easily diluted, dispersed, or degraded by high arterial flow, it tends to retain its consistency. When this procedure is performed by a novice, it can result in complete occlusion at the injection site or through embolization via antegrade or retrograde flow.

Poly-L-lactic Acid. Poly-L-lactic acid (PLLA; Sculptra) is a low-viscosity fluid comprised of synthetic polymer beads. The PLLA microparticles are not dissolvable or degradable by high arterial flow, and are designed to induce an inflammatory response with neocollagenesis.

Polymethyl Methacrylate. Polymethyl methacrylate (PMMA; Bellafil) consists of a combination of microscopic synthetic polymer beads suspended in a variety of substances. For facial enhancement, PMMA is usually suspended in HA or bovine collagen. Off-label use of silicon oils and gels such as PMMA are gaining in popularity—often with disastrous consequences such as acute arterial occlusion, bone erosion, and skin ulcerations.^2,3

Autologous Adipose Tissue. Plastic surgeons primarily use autologous adipose tissue to volumize the face, breasts, buttocks, and scars. Autologous fat grafts are typically placed in fat, superficial and deep muscles, and deep fat pads through a 2- to 2.5-mm facial fat grafting cannula using a multichannel technique that leaves minute amounts of fat in each channel. Fat embolization may occur when a nonfacial fat graft cannula or needle used to transplant the fat graft enters an artery either through direct sharp puncture or traumatic tear cannulation.^4-9

Adverse Events

The first recorded manufactured adverse event from an injectable dermal filler was in 1991. At that time, the US Food and Drug Administration warned of adverse events secondary to collagen injections, including open sores, abscess formation associated with delayed healing of the skin, and partial blindness.¹⁰

Arterial Embolization and Cannulation. The most serious complications from dermal fillers are accidental injection and/or embolization of the filler into the arterial system. Since 1991, an increased number of cases of soft tissue necrosis, blindness, and stroke have been reported as a result of injection of fillers in the glabella, forehead creases, temple, crow’s feet, nose, cheeks, nasolabial folds, and lower lip.^11-15

Accidental cannulation and inadvertent injection of fillers into the arterial vessels can have catastrophic complications. The potential of such inadvertent complications occurs despite skill level of the practitioner or surgeon. Therefore, recognition and treatment of a vascular occlusion must be immediate and aggressive to avoid devastating and potentially irreversible complications including blindness, stroke, and death.^11-15

Acute Blindness and Stroke. The issues and concerns associated with local intra-arterial dermal filler injection and distal embolism are well described in the literature. However, the mechanism of retinal artery occlusion is much more complex given the need for deep placement of products and the force necessary to cause distention and elevation of the dermis. Hence, higher g-forces are applied via the plunger, forcing the intra-arterial filler proximally past the origin of the retinal artery. When the clinician stops the injection, the arterial systolic pressure immediately embolizes the filler into the distal branches of the ophthalmic artery. This causes acute pain and blindness (Figure 5). Depending on the g-force applied, filler can enter into the internal carotid artery and embolize resulting in cerebral ischemia. Signs of cerebral ischemia may be mild or overt.^4-9

Management

Patients with intra-arterial dermal filler injection constitute a medical emergency requiring immediate intervention. We recommend clinicians initiate the treatment protocols outlined in the Box and Table 1.

Hyaluronidase. Injection of hyaluronidase may assist in degrading the HA around the arterial puncture site, relieving compression, which may increase blood flow. There is a risk of distal embolization from a dislodged HA emboli.

Fat Graft Injections. There are no known degradation products for fat, CaHA, PLLA, or PMMA products. The use of normal saline or hyaluronidase has no proven efficacy and may increase the compression pressure in the artery and surrounding tissue, causing further ischemia.

Long-term Sequelae

Despite aggressive intervention, permanent complications of cerebral ischemia, blindness, and severe soft tissue necrosis may occur. In six cases in the literature, patients treated with ocular massage therapy,^7,14 carbon dioxide rebreathing,¹⁴ HBO therapy,^7,14 oral and IV corticosteroids,^6-9 antiplatelet drugs,⁶ and fibrinolytic agents,^7,16 or mechanical thrombolysis¹⁶ showed no clinical effects. Neither the treated nor the untreated patients in any of these case studies had any return of vision.^4-7,9,20-27

Conclusion

Although artificial dermal fillers such as HA, CaHA, PLLA, and PMMA, and autologous adipose tissue grafts offer a minimally invasive alternative to plastic surgical procedures, they are not without complication or adverse effects, such as the acute arterial occlusion experienced by both of our patients. Patients presenting to the ED with adverse effects from such procedures must be managed promptly, employing the suggested management and treatment protocol, including consultation with ophthalmology, plastic surgery, and neurological services as indicated, to avoid permanent sequela and damage.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Tavakoli HR, et al. Kratom: a new product in an expanding substance abuse market. Fed Prac. 2016;33[11]:132-136. http://www.fedprac.com).

According to the United Nations Office on Drugs and Crime, the last decade saw an alarming rise in the use of recreational substances.¹ There was an escalation not only in the use of the more well-known street drugs (cannabis, stimulants, opioids, and hallucinogens), but also an exponential increase in the abuse of novel psychoactive substances. Although most emergency physicians (EPs) are at least relatively familiar with some of these designer drugs—often synthesized analogues of common street drugs—region-specific herbal products with psychoactive properties are now entering the market worldwide. Certainly, the cause of this increased use is multifactorial: Ease of access to these drugs and ambiguous legality are believed to be among the largest contributors. Infrastructure established through globalization promotes easy drug transportation and distribution across borders, and widespread Internet use makes knowledge of and accessibility to such substances exceedingly simple.^2,3

In particular, widespread online access has permanently altered the acquisition of knowledge in all realms—including drug use. Although Erowid Center remains one of the oldest and best-known of this type of Web site and bills itself as providing “harm reduction,” others have cropped up online and disseminate information about many forms of potentially psychoactive substances. Despite the purported raison d’être of these Web sites, recent studies have demonstrated these sites’ efficacy in promoting drug use under the guise of safety, particularly among adolescents and young adults. Among these is a qualitative study by Boyer et al⁴ of 12 drug users admitted to a pediatric psychiatry unit. Through extensive questioning about the patients’ digital habits, the researchers demonstrated that the majority of subjects used these Web sites and, as a result, either increased their drug use or learned about (and tried) new substances.

One drug that has benefited from globalization and the Internet is kratom (Mitragyna speciosa korth). This formerly regionally confined herbal psychoactive substance is native to Southeast Asia, where it has been used (and abused) for centuries as a mild stimulant, to prevent opioid withdrawal, and for recreational purposes. In recent years, kratom has been marketed as a psychotropic drug and has become increasingly popular in the United States and in the United Kingdom.^2,5,6 In the United States, this poses a problem for EPs who often are unaware of this plant’s existence, much less its abuse potential or health effects.² Also known as ketum, kakuam, thang, thom, or biak, kratom is marketed in stores and online as a cheap, safe alternative to opioids.

Although considered a “substance of concern” without any approved medical use by the US Drug Enforcement Agency (DEA), kratom is not a regulated or controlled substance in the United States.³ In late 2016, out of concern for public safety, the DEA placed a temporary ban on kratom. The Agency’s move was followed by a substantial negative reaction from kratom supporters and was quickly rescinded. As of April 2017, the DEA did not have a timetable for banning or scheduling the drug, though some states have banned it.

To that end, users consider kratom a legal high, and it is easily purchased online. A 2010 study in the United Kingdom examined Web sites where kratom and many other quasilegal substances (including Salvia divinorum and legal precursors to LSD) could be purchased for an average of £10 (about $13 US currency).⁵ This study’s authors also noted a significant lack of product information on these marketplaces. As these products are not overseen by any regulatory body, the risk of overdose or adulteration is extremely high.^2,3,6-8 In fact, Krypton, a kratom product sold online, was found to be adulterated with O-desmethyltramadol—the active metabolite of the synthetic opiate tramadol—and implicated in at least nine deaths.⁷

This article presents a case of kratom abuse. It describes a brief history of the substance, its pharmacological characteristics, the clinical presentation of kratom abuse, and the treatment of kratom-related illness and evaluation of potential toxic sequelae. In light of the rapid proliferation of kratom in the United States, a basic working knowledge of the drug is quickly becoming a must for EPs.

Case Presentation

At his employer’s request, a 33-year-old man presented to his family physician for a worsening of his uncontrolled back pain from a herniated lumbar disk resulting from a motor vehicle collision 3 months before. At his physician’s office he stated, “I don’t care if I live or die, I’m tired of the pain,” and “I’m going to go off on somebody if I can’t get this pain under control.” He also endorsed having auditory hallucinations for several years and a history of violence and homicide. The problem arose precipitously after he became concerned that he was abusing his opioid medication, and it was discontinued. The patient was transferred to the local ED and admitted to the psychiatric service for his suicidal ideations and risk of harming self and others.

On admission to the psychiatric service, the patient complained of body aches, chills, rhinorrhea, and significantly worsened irritability from his baseline, consistent with opioid withdrawal. Initial point-of-care (POC) admission drug testing had been negative as had expanded urine tests looking for synthetic opioids, cannabinoids, and cathinones. The patient reported no opioid use but was unable to explain his current symptom patterns, which were worsening his chronic pain and hampering any attempt to build rapport. On hospital day 3, the patient’s opioid withdrawal resolved, and psychiatric treatment was able to progress fully. On hospital day 4, the inpatient treatment team received a message from the patient’s primary care manager stating that a friend of the patient had found a bottle of herbal pills in the patient’s car. This was later revealed to be a kratom formulation that he had purchased online.

Background

Kratom is the colloquial name of a tree that is native to Thailand, Malaysia, and other countries in Southeast Asia. These trees, which can grow to 50 feet high and 15 feet wide, have long been the source of herbal remedies in Southeast Asia.^2,3 The leaves of these trees contain psychoactive substances that have a variety of effects when consumed. At low doses, kratom causes a stimulant effect (akin to the leaves of the coca plant in South America); laborers and farmers often use it to help boost their energy. At higher doses, kratom causes an opioid-like effect, which at mega doses produces an intense euphoric state and has led to a steady growth in abuse worldwide. Although the government of Thailand banned the planting of Mitragyna speciosa as early as 1943, its continued proliferation in Southeast Asia and throughout the world has not ceased.^2,3,6

In the United Kingdom, kratom is currently the second most common drug that is considered a legal high, only behind salvia (Salvia divinorum), a hallucinogenic herb that is better known as a result of its use by young celebrities over the past decade.^5,8

Kratom can be taken in a variety of ways: Crushed leaves often are placed in gel caps and swallowed; it can be drunk as a tea, juice, or boiled syrup; and it can be smoked or insufflated.^2,3,5,6

Pharmacology and Clinical Presentation

More than 20 psychoactive compounds have been isolated from kratom. Although a discussion of all these compounds is beyond the scope of this review, the two major compounds are mitragynine and 7-hydroxymitragynine.

Mitragynine

Mitragynine, the most abundant psychoactive compound found in kratom, is an indole alkaloid (Figure 1). Extraction and analysis of this compound has demonstrated numerous effects on multiple receptors, including mu-, delta-, and kappa-opioid receptors, leading to its opioid-like effects, including analgesia and euphoria. Also similar to common opioids, withdrawal symptomatology can present after only 5 days of daily use. There is limited evidence that mitragynine can activate postsynaptic alpha-2 adrenergic receptors, which may act synergistically with the mu-agonist with regard to its analgesic effect.^2,5

7-Hydroxymitragynine

7-hydroxymitragynine, despite being far less concentrated in kratom preparations, is about 13 times more potent than morphine and 46 times more potent than mitragynine. It is thought that its hydroxyl side chain added to C7 (Figure 2) adds to its lipophilicity and ability to cross the blood-brain barrier at a far more rapid rate than that of mitragynine.²

Mitragynine and 7-hydroxymitragynine remain the best-studied psychoactive components of kratom at this time. Other compounds that have been isolated, such as speciociliatine, paynantheine, and speciogynine, may play a role in kratom’s analgesic and psychoactive effects. Animal studies have demonstrated antimuscarinic properties in these compounds, but the properties do not seem to have any demonstrable effect at the opioid receptors.²

Intoxication and Withdrawal

Due to its increasing worldwide popularity, it is now imperative for EPs to be aware of the presentation of patients with kratom abuse as well as the management of withdrawal in light of its dependence potential. However, large-scale studies have not been performed, and much of the evidence comes not from the medical literature but from Web sites such as Erowid or SageWisdom.^2,5-9 To that end, such information will be discussed along with the limited research and expert consensuses available in peer-reviewed medical literature.

Kratom seems to have dose-dependent effects. At low doses (1-5 g of raw crushed leaves), kratom abusers often report a mild energizing effect, thought to be secondary to the stimulant properties of kratom’s multiple alkaloids. Users have reported mild euphoria and highs similar to those of the abuse of methylphenidate or modafinil.^2,9,10 Also similar to abuse of those substances, users have reported anxiety, irritability, and aggressiveness as a result of the stimulant-like effects.

At moderate-to-high doses (5-15 g of raw crushed leaves), it is believed that the mu-opiate receptor agonism overtakes the stimulant effects, leading to the euphoria, relaxation, and analgesia seen with conventional opioid use and abuse.^2,10 In light of the drug’s substantial binding and agonism of all opioid receptors, constipation and itching also are seen.² As such, if an individual is intoxicated, he or she should be managed with supportive and symptomatic care and continuous monitoring of heart rate, blood pressure, respiratory rate, and oxygen saturation.^2,10 Kratom intoxication can precipitate psychotic episodes similar to those caused by opiate intoxication, so monitoring for agitation or psychotic behaviors is also indicated.^9,10

The medical management of a patient with an acute kratom overdose (typically requiring ingestion of >15 g of crushed leaves) begins with addressing airway support, breathing, and circulation along with continuous vital sign monitoring and laboratory testing, including POC glucose testing, complete blood count, electrolytes, lactate, venous blood gas, and measurable drug levels (ethanol, acetaminophen, tricyclic antidepressants, as indicated).¹¹ If it is determined that kratom was the intoxicant, the greatest concern of death is similar to that of opioid overdose: respiratory depression. Although there are no large-scale human studies demonstrating efficacy, multiple authors suggest the use of naloxone in kratom-related hypoventilation.^9,10

The development of dependence on kratom and its subsequent withdrawal phenomena are thought to be similar to that of opioids, in light of its strong mu agonism.^2,5,9,10 Indeed, kratom has a long history of being used by opioid-dependent patients as an attempt to quit drug abuse or stave off debilitating withdrawal symptoms when they are unable to acquire their substance of choice.^2,5-10 As such, withdrawal and the treatment thereof will also mimic that of opioid withdrawal.

The kratom-dependent individual will often present with rhinorrhea, lacrimation, dry mouth, hostility, aggression, and emotional lability similar to the case study described earlier.^2,9,10 Kratom withdrawal, much like intoxication, also may precipitate or worsen psychotic symptoms, and monitoring is necessary throughout the detoxification process.^2,5,10 Withdrawal management should proceed along ambulatory clinic or hospital opioid withdrawal protocols that include step-down administration of opioids or with nonopioid medications for symptomatic relief, including muscle relaxants, alpha-2 agonists, and antidiarrheal agents.^5,9,10

Kratom Toxicity

A review of the available medical literature has demonstrated a number of toxic effects with kratom abuse, either as the sole agent or in concert with prescribed medications, recreational coingestants, or as a result of manufacturer’s adulteration with other chemicals or drugs. Of particular interest to EPs are manic or psychotic episode precipitation, seizure, hypothyroidism, intrahepatic cholestatic injury, and even sudden cardiac death.^2,3,5-10 In addition to the basic history, physical, and laboratory examination, the workup of patients identified as kratom users should include the following:

• Fastidious medication reconciliation with drug-interaction check;
• Exhaustive substance abuse history;
• Identification of the brand name and source of kratom purchased, to determine whether there are advertised coingestants or reports of adulteration;
• Electrocardiogram;
• Thyroid function testing;
• Hepatic function testing; and
• Comprehensive neurological and mental status examinations.

In chronic users of kratom, a number of effects have been seen whose etiologies have not yet been determined. These effects include depression, anxiety, tremulousness, weight loss, and psychosis.^3-7 Additionally, a study by Kittirattanapaiboon et al¹² correlated drug use by those with concurrent mental health disorders (in particular, kratom, which was used in 59% of the ≥14,000 individuals included in the study sample) with statistically significant higher suicide risk.

Detection

Because kratom is a relatively new compound in the United States, medical and forensic laboratories are only now implementing kratom detection protocols. Many laboratories now use high-performance liquid chromatography to analyze for mitragynine, 7-hydroxymitragynine, and two metabolites of mitragynine in urine.⁷ Le et al¹³ were able to detect mitragynine in the urine in levels as low as 1 ng/mL, which is clinically useful as mitragynine has a half-life determined in animal studies to be 3.85 hours. Similar detection limits for mitragynine and 7-hydroxymitragynine are used only at the Naval Medical Center Portsmouth in Virginia; however, kratom was not detected in the case study patient’s urine because a urine test was not done until hospital day 5.

Case Conclusion

When gently confronted about the kratom found in his car, the case study patient admitted that he had purchased kratom online after he was “cut off” from prescription opioids for his pain. He admitted that although it was beneficial for his pain, he did notice worsening in his aggression toward his spouse and coworkers. This progressed to an exacerbation of his psychotic symptoms of hallucinations and persecutory delusions. These symptoms remained well hidden—but were present for years prior to his presentation at the hospital. The patient was discharged from the inpatient psychiatric unit on hospital day 16 with a diagnosis of schizoaffective disorder, depressive type in addition to opioid-use disorder. The patient agreed to seek a pain management specialist and discontinue kratom use.

Conclusion

Kratom is an emerging drug of abuse in the Western world. Although significant research is being conducted on its possible medical uses, little is known about kratom beyond the “trip reports” of kratom users posted online. Because of its technically legal status in the United States and multiple other Western countries, kratom is easily accessible. Emergency physicians need to be aware of kratom, and during their evaluations, question appropriate patients about kratom and other legal highs.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Tavakoli HR, et al. Kratom: a new product in an expanding substance abuse market. Fed Prac. 2016;33[11]:132-136. http://www.fedprac.com).

According to the United Nations Office on Drugs and Crime, the last decade saw an alarming rise in the use of recreational substances.¹ There was an escalation not only in the use of the more well-known street drugs (cannabis, stimulants, opioids, and hallucinogens), but also an exponential increase in the abuse of novel psychoactive substances. Although most emergency physicians (EPs) are at least relatively familiar with some of these designer drugs—often synthesized analogues of common street drugs—region-specific herbal products with psychoactive properties are now entering the market worldwide. Certainly, the cause of this increased use is multifactorial: Ease of access to these drugs and ambiguous legality are believed to be among the largest contributors. Infrastructure established through globalization promotes easy drug transportation and distribution across borders, and widespread Internet use makes knowledge of and accessibility to such substances exceedingly simple.^2,3

In particular, widespread online access has permanently altered the acquisition of knowledge in all realms—including drug use. Although Erowid Center remains one of the oldest and best-known of this type of Web site and bills itself as providing “harm reduction,” others have cropped up online and disseminate information about many forms of potentially psychoactive substances. Despite the purported raison d’être of these Web sites, recent studies have demonstrated these sites’ efficacy in promoting drug use under the guise of safety, particularly among adolescents and young adults. Among these is a qualitative study by Boyer et al⁴ of 12 drug users admitted to a pediatric psychiatry unit. Through extensive questioning about the patients’ digital habits, the researchers demonstrated that the majority of subjects used these Web sites and, as a result, either increased their drug use or learned about (and tried) new substances.

One drug that has benefited from globalization and the Internet is kratom (Mitragyna speciosa korth). This formerly regionally confined herbal psychoactive substance is native to Southeast Asia, where it has been used (and abused) for centuries as a mild stimulant, to prevent opioid withdrawal, and for recreational purposes. In recent years, kratom has been marketed as a psychotropic drug and has become increasingly popular in the United States and in the United Kingdom.^2,5,6 In the United States, this poses a problem for EPs who often are unaware of this plant’s existence, much less its abuse potential or health effects.² Also known as ketum, kakuam, thang, thom, or biak, kratom is marketed in stores and online as a cheap, safe alternative to opioids.

Although considered a “substance of concern” without any approved medical use by the US Drug Enforcement Agency (DEA), kratom is not a regulated or controlled substance in the United States.³ In late 2016, out of concern for public safety, the DEA placed a temporary ban on kratom. The Agency’s move was followed by a substantial negative reaction from kratom supporters and was quickly rescinded. As of April 2017, the DEA did not have a timetable for banning or scheduling the drug, though some states have banned it.

To that end, users consider kratom a legal high, and it is easily purchased online. A 2010 study in the United Kingdom examined Web sites where kratom and many other quasilegal substances (including Salvia divinorum and legal precursors to LSD) could be purchased for an average of £10 (about $13 US currency).⁵ This study’s authors also noted a significant lack of product information on these marketplaces. As these products are not overseen by any regulatory body, the risk of overdose or adulteration is extremely high.^2,3,6-8 In fact, Krypton, a kratom product sold online, was found to be adulterated with O-desmethyltramadol—the active metabolite of the synthetic opiate tramadol—and implicated in at least nine deaths.⁷

This article presents a case of kratom abuse. It describes a brief history of the substance, its pharmacological characteristics, the clinical presentation of kratom abuse, and the treatment of kratom-related illness and evaluation of potential toxic sequelae. In light of the rapid proliferation of kratom in the United States, a basic working knowledge of the drug is quickly becoming a must for EPs.

Case Presentation

At his employer’s request, a 33-year-old man presented to his family physician for a worsening of his uncontrolled back pain from a herniated lumbar disk resulting from a motor vehicle collision 3 months before. At his physician’s office he stated, “I don’t care if I live or die, I’m tired of the pain,” and “I’m going to go off on somebody if I can’t get this pain under control.” He also endorsed having auditory hallucinations for several years and a history of violence and homicide. The problem arose precipitously after he became concerned that he was abusing his opioid medication, and it was discontinued. The patient was transferred to the local ED and admitted to the psychiatric service for his suicidal ideations and risk of harming self and others.

On admission to the psychiatric service, the patient complained of body aches, chills, rhinorrhea, and significantly worsened irritability from his baseline, consistent with opioid withdrawal. Initial point-of-care (POC) admission drug testing had been negative as had expanded urine tests looking for synthetic opioids, cannabinoids, and cathinones. The patient reported no opioid use but was unable to explain his current symptom patterns, which were worsening his chronic pain and hampering any attempt to build rapport. On hospital day 3, the patient’s opioid withdrawal resolved, and psychiatric treatment was able to progress fully. On hospital day 4, the inpatient treatment team received a message from the patient’s primary care manager stating that a friend of the patient had found a bottle of herbal pills in the patient’s car. This was later revealed to be a kratom formulation that he had purchased online.

Background

Kratom is the colloquial name of a tree that is native to Thailand, Malaysia, and other countries in Southeast Asia. These trees, which can grow to 50 feet high and 15 feet wide, have long been the source of herbal remedies in Southeast Asia.^2,3 The leaves of these trees contain psychoactive substances that have a variety of effects when consumed. At low doses, kratom causes a stimulant effect (akin to the leaves of the coca plant in South America); laborers and farmers often use it to help boost their energy. At higher doses, kratom causes an opioid-like effect, which at mega doses produces an intense euphoric state and has led to a steady growth in abuse worldwide. Although the government of Thailand banned the planting of Mitragyna speciosa as early as 1943, its continued proliferation in Southeast Asia and throughout the world has not ceased.^2,3,6

In the United Kingdom, kratom is currently the second most common drug that is considered a legal high, only behind salvia (Salvia divinorum), a hallucinogenic herb that is better known as a result of its use by young celebrities over the past decade.^5,8

Kratom can be taken in a variety of ways: Crushed leaves often are placed in gel caps and swallowed; it can be drunk as a tea, juice, or boiled syrup; and it can be smoked or insufflated.^2,3,5,6

Pharmacology and Clinical Presentation

More than 20 psychoactive compounds have been isolated from kratom. Although a discussion of all these compounds is beyond the scope of this review, the two major compounds are mitragynine and 7-hydroxymitragynine.

Mitragynine

Mitragynine, the most abundant psychoactive compound found in kratom, is an indole alkaloid (Figure 1). Extraction and analysis of this compound has demonstrated numerous effects on multiple receptors, including mu-, delta-, and kappa-opioid receptors, leading to its opioid-like effects, including analgesia and euphoria. Also similar to common opioids, withdrawal symptomatology can present after only 5 days of daily use. There is limited evidence that mitragynine can activate postsynaptic alpha-2 adrenergic receptors, which may act synergistically with the mu-agonist with regard to its analgesic effect.^2,5

7-Hydroxymitragynine

7-hydroxymitragynine, despite being far less concentrated in kratom preparations, is about 13 times more potent than morphine and 46 times more potent than mitragynine. It is thought that its hydroxyl side chain added to C7 (Figure 2) adds to its lipophilicity and ability to cross the blood-brain barrier at a far more rapid rate than that of mitragynine.²

Mitragynine and 7-hydroxymitragynine remain the best-studied psychoactive components of kratom at this time. Other compounds that have been isolated, such as speciociliatine, paynantheine, and speciogynine, may play a role in kratom’s analgesic and psychoactive effects. Animal studies have demonstrated antimuscarinic properties in these compounds, but the properties do not seem to have any demonstrable effect at the opioid receptors.²

Intoxication and Withdrawal

Due to its increasing worldwide popularity, it is now imperative for EPs to be aware of the presentation of patients with kratom abuse as well as the management of withdrawal in light of its dependence potential. However, large-scale studies have not been performed, and much of the evidence comes not from the medical literature but from Web sites such as Erowid or SageWisdom.^2,5-9 To that end, such information will be discussed along with the limited research and expert consensuses available in peer-reviewed medical literature.

Kratom seems to have dose-dependent effects. At low doses (1-5 g of raw crushed leaves), kratom abusers often report a mild energizing effect, thought to be secondary to the stimulant properties of kratom’s multiple alkaloids. Users have reported mild euphoria and highs similar to those of the abuse of methylphenidate or modafinil.^2,9,10 Also similar to abuse of those substances, users have reported anxiety, irritability, and aggressiveness as a result of the stimulant-like effects.

At moderate-to-high doses (5-15 g of raw crushed leaves), it is believed that the mu-opiate receptor agonism overtakes the stimulant effects, leading to the euphoria, relaxation, and analgesia seen with conventional opioid use and abuse.^2,10 In light of the drug’s substantial binding and agonism of all opioid receptors, constipation and itching also are seen.² As such, if an individual is intoxicated, he or she should be managed with supportive and symptomatic care and continuous monitoring of heart rate, blood pressure, respiratory rate, and oxygen saturation.^2,10 Kratom intoxication can precipitate psychotic episodes similar to those caused by opiate intoxication, so monitoring for agitation or psychotic behaviors is also indicated.^9,10

The medical management of a patient with an acute kratom overdose (typically requiring ingestion of >15 g of crushed leaves) begins with addressing airway support, breathing, and circulation along with continuous vital sign monitoring and laboratory testing, including POC glucose testing, complete blood count, electrolytes, lactate, venous blood gas, and measurable drug levels (ethanol, acetaminophen, tricyclic antidepressants, as indicated).¹¹ If it is determined that kratom was the intoxicant, the greatest concern of death is similar to that of opioid overdose: respiratory depression. Although there are no large-scale human studies demonstrating efficacy, multiple authors suggest the use of naloxone in kratom-related hypoventilation.^9,10

The development of dependence on kratom and its subsequent withdrawal phenomena are thought to be similar to that of opioids, in light of its strong mu agonism.^2,5,9,10 Indeed, kratom has a long history of being used by opioid-dependent patients as an attempt to quit drug abuse or stave off debilitating withdrawal symptoms when they are unable to acquire their substance of choice.^2,5-10 As such, withdrawal and the treatment thereof will also mimic that of opioid withdrawal.

The kratom-dependent individual will often present with rhinorrhea, lacrimation, dry mouth, hostility, aggression, and emotional lability similar to the case study described earlier.^2,9,10 Kratom withdrawal, much like intoxication, also may precipitate or worsen psychotic symptoms, and monitoring is necessary throughout the detoxification process.^2,5,10 Withdrawal management should proceed along ambulatory clinic or hospital opioid withdrawal protocols that include step-down administration of opioids or with nonopioid medications for symptomatic relief, including muscle relaxants, alpha-2 agonists, and antidiarrheal agents.^5,9,10

Kratom Toxicity

A review of the available medical literature has demonstrated a number of toxic effects with kratom abuse, either as the sole agent or in concert with prescribed medications, recreational coingestants, or as a result of manufacturer’s adulteration with other chemicals or drugs. Of particular interest to EPs are manic or psychotic episode precipitation, seizure, hypothyroidism, intrahepatic cholestatic injury, and even sudden cardiac death.^2,3,5-10 In addition to the basic history, physical, and laboratory examination, the workup of patients identified as kratom users should include the following:

• Fastidious medication reconciliation with drug-interaction check;
• Exhaustive substance abuse history;
• Identification of the brand name and source of kratom purchased, to determine whether there are advertised coingestants or reports of adulteration;
• Electrocardiogram;
• Thyroid function testing;
• Hepatic function testing; and
• Comprehensive neurological and mental status examinations.

In chronic users of kratom, a number of effects have been seen whose etiologies have not yet been determined. These effects include depression, anxiety, tremulousness, weight loss, and psychosis.^3-7 Additionally, a study by Kittirattanapaiboon et al¹² correlated drug use by those with concurrent mental health disorders (in particular, kratom, which was used in 59% of the ≥14,000 individuals included in the study sample) with statistically significant higher suicide risk.

Detection

Because kratom is a relatively new compound in the United States, medical and forensic laboratories are only now implementing kratom detection protocols. Many laboratories now use high-performance liquid chromatography to analyze for mitragynine, 7-hydroxymitragynine, and two metabolites of mitragynine in urine.⁷ Le et al¹³ were able to detect mitragynine in the urine in levels as low as 1 ng/mL, which is clinically useful as mitragynine has a half-life determined in animal studies to be 3.85 hours. Similar detection limits for mitragynine and 7-hydroxymitragynine are used only at the Naval Medical Center Portsmouth in Virginia; however, kratom was not detected in the case study patient’s urine because a urine test was not done until hospital day 5.

Case Conclusion

When gently confronted about the kratom found in his car, the case study patient admitted that he had purchased kratom online after he was “cut off” from prescription opioids for his pain. He admitted that although it was beneficial for his pain, he did notice worsening in his aggression toward his spouse and coworkers. This progressed to an exacerbation of his psychotic symptoms of hallucinations and persecutory delusions. These symptoms remained well hidden—but were present for years prior to his presentation at the hospital. The patient was discharged from the inpatient psychiatric unit on hospital day 16 with a diagnosis of schizoaffective disorder, depressive type in addition to opioid-use disorder. The patient agreed to seek a pain management specialist and discontinue kratom use.

Conclusion

Kratom is an emerging drug of abuse in the Western world. Although significant research is being conducted on its possible medical uses, little is known about kratom beyond the “trip reports” of kratom users posted online. Because of its technically legal status in the United States and multiple other Western countries, kratom is easily accessible. Emergency physicians need to be aware of kratom, and during their evaluations, question appropriate patients about kratom and other legal highs.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Tavakoli HR, et al. Kratom: a new product in an expanding substance abuse market. Fed Prac. 2016;33[11]:132-136. http://www.fedprac.com).

According to the United Nations Office on Drugs and Crime, the last decade saw an alarming rise in the use of recreational substances.¹ There was an escalation not only in the use of the more well-known street drugs (cannabis, stimulants, opioids, and hallucinogens), but also an exponential increase in the abuse of novel psychoactive substances. Although most emergency physicians (EPs) are at least relatively familiar with some of these designer drugs—often synthesized analogues of common street drugs—region-specific herbal products with psychoactive properties are now entering the market worldwide. Certainly, the cause of this increased use is multifactorial: Ease of access to these drugs and ambiguous legality are believed to be among the largest contributors. Infrastructure established through globalization promotes easy drug transportation and distribution across borders, and widespread Internet use makes knowledge of and accessibility to such substances exceedingly simple.^2,3

In particular, widespread online access has permanently altered the acquisition of knowledge in all realms—including drug use. Although Erowid Center remains one of the oldest and best-known of this type of Web site and bills itself as providing “harm reduction,” others have cropped up online and disseminate information about many forms of potentially psychoactive substances. Despite the purported raison d’être of these Web sites, recent studies have demonstrated these sites’ efficacy in promoting drug use under the guise of safety, particularly among adolescents and young adults. Among these is a qualitative study by Boyer et al⁴ of 12 drug users admitted to a pediatric psychiatry unit. Through extensive questioning about the patients’ digital habits, the researchers demonstrated that the majority of subjects used these Web sites and, as a result, either increased their drug use or learned about (and tried) new substances.

One drug that has benefited from globalization and the Internet is kratom (Mitragyna speciosa korth). This formerly regionally confined herbal psychoactive substance is native to Southeast Asia, where it has been used (and abused) for centuries as a mild stimulant, to prevent opioid withdrawal, and for recreational purposes. In recent years, kratom has been marketed as a psychotropic drug and has become increasingly popular in the United States and in the United Kingdom.^2,5,6 In the United States, this poses a problem for EPs who often are unaware of this plant’s existence, much less its abuse potential or health effects.² Also known as ketum, kakuam, thang, thom, or biak, kratom is marketed in stores and online as a cheap, safe alternative to opioids.

Although considered a “substance of concern” without any approved medical use by the US Drug Enforcement Agency (DEA), kratom is not a regulated or controlled substance in the United States.³ In late 2016, out of concern for public safety, the DEA placed a temporary ban on kratom. The Agency’s move was followed by a substantial negative reaction from kratom supporters and was quickly rescinded. As of April 2017, the DEA did not have a timetable for banning or scheduling the drug, though some states have banned it.

To that end, users consider kratom a legal high, and it is easily purchased online. A 2010 study in the United Kingdom examined Web sites where kratom and many other quasilegal substances (including Salvia divinorum and legal precursors to LSD) could be purchased for an average of £10 (about $13 US currency).⁵ This study’s authors also noted a significant lack of product information on these marketplaces. As these products are not overseen by any regulatory body, the risk of overdose or adulteration is extremely high.^2,3,6-8 In fact, Krypton, a kratom product sold online, was found to be adulterated with O-desmethyltramadol—the active metabolite of the synthetic opiate tramadol—and implicated in at least nine deaths.⁷

This article presents a case of kratom abuse. It describes a brief history of the substance, its pharmacological characteristics, the clinical presentation of kratom abuse, and the treatment of kratom-related illness and evaluation of potential toxic sequelae. In light of the rapid proliferation of kratom in the United States, a basic working knowledge of the drug is quickly becoming a must for EPs.

Case Presentation

At his employer’s request, a 33-year-old man presented to his family physician for a worsening of his uncontrolled back pain from a herniated lumbar disk resulting from a motor vehicle collision 3 months before. At his physician’s office he stated, “I don’t care if I live or die, I’m tired of the pain,” and “I’m going to go off on somebody if I can’t get this pain under control.” He also endorsed having auditory hallucinations for several years and a history of violence and homicide. The problem arose precipitously after he became concerned that he was abusing his opioid medication, and it was discontinued. The patient was transferred to the local ED and admitted to the psychiatric service for his suicidal ideations and risk of harming self and others.

On admission to the psychiatric service, the patient complained of body aches, chills, rhinorrhea, and significantly worsened irritability from his baseline, consistent with opioid withdrawal. Initial point-of-care (POC) admission drug testing had been negative as had expanded urine tests looking for synthetic opioids, cannabinoids, and cathinones. The patient reported no opioid use but was unable to explain his current symptom patterns, which were worsening his chronic pain and hampering any attempt to build rapport. On hospital day 3, the patient’s opioid withdrawal resolved, and psychiatric treatment was able to progress fully. On hospital day 4, the inpatient treatment team received a message from the patient’s primary care manager stating that a friend of the patient had found a bottle of herbal pills in the patient’s car. This was later revealed to be a kratom formulation that he had purchased online.

Background

Kratom is the colloquial name of a tree that is native to Thailand, Malaysia, and other countries in Southeast Asia. These trees, which can grow to 50 feet high and 15 feet wide, have long been the source of herbal remedies in Southeast Asia.^2,3 The leaves of these trees contain psychoactive substances that have a variety of effects when consumed. At low doses, kratom causes a stimulant effect (akin to the leaves of the coca plant in South America); laborers and farmers often use it to help boost their energy. At higher doses, kratom causes an opioid-like effect, which at mega doses produces an intense euphoric state and has led to a steady growth in abuse worldwide. Although the government of Thailand banned the planting of Mitragyna speciosa as early as 1943, its continued proliferation in Southeast Asia and throughout the world has not ceased.^2,3,6

In the United Kingdom, kratom is currently the second most common drug that is considered a legal high, only behind salvia (Salvia divinorum), a hallucinogenic herb that is better known as a result of its use by young celebrities over the past decade.^5,8

Kratom can be taken in a variety of ways: Crushed leaves often are placed in gel caps and swallowed; it can be drunk as a tea, juice, or boiled syrup; and it can be smoked or insufflated.^2,3,5,6

Pharmacology and Clinical Presentation

More than 20 psychoactive compounds have been isolated from kratom. Although a discussion of all these compounds is beyond the scope of this review, the two major compounds are mitragynine and 7-hydroxymitragynine.

Mitragynine

Mitragynine, the most abundant psychoactive compound found in kratom, is an indole alkaloid (Figure 1). Extraction and analysis of this compound has demonstrated numerous effects on multiple receptors, including mu-, delta-, and kappa-opioid receptors, leading to its opioid-like effects, including analgesia and euphoria. Also similar to common opioids, withdrawal symptomatology can present after only 5 days of daily use. There is limited evidence that mitragynine can activate postsynaptic alpha-2 adrenergic receptors, which may act synergistically with the mu-agonist with regard to its analgesic effect.^2,5

7-Hydroxymitragynine

7-hydroxymitragynine, despite being far less concentrated in kratom preparations, is about 13 times more potent than morphine and 46 times more potent than mitragynine. It is thought that its hydroxyl side chain added to C7 (Figure 2) adds to its lipophilicity and ability to cross the blood-brain barrier at a far more rapid rate than that of mitragynine.²

Mitragynine and 7-hydroxymitragynine remain the best-studied psychoactive components of kratom at this time. Other compounds that have been isolated, such as speciociliatine, paynantheine, and speciogynine, may play a role in kratom’s analgesic and psychoactive effects. Animal studies have demonstrated antimuscarinic properties in these compounds, but the properties do not seem to have any demonstrable effect at the opioid receptors.²

Intoxication and Withdrawal

Due to its increasing worldwide popularity, it is now imperative for EPs to be aware of the presentation of patients with kratom abuse as well as the management of withdrawal in light of its dependence potential. However, large-scale studies have not been performed, and much of the evidence comes not from the medical literature but from Web sites such as Erowid or SageWisdom.^2,5-9 To that end, such information will be discussed along with the limited research and expert consensuses available in peer-reviewed medical literature.

Kratom seems to have dose-dependent effects. At low doses (1-5 g of raw crushed leaves), kratom abusers often report a mild energizing effect, thought to be secondary to the stimulant properties of kratom’s multiple alkaloids. Users have reported mild euphoria and highs similar to those of the abuse of methylphenidate or modafinil.^2,9,10 Also similar to abuse of those substances, users have reported anxiety, irritability, and aggressiveness as a result of the stimulant-like effects.

At moderate-to-high doses (5-15 g of raw crushed leaves), it is believed that the mu-opiate receptor agonism overtakes the stimulant effects, leading to the euphoria, relaxation, and analgesia seen with conventional opioid use and abuse.^2,10 In light of the drug’s substantial binding and agonism of all opioid receptors, constipation and itching also are seen.² As such, if an individual is intoxicated, he or she should be managed with supportive and symptomatic care and continuous monitoring of heart rate, blood pressure, respiratory rate, and oxygen saturation.^2,10 Kratom intoxication can precipitate psychotic episodes similar to those caused by opiate intoxication, so monitoring for agitation or psychotic behaviors is also indicated.^9,10

The medical management of a patient with an acute kratom overdose (typically requiring ingestion of >15 g of crushed leaves) begins with addressing airway support, breathing, and circulation along with continuous vital sign monitoring and laboratory testing, including POC glucose testing, complete blood count, electrolytes, lactate, venous blood gas, and measurable drug levels (ethanol, acetaminophen, tricyclic antidepressants, as indicated).¹¹ If it is determined that kratom was the intoxicant, the greatest concern of death is similar to that of opioid overdose: respiratory depression. Although there are no large-scale human studies demonstrating efficacy, multiple authors suggest the use of naloxone in kratom-related hypoventilation.^9,10

The development of dependence on kratom and its subsequent withdrawal phenomena are thought to be similar to that of opioids, in light of its strong mu agonism.^2,5,9,10 Indeed, kratom has a long history of being used by opioid-dependent patients as an attempt to quit drug abuse or stave off debilitating withdrawal symptoms when they are unable to acquire their substance of choice.^2,5-10 As such, withdrawal and the treatment thereof will also mimic that of opioid withdrawal.

The kratom-dependent individual will often present with rhinorrhea, lacrimation, dry mouth, hostility, aggression, and emotional lability similar to the case study described earlier.^2,9,10 Kratom withdrawal, much like intoxication, also may precipitate or worsen psychotic symptoms, and monitoring is necessary throughout the detoxification process.^2,5,10 Withdrawal management should proceed along ambulatory clinic or hospital opioid withdrawal protocols that include step-down administration of opioids or with nonopioid medications for symptomatic relief, including muscle relaxants, alpha-2 agonists, and antidiarrheal agents.^5,9,10

Kratom Toxicity

A review of the available medical literature has demonstrated a number of toxic effects with kratom abuse, either as the sole agent or in concert with prescribed medications, recreational coingestants, or as a result of manufacturer’s adulteration with other chemicals or drugs. Of particular interest to EPs are manic or psychotic episode precipitation, seizure, hypothyroidism, intrahepatic cholestatic injury, and even sudden cardiac death.^2,3,5-10 In addition to the basic history, physical, and laboratory examination, the workup of patients identified as kratom users should include the following:

• Fastidious medication reconciliation with drug-interaction check;
• Exhaustive substance abuse history;
• Identification of the brand name and source of kratom purchased, to determine whether there are advertised coingestants or reports of adulteration;
• Electrocardiogram;
• Thyroid function testing;
• Hepatic function testing; and
• Comprehensive neurological and mental status examinations.

In chronic users of kratom, a number of effects have been seen whose etiologies have not yet been determined. These effects include depression, anxiety, tremulousness, weight loss, and psychosis.^3-7 Additionally, a study by Kittirattanapaiboon et al¹² correlated drug use by those with concurrent mental health disorders (in particular, kratom, which was used in 59% of the ≥14,000 individuals included in the study sample) with statistically significant higher suicide risk.

Detection

Because kratom is a relatively new compound in the United States, medical and forensic laboratories are only now implementing kratom detection protocols. Many laboratories now use high-performance liquid chromatography to analyze for mitragynine, 7-hydroxymitragynine, and two metabolites of mitragynine in urine.⁷ Le et al¹³ were able to detect mitragynine in the urine in levels as low as 1 ng/mL, which is clinically useful as mitragynine has a half-life determined in animal studies to be 3.85 hours. Similar detection limits for mitragynine and 7-hydroxymitragynine are used only at the Naval Medical Center Portsmouth in Virginia; however, kratom was not detected in the case study patient’s urine because a urine test was not done until hospital day 5.

Case Conclusion

When gently confronted about the kratom found in his car, the case study patient admitted that he had purchased kratom online after he was “cut off” from prescription opioids for his pain. He admitted that although it was beneficial for his pain, he did notice worsening in his aggression toward his spouse and coworkers. This progressed to an exacerbation of his psychotic symptoms of hallucinations and persecutory delusions. These symptoms remained well hidden—but were present for years prior to his presentation at the hospital. The patient was discharged from the inpatient psychiatric unit on hospital day 16 with a diagnosis of schizoaffective disorder, depressive type in addition to opioid-use disorder. The patient agreed to seek a pain management specialist and discontinue kratom use.

Conclusion

Kratom is an emerging drug of abuse in the Western world. Although significant research is being conducted on its possible medical uses, little is known about kratom beyond the “trip reports” of kratom users posted online. Because of its technically legal status in the United States and multiple other Western countries, kratom is easily accessible. Emergency physicians need to be aware of kratom, and during their evaluations, question appropriate patients about kratom and other legal highs.

In a historic collaboration, 10 major emergency medicine organizations have joined forces to create The Coalition to Oppose Medical Merit Badges (COMMB). In its news release, the Coalition stated it “…believes that board-certified emergency physicians who actively maintain their board certification should not be required to complete short-course certification or acquire condition-specific continuing medical education credits in advanced resuscitation, trauma care, stroke care, cardiovascular care, procedural sedation, or pediatric care in order to obtain or maintain medical staff privileges to work in an emergency department.”

The COMMB consists of the American Academy of Emergency Medicine (AAEM), American Academy of Emergency Medicine/Resident and Student Association (AAEM/RSA), American Board of Emergency Medicine (ABEM), American College of Emergency Physicians (ACEP), Association of Academic Chairs of Emergency Medicine (AACEM), Council of Emergency Medicine Residency Directors (CORD), Emergency Medicine Residents’ Association (EMRA), Society for Academic Emergency Medicine (SAEM), American Osteopathic Board of Emergency Medicine (AOBEM), and American College of Osteopathic Emergency Physicians (ACOEP).

In a written statement signed by the president/chair of each member organization, COMMB further asserted:

Similarly, mandatory targeted continuing medical education (CME) requirements do not offer any meaningful value for the public or for the emergency physician who has achieved and maintained board certification. Such requirements are often promulgated by others who incompletely understand the foundation of knowledge and skills acquired by successfully completing an Accreditation Council for Graduate Medical Education-accredited or American Osteopathic Association-approved Emergency Medicine Residency Program. These “merit badges” add no additional value for board-certified emergency physicians. Instead, they devalue the board certification process, failing to recognize the rigor of the ABEM Maintenance of Certification (MOC) Program. In essence, medical merit badges set a lower bar than a diplomate’s education, training, and ongoing learning, as measured by initial board certification and maintenance of certification.

The Coalition finds no rational justification to require medical merit badges for board-certified emergency physicians who maintain their board certification. Our committed professional organizations provide the best opportunities for continuous professional development and medical merit badges dismiss the quality of those educational efforts.

Opposing the requirements for medical merit badges will be a long and challenging struggle. It will take time to help administrators and regulatory bodies to better understand the rigorous standards to which we adhere as board-certified emergency physicians. In the coming months, we will develop our long-term strategy to create success and a pathway to recognize clinical excellence. We welcome your thoughts and suggestions as to how we can best succeed. In the near future, we will ask for strong support and a loud and unified voice.

We will persist and we are up to the challenge—we are board-certified emergency physicians. Opposing medical merit badges is the right thing to do for our specialty. We will forever demonstrate a lifelong commitment to caring for anyone who is ill or injured, at any time, for any reason.

Study Nixed Magnesium for Infants With Acute Bronchiolitis

AMY KARON

FRONTLINE MEDICAL news

Intravenous (IV) magnesium does not benefit, and may harm, infants with moderate-to-severe acute bronchiolitis, investigators reported. Compared with placebo, adding a single IV dose of magnesium sulfate (100 mg/kg) to usual care did not reduce time to medical readiness for discharge, even when patients had eczema or a family history of asthma, and was tied to a more than 3-fold rise in the rate of short-term readmissions, Khalid Al Ansari, MD, of Hamad Medical Corp in Doha, Qatar, and his associates wrote in Chest. “To our knowledge, this is the first randomized study to investigate the effect of intravenous magnesium in a bronchiolitis population,” they added.

Bronchiolitis lacks new, inexpensive, readily available treatments, despite being a common reason for hospital admission, the researchers noted. For older children with moderate-to-severe exacerbations of asthma, a meta-analysis found that the addition of magnesium to usual care appeared to cut readmissions and shorten lengths of stay, compared with placebo. To explore magnesium therapy in younger children, the investigators enrolled 162 previously healthy infants up to 18 months old who had been admitted to the short-stay unit of a pediatric emergency center with a diagnosis of moderate-to-severe viral bronchiolitis. Patients received usual care with oral dexamethasone and nebulized 5% hypertonic saline in 1 mL of 1:1000 epinephrine, plus a 60-minute IV infusion with a blinded syringe of either 0.9% saline placebo or magnesium sulfate (100 mg/kg).

The primary endpoint, time to medical readiness for discharge, did not statistically differ between groups, averaging 24.1 (95% confidence interval [CI], 20.0-29.1) hours with magnesium and 25.3 (95% CI, 20.3-31.5) hours with placebo (P = .91). Among patients with a history of eczema or a family history of asthma, mean times to readiness for discharge resembled those for the entire cohort and did not statistically differ based on treatment. Average Wang bronchiolitis severity scores also were similar between groups, as were rates of outpatient clinic visits (33.8% with magnesium and 27.2% with placebo). Thus, the trial identified “no benefit in adding intravenous magnesium for infant bronchiolitis, even in patients characterized to be at a higher risk for asthma,” the researchers concluded.

Strikingly, 2-week readmission rates were 19.5% with magnesium (95% CI, 11.3-30.1) and 6.2% with placebo (95% CI, 0.02-13.8; P = .016). Among patients with eczema or a family history of asthma, 2-week readmission rates also were significantly higher with magnesium (26.3%; 95% CI, 13.4-43.1) than with placebo (7.5%; 95% CI, 1.6-20.4; P = .034) These might have been chance findings, or magnesium might have masked worse bronchiolitis, prolonged the disease course, or interacted with 5% hypertonic saline or systemic corticosteroids, the investigators said. Intravenous magnesium might contribute to secondary relapse, especially among patients with eczema or a family history of asthma, they added.

Patients in this study had a median age of 3.7 months (range, 22 days to 17.6 months), about half had eczema or a family history of asthma, and 86% had positive nasopharyngeal virus swabs. Cardiopulmonary monitoring revealed no acute events during treatment. Of 16 readmissions in the magnesium group, 11 entered the infirmary and four entered the hospital. The five placebo readmissions included four to the infirmary and one to the hospital.

“As with other ‘negative studies,’ we may have failed to identify a benefit from intravenous magnesium in a patient subgroup because of our limited sample size,” the investigators wrote. “But we think our findings are generalizable to a similarly heterogeneous group of patients presenting for bronchiolitis care in a busy urban emergency department.”

Alansari K, Sayyed R, Davidson BL, Al Jawala S, Ghadier M. Intravenous magnesium sulfate for bronchiolitis: A randomized trial. Chest. 2017;pii:S0012-3692(17):30361-30366. doi:10.1016/j.chest.2017.03.002. [Epub ahead of print]

CDC: Some Shigella Strains Show Reduced Ciprofloxacin Susceptibility

SHARON WORCESTER

FRONTLINE MEDICAL NEWS

The Centers for Disease Control and Prevention (CDC) has identified an increase in Shigella isolates with reduced susceptibility to ciprofloxacin, and has released an official health advisory outlining new recommendations for clinical diagnosis, management, and reporting, as well as for laboratories and public health officials.

The Shigella isolates of concern in the United States have minimum inhibitory concentration (MIC) values of 0.12-1 mcg/mL for ciprofloxacin, which is within the range considered susceptible. These strains, however, “often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics,” such as ciprofloxacin, according to the CDC advisory.

It is possible that strains with MIC in the 0.12-1 mcg/mL range may have worse clinical outcome or increased risk of transmission, so the CDC made the following recommendations to clinicians:

• Order a stool culture to obtain isolates for antimicrobial susceptibility testing in suspected cases.
• Order antimicrobial susceptibility testing when ordering a stool culture for Shigella.
• Avoid routine prescribing of antibiotic therapy for Shigella infection, instead reserving antibiotics for patients with a clinical indication or when advised by public health officials in an outbreak setting.
• Tailor antibiotic choice (when antibiotics are indicated) to susceptibility results as soon as possible—with special attention given to the MIC for fluoroquinolone antibiotics.
• Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
• Consult local or state health departments for guidance on when patients may return to childcare, school, or work.
• Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.

Additionally, the CDC noted that shigellosis is a nationally notifiable condition, and all cases should be reported to one’s local health department. If a patient with shigellosis and a ciprofloxacin MIC of 0.12-1 mcg/mL is identified, this information should be included in the report to facilitate further testing of the isolate.

The CDC reported that it is working with state and local public health departments and clinical partners to determine if outcomes are indeed worse for patients treated with ciprofloxacin for Shigella strains harboring a quinolone resistance gene, and it will continue to monitor trends in susceptibility of Shigella isolates and to perform genetic testing on select strains to confirm the presence and type of resistance genes.

Prenotification, Unequivocal Stroke Promote Ultrafast Door-to-Needle Time

SHARON WORCESTER

FRONTLINE MEDICAL NEWS

Ultrafast door-to-needle times (DNTs) of 10 minutes or less for IV acute ischemic stroke thrombolysis can be safely achieved in carefully selected cases, according to a review of cases at an Austrian teaching hospital.

Raffi Topakian, MD, and his colleagues at the Academic Teaching Hospital Wels-Grieskirchen in Wels, Austria, followed a multidisciplinary intervention to reinforce key components of the well-known Helsinki model of acute stroke care to improve the IV thrombolysis rate and the median DNT at the teaching hospital, and analyzed data from 361 patients who underwent intravenous thrombolysis (IVT) for stroke there between July 2014 and September 2016. The IVT rate increased from 19% to about 27% after intervention, and the DNT during the study period was 60 minutes or less in 316 patients (87.5%), 30 minutes or less in 181 patients (50.1%), and 10 minutes or less in 63 patients (17.5%).

“Over the study period, we reduced the DNT time from 49 minutes to 25 minutes. This was significant, and the door-to-needle times were astonishingly similar for the in-hours service and the out-of-hour service,” he said at the annual meeting of the American Academy of Neurology.

Further, the rate of prenotifications from emergency medical services (EMS) rose from about 30% to 63% during the study period.

Patients with ultrafast DNT vs those with slower DNT were older, had more chronic heart failure, had more severe stroke (National Institutes of Health Stroke Scale score of 10 vs 5), had more anterior circulation stroke and cardioembolic stroke, and had clear onset of stroke. Independent predictors of ultrafast DNT included prenotification by EMS, anterior circulation syndrome, chronic heart failure, and having a stroke neurologist on duty, Dr Topakian said.

“Ultrashort DNTs can be achieved safely. The key is that we are prenotified by the EMS, that we can get all the relevant history details during transport, that there is a dedicated multidisciplinary stroke team and EMS staff, and that we have a seemingly unequivocal clinical scenario,” he said. “Out-of-hours DNT matched in-hours DNT, but the caveat is we’re talking about highly selected candidates; safety must not be sacrificed for the sake of speed, in all of our patients.”

In a historic collaboration, 10 major emergency medicine organizations have joined forces to create The Coalition to Oppose Medical Merit Badges (COMMB). In its news release, the Coalition stated it “…believes that board-certified emergency physicians who actively maintain their board certification should not be required to complete short-course certification or acquire condition-specific continuing medical education credits in advanced resuscitation, trauma care, stroke care, cardiovascular care, procedural sedation, or pediatric care in order to obtain or maintain medical staff privileges to work in an emergency department.”

The COMMB consists of the American Academy of Emergency Medicine (AAEM), American Academy of Emergency Medicine/Resident and Student Association (AAEM/RSA), American Board of Emergency Medicine (ABEM), American College of Emergency Physicians (ACEP), Association of Academic Chairs of Emergency Medicine (AACEM), Council of Emergency Medicine Residency Directors (CORD), Emergency Medicine Residents’ Association (EMRA), Society for Academic Emergency Medicine (SAEM), American Osteopathic Board of Emergency Medicine (AOBEM), and American College of Osteopathic Emergency Physicians (ACOEP).

In a written statement signed by the president/chair of each member organization, COMMB further asserted:

Similarly, mandatory targeted continuing medical education (CME) requirements do not offer any meaningful value for the public or for the emergency physician who has achieved and maintained board certification. Such requirements are often promulgated by others who incompletely understand the foundation of knowledge and skills acquired by successfully completing an Accreditation Council for Graduate Medical Education-accredited or American Osteopathic Association-approved Emergency Medicine Residency Program. These “merit badges” add no additional value for board-certified emergency physicians. Instead, they devalue the board certification process, failing to recognize the rigor of the ABEM Maintenance of Certification (MOC) Program. In essence, medical merit badges set a lower bar than a diplomate’s education, training, and ongoing learning, as measured by initial board certification and maintenance of certification.

The Coalition finds no rational justification to require medical merit badges for board-certified emergency physicians who maintain their board certification. Our committed professional organizations provide the best opportunities for continuous professional development and medical merit badges dismiss the quality of those educational efforts.

Opposing the requirements for medical merit badges will be a long and challenging struggle. It will take time to help administrators and regulatory bodies to better understand the rigorous standards to which we adhere as board-certified emergency physicians. In the coming months, we will develop our long-term strategy to create success and a pathway to recognize clinical excellence. We welcome your thoughts and suggestions as to how we can best succeed. In the near future, we will ask for strong support and a loud and unified voice.

We will persist and we are up to the challenge—we are board-certified emergency physicians. Opposing medical merit badges is the right thing to do for our specialty. We will forever demonstrate a lifelong commitment to caring for anyone who is ill or injured, at any time, for any reason.

Study Nixed Magnesium for Infants With Acute Bronchiolitis

AMY KARON

FRONTLINE MEDICAL news

Intravenous (IV) magnesium does not benefit, and may harm, infants with moderate-to-severe acute bronchiolitis, investigators reported. Compared with placebo, adding a single IV dose of magnesium sulfate (100 mg/kg) to usual care did not reduce time to medical readiness for discharge, even when patients had eczema or a family history of asthma, and was tied to a more than 3-fold rise in the rate of short-term readmissions, Khalid Al Ansari, MD, of Hamad Medical Corp in Doha, Qatar, and his associates wrote in Chest. “To our knowledge, this is the first randomized study to investigate the effect of intravenous magnesium in a bronchiolitis population,” they added.

Bronchiolitis lacks new, inexpensive, readily available treatments, despite being a common reason for hospital admission, the researchers noted. For older children with moderate-to-severe exacerbations of asthma, a meta-analysis found that the addition of magnesium to usual care appeared to cut readmissions and shorten lengths of stay, compared with placebo. To explore magnesium therapy in younger children, the investigators enrolled 162 previously healthy infants up to 18 months old who had been admitted to the short-stay unit of a pediatric emergency center with a diagnosis of moderate-to-severe viral bronchiolitis. Patients received usual care with oral dexamethasone and nebulized 5% hypertonic saline in 1 mL of 1:1000 epinephrine, plus a 60-minute IV infusion with a blinded syringe of either 0.9% saline placebo or magnesium sulfate (100 mg/kg).

The primary endpoint, time to medical readiness for discharge, did not statistically differ between groups, averaging 24.1 (95% confidence interval [CI], 20.0-29.1) hours with magnesium and 25.3 (95% CI, 20.3-31.5) hours with placebo (P = .91). Among patients with a history of eczema or a family history of asthma, mean times to readiness for discharge resembled those for the entire cohort and did not statistically differ based on treatment. Average Wang bronchiolitis severity scores also were similar between groups, as were rates of outpatient clinic visits (33.8% with magnesium and 27.2% with placebo). Thus, the trial identified “no benefit in adding intravenous magnesium for infant bronchiolitis, even in patients characterized to be at a higher risk for asthma,” the researchers concluded.

Strikingly, 2-week readmission rates were 19.5% with magnesium (95% CI, 11.3-30.1) and 6.2% with placebo (95% CI, 0.02-13.8; P = .016). Among patients with eczema or a family history of asthma, 2-week readmission rates also were significantly higher with magnesium (26.3%; 95% CI, 13.4-43.1) than with placebo (7.5%; 95% CI, 1.6-20.4; P = .034) These might have been chance findings, or magnesium might have masked worse bronchiolitis, prolonged the disease course, or interacted with 5% hypertonic saline or systemic corticosteroids, the investigators said. Intravenous magnesium might contribute to secondary relapse, especially among patients with eczema or a family history of asthma, they added.

Patients in this study had a median age of 3.7 months (range, 22 days to 17.6 months), about half had eczema or a family history of asthma, and 86% had positive nasopharyngeal virus swabs. Cardiopulmonary monitoring revealed no acute events during treatment. Of 16 readmissions in the magnesium group, 11 entered the infirmary and four entered the hospital. The five placebo readmissions included four to the infirmary and one to the hospital.

“As with other ‘negative studies,’ we may have failed to identify a benefit from intravenous magnesium in a patient subgroup because of our limited sample size,” the investigators wrote. “But we think our findings are generalizable to a similarly heterogeneous group of patients presenting for bronchiolitis care in a busy urban emergency department.”

Alansari K, Sayyed R, Davidson BL, Al Jawala S, Ghadier M. Intravenous magnesium sulfate for bronchiolitis: A randomized trial. Chest. 2017;pii:S0012-3692(17):30361-30366. doi:10.1016/j.chest.2017.03.002. [Epub ahead of print]

CDC: Some Shigella Strains Show Reduced Ciprofloxacin Susceptibility

SHARON WORCESTER

FRONTLINE MEDICAL NEWS

The Centers for Disease Control and Prevention (CDC) has identified an increase in Shigella isolates with reduced susceptibility to ciprofloxacin, and has released an official health advisory outlining new recommendations for clinical diagnosis, management, and reporting, as well as for laboratories and public health officials.

The Shigella isolates of concern in the United States have minimum inhibitory concentration (MIC) values of 0.12-1 mcg/mL for ciprofloxacin, which is within the range considered susceptible. These strains, however, “often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics,” such as ciprofloxacin, according to the CDC advisory.

It is possible that strains with MIC in the 0.12-1 mcg/mL range may have worse clinical outcome or increased risk of transmission, so the CDC made the following recommendations to clinicians:

• Order a stool culture to obtain isolates for antimicrobial susceptibility testing in suspected cases.
• Order antimicrobial susceptibility testing when ordering a stool culture for Shigella.
• Avoid routine prescribing of antibiotic therapy for Shigella infection, instead reserving antibiotics for patients with a clinical indication or when advised by public health officials in an outbreak setting.
• Tailor antibiotic choice (when antibiotics are indicated) to susceptibility results as soon as possible—with special attention given to the MIC for fluoroquinolone antibiotics.
• Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
• Consult local or state health departments for guidance on when patients may return to childcare, school, or work.
• Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.

Additionally, the CDC noted that shigellosis is a nationally notifiable condition, and all cases should be reported to one’s local health department. If a patient with shigellosis and a ciprofloxacin MIC of 0.12-1 mcg/mL is identified, this information should be included in the report to facilitate further testing of the isolate.

The CDC reported that it is working with state and local public health departments and clinical partners to determine if outcomes are indeed worse for patients treated with ciprofloxacin for Shigella strains harboring a quinolone resistance gene, and it will continue to monitor trends in susceptibility of Shigella isolates and to perform genetic testing on select strains to confirm the presence and type of resistance genes.

Prenotification, Unequivocal Stroke Promote Ultrafast Door-to-Needle Time

SHARON WORCESTER

FRONTLINE MEDICAL NEWS

Ultrafast door-to-needle times (DNTs) of 10 minutes or less for IV acute ischemic stroke thrombolysis can be safely achieved in carefully selected cases, according to a review of cases at an Austrian teaching hospital.

Raffi Topakian, MD, and his colleagues at the Academic Teaching Hospital Wels-Grieskirchen in Wels, Austria, followed a multidisciplinary intervention to reinforce key components of the well-known Helsinki model of acute stroke care to improve the IV thrombolysis rate and the median DNT at the teaching hospital, and analyzed data from 361 patients who underwent intravenous thrombolysis (IVT) for stroke there between July 2014 and September 2016. The IVT rate increased from 19% to about 27% after intervention, and the DNT during the study period was 60 minutes or less in 316 patients (87.5%), 30 minutes or less in 181 patients (50.1%), and 10 minutes or less in 63 patients (17.5%).

“Over the study period, we reduced the DNT time from 49 minutes to 25 minutes. This was significant, and the door-to-needle times were astonishingly similar for the in-hours service and the out-of-hour service,” he said at the annual meeting of the American Academy of Neurology.

Further, the rate of prenotifications from emergency medical services (EMS) rose from about 30% to 63% during the study period.

Patients with ultrafast DNT vs those with slower DNT were older, had more chronic heart failure, had more severe stroke (National Institutes of Health Stroke Scale score of 10 vs 5), had more anterior circulation stroke and cardioembolic stroke, and had clear onset of stroke. Independent predictors of ultrafast DNT included prenotification by EMS, anterior circulation syndrome, chronic heart failure, and having a stroke neurologist on duty, Dr Topakian said.

“Ultrashort DNTs can be achieved safely. The key is that we are prenotified by the EMS, that we can get all the relevant history details during transport, that there is a dedicated multidisciplinary stroke team and EMS staff, and that we have a seemingly unequivocal clinical scenario,” he said. “Out-of-hours DNT matched in-hours DNT, but the caveat is we’re talking about highly selected candidates; safety must not be sacrificed for the sake of speed, in all of our patients.”

In a historic collaboration, 10 major emergency medicine organizations have joined forces to create The Coalition to Oppose Medical Merit Badges (COMMB). In its news release, the Coalition stated it “…believes that board-certified emergency physicians who actively maintain their board certification should not be required to complete short-course certification or acquire condition-specific continuing medical education credits in advanced resuscitation, trauma care, stroke care, cardiovascular care, procedural sedation, or pediatric care in order to obtain or maintain medical staff privileges to work in an emergency department.”

The COMMB consists of the American Academy of Emergency Medicine (AAEM), American Academy of Emergency Medicine/Resident and Student Association (AAEM/RSA), American Board of Emergency Medicine (ABEM), American College of Emergency Physicians (ACEP), Association of Academic Chairs of Emergency Medicine (AACEM), Council of Emergency Medicine Residency Directors (CORD), Emergency Medicine Residents’ Association (EMRA), Society for Academic Emergency Medicine (SAEM), American Osteopathic Board of Emergency Medicine (AOBEM), and American College of Osteopathic Emergency Physicians (ACOEP).

In a written statement signed by the president/chair of each member organization, COMMB further asserted:

Similarly, mandatory targeted continuing medical education (CME) requirements do not offer any meaningful value for the public or for the emergency physician who has achieved and maintained board certification. Such requirements are often promulgated by others who incompletely understand the foundation of knowledge and skills acquired by successfully completing an Accreditation Council for Graduate Medical Education-accredited or American Osteopathic Association-approved Emergency Medicine Residency Program. These “merit badges” add no additional value for board-certified emergency physicians. Instead, they devalue the board certification process, failing to recognize the rigor of the ABEM Maintenance of Certification (MOC) Program. In essence, medical merit badges set a lower bar than a diplomate’s education, training, and ongoing learning, as measured by initial board certification and maintenance of certification.

The Coalition finds no rational justification to require medical merit badges for board-certified emergency physicians who maintain their board certification. Our committed professional organizations provide the best opportunities for continuous professional development and medical merit badges dismiss the quality of those educational efforts.

Opposing the requirements for medical merit badges will be a long and challenging struggle. It will take time to help administrators and regulatory bodies to better understand the rigorous standards to which we adhere as board-certified emergency physicians. In the coming months, we will develop our long-term strategy to create success and a pathway to recognize clinical excellence. We welcome your thoughts and suggestions as to how we can best succeed. In the near future, we will ask for strong support and a loud and unified voice.

We will persist and we are up to the challenge—we are board-certified emergency physicians. Opposing medical merit badges is the right thing to do for our specialty. We will forever demonstrate a lifelong commitment to caring for anyone who is ill or injured, at any time, for any reason.

Study Nixed Magnesium for Infants With Acute Bronchiolitis

AMY KARON

FRONTLINE MEDICAL news

Intravenous (IV) magnesium does not benefit, and may harm, infants with moderate-to-severe acute bronchiolitis, investigators reported. Compared with placebo, adding a single IV dose of magnesium sulfate (100 mg/kg) to usual care did not reduce time to medical readiness for discharge, even when patients had eczema or a family history of asthma, and was tied to a more than 3-fold rise in the rate of short-term readmissions, Khalid Al Ansari, MD, of Hamad Medical Corp in Doha, Qatar, and his associates wrote in Chest. “To our knowledge, this is the first randomized study to investigate the effect of intravenous magnesium in a bronchiolitis population,” they added.

Bronchiolitis lacks new, inexpensive, readily available treatments, despite being a common reason for hospital admission, the researchers noted. For older children with moderate-to-severe exacerbations of asthma, a meta-analysis found that the addition of magnesium to usual care appeared to cut readmissions and shorten lengths of stay, compared with placebo. To explore magnesium therapy in younger children, the investigators enrolled 162 previously healthy infants up to 18 months old who had been admitted to the short-stay unit of a pediatric emergency center with a diagnosis of moderate-to-severe viral bronchiolitis. Patients received usual care with oral dexamethasone and nebulized 5% hypertonic saline in 1 mL of 1:1000 epinephrine, plus a 60-minute IV infusion with a blinded syringe of either 0.9% saline placebo or magnesium sulfate (100 mg/kg).

The primary endpoint, time to medical readiness for discharge, did not statistically differ between groups, averaging 24.1 (95% confidence interval [CI], 20.0-29.1) hours with magnesium and 25.3 (95% CI, 20.3-31.5) hours with placebo (P = .91). Among patients with a history of eczema or a family history of asthma, mean times to readiness for discharge resembled those for the entire cohort and did not statistically differ based on treatment. Average Wang bronchiolitis severity scores also were similar between groups, as were rates of outpatient clinic visits (33.8% with magnesium and 27.2% with placebo). Thus, the trial identified “no benefit in adding intravenous magnesium for infant bronchiolitis, even in patients characterized to be at a higher risk for asthma,” the researchers concluded.

Strikingly, 2-week readmission rates were 19.5% with magnesium (95% CI, 11.3-30.1) and 6.2% with placebo (95% CI, 0.02-13.8; P = .016). Among patients with eczema or a family history of asthma, 2-week readmission rates also were significantly higher with magnesium (26.3%; 95% CI, 13.4-43.1) than with placebo (7.5%; 95% CI, 1.6-20.4; P = .034) These might have been chance findings, or magnesium might have masked worse bronchiolitis, prolonged the disease course, or interacted with 5% hypertonic saline or systemic corticosteroids, the investigators said. Intravenous magnesium might contribute to secondary relapse, especially among patients with eczema or a family history of asthma, they added.

Patients in this study had a median age of 3.7 months (range, 22 days to 17.6 months), about half had eczema or a family history of asthma, and 86% had positive nasopharyngeal virus swabs. Cardiopulmonary monitoring revealed no acute events during treatment. Of 16 readmissions in the magnesium group, 11 entered the infirmary and four entered the hospital. The five placebo readmissions included four to the infirmary and one to the hospital.

“As with other ‘negative studies,’ we may have failed to identify a benefit from intravenous magnesium in a patient subgroup because of our limited sample size,” the investigators wrote. “But we think our findings are generalizable to a similarly heterogeneous group of patients presenting for bronchiolitis care in a busy urban emergency department.”

Alansari K, Sayyed R, Davidson BL, Al Jawala S, Ghadier M. Intravenous magnesium sulfate for bronchiolitis: A randomized trial. Chest. 2017;pii:S0012-3692(17):30361-30366. doi:10.1016/j.chest.2017.03.002. [Epub ahead of print]

CDC: Some Shigella Strains Show Reduced Ciprofloxacin Susceptibility

SHARON WORCESTER

FRONTLINE MEDICAL NEWS

The Centers for Disease Control and Prevention (CDC) has identified an increase in Shigella isolates with reduced susceptibility to ciprofloxacin, and has released an official health advisory outlining new recommendations for clinical diagnosis, management, and reporting, as well as for laboratories and public health officials.

The Shigella isolates of concern in the United States have minimum inhibitory concentration (MIC) values of 0.12-1 mcg/mL for ciprofloxacin, which is within the range considered susceptible. These strains, however, “often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics,” such as ciprofloxacin, according to the CDC advisory.

It is possible that strains with MIC in the 0.12-1 mcg/mL range may have worse clinical outcome or increased risk of transmission, so the CDC made the following recommendations to clinicians:

• Order a stool culture to obtain isolates for antimicrobial susceptibility testing in suspected cases.
• Order antimicrobial susceptibility testing when ordering a stool culture for Shigella.
• Avoid routine prescribing of antibiotic therapy for Shigella infection, instead reserving antibiotics for patients with a clinical indication or when advised by public health officials in an outbreak setting.
• Tailor antibiotic choice (when antibiotics are indicated) to susceptibility results as soon as possible—with special attention given to the MIC for fluoroquinolone antibiotics.
• Obtain follow-up stool cultures in shigellosis patients who have continued or worsening symptoms despite antibiotic therapy.
• Consult local or state health departments for guidance on when patients may return to childcare, school, or work.
• Counsel patients with active diarrhea on how they can prevent spreading the infection to others, regardless of whether antibiotic treatment is prescribed.

Additionally, the CDC noted that shigellosis is a nationally notifiable condition, and all cases should be reported to one’s local health department. If a patient with shigellosis and a ciprofloxacin MIC of 0.12-1 mcg/mL is identified, this information should be included in the report to facilitate further testing of the isolate.

The CDC reported that it is working with state and local public health departments and clinical partners to determine if outcomes are indeed worse for patients treated with ciprofloxacin for Shigella strains harboring a quinolone resistance gene, and it will continue to monitor trends in susceptibility of Shigella isolates and to perform genetic testing on select strains to confirm the presence and type of resistance genes.

Prenotification, Unequivocal Stroke Promote Ultrafast Door-to-Needle Time

SHARON WORCESTER

FRONTLINE MEDICAL NEWS

Ultrafast door-to-needle times (DNTs) of 10 minutes or less for IV acute ischemic stroke thrombolysis can be safely achieved in carefully selected cases, according to a review of cases at an Austrian teaching hospital.

Raffi Topakian, MD, and his colleagues at the Academic Teaching Hospital Wels-Grieskirchen in Wels, Austria, followed a multidisciplinary intervention to reinforce key components of the well-known Helsinki model of acute stroke care to improve the IV thrombolysis rate and the median DNT at the teaching hospital, and analyzed data from 361 patients who underwent intravenous thrombolysis (IVT) for stroke there between July 2014 and September 2016. The IVT rate increased from 19% to about 27% after intervention, and the DNT during the study period was 60 minutes or less in 316 patients (87.5%), 30 minutes or less in 181 patients (50.1%), and 10 minutes or less in 63 patients (17.5%).

“Over the study period, we reduced the DNT time from 49 minutes to 25 minutes. This was significant, and the door-to-needle times were astonishingly similar for the in-hours service and the out-of-hour service,” he said at the annual meeting of the American Academy of Neurology.

Further, the rate of prenotifications from emergency medical services (EMS) rose from about 30% to 63% during the study period.

Patients with ultrafast DNT vs those with slower DNT were older, had more chronic heart failure, had more severe stroke (National Institutes of Health Stroke Scale score of 10 vs 5), had more anterior circulation stroke and cardioembolic stroke, and had clear onset of stroke. Independent predictors of ultrafast DNT included prenotification by EMS, anterior circulation syndrome, chronic heart failure, and having a stroke neurologist on duty, Dr Topakian said.

“Ultrashort DNTs can be achieved safely. The key is that we are prenotified by the EMS, that we can get all the relevant history details during transport, that there is a dedicated multidisciplinary stroke team and EMS staff, and that we have a seemingly unequivocal clinical scenario,” he said. “Out-of-hours DNT matched in-hours DNT, but the caveat is we’re talking about highly selected candidates; safety must not be sacrificed for the sake of speed, in all of our patients.”

Take-Home Points

• Hockey is a high-speed collision sport with one of the highest injury rates among all sports.
• Use of a helmet with visors or full-face shields significantly reduces the risk for eye injury.
• Broken portions of teeth should be found and placed in a protective medium such as saline, saliva, or milk for transport.
• A player with unresolved concussion symptoms should not be allowed to return to the ice.
• Shoulder dominance, which determines stick grip, is an important consideration in the treatment of shoulder instability in an ice hockey player.

On a surface of ice in Windsor, Nova Scotia in the middle of the 19th century, the modern game of ice hockey evolved.¹ A blend of hurley, a Gaelic sport, and lacrosse, from the native Mi’kmaq culture, the sport of ice hockey gained rapidly in popularity throughout Canada and is now the country’s national sport. Hockey quickly spread to the United States and then Europe. It is presently played in 77 countries across the world.²

Hockey players can reach speeds of up to 48 km (~30 miles) per hour on razor-sharp skates on an ice surface surrounded by rigid plastic composite boards topped with plexiglass.³ They use sticks made of wood, aluminum, or a composite material to advance a 6-ounce vulcanized rubber puck on the opposing goal, and this puck sometimes reaches speeds over 160 km (~100 miles) per hour. Older, male players are allowed to make physical contact with their opposing counterparts to separate them from the puck (body-checking). Not surprisingly, the potential risk for injury in hockey is high. At the 2010 Winter Olympics, men’s ice hockey players had the highest rate of injury of any other competitors there—more than 30% were affected.⁴

Evaluation and Management of Common Hockey Injuries

Eye Injuries

Although eye injuries are less common than musculoskeletal injuries and concussions in hockey, they are a serious risk for recreational and competitive players alike. Furthermore, recovery may be difficult, and eye injuries can have serious lifelong consequences.⁸ In hockey, the most commonly reported eye injuries are periorbital contusions and lacerations, hyphema, corneal and conjunctival abrasions, orbital fractures, and ruptured globes (Table 2).^9,10

As a contact sport, hockey often involves high-impact, blunt-force trauma. The trauma in hockey results from collisions with other players, the boards, hockey sticks, and pucks. It is therefore not surprising that the most common ocular injuries in this sport are periorbital contusions. Although most contusions cause only mild swelling and ecchymosis of the soft tissues around the eye, there is potential for serious consequences. In a Scandinavia study, Leivo and colleagues¹⁰ found that 9% of patients who sustained a periocular contusion also had a clinically significant secondary diagnosis, such as retinal tear or hemorrhage, eyelid laceration, vitreous hemorrhage, or retinal detachment. Although the study was hospital-based, and therefore biased toward more severe cases, its findings highlight the potential severity of eye injuries in hockey. Furthermore, the study found that the majority of players who sustained blunt trauma to the eye itself required lifelong follow-up because of increased risk for glaucoma. This is particularly true for hyphema, as this finding indicates significant damage to intraocular tissues.¹⁰Players can also sustain fractures of the orbital bones, including orbital blowout fractures. Typical signs and symptoms of blowout fractures include diplopia, proptosis or enophthalmos, infraorbital hypoesthesia, painful and decreased extraocular movement (particularly upgaze), and palpable crepitance caused by sinus air entering the lower eyelid.¹¹ If orbital fracture is suspected, as it should be in any case in which the injured player experiences pain with eye movement or diplopia, the player should be referred to the ED for computed tomography (CT) and ophthalmologic evaluation.¹² Continued participation seriously risks making the injury much worse, particularly should another impact occur. In addition, given the impact needed to cause orbital fractures, consideration must be given to the potential for a coexisting concussion injury.

Severe direct trauma to the eye—from a puck, a stick, or a fist—can result in a ruptured globe, a particularly serious injury that requires immediate surgical attention. Signs and symptoms of a ruptured globe are rarely subtle, but associated eyelid swelling or laceration may obscure the injury, delaying proper diagnosis and treatment. More obvious signs include severely reduced vision, hemorrhagic chemosis (swelling) of the conjunctiva, and an irregular or peaked pupil. If a rupture or any significant intraocular injury is suspected, it is crucial to avoid applying any pressure to the globe, as this can significantly worsen the damage to the intraocular tissues. Use of a helmet with protective shields and cages attached markedly reduces the risk for such injuries.¹³All eye injuries require prompt assessment, which allows for appropriate management and prevention of secondary damage.¹⁴ Initial evaluation of a patient with ocular trauma should begin with external examination for lacerations, swelling, or orbital rim step-off deformity. The physician should also check visual acuity in order to assess for significant vision impairment (counting fingers or reading a sign in the arena; confrontation visual fields). This should be done before attending to any periocular injuries, with the uninjured side serving as a control. Next, the physician should assess the extraocular eye movements as well as the size, shape, and reactivity of the pupils. Particular attention should be paid to detecting any deficit in extraocular movement or irregularity in pupil size, shape, or reactivity, as such findings are highly suggestive of serious injury to the globe.¹³ Hyphema (blood in anterior chamber of eye anterior to pupil) should be suspected if vision is reduced and the pupil cannot be clearly visualized. However, a bright red clot is not always apparent at time of injury or if the amount of blood is small. An irregular pupil, or a pupil that does not constrict well to light, is also a red flag for serious contusion injury to the eye, and requires ophthalmologic evaluation. It is important to keep in mind that blunt trauma severe enough to produce hyphema or an irregular and poorly reactive pupil is often associated with retinal damage as well, including retinal edema or detachment.

Minor injuries (eg, small foreign bodies, minor periocular contusions and lacerations) can often be managed rink-side. Foreign bodies not embedded in the cornea, but lodged under the upper eyelid, can sometimes be removed by everting the eyelid and sweeping with a moistened cotton swab or using diffuse, sterile saline irrigation.¹¹ Corneal abrasions generally cause severe pain, photophobia, and tearing and are easily diagnosed with use of topical fluorescein and a blue light. A topical anesthetic can be extremely helpful in this setting, as it allows for proper pain-free evaluation, but should never be used in an ongoing manner for pain relief. Small lacerations of the brow can be sutured with 5-0 or 6-0 nylon or closed with 2-Octyl cyanoacrylate tissue adhesive (Dermabond). Eyelid lacerations, unless very small, are best managed by an ophthalmologist; care must be taken to rule out injury to the deeper orbital tissues and eye. If serious injury is suspected, or the eye cannot be appropriately evaluated, it should be stabilized and protected with a protective shield or plastic cup, and the player should be transferred to an ED for appropriate ophthalmologic evaluation.¹³Most eye injuries are accidental, caused by sticks or deflected pucks, but 18% are acquired in fights.⁸ Use of visors or full-face cages effectively minimizes the rate of eye injuries.^8,13,15,16 In a cohort study of 282 elite amateur ice hockey players, the risk of eye injury was 4.7 times higher in players without face protection than in players who used half-face shields; there were no eye injuries in players who used full-face protection.¹³ For visors to prevent eye injury, they must be positioned to cover the eyes and the lower edge of the nose in all projections.¹⁰

Dental Injuries

The incidence and type of facial and dental injuries depend directly on the type of face protection used.^11,17,18 In a study of face, head, and neck injuries in elite amateur ice hockey players, Stuart and colleagues¹³ found game-related injury rates of 158.9 per 1000 player-hours in players without face protection, 73.5 in players who used half-face shields, and 23.2 in players who used full-face shields. Players who wore full-face shields had facial, head, and neck injury rates of only 23.2 per 1000 player-game hours.¹³ Other studies clearly support the important role face shields play in lowering injury risk in hockey. Face and head injuries account for 20% to 40% of all hockey-related injuries,^3,16,19 and dental injuries up to 11.5%.²⁰ In a study from Finland, Lahti and colleagues¹⁹ found that over a 2-year period, 479 hockey players sustained injuries, including 650 separate dental injuries. The most commonly diagnosed dental injury was an uncomplicated crown fracture, and the most common cause was a hit with a hockey stick, which accounted for 52.7% and 40.3% of dental injuries in games and practices, respectively.¹⁹

In the management of dental fractures, the broken portions of teeth should be found and placed in a transportation-protective medium, such as saline, saliva, or milk,¹⁶ which can improve functional and esthetic replacement outcomes.^21,22 Loose pieces of teeth should not be left in the player’s mouth. The residual tooth should be stabilized and exposure to air and occlusion limited. Dental fractures can affect the enamel, the enamel and dentin structures (uncomplicated fracture), or enamel, dentin, and pulp (complicated).²³ Fractures involving only the enamel do not require urgent dental evaluation. Dentin or pulp involvement may cause temperature and air sensitivity.²³ If a tooth is air-sensitive, the player should be referred to a specialist immediately.¹¹

Direct trauma can cause instability without displacement (subluxation) or complete displacement of the tooth from its alveolar socket (avulsion).²³ An avulsed tooth should be handled by the crown to avoid further damage to the root and periodontal ligament.^16,24 The tooth should be rinsed gently with saline and reimplanted in its socket, ideally within 5 to 10 minutes,²³with the athlete biting down gently on gauze to hold the tooth in place. A 1-mL supraperiosteal infiltration of 1% or 2% lidocaine hydrochloride (1:100,000 epinephrine) can be given into the apex of the tooth being anesthetized (Figure 1).

Concussions

A concussion is a “complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces.”²⁵ Concussion is largely a functional disturbance instead of a structural injury, owing to the rotational and/or shearing forces involved. Many studies have identified concussion as the most common type of injury in all of youth hockey.²⁶ Concussions account for up to 19% of all injuries in men’s collegiate hockey.³

Concussion can be challenging to diagnose on the ice. The most important factor in concussion management is symptom reporting by the athlete.²⁷ Despite significant efforts in education and awareness, student athletes, especially hockey players, withhold reporting a possible concussion.²⁸ Reasons for underreporting include fear of letting down other players and coaches, thinking the injury is not severe enough to warrant evaluation, and fear of losing standing with the current team or future teams.²⁸

Cervical Spine Injuries

Whereas American football is associated with a higher annual number of nonfatal catastrophic neck injuries, hockey has a 3 to 6 times higher incidence of cervical spine injuries and spinal cord damage.^38,39 A Canadian Ice Hockey Spinal Injuries Registry review of the period 2006 to 2011 identified 44 cervical spine injuries, 7.3 per year on average.⁴⁰ Severe injury, defined as complete motor and sensory loss, complete motor loss and incomplete sensory, or complete motor loss, occurred in 4 (9.1%) of the 44 injured players. In hockey, a major mechanism of cervical spine injury is an axial load to the slightly flexed spine.³⁹ Of 355 hockey-related cervical spine injuries in a Canada study, 95 (35.5%) were caused by a check from behind.^40,41 The Canadian neurosurgeons’ work led to rule changes prohibiting checks from behind, and this prohibition has reduced the incidence of cervical spine injuries in ice hockey.^38,40

Team physicians should be comfortable managing serious neck and spine injuries on the ice. Initial evaluation should follow the standard ABCs (airway, breathing, circulation). The physician places a hand on each side of the head to stabilize the neck until the initial examination is complete. The goal is to minimize cervical spine motion until transportation to the hospital for advanced imaging and definitive treatment.³⁷ The decision to remove or leave on the helmet is now controversial. Hockey helmets differ from football helmets in that their chinstraps do not afford significant cervical stabilization, and the helmets have less padding and cover less of the head; in addition, a shockingly high percentage of hockey players do not wear properly fitting helmets.³⁷ In one study, 3-dimensional motion analysis of a hockey player during the logroll technique showed less transverse and sagittal cervical plane motion with the helmet removed than with the helmet (properly fitting or not) in place; the authors recommended removing the helmet to limit extraneous cervical spine motion during the technique.³⁷ However, 2 other studies found that helmet removal can result in significantly increased cervical spine motion of the immobilized hockey player.^42,43Recommendation 4 of the recently released interassociation consensus statement of the National Athletic Trainers’ Association reads, “Protective athletic equipment should be removed before transport to an emergency facility for an athlete-patient with suspected cervical spine instability.”⁴⁴ This represents a shift from leaving the helmet and shoulder pads in place. For ice hockey players with suspected cervical spine injury, more research is needed on cervical motion during the entire sequence—partial logrolls, spine-boarding, placement of cervical collar before or after logroll, and different immobilization techniques for transport.³⁷

The athlete must be carefully transferred to a spine board with either logroll or lift-and-slide. Although an extrication cervical collar can be placed before the spine board is placed, the effectiveness of this collar in executing the spine-board transfer is not proven.⁴⁵ When the player is on the spine board, the head can be secured with pads and straps en route to the hospital.

Return-to-Play Criteria for Cervical Spine Injuries There is no clear consensus on return-to-play guidelines for cervical spine injuries in athletes.⁴⁶

Shoulder Injuries

For hockey players, the upper extremity traditionally has been considered a well-protected area.⁴⁸ However, shoulder pads are considerably more flexible in hockey than in football and other collision sports. In addition, hockey gloves allow a fair amount of motion for stick handling, and the wrist may be in maximal flexion or extension when a hit against the boards or the ice occurs. Open-ice checking, board collisions, and hockey stick use have been postulated as reasons for the high incidence of upper extremity injuries in hockey. Researchers in Finland found that upper extremity injuries accounted for up to 31% of all hockey injuries.⁴⁹ More than 50% of these injuries resulted from checking or board collisions. Furthermore, study findings highlighted a low rate of injury in younger players and indicated the rate increases with age.^49,50

In hockey players, the acromioclavicular (AC) joint is the most commonly injured shoulder structure.⁵¹ The mechanism of injury can be a board collision or an open-ice hit, but most often is a direct blow to the shoulder. The collision disrupts the AC joint and can sprain or tear the coracoclavicular ligaments. The Rockwood classification is used to categorize AC joint injuries (Figure 2).

Summary

Hockey is a high-speed collision sport with one of the highest injury rates among all sports. Physicians caring for youth, amateur, and senior hockey teams see a range of acute head, neck, and shoulder injuries. Although treatment of eye injuries, dental injuries, and concussions is not always considered orthopedic care, an orthopedic surgeon who is covering hockey needs to be comfortable managing these injuries acutely. Quality rink-side care minimizes the impact of the injury, maximizes the functional result, and expedites the safe return of the injured player back to the ice.

Am J Orthop. 2017;46(3):123-134. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Hockey is a high-speed collision sport with one of the highest injury rates among all sports.
• Use of a helmet with visors or full-face shields significantly reduces the risk for eye injury.
• Broken portions of teeth should be found and placed in a protective medium such as saline, saliva, or milk for transport.
• A player with unresolved concussion symptoms should not be allowed to return to the ice.
• Shoulder dominance, which determines stick grip, is an important consideration in the treatment of shoulder instability in an ice hockey player.

On a surface of ice in Windsor, Nova Scotia in the middle of the 19th century, the modern game of ice hockey evolved.¹ A blend of hurley, a Gaelic sport, and lacrosse, from the native Mi’kmaq culture, the sport of ice hockey gained rapidly in popularity throughout Canada and is now the country’s national sport. Hockey quickly spread to the United States and then Europe. It is presently played in 77 countries across the world.²

Hockey players can reach speeds of up to 48 km (~30 miles) per hour on razor-sharp skates on an ice surface surrounded by rigid plastic composite boards topped with plexiglass.³ They use sticks made of wood, aluminum, or a composite material to advance a 6-ounce vulcanized rubber puck on the opposing goal, and this puck sometimes reaches speeds over 160 km (~100 miles) per hour. Older, male players are allowed to make physical contact with their opposing counterparts to separate them from the puck (body-checking). Not surprisingly, the potential risk for injury in hockey is high. At the 2010 Winter Olympics, men’s ice hockey players had the highest rate of injury of any other competitors there—more than 30% were affected.⁴

Evaluation and Management of Common Hockey Injuries

Eye Injuries

Although eye injuries are less common than musculoskeletal injuries and concussions in hockey, they are a serious risk for recreational and competitive players alike. Furthermore, recovery may be difficult, and eye injuries can have serious lifelong consequences.⁸ In hockey, the most commonly reported eye injuries are periorbital contusions and lacerations, hyphema, corneal and conjunctival abrasions, orbital fractures, and ruptured globes (Table 2).^9,10

As a contact sport, hockey often involves high-impact, blunt-force trauma. The trauma in hockey results from collisions with other players, the boards, hockey sticks, and pucks. It is therefore not surprising that the most common ocular injuries in this sport are periorbital contusions. Although most contusions cause only mild swelling and ecchymosis of the soft tissues around the eye, there is potential for serious consequences. In a Scandinavia study, Leivo and colleagues¹⁰ found that 9% of patients who sustained a periocular contusion also had a clinically significant secondary diagnosis, such as retinal tear or hemorrhage, eyelid laceration, vitreous hemorrhage, or retinal detachment. Although the study was hospital-based, and therefore biased toward more severe cases, its findings highlight the potential severity of eye injuries in hockey. Furthermore, the study found that the majority of players who sustained blunt trauma to the eye itself required lifelong follow-up because of increased risk for glaucoma. This is particularly true for hyphema, as this finding indicates significant damage to intraocular tissues.¹⁰Players can also sustain fractures of the orbital bones, including orbital blowout fractures. Typical signs and symptoms of blowout fractures include diplopia, proptosis or enophthalmos, infraorbital hypoesthesia, painful and decreased extraocular movement (particularly upgaze), and palpable crepitance caused by sinus air entering the lower eyelid.¹¹ If orbital fracture is suspected, as it should be in any case in which the injured player experiences pain with eye movement or diplopia, the player should be referred to the ED for computed tomography (CT) and ophthalmologic evaluation.¹² Continued participation seriously risks making the injury much worse, particularly should another impact occur. In addition, given the impact needed to cause orbital fractures, consideration must be given to the potential for a coexisting concussion injury.

Severe direct trauma to the eye—from a puck, a stick, or a fist—can result in a ruptured globe, a particularly serious injury that requires immediate surgical attention. Signs and symptoms of a ruptured globe are rarely subtle, but associated eyelid swelling or laceration may obscure the injury, delaying proper diagnosis and treatment. More obvious signs include severely reduced vision, hemorrhagic chemosis (swelling) of the conjunctiva, and an irregular or peaked pupil. If a rupture or any significant intraocular injury is suspected, it is crucial to avoid applying any pressure to the globe, as this can significantly worsen the damage to the intraocular tissues. Use of a helmet with protective shields and cages attached markedly reduces the risk for such injuries.¹³All eye injuries require prompt assessment, which allows for appropriate management and prevention of secondary damage.¹⁴ Initial evaluation of a patient with ocular trauma should begin with external examination for lacerations, swelling, or orbital rim step-off deformity. The physician should also check visual acuity in order to assess for significant vision impairment (counting fingers or reading a sign in the arena; confrontation visual fields). This should be done before attending to any periocular injuries, with the uninjured side serving as a control. Next, the physician should assess the extraocular eye movements as well as the size, shape, and reactivity of the pupils. Particular attention should be paid to detecting any deficit in extraocular movement or irregularity in pupil size, shape, or reactivity, as such findings are highly suggestive of serious injury to the globe.¹³ Hyphema (blood in anterior chamber of eye anterior to pupil) should be suspected if vision is reduced and the pupil cannot be clearly visualized. However, a bright red clot is not always apparent at time of injury or if the amount of blood is small. An irregular pupil, or a pupil that does not constrict well to light, is also a red flag for serious contusion injury to the eye, and requires ophthalmologic evaluation. It is important to keep in mind that blunt trauma severe enough to produce hyphema or an irregular and poorly reactive pupil is often associated with retinal damage as well, including retinal edema or detachment.

Minor injuries (eg, small foreign bodies, minor periocular contusions and lacerations) can often be managed rink-side. Foreign bodies not embedded in the cornea, but lodged under the upper eyelid, can sometimes be removed by everting the eyelid and sweeping with a moistened cotton swab or using diffuse, sterile saline irrigation.¹¹ Corneal abrasions generally cause severe pain, photophobia, and tearing and are easily diagnosed with use of topical fluorescein and a blue light. A topical anesthetic can be extremely helpful in this setting, as it allows for proper pain-free evaluation, but should never be used in an ongoing manner for pain relief. Small lacerations of the brow can be sutured with 5-0 or 6-0 nylon or closed with 2-Octyl cyanoacrylate tissue adhesive (Dermabond). Eyelid lacerations, unless very small, are best managed by an ophthalmologist; care must be taken to rule out injury to the deeper orbital tissues and eye. If serious injury is suspected, or the eye cannot be appropriately evaluated, it should be stabilized and protected with a protective shield or plastic cup, and the player should be transferred to an ED for appropriate ophthalmologic evaluation.¹³Most eye injuries are accidental, caused by sticks or deflected pucks, but 18% are acquired in fights.⁸ Use of visors or full-face cages effectively minimizes the rate of eye injuries.^8,13,15,16 In a cohort study of 282 elite amateur ice hockey players, the risk of eye injury was 4.7 times higher in players without face protection than in players who used half-face shields; there were no eye injuries in players who used full-face protection.¹³ For visors to prevent eye injury, they must be positioned to cover the eyes and the lower edge of the nose in all projections.¹⁰

Dental Injuries

The incidence and type of facial and dental injuries depend directly on the type of face protection used.^11,17,18 In a study of face, head, and neck injuries in elite amateur ice hockey players, Stuart and colleagues¹³ found game-related injury rates of 158.9 per 1000 player-hours in players without face protection, 73.5 in players who used half-face shields, and 23.2 in players who used full-face shields. Players who wore full-face shields had facial, head, and neck injury rates of only 23.2 per 1000 player-game hours.¹³ Other studies clearly support the important role face shields play in lowering injury risk in hockey. Face and head injuries account for 20% to 40% of all hockey-related injuries,^3,16,19 and dental injuries up to 11.5%.²⁰ In a study from Finland, Lahti and colleagues¹⁹ found that over a 2-year period, 479 hockey players sustained injuries, including 650 separate dental injuries. The most commonly diagnosed dental injury was an uncomplicated crown fracture, and the most common cause was a hit with a hockey stick, which accounted for 52.7% and 40.3% of dental injuries in games and practices, respectively.¹⁹

In the management of dental fractures, the broken portions of teeth should be found and placed in a transportation-protective medium, such as saline, saliva, or milk,¹⁶ which can improve functional and esthetic replacement outcomes.^21,22 Loose pieces of teeth should not be left in the player’s mouth. The residual tooth should be stabilized and exposure to air and occlusion limited. Dental fractures can affect the enamel, the enamel and dentin structures (uncomplicated fracture), or enamel, dentin, and pulp (complicated).²³ Fractures involving only the enamel do not require urgent dental evaluation. Dentin or pulp involvement may cause temperature and air sensitivity.²³ If a tooth is air-sensitive, the player should be referred to a specialist immediately.¹¹

Direct trauma can cause instability without displacement (subluxation) or complete displacement of the tooth from its alveolar socket (avulsion).²³ An avulsed tooth should be handled by the crown to avoid further damage to the root and periodontal ligament.^16,24 The tooth should be rinsed gently with saline and reimplanted in its socket, ideally within 5 to 10 minutes,²³with the athlete biting down gently on gauze to hold the tooth in place. A 1-mL supraperiosteal infiltration of 1% or 2% lidocaine hydrochloride (1:100,000 epinephrine) can be given into the apex of the tooth being anesthetized (Figure 1).

Concussions

A concussion is a “complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces.”²⁵ Concussion is largely a functional disturbance instead of a structural injury, owing to the rotational and/or shearing forces involved. Many studies have identified concussion as the most common type of injury in all of youth hockey.²⁶ Concussions account for up to 19% of all injuries in men’s collegiate hockey.³

Concussion can be challenging to diagnose on the ice. The most important factor in concussion management is symptom reporting by the athlete.²⁷ Despite significant efforts in education and awareness, student athletes, especially hockey players, withhold reporting a possible concussion.²⁸ Reasons for underreporting include fear of letting down other players and coaches, thinking the injury is not severe enough to warrant evaluation, and fear of losing standing with the current team or future teams.²⁸

Cervical Spine Injuries

Whereas American football is associated with a higher annual number of nonfatal catastrophic neck injuries, hockey has a 3 to 6 times higher incidence of cervical spine injuries and spinal cord damage.^38,39 A Canadian Ice Hockey Spinal Injuries Registry review of the period 2006 to 2011 identified 44 cervical spine injuries, 7.3 per year on average.⁴⁰ Severe injury, defined as complete motor and sensory loss, complete motor loss and incomplete sensory, or complete motor loss, occurred in 4 (9.1%) of the 44 injured players. In hockey, a major mechanism of cervical spine injury is an axial load to the slightly flexed spine.³⁹ Of 355 hockey-related cervical spine injuries in a Canada study, 95 (35.5%) were caused by a check from behind.^40,41 The Canadian neurosurgeons’ work led to rule changes prohibiting checks from behind, and this prohibition has reduced the incidence of cervical spine injuries in ice hockey.^38,40

Team physicians should be comfortable managing serious neck and spine injuries on the ice. Initial evaluation should follow the standard ABCs (airway, breathing, circulation). The physician places a hand on each side of the head to stabilize the neck until the initial examination is complete. The goal is to minimize cervical spine motion until transportation to the hospital for advanced imaging and definitive treatment.³⁷ The decision to remove or leave on the helmet is now controversial. Hockey helmets differ from football helmets in that their chinstraps do not afford significant cervical stabilization, and the helmets have less padding and cover less of the head; in addition, a shockingly high percentage of hockey players do not wear properly fitting helmets.³⁷ In one study, 3-dimensional motion analysis of a hockey player during the logroll technique showed less transverse and sagittal cervical plane motion with the helmet removed than with the helmet (properly fitting or not) in place; the authors recommended removing the helmet to limit extraneous cervical spine motion during the technique.³⁷ However, 2 other studies found that helmet removal can result in significantly increased cervical spine motion of the immobilized hockey player.^42,43Recommendation 4 of the recently released interassociation consensus statement of the National Athletic Trainers’ Association reads, “Protective athletic equipment should be removed before transport to an emergency facility for an athlete-patient with suspected cervical spine instability.”⁴⁴ This represents a shift from leaving the helmet and shoulder pads in place. For ice hockey players with suspected cervical spine injury, more research is needed on cervical motion during the entire sequence—partial logrolls, spine-boarding, placement of cervical collar before or after logroll, and different immobilization techniques for transport.³⁷

The athlete must be carefully transferred to a spine board with either logroll or lift-and-slide. Although an extrication cervical collar can be placed before the spine board is placed, the effectiveness of this collar in executing the spine-board transfer is not proven.⁴⁵ When the player is on the spine board, the head can be secured with pads and straps en route to the hospital.

Return-to-Play Criteria for Cervical Spine Injuries There is no clear consensus on return-to-play guidelines for cervical spine injuries in athletes.⁴⁶

Shoulder Injuries

For hockey players, the upper extremity traditionally has been considered a well-protected area.⁴⁸ However, shoulder pads are considerably more flexible in hockey than in football and other collision sports. In addition, hockey gloves allow a fair amount of motion for stick handling, and the wrist may be in maximal flexion or extension when a hit against the boards or the ice occurs. Open-ice checking, board collisions, and hockey stick use have been postulated as reasons for the high incidence of upper extremity injuries in hockey. Researchers in Finland found that upper extremity injuries accounted for up to 31% of all hockey injuries.⁴⁹ More than 50% of these injuries resulted from checking or board collisions. Furthermore, study findings highlighted a low rate of injury in younger players and indicated the rate increases with age.^49,50

In hockey players, the acromioclavicular (AC) joint is the most commonly injured shoulder structure.⁵¹ The mechanism of injury can be a board collision or an open-ice hit, but most often is a direct blow to the shoulder. The collision disrupts the AC joint and can sprain or tear the coracoclavicular ligaments. The Rockwood classification is used to categorize AC joint injuries (Figure 2).

Summary

Hockey is a high-speed collision sport with one of the highest injury rates among all sports. Physicians caring for youth, amateur, and senior hockey teams see a range of acute head, neck, and shoulder injuries. Although treatment of eye injuries, dental injuries, and concussions is not always considered orthopedic care, an orthopedic surgeon who is covering hockey needs to be comfortable managing these injuries acutely. Quality rink-side care minimizes the impact of the injury, maximizes the functional result, and expedites the safe return of the injured player back to the ice.

Am J Orthop. 2017;46(3):123-134. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Hockey is a high-speed collision sport with one of the highest injury rates among all sports.
• Use of a helmet with visors or full-face shields significantly reduces the risk for eye injury.
• Broken portions of teeth should be found and placed in a protective medium such as saline, saliva, or milk for transport.
• A player with unresolved concussion symptoms should not be allowed to return to the ice.
• Shoulder dominance, which determines stick grip, is an important consideration in the treatment of shoulder instability in an ice hockey player.

On a surface of ice in Windsor, Nova Scotia in the middle of the 19th century, the modern game of ice hockey evolved.¹ A blend of hurley, a Gaelic sport, and lacrosse, from the native Mi’kmaq culture, the sport of ice hockey gained rapidly in popularity throughout Canada and is now the country’s national sport. Hockey quickly spread to the United States and then Europe. It is presently played in 77 countries across the world.²

Hockey players can reach speeds of up to 48 km (~30 miles) per hour on razor-sharp skates on an ice surface surrounded by rigid plastic composite boards topped with plexiglass.³ They use sticks made of wood, aluminum, or a composite material to advance a 6-ounce vulcanized rubber puck on the opposing goal, and this puck sometimes reaches speeds over 160 km (~100 miles) per hour. Older, male players are allowed to make physical contact with their opposing counterparts to separate them from the puck (body-checking). Not surprisingly, the potential risk for injury in hockey is high. At the 2010 Winter Olympics, men’s ice hockey players had the highest rate of injury of any other competitors there—more than 30% were affected.⁴

Evaluation and Management of Common Hockey Injuries

Eye Injuries

Although eye injuries are less common than musculoskeletal injuries and concussions in hockey, they are a serious risk for recreational and competitive players alike. Furthermore, recovery may be difficult, and eye injuries can have serious lifelong consequences.⁸ In hockey, the most commonly reported eye injuries are periorbital contusions and lacerations, hyphema, corneal and conjunctival abrasions, orbital fractures, and ruptured globes (Table 2).^9,10

As a contact sport, hockey often involves high-impact, blunt-force trauma. The trauma in hockey results from collisions with other players, the boards, hockey sticks, and pucks. It is therefore not surprising that the most common ocular injuries in this sport are periorbital contusions. Although most contusions cause only mild swelling and ecchymosis of the soft tissues around the eye, there is potential for serious consequences. In a Scandinavia study, Leivo and colleagues¹⁰ found that 9% of patients who sustained a periocular contusion also had a clinically significant secondary diagnosis, such as retinal tear or hemorrhage, eyelid laceration, vitreous hemorrhage, or retinal detachment. Although the study was hospital-based, and therefore biased toward more severe cases, its findings highlight the potential severity of eye injuries in hockey. Furthermore, the study found that the majority of players who sustained blunt trauma to the eye itself required lifelong follow-up because of increased risk for glaucoma. This is particularly true for hyphema, as this finding indicates significant damage to intraocular tissues.¹⁰Players can also sustain fractures of the orbital bones, including orbital blowout fractures. Typical signs and symptoms of blowout fractures include diplopia, proptosis or enophthalmos, infraorbital hypoesthesia, painful and decreased extraocular movement (particularly upgaze), and palpable crepitance caused by sinus air entering the lower eyelid.¹¹ If orbital fracture is suspected, as it should be in any case in which the injured player experiences pain with eye movement or diplopia, the player should be referred to the ED for computed tomography (CT) and ophthalmologic evaluation.¹² Continued participation seriously risks making the injury much worse, particularly should another impact occur. In addition, given the impact needed to cause orbital fractures, consideration must be given to the potential for a coexisting concussion injury.

Severe direct trauma to the eye—from a puck, a stick, or a fist—can result in a ruptured globe, a particularly serious injury that requires immediate surgical attention. Signs and symptoms of a ruptured globe are rarely subtle, but associated eyelid swelling or laceration may obscure the injury, delaying proper diagnosis and treatment. More obvious signs include severely reduced vision, hemorrhagic chemosis (swelling) of the conjunctiva, and an irregular or peaked pupil. If a rupture or any significant intraocular injury is suspected, it is crucial to avoid applying any pressure to the globe, as this can significantly worsen the damage to the intraocular tissues. Use of a helmet with protective shields and cages attached markedly reduces the risk for such injuries.¹³All eye injuries require prompt assessment, which allows for appropriate management and prevention of secondary damage.¹⁴ Initial evaluation of a patient with ocular trauma should begin with external examination for lacerations, swelling, or orbital rim step-off deformity. The physician should also check visual acuity in order to assess for significant vision impairment (counting fingers or reading a sign in the arena; confrontation visual fields). This should be done before attending to any periocular injuries, with the uninjured side serving as a control. Next, the physician should assess the extraocular eye movements as well as the size, shape, and reactivity of the pupils. Particular attention should be paid to detecting any deficit in extraocular movement or irregularity in pupil size, shape, or reactivity, as such findings are highly suggestive of serious injury to the globe.¹³ Hyphema (blood in anterior chamber of eye anterior to pupil) should be suspected if vision is reduced and the pupil cannot be clearly visualized. However, a bright red clot is not always apparent at time of injury or if the amount of blood is small. An irregular pupil, or a pupil that does not constrict well to light, is also a red flag for serious contusion injury to the eye, and requires ophthalmologic evaluation. It is important to keep in mind that blunt trauma severe enough to produce hyphema or an irregular and poorly reactive pupil is often associated with retinal damage as well, including retinal edema or detachment.

Minor injuries (eg, small foreign bodies, minor periocular contusions and lacerations) can often be managed rink-side. Foreign bodies not embedded in the cornea, but lodged under the upper eyelid, can sometimes be removed by everting the eyelid and sweeping with a moistened cotton swab or using diffuse, sterile saline irrigation.¹¹ Corneal abrasions generally cause severe pain, photophobia, and tearing and are easily diagnosed with use of topical fluorescein and a blue light. A topical anesthetic can be extremely helpful in this setting, as it allows for proper pain-free evaluation, but should never be used in an ongoing manner for pain relief. Small lacerations of the brow can be sutured with 5-0 or 6-0 nylon or closed with 2-Octyl cyanoacrylate tissue adhesive (Dermabond). Eyelid lacerations, unless very small, are best managed by an ophthalmologist; care must be taken to rule out injury to the deeper orbital tissues and eye. If serious injury is suspected, or the eye cannot be appropriately evaluated, it should be stabilized and protected with a protective shield or plastic cup, and the player should be transferred to an ED for appropriate ophthalmologic evaluation.¹³Most eye injuries are accidental, caused by sticks or deflected pucks, but 18% are acquired in fights.⁸ Use of visors or full-face cages effectively minimizes the rate of eye injuries.^8,13,15,16 In a cohort study of 282 elite amateur ice hockey players, the risk of eye injury was 4.7 times higher in players without face protection than in players who used half-face shields; there were no eye injuries in players who used full-face protection.¹³ For visors to prevent eye injury, they must be positioned to cover the eyes and the lower edge of the nose in all projections.¹⁰

Dental Injuries

The incidence and type of facial and dental injuries depend directly on the type of face protection used.^11,17,18 In a study of face, head, and neck injuries in elite amateur ice hockey players, Stuart and colleagues¹³ found game-related injury rates of 158.9 per 1000 player-hours in players without face protection, 73.5 in players who used half-face shields, and 23.2 in players who used full-face shields. Players who wore full-face shields had facial, head, and neck injury rates of only 23.2 per 1000 player-game hours.¹³ Other studies clearly support the important role face shields play in lowering injury risk in hockey. Face and head injuries account for 20% to 40% of all hockey-related injuries,^3,16,19 and dental injuries up to 11.5%.²⁰ In a study from Finland, Lahti and colleagues¹⁹ found that over a 2-year period, 479 hockey players sustained injuries, including 650 separate dental injuries. The most commonly diagnosed dental injury was an uncomplicated crown fracture, and the most common cause was a hit with a hockey stick, which accounted for 52.7% and 40.3% of dental injuries in games and practices, respectively.¹⁹

In the management of dental fractures, the broken portions of teeth should be found and placed in a transportation-protective medium, such as saline, saliva, or milk,¹⁶ which can improve functional and esthetic replacement outcomes.^21,22 Loose pieces of teeth should not be left in the player’s mouth. The residual tooth should be stabilized and exposure to air and occlusion limited. Dental fractures can affect the enamel, the enamel and dentin structures (uncomplicated fracture), or enamel, dentin, and pulp (complicated).²³ Fractures involving only the enamel do not require urgent dental evaluation. Dentin or pulp involvement may cause temperature and air sensitivity.²³ If a tooth is air-sensitive, the player should be referred to a specialist immediately.¹¹

Direct trauma can cause instability without displacement (subluxation) or complete displacement of the tooth from its alveolar socket (avulsion).²³ An avulsed tooth should be handled by the crown to avoid further damage to the root and periodontal ligament.^16,24 The tooth should be rinsed gently with saline and reimplanted in its socket, ideally within 5 to 10 minutes,²³with the athlete biting down gently on gauze to hold the tooth in place. A 1-mL supraperiosteal infiltration of 1% or 2% lidocaine hydrochloride (1:100,000 epinephrine) can be given into the apex of the tooth being anesthetized (Figure 1).

Concussions

A concussion is a “complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces.”²⁵ Concussion is largely a functional disturbance instead of a structural injury, owing to the rotational and/or shearing forces involved. Many studies have identified concussion as the most common type of injury in all of youth hockey.²⁶ Concussions account for up to 19% of all injuries in men’s collegiate hockey.³

Concussion can be challenging to diagnose on the ice. The most important factor in concussion management is symptom reporting by the athlete.²⁷ Despite significant efforts in education and awareness, student athletes, especially hockey players, withhold reporting a possible concussion.²⁸ Reasons for underreporting include fear of letting down other players and coaches, thinking the injury is not severe enough to warrant evaluation, and fear of losing standing with the current team or future teams.²⁸

Cervical Spine Injuries

Whereas American football is associated with a higher annual number of nonfatal catastrophic neck injuries, hockey has a 3 to 6 times higher incidence of cervical spine injuries and spinal cord damage.^38,39 A Canadian Ice Hockey Spinal Injuries Registry review of the period 2006 to 2011 identified 44 cervical spine injuries, 7.3 per year on average.⁴⁰ Severe injury, defined as complete motor and sensory loss, complete motor loss and incomplete sensory, or complete motor loss, occurred in 4 (9.1%) of the 44 injured players. In hockey, a major mechanism of cervical spine injury is an axial load to the slightly flexed spine.³⁹ Of 355 hockey-related cervical spine injuries in a Canada study, 95 (35.5%) were caused by a check from behind.^40,41 The Canadian neurosurgeons’ work led to rule changes prohibiting checks from behind, and this prohibition has reduced the incidence of cervical spine injuries in ice hockey.^38,40

Team physicians should be comfortable managing serious neck and spine injuries on the ice. Initial evaluation should follow the standard ABCs (airway, breathing, circulation). The physician places a hand on each side of the head to stabilize the neck until the initial examination is complete. The goal is to minimize cervical spine motion until transportation to the hospital for advanced imaging and definitive treatment.³⁷ The decision to remove or leave on the helmet is now controversial. Hockey helmets differ from football helmets in that their chinstraps do not afford significant cervical stabilization, and the helmets have less padding and cover less of the head; in addition, a shockingly high percentage of hockey players do not wear properly fitting helmets.³⁷ In one study, 3-dimensional motion analysis of a hockey player during the logroll technique showed less transverse and sagittal cervical plane motion with the helmet removed than with the helmet (properly fitting or not) in place; the authors recommended removing the helmet to limit extraneous cervical spine motion during the technique.³⁷ However, 2 other studies found that helmet removal can result in significantly increased cervical spine motion of the immobilized hockey player.^42,43Recommendation 4 of the recently released interassociation consensus statement of the National Athletic Trainers’ Association reads, “Protective athletic equipment should be removed before transport to an emergency facility for an athlete-patient with suspected cervical spine instability.”⁴⁴ This represents a shift from leaving the helmet and shoulder pads in place. For ice hockey players with suspected cervical spine injury, more research is needed on cervical motion during the entire sequence—partial logrolls, spine-boarding, placement of cervical collar before or after logroll, and different immobilization techniques for transport.³⁷

The athlete must be carefully transferred to a spine board with either logroll or lift-and-slide. Although an extrication cervical collar can be placed before the spine board is placed, the effectiveness of this collar in executing the spine-board transfer is not proven.⁴⁵ When the player is on the spine board, the head can be secured with pads and straps en route to the hospital.

Return-to-Play Criteria for Cervical Spine Injuries There is no clear consensus on return-to-play guidelines for cervical spine injuries in athletes.⁴⁶

Shoulder Injuries

For hockey players, the upper extremity traditionally has been considered a well-protected area.⁴⁸ However, shoulder pads are considerably more flexible in hockey than in football and other collision sports. In addition, hockey gloves allow a fair amount of motion for stick handling, and the wrist may be in maximal flexion or extension when a hit against the boards or the ice occurs. Open-ice checking, board collisions, and hockey stick use have been postulated as reasons for the high incidence of upper extremity injuries in hockey. Researchers in Finland found that upper extremity injuries accounted for up to 31% of all hockey injuries.⁴⁹ More than 50% of these injuries resulted from checking or board collisions. Furthermore, study findings highlighted a low rate of injury in younger players and indicated the rate increases with age.^49,50

In hockey players, the acromioclavicular (AC) joint is the most commonly injured shoulder structure.⁵¹ The mechanism of injury can be a board collision or an open-ice hit, but most often is a direct blow to the shoulder. The collision disrupts the AC joint and can sprain or tear the coracoclavicular ligaments. The Rockwood classification is used to categorize AC joint injuries (Figure 2).

Summary

Hockey is a high-speed collision sport with one of the highest injury rates among all sports. Physicians caring for youth, amateur, and senior hockey teams see a range of acute head, neck, and shoulder injuries. Although treatment of eye injuries, dental injuries, and concussions is not always considered orthopedic care, an orthopedic surgeon who is covering hockey needs to be comfortable managing these injuries acutely. Quality rink-side care minimizes the impact of the injury, maximizes the functional result, and expedites the safe return of the injured player back to the ice.

Am J Orthop. 2017;46(3):123-134. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Patellofemoral osteotomies can provide excellent and reliable symptomatic relief for many patients with symptomatic isolated PFOA.
• PLPF of 1 cm to 1.5 cm of lateral bone can provide excellent pain relief in patients with isolated lateral facet arthritis and overhanging osteophytes without diffuse chondromalacia or hypermobility.
• At 5-year follow-up, >80% of partial lateral facetectomy patients have symptomatic relief.
• Tibial tubercle AMZ (Fulkerson procedure) can provide excellent results in patients with distal and lateral patella chondropathy.
• Avoidance of overmedialization, early range of motion, and limited weight-bearing can help avoid complications associated with tibial tubercle AMZ.

Isolated patellofemoral osteoarthritis (PFOA) is a relatively common disorder. Based on radiological evidence, its prevalence is 24% in women and 11% in men aged over 55 years.¹ However, the presence of PFOA on radiographic images does not always correlate with clinical symptoms. PFOA is symptomatic in only 8% of women and 2% of men aged over 55 years,¹ and a mismatch often occurs between the symptoms and radiological severity (Figures 1A-1E).

PFOA surgery may be considered when nonsurgical treatment is ineffective and pain becomes disabling. However, which surgical treatment for isolated PFOA is optimal remains controversial. The largest setback in weighing nonarthroplasty surgical options for isolated PFOA is that few studies have been published. Furthermore, published studies offer little scientific evidence; they include case series with few patients and retrospective analyses with limited follow-up and no control group for comparison.

This article focuses on osteotomies, which are described in only 15 articles found through PubMed. The small number is logical given that the prevalence of symptomatic isolated PFOA is low¹ and that the majority of patients do not need surgical treatment. A complicating factor is that osteotomy is often associated with other surgical procedures, such as lateral retinaculum release. In descriptions of these cases, it is not clear if the outcome for PFOA is attributable to the osteotomy, is secondary to the associated procedure, or both.

Several alternatives to patellofemoral arthroplasty—partial lateral patellar facetectomy (PLPF), patella-thinning osteotomy (PTO), anteromedialization (AMZ), and sulcus-deepening trochleoplasty (SDT)—are available for the management of isolated PFOA. In this article, we analyze the value of each of these techniques in preserving the patellofemoral joint in the presence of PFOA. These techniques combine the US and European perspectives. The ultimate objective with these surgical techniques is to delay arthroplasty as long as possible.

Partial Lateral Patellar Facetectomy

PLPF is a relatively simple and effective surgical treatment for isolated PFOA in active middle-aged to elderly patients who want to maintain their activity level.^3-6 Using an oscillating saw to resect 1 cm to 1.5 cm of the lateral facet of the patella reduces lateral retinaculum tension and thereby decreases lateral patellofemoral contact pressures (Figures 2A, 2B).

PLPF improves pain and function over the long-term and delays the need for major surgery. Wetzels and Bellemans⁵ evaluated 155 consecutive patients (168 knees) with mean post-PLPF follow-up of 10.9 years. By final follow-up, 62 knees (36.9%) had failed and been revised to total knee arthroplasty (TKA) (60 knees), patellofemoral arthroplasty (1 knee), or total patellectomy (1 knee). Mean time to reoperation was 8 years. Kaplan-Meier survival rates with reoperation as the endpoint were 85% at 5 years, 67.2% at 10 years, and 46.7% at 20 years. At final follow-up, 79 (74.5%) of the 106 knees that had not been revised were rated good or fair, which accounts for 47% of the original group of 168 knees. The key finding is that the effects of PLPF lasted through the 10-year follow-up in half of the patients.⁵ Paulos and colleagues⁴ found 5 years of symptomatic relief in more than 80% of carefully selected patients who did not have significant (grade IV) arthritis in the medial or lateral knee compartments.

PLPF is a safe, low-cost, and relatively minor surgery with a low morbidity rate and fast recovery. Also, it does not close the door on other surgery and can easily be converted to TKA. Wetzels and Bellemans⁵ found that 36.9% of reoperations were TKAs, and López-Franco and colleagues³ found that 30% of knees required secondary TKA.

Patella-Thinning Osteotomy

In patients who are under 65 years old and have disabling anterior knee pain recalcitrant to conservative treatment, PTO may be considered for isolated PFOA with any type of chondral lesion (including severe diffuse chondropathy with exposed bone) (Figures 3A-3C), patellofemoral joint space reduced by more than 50% on skyline view, patellar thickness of 20 mm or more, and normal TT-TG distance.⁷

Vaquero and colleagues⁷ analyzed PTO outcomes in 31 patients (35 knees) with mean follow-up of 9 years and noted significant improvements in functional scores and radiologic parameters. All patients except 1 were satisfied with the operation. Radiologic progression of PFOA was slowed, but radiologic femorotibial osteoarthritis progressed in 23 cases (65%), and 4 required TKA. The authors found satisfactory clinical and radiologic outcomes—only 4 patients (12.5%) required TKA—and good functional outcomes.⁷

PTO, a low-morbidity surgery with good functional outcomes, does not close the door on other surgery, such as TKA.⁷

Tibial Tubercle Anteromedialization Osteotomy

Whereas PLPF and PTO are indicated in knees with normal TT-TG distance, Fulkerson AMZ osteotomy must be considered in isolated PFOA with articular cartilage lesions at the distal or lateral patellar facets resulting from long-standing malalignment with increased TT-TG distance (Figures 4A, 4B).

AMZ unloads the distal and lateral facets of the patella while improving the extensor mechanism.^11,12 A successful AMZ outcome requires preservation of some of the medial and proximal articular cartilage of the patella. In 1983, Fulkerson¹³ described use of tibial tubercle AMZ osteotomy to address patellofemoral pain associated with patellofemoral chondrosis in conjunction with patellofemoral tilt and/or chronic patellar subluxation. This technique is indicated when the patella needs to be realigned for relief of elevated contact stress and centralization. Currently the technique is used not only in patients with isolated PFOA but in patients with chronic lateral patellar instability. Fulkerson osteotomy combines the benefits of the Maquet technique (unloading) and the Elmslie-Trillat technique (tracking improvement) in a single osteotomy, with no distraction of the osteotomy site with bone graft and without the complication rate of Maquet tibial tubercle elevation. Before surgery, computed tomography (CT) or magnetic resonance imaging (MRI) is routinely used to measure TT-TG distance to determine the tibial tubercle medialization required in the Fulkerson osteotomy. However, TT-TG distance must be used with caution, as it cannot be determined in cases with trochlear dysplasia. Consequently, physical examination and arthroscopic examination for evaluation of patellofemoral tracking and location of chondral defects should be performed before the Fulkerson osteotomy.

Rationale; Indications and Contraindications; Preoperative Planning

As already noted, AMZ unloads the distal and lateral facets of the patella. Beck and colleagues¹⁴ suggested AMZ is appropriate for unloading the lateral trochlea. However, it is not useful for central chondral defects and may actually increase the load in patients with medial chondral defects. As AMZ shifts contact force to the medial trochlea, Fulkerson osteotomy is appropriate when distal and lateral chondral lesions must be unloaded. Because this procedure moves the tibial tubercle medially and anteriorly, loads are transferred to the proximal and medial facets of the patella. Therefore, the procedure is contraindicated when diffuse, proximal, or medial chondral lesions are present. Moreover, AMZ is contraindicated in patients with normal TT-TG distance because there is the risk that overmedialization will cause symptomatic medial subluxation. Grade III or IV central trochlear cartilage lesions are also less likely to have successful AMZ outcomes. Therefore, before Fulkerson osteotomy is performed, MRI should be obtained to evaluate the patellofemoral articular surface and TT-TG distance. MRI provides information that is useful for preoperative planning because it allows assessment of articular cartilage lesions, including their location and severity. Moreover, because the osseous and cartilaginous contours of the patella differ, MRI gives a more accurate picture of the patellofemoral congruence than CT does. Last, before the open surgery is performed, the patellofemoral joint should be arthroscopically examined to determine the location of chondral lesions. Cartilage lesion mapping is important because Fulkerson osteotomy outcomes depend on chondral lesion location. Pidoriano and colleagues¹⁵ correlated AMZ outcomes with articular lesion location and noted optimal outcomes in patients with distal and lateral patellar articular lesions and intact trochlear cartilage (87% good and excellent outcomes). Patients with medial lesions and proximal or diffuse lesions generally did poorly (55% good and excellent outcomes in medial lesions vs 20% good and excellent outcomes in proximal and diffuse lesions). Central trochlear lesions were associated with medial patellar lesions, and all patients with central trochlear lesions had poor outcomes. Interestingly, Outerbridge grading of patellar lesions was not significantly correlated with overall outcomes.¹⁵ Even in cases of severe chondropathy, including bone-on-bone arthritis, AMZ has had reliable outcomes and may be superior to arthroplasty because of joint preservation, duration up to 8 years, and restoration of patellofemoral tracking. It should be noted that a resurfacing technique such as patellofemoral arthroplasty is not a substitute for patella realignment. Any patellofemoral maltracking must be corrected before patellofemoral arthroplasty. Fulkerson osteotomy does not preclude subsequent surgery (eg, TKA). Furthermore, AMZ may prevent the natural progression of PFOA related to chronic lateral tracking.

AMZ osteotomy can be adjusted for the specific indication and for the location of chondral defects. If the primary goal is unloading a lateral lesion, or lateral maltracking, then a flatter osteotomy may be performed to increase the relative medialization of the tubercle; however, if the primary goal is unloading a distal lesion, then a relatively more oblique or vertical osteotomy may be performed to transfer the load more proximally. This is the technique preferred by authors in most cases in which more anteriorization is desired.

When TT-TG distance is used to guide surgical realignment, patellofemoral chondrosis associated with normal TT-TG distance can be addressed with directly anterior displacement of the tibial tubercle. Anteriorization of the tibial tubercle can be obtained by inserting a bone block between the tubercle and the tibial cut (Figure 5A).¹⁶ The medialization can be neutralized by making this block as thick as the measured medialization.¹⁶

Surgical Outcomes of Anteromedialization in Patellofemoral Osteoarthritis

Fulkerson and colleagues¹⁰ followed 30 patients for more than 2 years after they underwent AMZ of the tibial tubercle for persistent patellofemoral pain associated with patellar articular degeneration. Of these 30 patients, 12 were followed for more than 5 years. The authors reported 93% good and excellent subjective outcomes and 89% good and excellent objective outcomes. Quality of improvement was sustained for all 12 patients reevaluated more than 5 years after surgery. When examined separately, 75% of patients with advanced PFOA had a good outcome, but none had an excellent outcome. Carofino and Fulkerson¹⁷ retrospectively evaluated tibial tubercle AMZ for isolated PFOA in 22 knees (17 active patients older than 50 years at time of surgery; mean age, 55 years) with minimum follow-up of 2 years (mean, 77 months). Mean postoperative Lysholm score was 83. According to Lysholm scores, outcomes were good to excellent in 12 cases, fair in 6, and poor in 1. The authors concluded that tibial tubercle AMZ is a definitive treatment option for isolated PFOA in active older patients. Morshuis and colleagues¹⁸ retrospectively evaluated 22 patients (25 knees) who underwent Fulkerson osteotomy for patellofemoral pain. Outcomes were evaluated a mean of 12 and 30 months after surgery. At the first evaluation, 84% of patients had satisfactory outcomes, and, at the second (≤38 months after surgery), 70%. Only in relatively young patients without signs of PFOA did outcomes remain satisfactory in all cases. At the later evaluation, 60% of patients with PFOA and/or lateralization had satisfactory outcomes.

Tips and Tricks to Avoid Complications

For some patients, AMZ performed technically correctly produced unhappiness—an outcome that may arise from incorrect patient selection or failure to meet patient expectations. It is important to discuss objectives and expectations with the patient before surgery. With correct patient selection and meticulous surgical technique (with customization of osteotomy angle and translation based on underlying lesion), surgeons have obtained excellent outcomes with infrequent complications (Table).

Intraoperative complications may involve neurovascular structures. The anterior tibial artery and the peroneal nerve are at risk during Fulkerson osteotomy. Decreased anterior sensation related to the infrapatellar branch of the saphenous nerve is not uncommon. Reducing the risk of neurovascular injury requires use of retractors and keeping the saw blade visible at all times. Another potential devastating complication is injury of the posterior vascular structures during bicortical tibial drilling for screw placement. According to Kline and colleagues,¹⁹ bicortical drilling may occur precariously near the posterior vascular structures of the knee. They advised extreme caution in drilling the posterior cortex during this procedure. To avoid the risk of compartment syndrome, surgeons can leave the anterior compartment fascia open or pie crust it by making multiple small perforations to decrease tension. Tibial fracture is another potential complication with this osteotomy. Reducing the risk of fracture involves tapering the distal cut anteriorly and avoiding a “notched” osteotomy (Figures 6A-6C).

Sulcus-Deepening Trochleoplasty

High-grade trochlear dysplasia with a prominence, frequently present in lateral patellar instability, is thought to correlate with PFOA because it produces an anti-Maquet effect.²⁴ The dysplasia provokes an increment of the patellofemoral joint pressure that could explain patellofemoral chondropathy and ultimately PFOA. In fact, 33% of patients with isolated PFOA have a history of objective patellar dislocation.²⁴ In these cases, SDT could be considered. Several studies have examined use of this technique in the treatment of instability, but not PFOA.²⁵ After SDT, pain resolves despite the chondral lesions being left alone (Figures 7A, 7B).

Conclusion

Patellofemoral joint replacement is an option for patellofemoral pain only in very select cases. Preserving the joint is always a primary goal. As not all PFOA cases are equal, joint-preserving surgery must be tailored to the patient. The keys to success are good indication, precise surgery, proper rehabilitation, and, above all, doing only what is needed.

Am J Orthop. 2017;46(3):139-145. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Patellofemoral osteotomies can provide excellent and reliable symptomatic relief for many patients with symptomatic isolated PFOA.
• PLPF of 1 cm to 1.5 cm of lateral bone can provide excellent pain relief in patients with isolated lateral facet arthritis and overhanging osteophytes without diffuse chondromalacia or hypermobility.
• At 5-year follow-up, >80% of partial lateral facetectomy patients have symptomatic relief.
• Tibial tubercle AMZ (Fulkerson procedure) can provide excellent results in patients with distal and lateral patella chondropathy.
• Avoidance of overmedialization, early range of motion, and limited weight-bearing can help avoid complications associated with tibial tubercle AMZ.

Isolated patellofemoral osteoarthritis (PFOA) is a relatively common disorder. Based on radiological evidence, its prevalence is 24% in women and 11% in men aged over 55 years.¹ However, the presence of PFOA on radiographic images does not always correlate with clinical symptoms. PFOA is symptomatic in only 8% of women and 2% of men aged over 55 years,¹ and a mismatch often occurs between the symptoms and radiological severity (Figures 1A-1E).

PFOA surgery may be considered when nonsurgical treatment is ineffective and pain becomes disabling. However, which surgical treatment for isolated PFOA is optimal remains controversial. The largest setback in weighing nonarthroplasty surgical options for isolated PFOA is that few studies have been published. Furthermore, published studies offer little scientific evidence; they include case series with few patients and retrospective analyses with limited follow-up and no control group for comparison.

This article focuses on osteotomies, which are described in only 15 articles found through PubMed. The small number is logical given that the prevalence of symptomatic isolated PFOA is low¹ and that the majority of patients do not need surgical treatment. A complicating factor is that osteotomy is often associated with other surgical procedures, such as lateral retinaculum release. In descriptions of these cases, it is not clear if the outcome for PFOA is attributable to the osteotomy, is secondary to the associated procedure, or both.

Several alternatives to patellofemoral arthroplasty—partial lateral patellar facetectomy (PLPF), patella-thinning osteotomy (PTO), anteromedialization (AMZ), and sulcus-deepening trochleoplasty (SDT)—are available for the management of isolated PFOA. In this article, we analyze the value of each of these techniques in preserving the patellofemoral joint in the presence of PFOA. These techniques combine the US and European perspectives. The ultimate objective with these surgical techniques is to delay arthroplasty as long as possible.

Partial Lateral Patellar Facetectomy

PLPF is a relatively simple and effective surgical treatment for isolated PFOA in active middle-aged to elderly patients who want to maintain their activity level.^3-6 Using an oscillating saw to resect 1 cm to 1.5 cm of the lateral facet of the patella reduces lateral retinaculum tension and thereby decreases lateral patellofemoral contact pressures (Figures 2A, 2B).

PLPF improves pain and function over the long-term and delays the need for major surgery. Wetzels and Bellemans⁵ evaluated 155 consecutive patients (168 knees) with mean post-PLPF follow-up of 10.9 years. By final follow-up, 62 knees (36.9%) had failed and been revised to total knee arthroplasty (TKA) (60 knees), patellofemoral arthroplasty (1 knee), or total patellectomy (1 knee). Mean time to reoperation was 8 years. Kaplan-Meier survival rates with reoperation as the endpoint were 85% at 5 years, 67.2% at 10 years, and 46.7% at 20 years. At final follow-up, 79 (74.5%) of the 106 knees that had not been revised were rated good or fair, which accounts for 47% of the original group of 168 knees. The key finding is that the effects of PLPF lasted through the 10-year follow-up in half of the patients.⁵ Paulos and colleagues⁴ found 5 years of symptomatic relief in more than 80% of carefully selected patients who did not have significant (grade IV) arthritis in the medial or lateral knee compartments.

PLPF is a safe, low-cost, and relatively minor surgery with a low morbidity rate and fast recovery. Also, it does not close the door on other surgery and can easily be converted to TKA. Wetzels and Bellemans⁵ found that 36.9% of reoperations were TKAs, and López-Franco and colleagues³ found that 30% of knees required secondary TKA.

Patella-Thinning Osteotomy

In patients who are under 65 years old and have disabling anterior knee pain recalcitrant to conservative treatment, PTO may be considered for isolated PFOA with any type of chondral lesion (including severe diffuse chondropathy with exposed bone) (Figures 3A-3C), patellofemoral joint space reduced by more than 50% on skyline view, patellar thickness of 20 mm or more, and normal TT-TG distance.⁷

Vaquero and colleagues⁷ analyzed PTO outcomes in 31 patients (35 knees) with mean follow-up of 9 years and noted significant improvements in functional scores and radiologic parameters. All patients except 1 were satisfied with the operation. Radiologic progression of PFOA was slowed, but radiologic femorotibial osteoarthritis progressed in 23 cases (65%), and 4 required TKA. The authors found satisfactory clinical and radiologic outcomes—only 4 patients (12.5%) required TKA—and good functional outcomes.⁷

PTO, a low-morbidity surgery with good functional outcomes, does not close the door on other surgery, such as TKA.⁷

Tibial Tubercle Anteromedialization Osteotomy

Whereas PLPF and PTO are indicated in knees with normal TT-TG distance, Fulkerson AMZ osteotomy must be considered in isolated PFOA with articular cartilage lesions at the distal or lateral patellar facets resulting from long-standing malalignment with increased TT-TG distance (Figures 4A, 4B).

AMZ unloads the distal and lateral facets of the patella while improving the extensor mechanism.^11,12 A successful AMZ outcome requires preservation of some of the medial and proximal articular cartilage of the patella. In 1983, Fulkerson¹³ described use of tibial tubercle AMZ osteotomy to address patellofemoral pain associated with patellofemoral chondrosis in conjunction with patellofemoral tilt and/or chronic patellar subluxation. This technique is indicated when the patella needs to be realigned for relief of elevated contact stress and centralization. Currently the technique is used not only in patients with isolated PFOA but in patients with chronic lateral patellar instability. Fulkerson osteotomy combines the benefits of the Maquet technique (unloading) and the Elmslie-Trillat technique (tracking improvement) in a single osteotomy, with no distraction of the osteotomy site with bone graft and without the complication rate of Maquet tibial tubercle elevation. Before surgery, computed tomography (CT) or magnetic resonance imaging (MRI) is routinely used to measure TT-TG distance to determine the tibial tubercle medialization required in the Fulkerson osteotomy. However, TT-TG distance must be used with caution, as it cannot be determined in cases with trochlear dysplasia. Consequently, physical examination and arthroscopic examination for evaluation of patellofemoral tracking and location of chondral defects should be performed before the Fulkerson osteotomy.

Rationale; Indications and Contraindications; Preoperative Planning

As already noted, AMZ unloads the distal and lateral facets of the patella. Beck and colleagues¹⁴ suggested AMZ is appropriate for unloading the lateral trochlea. However, it is not useful for central chondral defects and may actually increase the load in patients with medial chondral defects. As AMZ shifts contact force to the medial trochlea, Fulkerson osteotomy is appropriate when distal and lateral chondral lesions must be unloaded. Because this procedure moves the tibial tubercle medially and anteriorly, loads are transferred to the proximal and medial facets of the patella. Therefore, the procedure is contraindicated when diffuse, proximal, or medial chondral lesions are present. Moreover, AMZ is contraindicated in patients with normal TT-TG distance because there is the risk that overmedialization will cause symptomatic medial subluxation. Grade III or IV central trochlear cartilage lesions are also less likely to have successful AMZ outcomes. Therefore, before Fulkerson osteotomy is performed, MRI should be obtained to evaluate the patellofemoral articular surface and TT-TG distance. MRI provides information that is useful for preoperative planning because it allows assessment of articular cartilage lesions, including their location and severity. Moreover, because the osseous and cartilaginous contours of the patella differ, MRI gives a more accurate picture of the patellofemoral congruence than CT does. Last, before the open surgery is performed, the patellofemoral joint should be arthroscopically examined to determine the location of chondral lesions. Cartilage lesion mapping is important because Fulkerson osteotomy outcomes depend on chondral lesion location. Pidoriano and colleagues¹⁵ correlated AMZ outcomes with articular lesion location and noted optimal outcomes in patients with distal and lateral patellar articular lesions and intact trochlear cartilage (87% good and excellent outcomes). Patients with medial lesions and proximal or diffuse lesions generally did poorly (55% good and excellent outcomes in medial lesions vs 20% good and excellent outcomes in proximal and diffuse lesions). Central trochlear lesions were associated with medial patellar lesions, and all patients with central trochlear lesions had poor outcomes. Interestingly, Outerbridge grading of patellar lesions was not significantly correlated with overall outcomes.¹⁵ Even in cases of severe chondropathy, including bone-on-bone arthritis, AMZ has had reliable outcomes and may be superior to arthroplasty because of joint preservation, duration up to 8 years, and restoration of patellofemoral tracking. It should be noted that a resurfacing technique such as patellofemoral arthroplasty is not a substitute for patella realignment. Any patellofemoral maltracking must be corrected before patellofemoral arthroplasty. Fulkerson osteotomy does not preclude subsequent surgery (eg, TKA). Furthermore, AMZ may prevent the natural progression of PFOA related to chronic lateral tracking.

AMZ osteotomy can be adjusted for the specific indication and for the location of chondral defects. If the primary goal is unloading a lateral lesion, or lateral maltracking, then a flatter osteotomy may be performed to increase the relative medialization of the tubercle; however, if the primary goal is unloading a distal lesion, then a relatively more oblique or vertical osteotomy may be performed to transfer the load more proximally. This is the technique preferred by authors in most cases in which more anteriorization is desired.

When TT-TG distance is used to guide surgical realignment, patellofemoral chondrosis associated with normal TT-TG distance can be addressed with directly anterior displacement of the tibial tubercle. Anteriorization of the tibial tubercle can be obtained by inserting a bone block between the tubercle and the tibial cut (Figure 5A).¹⁶ The medialization can be neutralized by making this block as thick as the measured medialization.¹⁶

Surgical Outcomes of Anteromedialization in Patellofemoral Osteoarthritis

Fulkerson and colleagues¹⁰ followed 30 patients for more than 2 years after they underwent AMZ of the tibial tubercle for persistent patellofemoral pain associated with patellar articular degeneration. Of these 30 patients, 12 were followed for more than 5 years. The authors reported 93% good and excellent subjective outcomes and 89% good and excellent objective outcomes. Quality of improvement was sustained for all 12 patients reevaluated more than 5 years after surgery. When examined separately, 75% of patients with advanced PFOA had a good outcome, but none had an excellent outcome. Carofino and Fulkerson¹⁷ retrospectively evaluated tibial tubercle AMZ for isolated PFOA in 22 knees (17 active patients older than 50 years at time of surgery; mean age, 55 years) with minimum follow-up of 2 years (mean, 77 months). Mean postoperative Lysholm score was 83. According to Lysholm scores, outcomes were good to excellent in 12 cases, fair in 6, and poor in 1. The authors concluded that tibial tubercle AMZ is a definitive treatment option for isolated PFOA in active older patients. Morshuis and colleagues¹⁸ retrospectively evaluated 22 patients (25 knees) who underwent Fulkerson osteotomy for patellofemoral pain. Outcomes were evaluated a mean of 12 and 30 months after surgery. At the first evaluation, 84% of patients had satisfactory outcomes, and, at the second (≤38 months after surgery), 70%. Only in relatively young patients without signs of PFOA did outcomes remain satisfactory in all cases. At the later evaluation, 60% of patients with PFOA and/or lateralization had satisfactory outcomes.

Tips and Tricks to Avoid Complications

For some patients, AMZ performed technically correctly produced unhappiness—an outcome that may arise from incorrect patient selection or failure to meet patient expectations. It is important to discuss objectives and expectations with the patient before surgery. With correct patient selection and meticulous surgical technique (with customization of osteotomy angle and translation based on underlying lesion), surgeons have obtained excellent outcomes with infrequent complications (Table).

Intraoperative complications may involve neurovascular structures. The anterior tibial artery and the peroneal nerve are at risk during Fulkerson osteotomy. Decreased anterior sensation related to the infrapatellar branch of the saphenous nerve is not uncommon. Reducing the risk of neurovascular injury requires use of retractors and keeping the saw blade visible at all times. Another potential devastating complication is injury of the posterior vascular structures during bicortical tibial drilling for screw placement. According to Kline and colleagues,¹⁹ bicortical drilling may occur precariously near the posterior vascular structures of the knee. They advised extreme caution in drilling the posterior cortex during this procedure. To avoid the risk of compartment syndrome, surgeons can leave the anterior compartment fascia open or pie crust it by making multiple small perforations to decrease tension. Tibial fracture is another potential complication with this osteotomy. Reducing the risk of fracture involves tapering the distal cut anteriorly and avoiding a “notched” osteotomy (Figures 6A-6C).

Sulcus-Deepening Trochleoplasty

High-grade trochlear dysplasia with a prominence, frequently present in lateral patellar instability, is thought to correlate with PFOA because it produces an anti-Maquet effect.²⁴ The dysplasia provokes an increment of the patellofemoral joint pressure that could explain patellofemoral chondropathy and ultimately PFOA. In fact, 33% of patients with isolated PFOA have a history of objective patellar dislocation.²⁴ In these cases, SDT could be considered. Several studies have examined use of this technique in the treatment of instability, but not PFOA.²⁵ After SDT, pain resolves despite the chondral lesions being left alone (Figures 7A, 7B).

Conclusion

Patellofemoral joint replacement is an option for patellofemoral pain only in very select cases. Preserving the joint is always a primary goal. As not all PFOA cases are equal, joint-preserving surgery must be tailored to the patient. The keys to success are good indication, precise surgery, proper rehabilitation, and, above all, doing only what is needed.

Am J Orthop. 2017;46(3):139-145. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Patellofemoral osteotomies can provide excellent and reliable symptomatic relief for many patients with symptomatic isolated PFOA.
• PLPF of 1 cm to 1.5 cm of lateral bone can provide excellent pain relief in patients with isolated lateral facet arthritis and overhanging osteophytes without diffuse chondromalacia or hypermobility.
• At 5-year follow-up, >80% of partial lateral facetectomy patients have symptomatic relief.
• Tibial tubercle AMZ (Fulkerson procedure) can provide excellent results in patients with distal and lateral patella chondropathy.
• Avoidance of overmedialization, early range of motion, and limited weight-bearing can help avoid complications associated with tibial tubercle AMZ.

Isolated patellofemoral osteoarthritis (PFOA) is a relatively common disorder. Based on radiological evidence, its prevalence is 24% in women and 11% in men aged over 55 years.¹ However, the presence of PFOA on radiographic images does not always correlate with clinical symptoms. PFOA is symptomatic in only 8% of women and 2% of men aged over 55 years,¹ and a mismatch often occurs between the symptoms and radiological severity (Figures 1A-1E).

PFOA surgery may be considered when nonsurgical treatment is ineffective and pain becomes disabling. However, which surgical treatment for isolated PFOA is optimal remains controversial. The largest setback in weighing nonarthroplasty surgical options for isolated PFOA is that few studies have been published. Furthermore, published studies offer little scientific evidence; they include case series with few patients and retrospective analyses with limited follow-up and no control group for comparison.

This article focuses on osteotomies, which are described in only 15 articles found through PubMed. The small number is logical given that the prevalence of symptomatic isolated PFOA is low¹ and that the majority of patients do not need surgical treatment. A complicating factor is that osteotomy is often associated with other surgical procedures, such as lateral retinaculum release. In descriptions of these cases, it is not clear if the outcome for PFOA is attributable to the osteotomy, is secondary to the associated procedure, or both.

Several alternatives to patellofemoral arthroplasty—partial lateral patellar facetectomy (PLPF), patella-thinning osteotomy (PTO), anteromedialization (AMZ), and sulcus-deepening trochleoplasty (SDT)—are available for the management of isolated PFOA. In this article, we analyze the value of each of these techniques in preserving the patellofemoral joint in the presence of PFOA. These techniques combine the US and European perspectives. The ultimate objective with these surgical techniques is to delay arthroplasty as long as possible.

Partial Lateral Patellar Facetectomy

PLPF is a relatively simple and effective surgical treatment for isolated PFOA in active middle-aged to elderly patients who want to maintain their activity level.^3-6 Using an oscillating saw to resect 1 cm to 1.5 cm of the lateral facet of the patella reduces lateral retinaculum tension and thereby decreases lateral patellofemoral contact pressures (Figures 2A, 2B).

PLPF improves pain and function over the long-term and delays the need for major surgery. Wetzels and Bellemans⁵ evaluated 155 consecutive patients (168 knees) with mean post-PLPF follow-up of 10.9 years. By final follow-up, 62 knees (36.9%) had failed and been revised to total knee arthroplasty (TKA) (60 knees), patellofemoral arthroplasty (1 knee), or total patellectomy (1 knee). Mean time to reoperation was 8 years. Kaplan-Meier survival rates with reoperation as the endpoint were 85% at 5 years, 67.2% at 10 years, and 46.7% at 20 years. At final follow-up, 79 (74.5%) of the 106 knees that had not been revised were rated good or fair, which accounts for 47% of the original group of 168 knees. The key finding is that the effects of PLPF lasted through the 10-year follow-up in half of the patients.⁵ Paulos and colleagues⁴ found 5 years of symptomatic relief in more than 80% of carefully selected patients who did not have significant (grade IV) arthritis in the medial or lateral knee compartments.

PLPF is a safe, low-cost, and relatively minor surgery with a low morbidity rate and fast recovery. Also, it does not close the door on other surgery and can easily be converted to TKA. Wetzels and Bellemans⁵ found that 36.9% of reoperations were TKAs, and López-Franco and colleagues³ found that 30% of knees required secondary TKA.

Patella-Thinning Osteotomy

In patients who are under 65 years old and have disabling anterior knee pain recalcitrant to conservative treatment, PTO may be considered for isolated PFOA with any type of chondral lesion (including severe diffuse chondropathy with exposed bone) (Figures 3A-3C), patellofemoral joint space reduced by more than 50% on skyline view, patellar thickness of 20 mm or more, and normal TT-TG distance.⁷

Vaquero and colleagues⁷ analyzed PTO outcomes in 31 patients (35 knees) with mean follow-up of 9 years and noted significant improvements in functional scores and radiologic parameters. All patients except 1 were satisfied with the operation. Radiologic progression of PFOA was slowed, but radiologic femorotibial osteoarthritis progressed in 23 cases (65%), and 4 required TKA. The authors found satisfactory clinical and radiologic outcomes—only 4 patients (12.5%) required TKA—and good functional outcomes.⁷

PTO, a low-morbidity surgery with good functional outcomes, does not close the door on other surgery, such as TKA.⁷

Tibial Tubercle Anteromedialization Osteotomy

Whereas PLPF and PTO are indicated in knees with normal TT-TG distance, Fulkerson AMZ osteotomy must be considered in isolated PFOA with articular cartilage lesions at the distal or lateral patellar facets resulting from long-standing malalignment with increased TT-TG distance (Figures 4A, 4B).

AMZ unloads the distal and lateral facets of the patella while improving the extensor mechanism.^11,12 A successful AMZ outcome requires preservation of some of the medial and proximal articular cartilage of the patella. In 1983, Fulkerson¹³ described use of tibial tubercle AMZ osteotomy to address patellofemoral pain associated with patellofemoral chondrosis in conjunction with patellofemoral tilt and/or chronic patellar subluxation. This technique is indicated when the patella needs to be realigned for relief of elevated contact stress and centralization. Currently the technique is used not only in patients with isolated PFOA but in patients with chronic lateral patellar instability. Fulkerson osteotomy combines the benefits of the Maquet technique (unloading) and the Elmslie-Trillat technique (tracking improvement) in a single osteotomy, with no distraction of the osteotomy site with bone graft and without the complication rate of Maquet tibial tubercle elevation. Before surgery, computed tomography (CT) or magnetic resonance imaging (MRI) is routinely used to measure TT-TG distance to determine the tibial tubercle medialization required in the Fulkerson osteotomy. However, TT-TG distance must be used with caution, as it cannot be determined in cases with trochlear dysplasia. Consequently, physical examination and arthroscopic examination for evaluation of patellofemoral tracking and location of chondral defects should be performed before the Fulkerson osteotomy.

Rationale; Indications and Contraindications; Preoperative Planning

As already noted, AMZ unloads the distal and lateral facets of the patella. Beck and colleagues¹⁴ suggested AMZ is appropriate for unloading the lateral trochlea. However, it is not useful for central chondral defects and may actually increase the load in patients with medial chondral defects. As AMZ shifts contact force to the medial trochlea, Fulkerson osteotomy is appropriate when distal and lateral chondral lesions must be unloaded. Because this procedure moves the tibial tubercle medially and anteriorly, loads are transferred to the proximal and medial facets of the patella. Therefore, the procedure is contraindicated when diffuse, proximal, or medial chondral lesions are present. Moreover, AMZ is contraindicated in patients with normal TT-TG distance because there is the risk that overmedialization will cause symptomatic medial subluxation. Grade III or IV central trochlear cartilage lesions are also less likely to have successful AMZ outcomes. Therefore, before Fulkerson osteotomy is performed, MRI should be obtained to evaluate the patellofemoral articular surface and TT-TG distance. MRI provides information that is useful for preoperative planning because it allows assessment of articular cartilage lesions, including their location and severity. Moreover, because the osseous and cartilaginous contours of the patella differ, MRI gives a more accurate picture of the patellofemoral congruence than CT does. Last, before the open surgery is performed, the patellofemoral joint should be arthroscopically examined to determine the location of chondral lesions. Cartilage lesion mapping is important because Fulkerson osteotomy outcomes depend on chondral lesion location. Pidoriano and colleagues¹⁵ correlated AMZ outcomes with articular lesion location and noted optimal outcomes in patients with distal and lateral patellar articular lesions and intact trochlear cartilage (87% good and excellent outcomes). Patients with medial lesions and proximal or diffuse lesions generally did poorly (55% good and excellent outcomes in medial lesions vs 20% good and excellent outcomes in proximal and diffuse lesions). Central trochlear lesions were associated with medial patellar lesions, and all patients with central trochlear lesions had poor outcomes. Interestingly, Outerbridge grading of patellar lesions was not significantly correlated with overall outcomes.¹⁵ Even in cases of severe chondropathy, including bone-on-bone arthritis, AMZ has had reliable outcomes and may be superior to arthroplasty because of joint preservation, duration up to 8 years, and restoration of patellofemoral tracking. It should be noted that a resurfacing technique such as patellofemoral arthroplasty is not a substitute for patella realignment. Any patellofemoral maltracking must be corrected before patellofemoral arthroplasty. Fulkerson osteotomy does not preclude subsequent surgery (eg, TKA). Furthermore, AMZ may prevent the natural progression of PFOA related to chronic lateral tracking.

AMZ osteotomy can be adjusted for the specific indication and for the location of chondral defects. If the primary goal is unloading a lateral lesion, or lateral maltracking, then a flatter osteotomy may be performed to increase the relative medialization of the tubercle; however, if the primary goal is unloading a distal lesion, then a relatively more oblique or vertical osteotomy may be performed to transfer the load more proximally. This is the technique preferred by authors in most cases in which more anteriorization is desired.

When TT-TG distance is used to guide surgical realignment, patellofemoral chondrosis associated with normal TT-TG distance can be addressed with directly anterior displacement of the tibial tubercle. Anteriorization of the tibial tubercle can be obtained by inserting a bone block between the tubercle and the tibial cut (Figure 5A).¹⁶ The medialization can be neutralized by making this block as thick as the measured medialization.¹⁶

Surgical Outcomes of Anteromedialization in Patellofemoral Osteoarthritis

Fulkerson and colleagues¹⁰ followed 30 patients for more than 2 years after they underwent AMZ of the tibial tubercle for persistent patellofemoral pain associated with patellar articular degeneration. Of these 30 patients, 12 were followed for more than 5 years. The authors reported 93% good and excellent subjective outcomes and 89% good and excellent objective outcomes. Quality of improvement was sustained for all 12 patients reevaluated more than 5 years after surgery. When examined separately, 75% of patients with advanced PFOA had a good outcome, but none had an excellent outcome. Carofino and Fulkerson¹⁷ retrospectively evaluated tibial tubercle AMZ for isolated PFOA in 22 knees (17 active patients older than 50 years at time of surgery; mean age, 55 years) with minimum follow-up of 2 years (mean, 77 months). Mean postoperative Lysholm score was 83. According to Lysholm scores, outcomes were good to excellent in 12 cases, fair in 6, and poor in 1. The authors concluded that tibial tubercle AMZ is a definitive treatment option for isolated PFOA in active older patients. Morshuis and colleagues¹⁸ retrospectively evaluated 22 patients (25 knees) who underwent Fulkerson osteotomy for patellofemoral pain. Outcomes were evaluated a mean of 12 and 30 months after surgery. At the first evaluation, 84% of patients had satisfactory outcomes, and, at the second (≤38 months after surgery), 70%. Only in relatively young patients without signs of PFOA did outcomes remain satisfactory in all cases. At the later evaluation, 60% of patients with PFOA and/or lateralization had satisfactory outcomes.

Tips and Tricks to Avoid Complications

For some patients, AMZ performed technically correctly produced unhappiness—an outcome that may arise from incorrect patient selection or failure to meet patient expectations. It is important to discuss objectives and expectations with the patient before surgery. With correct patient selection and meticulous surgical technique (with customization of osteotomy angle and translation based on underlying lesion), surgeons have obtained excellent outcomes with infrequent complications (Table).

Intraoperative complications may involve neurovascular structures. The anterior tibial artery and the peroneal nerve are at risk during Fulkerson osteotomy. Decreased anterior sensation related to the infrapatellar branch of the saphenous nerve is not uncommon. Reducing the risk of neurovascular injury requires use of retractors and keeping the saw blade visible at all times. Another potential devastating complication is injury of the posterior vascular structures during bicortical tibial drilling for screw placement. According to Kline and colleagues,¹⁹ bicortical drilling may occur precariously near the posterior vascular structures of the knee. They advised extreme caution in drilling the posterior cortex during this procedure. To avoid the risk of compartment syndrome, surgeons can leave the anterior compartment fascia open or pie crust it by making multiple small perforations to decrease tension. Tibial fracture is another potential complication with this osteotomy. Reducing the risk of fracture involves tapering the distal cut anteriorly and avoiding a “notched” osteotomy (Figures 6A-6C).

Sulcus-Deepening Trochleoplasty

High-grade trochlear dysplasia with a prominence, frequently present in lateral patellar instability, is thought to correlate with PFOA because it produces an anti-Maquet effect.²⁴ The dysplasia provokes an increment of the patellofemoral joint pressure that could explain patellofemoral chondropathy and ultimately PFOA. In fact, 33% of patients with isolated PFOA have a history of objective patellar dislocation.²⁴ In these cases, SDT could be considered. Several studies have examined use of this technique in the treatment of instability, but not PFOA.²⁵ After SDT, pain resolves despite the chondral lesions being left alone (Figures 7A, 7B).

Conclusion

Patellofemoral joint replacement is an option for patellofemoral pain only in very select cases. Preserving the joint is always a primary goal. As not all PFOA cases are equal, joint-preserving surgery must be tailored to the patient. The keys to success are good indication, precise surgery, proper rehabilitation, and, above all, doing only what is needed.

Am J Orthop. 2017;46(3):139-145. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Radiographic assessment of TT position is most commonly performed by measuring TT-TG distance, which is the distance between the extensor mechanism attachment at the TT and the center of the TG.
• TT-TG distances of more than 15 mm or 20 mm have been reported as indications for TT osteotomy.
• TT-TG distance criteria should serve as a guide, rather than a rigid threshold, in the context of imaging and patient factors when deciding whether to perform TT osteotomy for patellar instability.
• Factors such as knee flexion angle, imaging modality, and landmarks used for the measurements should be considered when using TT-TG distance as an indication for surgery.

• There has been significant variability in reported TT-TG measurements. A surgeon using this measurement should understand how it is obtained because many technical factors are involved.

Assessment of malalignment is an important factor in determining surgical treatment options for patellar instability. Although soft-tissue reconstruction of the medial soft-tissue stabilizers is often performed to address patellar instability, bony malalignment may increase stress on the medial soft tissues; therefore, it must be adequately identified and addressed.

Bony malalignment, which is often thought of as lateralization of the tibial tubercle (TT), can be influenced by tibiofemoral alignment, external tibial torsion, and femoral anteversion.

Clinically, coronal alignment can be assessed with a measurement such as quadriceps (Q) angle, but this has been reported to have low interrater reliability and high variability in the reported optimal conditions and positions in which the measurement should be made.^1-3An anatomically lateralized TT pulls the extensor mechanism laterally with respect to the trochlear groove (TG), and this can accentuate problems related to patellofemoral instability. A recent biomechanical study found that increased TT lateralization significantly increased lateral patellar translation and tilt in the setting of medial patellofemoral ligament (MPFL) deficiency.⁴ Although MPFL reconstruction restored patellar kinematics and contact mechanics, this restoration did not occur when the TT was lateralized more than 10 mm relative to its normal position.

Realigning the extensor mechanism by moving the TT medially decreases the lateralizing forces on the patella and the stress on the soft-tissue restraints. This raises the issues of when to correct a lateralized TT and how to identify and measure malalignment.

Radiographic assessment of TT position is most commonly performed by measuring TT-TG distance, which is the distance between the extensor mechanism attachment at the TT and the center of the TG. Originally described on radiographs and subsequently on computed tomography (CT) and magnetic resonance imaging (MRI) scans, distances of more than 15 mm or 20 mm have been reported as indications for TT osteotomy.^5,6However, there has been significant variability in reported TT-TG measurements. Studies have found that TT-TG distance is 3.8 mm larger on CT scans than on MRI scans.⁷ Furthermore, factors such as knee flexion angle at time of imaging have been found to reduce TT-TG distance.¹ More recently, patient size and TT-TG ratios relative to patellar and trochlear width were identified as important factors in assessing TT-TG distance.⁸ Therefore, TT-TG distance measurements should serve as a guide rather than a rigid threshold in the context of imaging and patient factors when deciding whether to perform TT osteotomy for patellar instability.

What You Need to Know About Measuring Patellofemoral Malalignment

TT-TG distance can guide decisions about performing a medializing TT osteotomy for patellar instability because the measurement can aid in assessing bony malalignment caused by an anatomically lateralized tubercle. TT-TG distance can be used to determine when and how far to move the tubercle in TT osteotomy.

Background

A normal TT-TG value is approximately 10 mm. The measurement originally used bony landmarks, including the deepest part of the bony TG and the anterior-most part of the TT, as described by Goutallier and colleagues.⁹ In their original study, Dejour and colleagues⁵ found that patients with recurrent symptoms of patellar instability had TT-TG distances >20 mm.

Increased TT-TG distance has been shown to correlate with patellar position, including increased lateral shift and lateral tilt of the patella. In a study using dynamic CT scans of patients with recurrent patellar instability, we found that TT-TG distance increased with knee extension, and that this increase correlated with the lateral shift and lateral tilt of the patella.¹⁰An excessively lateralized TT can be corrected with a medializing osteotomy that reduces TT-TG distance to within the normal range. TT surgery can be performed with flat osteotomy, as described by Elmslie and Trillat,¹¹ or with oblique osteotomy, as described by Fulkerson,⁶ to obtain concomitant anteriorization. In a computational study, Elias and colleagues¹² found that medializing TT osteotomy not only reduced TT-TG distance but led to correction of lateral patellar tilt and displacement. Patellofemoral contact forces have also shown to be reduced with anteromedialization.⁶Although reported outcomes of TT osteotomy have been excellent for patients with patellar instability, the procedure has higher risks and longer rehabilitation relative to a soft-tissue procedure alone. Reported risks associated with TT osteotomy include fracture, nonunion, delayed union, painful screws, and deep vein thrombosis.^6,10,13,14Understanding the limitations of and variability in radiographic assessments of TT and TG positions can help when deciding whether to perform TT osteotomy for patellar instability.

Discussion

When considering TT osteotomy for patellar instability, some surgeons use a TT-TG distance of more than 15 mm or 20 mm as a threshold for performing medialization. The variability is based on the multiple patient and imaging factors that can influence TT-TG distance measurement.

Several TG and TT landmarks have been used to measure TT-TG distance. The deepest part of the TG, based on bony anatomy, was used originally, but the cartilaginous landmark at the deepest part of the cartilaginous TG has also been described.¹⁵ Similarly, on the TT, the original description of TT-TG distance, by Goutallier and colleagues,⁹ involved the anterior-most part of the TT on CT scan, though the central part of the TT has also been described.¹⁵ We found a 4.2-mm difference in TT-TG distance with use of different landmarks (central tubercle, anterior tubercle) within the same study population.¹⁶ Therefore, within a practice, the distance used as an indication for TT osteotomy should be measured consistently.

Knee flexion angle at the time of imaging can also affect measurement of TT-TG distance. Several authors have reported smaller TT-TG distance with increased knee flexion angle.^10,16,17 In a study of patients with symptomatic patellar instability, we found that TT-TG distance decreases by an estimated 1 mm for every 4.4° of knee flexion >0°.¹⁰ In measurements of TT-TG distance, the sagittal view can be used to assess knee flexion angle because positioning protocols and patient comfort at the time of imaging may produce variable knee flexion angles.

Given the variability that occurs in TT-TG distance with knee flexion angles, some surgeons use TT–posterior cruciate ligament (PCL) distance as another measurement of TT lateralization.¹⁸ This measurement is made with both tibial landmarks, from the TT to the medial border of the PCL insertion on the tibia, and theoretically eliminates knee flexion angle as a measurement factor. Seitlinger and colleagues¹⁸ found that values >24 mm were associated with symptoms of patellar instability. More study is needed to determine the precise indications for TT osteotomy with use of this measurement.

In addition to patient positioning during knee imaging, patient size should be considered when TT-TG distance is used for malalignment measurement. Camp and colleagues⁸ discussed the importance of “individualizing” TT-TG distance on the basis of patient size and bony structure. They reported that the ratio of TT-TG distance to trochlear width or patellar width more effectively predicted recurrent patellar instability than TT-TG distance alone.

Measurement of TT-TG distance is valuable in planning surgical treatment for patellar instability because it quantifies a component of malalignment and aids in deciding whether to perform TT osteotomy. However, this distance should be understood in the context of many measurement factors to allow for an individualized procedure that addresses the specific contributors to patellar instability in each patient.

Am J Orthop. 2017;46(3):148-151. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Radiographic assessment of TT position is most commonly performed by measuring TT-TG distance, which is the distance between the extensor mechanism attachment at the TT and the center of the TG.
• TT-TG distances of more than 15 mm or 20 mm have been reported as indications for TT osteotomy.
• TT-TG distance criteria should serve as a guide, rather than a rigid threshold, in the context of imaging and patient factors when deciding whether to perform TT osteotomy for patellar instability.
• Factors such as knee flexion angle, imaging modality, and landmarks used for the measurements should be considered when using TT-TG distance as an indication for surgery.

• There has been significant variability in reported TT-TG measurements. A surgeon using this measurement should understand how it is obtained because many technical factors are involved.

Assessment of malalignment is an important factor in determining surgical treatment options for patellar instability. Although soft-tissue reconstruction of the medial soft-tissue stabilizers is often performed to address patellar instability, bony malalignment may increase stress on the medial soft tissues; therefore, it must be adequately identified and addressed.

Bony malalignment, which is often thought of as lateralization of the tibial tubercle (TT), can be influenced by tibiofemoral alignment, external tibial torsion, and femoral anteversion.

Clinically, coronal alignment can be assessed with a measurement such as quadriceps (Q) angle, but this has been reported to have low interrater reliability and high variability in the reported optimal conditions and positions in which the measurement should be made.^1-3An anatomically lateralized TT pulls the extensor mechanism laterally with respect to the trochlear groove (TG), and this can accentuate problems related to patellofemoral instability. A recent biomechanical study found that increased TT lateralization significantly increased lateral patellar translation and tilt in the setting of medial patellofemoral ligament (MPFL) deficiency.⁴ Although MPFL reconstruction restored patellar kinematics and contact mechanics, this restoration did not occur when the TT was lateralized more than 10 mm relative to its normal position.

Realigning the extensor mechanism by moving the TT medially decreases the lateralizing forces on the patella and the stress on the soft-tissue restraints. This raises the issues of when to correct a lateralized TT and how to identify and measure malalignment.

Radiographic assessment of TT position is most commonly performed by measuring TT-TG distance, which is the distance between the extensor mechanism attachment at the TT and the center of the TG. Originally described on radiographs and subsequently on computed tomography (CT) and magnetic resonance imaging (MRI) scans, distances of more than 15 mm or 20 mm have been reported as indications for TT osteotomy.^5,6However, there has been significant variability in reported TT-TG measurements. Studies have found that TT-TG distance is 3.8 mm larger on CT scans than on MRI scans.⁷ Furthermore, factors such as knee flexion angle at time of imaging have been found to reduce TT-TG distance.¹ More recently, patient size and TT-TG ratios relative to patellar and trochlear width were identified as important factors in assessing TT-TG distance.⁸ Therefore, TT-TG distance measurements should serve as a guide rather than a rigid threshold in the context of imaging and patient factors when deciding whether to perform TT osteotomy for patellar instability.

What You Need to Know About Measuring Patellofemoral Malalignment

TT-TG distance can guide decisions about performing a medializing TT osteotomy for patellar instability because the measurement can aid in assessing bony malalignment caused by an anatomically lateralized tubercle. TT-TG distance can be used to determine when and how far to move the tubercle in TT osteotomy.

Background

A normal TT-TG value is approximately 10 mm. The measurement originally used bony landmarks, including the deepest part of the bony TG and the anterior-most part of the TT, as described by Goutallier and colleagues.⁹ In their original study, Dejour and colleagues⁵ found that patients with recurrent symptoms of patellar instability had TT-TG distances >20 mm.

Increased TT-TG distance has been shown to correlate with patellar position, including increased lateral shift and lateral tilt of the patella. In a study using dynamic CT scans of patients with recurrent patellar instability, we found that TT-TG distance increased with knee extension, and that this increase correlated with the lateral shift and lateral tilt of the patella.¹⁰An excessively lateralized TT can be corrected with a medializing osteotomy that reduces TT-TG distance to within the normal range. TT surgery can be performed with flat osteotomy, as described by Elmslie and Trillat,¹¹ or with oblique osteotomy, as described by Fulkerson,⁶ to obtain concomitant anteriorization. In a computational study, Elias and colleagues¹² found that medializing TT osteotomy not only reduced TT-TG distance but led to correction of lateral patellar tilt and displacement. Patellofemoral contact forces have also shown to be reduced with anteromedialization.⁶Although reported outcomes of TT osteotomy have been excellent for patients with patellar instability, the procedure has higher risks and longer rehabilitation relative to a soft-tissue procedure alone. Reported risks associated with TT osteotomy include fracture, nonunion, delayed union, painful screws, and deep vein thrombosis.^6,10,13,14Understanding the limitations of and variability in radiographic assessments of TT and TG positions can help when deciding whether to perform TT osteotomy for patellar instability.

Discussion

When considering TT osteotomy for patellar instability, some surgeons use a TT-TG distance of more than 15 mm or 20 mm as a threshold for performing medialization. The variability is based on the multiple patient and imaging factors that can influence TT-TG distance measurement.

Several TG and TT landmarks have been used to measure TT-TG distance. The deepest part of the TG, based on bony anatomy, was used originally, but the cartilaginous landmark at the deepest part of the cartilaginous TG has also been described.¹⁵ Similarly, on the TT, the original description of TT-TG distance, by Goutallier and colleagues,⁹ involved the anterior-most part of the TT on CT scan, though the central part of the TT has also been described.¹⁵ We found a 4.2-mm difference in TT-TG distance with use of different landmarks (central tubercle, anterior tubercle) within the same study population.¹⁶ Therefore, within a practice, the distance used as an indication for TT osteotomy should be measured consistently.

Knee flexion angle at the time of imaging can also affect measurement of TT-TG distance. Several authors have reported smaller TT-TG distance with increased knee flexion angle.^10,16,17 In a study of patients with symptomatic patellar instability, we found that TT-TG distance decreases by an estimated 1 mm for every 4.4° of knee flexion >0°.¹⁰ In measurements of TT-TG distance, the sagittal view can be used to assess knee flexion angle because positioning protocols and patient comfort at the time of imaging may produce variable knee flexion angles.

Given the variability that occurs in TT-TG distance with knee flexion angles, some surgeons use TT–posterior cruciate ligament (PCL) distance as another measurement of TT lateralization.¹⁸ This measurement is made with both tibial landmarks, from the TT to the medial border of the PCL insertion on the tibia, and theoretically eliminates knee flexion angle as a measurement factor. Seitlinger and colleagues¹⁸ found that values >24 mm were associated with symptoms of patellar instability. More study is needed to determine the precise indications for TT osteotomy with use of this measurement.

In addition to patient positioning during knee imaging, patient size should be considered when TT-TG distance is used for malalignment measurement. Camp and colleagues⁸ discussed the importance of “individualizing” TT-TG distance on the basis of patient size and bony structure. They reported that the ratio of TT-TG distance to trochlear width or patellar width more effectively predicted recurrent patellar instability than TT-TG distance alone.

Measurement of TT-TG distance is valuable in planning surgical treatment for patellar instability because it quantifies a component of malalignment and aids in deciding whether to perform TT osteotomy. However, this distance should be understood in the context of many measurement factors to allow for an individualized procedure that addresses the specific contributors to patellar instability in each patient.

Am J Orthop. 2017;46(3):148-151. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Radiographic assessment of TT position is most commonly performed by measuring TT-TG distance, which is the distance between the extensor mechanism attachment at the TT and the center of the TG.
• TT-TG distances of more than 15 mm or 20 mm have been reported as indications for TT osteotomy.
• TT-TG distance criteria should serve as a guide, rather than a rigid threshold, in the context of imaging and patient factors when deciding whether to perform TT osteotomy for patellar instability.
• Factors such as knee flexion angle, imaging modality, and landmarks used for the measurements should be considered when using TT-TG distance as an indication for surgery.

• There has been significant variability in reported TT-TG measurements. A surgeon using this measurement should understand how it is obtained because many technical factors are involved.

Assessment of malalignment is an important factor in determining surgical treatment options for patellar instability. Although soft-tissue reconstruction of the medial soft-tissue stabilizers is often performed to address patellar instability, bony malalignment may increase stress on the medial soft tissues; therefore, it must be adequately identified and addressed.

Bony malalignment, which is often thought of as lateralization of the tibial tubercle (TT), can be influenced by tibiofemoral alignment, external tibial torsion, and femoral anteversion.

Clinically, coronal alignment can be assessed with a measurement such as quadriceps (Q) angle, but this has been reported to have low interrater reliability and high variability in the reported optimal conditions and positions in which the measurement should be made.^1-3An anatomically lateralized TT pulls the extensor mechanism laterally with respect to the trochlear groove (TG), and this can accentuate problems related to patellofemoral instability. A recent biomechanical study found that increased TT lateralization significantly increased lateral patellar translation and tilt in the setting of medial patellofemoral ligament (MPFL) deficiency.⁴ Although MPFL reconstruction restored patellar kinematics and contact mechanics, this restoration did not occur when the TT was lateralized more than 10 mm relative to its normal position.

Realigning the extensor mechanism by moving the TT medially decreases the lateralizing forces on the patella and the stress on the soft-tissue restraints. This raises the issues of when to correct a lateralized TT and how to identify and measure malalignment.

Radiographic assessment of TT position is most commonly performed by measuring TT-TG distance, which is the distance between the extensor mechanism attachment at the TT and the center of the TG. Originally described on radiographs and subsequently on computed tomography (CT) and magnetic resonance imaging (MRI) scans, distances of more than 15 mm or 20 mm have been reported as indications for TT osteotomy.^5,6However, there has been significant variability in reported TT-TG measurements. Studies have found that TT-TG distance is 3.8 mm larger on CT scans than on MRI scans.⁷ Furthermore, factors such as knee flexion angle at time of imaging have been found to reduce TT-TG distance.¹ More recently, patient size and TT-TG ratios relative to patellar and trochlear width were identified as important factors in assessing TT-TG distance.⁸ Therefore, TT-TG distance measurements should serve as a guide rather than a rigid threshold in the context of imaging and patient factors when deciding whether to perform TT osteotomy for patellar instability.

What You Need to Know About Measuring Patellofemoral Malalignment

TT-TG distance can guide decisions about performing a medializing TT osteotomy for patellar instability because the measurement can aid in assessing bony malalignment caused by an anatomically lateralized tubercle. TT-TG distance can be used to determine when and how far to move the tubercle in TT osteotomy.

Background

A normal TT-TG value is approximately 10 mm. The measurement originally used bony landmarks, including the deepest part of the bony TG and the anterior-most part of the TT, as described by Goutallier and colleagues.⁹ In their original study, Dejour and colleagues⁵ found that patients with recurrent symptoms of patellar instability had TT-TG distances >20 mm.

Increased TT-TG distance has been shown to correlate with patellar position, including increased lateral shift and lateral tilt of the patella. In a study using dynamic CT scans of patients with recurrent patellar instability, we found that TT-TG distance increased with knee extension, and that this increase correlated with the lateral shift and lateral tilt of the patella.¹⁰An excessively lateralized TT can be corrected with a medializing osteotomy that reduces TT-TG distance to within the normal range. TT surgery can be performed with flat osteotomy, as described by Elmslie and Trillat,¹¹ or with oblique osteotomy, as described by Fulkerson,⁶ to obtain concomitant anteriorization. In a computational study, Elias and colleagues¹² found that medializing TT osteotomy not only reduced TT-TG distance but led to correction of lateral patellar tilt and displacement. Patellofemoral contact forces have also shown to be reduced with anteromedialization.⁶Although reported outcomes of TT osteotomy have been excellent for patients with patellar instability, the procedure has higher risks and longer rehabilitation relative to a soft-tissue procedure alone. Reported risks associated with TT osteotomy include fracture, nonunion, delayed union, painful screws, and deep vein thrombosis.^6,10,13,14Understanding the limitations of and variability in radiographic assessments of TT and TG positions can help when deciding whether to perform TT osteotomy for patellar instability.

Discussion

When considering TT osteotomy for patellar instability, some surgeons use a TT-TG distance of more than 15 mm or 20 mm as a threshold for performing medialization. The variability is based on the multiple patient and imaging factors that can influence TT-TG distance measurement.

Several TG and TT landmarks have been used to measure TT-TG distance. The deepest part of the TG, based on bony anatomy, was used originally, but the cartilaginous landmark at the deepest part of the cartilaginous TG has also been described.¹⁵ Similarly, on the TT, the original description of TT-TG distance, by Goutallier and colleagues,⁹ involved the anterior-most part of the TT on CT scan, though the central part of the TT has also been described.¹⁵ We found a 4.2-mm difference in TT-TG distance with use of different landmarks (central tubercle, anterior tubercle) within the same study population.¹⁶ Therefore, within a practice, the distance used as an indication for TT osteotomy should be measured consistently.

Knee flexion angle at the time of imaging can also affect measurement of TT-TG distance. Several authors have reported smaller TT-TG distance with increased knee flexion angle.^10,16,17 In a study of patients with symptomatic patellar instability, we found that TT-TG distance decreases by an estimated 1 mm for every 4.4° of knee flexion >0°.¹⁰ In measurements of TT-TG distance, the sagittal view can be used to assess knee flexion angle because positioning protocols and patient comfort at the time of imaging may produce variable knee flexion angles.

Given the variability that occurs in TT-TG distance with knee flexion angles, some surgeons use TT–posterior cruciate ligament (PCL) distance as another measurement of TT lateralization.¹⁸ This measurement is made with both tibial landmarks, from the TT to the medial border of the PCL insertion on the tibia, and theoretically eliminates knee flexion angle as a measurement factor. Seitlinger and colleagues¹⁸ found that values >24 mm were associated with symptoms of patellar instability. More study is needed to determine the precise indications for TT osteotomy with use of this measurement.

In addition to patient positioning during knee imaging, patient size should be considered when TT-TG distance is used for malalignment measurement. Camp and colleagues⁸ discussed the importance of “individualizing” TT-TG distance on the basis of patient size and bony structure. They reported that the ratio of TT-TG distance to trochlear width or patellar width more effectively predicted recurrent patellar instability than TT-TG distance alone.

Measurement of TT-TG distance is valuable in planning surgical treatment for patellar instability because it quantifies a component of malalignment and aids in deciding whether to perform TT osteotomy. However, this distance should be understood in the context of many measurement factors to allow for an individualized procedure that addresses the specific contributors to patellar instability in each patient.

Am J Orthop. 2017;46(3):148-151. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

INTRODUCTION

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading nonobstetric cause of maternal death in the United States and in developed countries.^1,2 During pregnancy, the risk for VTE increases four- to six-fold, and although the risk is present throughout pregnancy, the mother is at highest risk immediately postpartum.^3–5

VTE risk is increased due to physiologic and anatomic changes that occur in pregnancy. These changes include hypercoagulability, progesterone-induced venous stasis, decreased venous outflow, compression of the inferior vena cava and pelvic veins by the expanding uterus, and decreased mobility. The hypercoagulability of pregnancy is due to increased levels of coagulation factors I (fibrinogen), VII, VIII, and X, and von Willebrand factor; decreased free protein S, a natural anticoagulant; acquired resistance to activated protein C; and decreased fibrinolysis due to increased levels of plasminogen activator inhibitor-1 and -2.^6,7 These changes confer increased hemostasis to the mother for delivery but also place her at higher risk for thrombosis.

A review of the literature found that more than 70% of pregnancy-associated DVTs are located in the ileofemoral region, as compared with approximately 9% in non-pregnant patients.⁸ The proximal location is associated with a higher risk for post-thrombotic syndrome and embolization as compared with calf DVTs.⁹ Proximal postnatal thrombosis, smoking, and older age are independent predictors of the development of post-thrombotic syndrome.¹⁰

RISK FACTORS

Clinical risk factors that increase the risk for VTE during pregnancy include a prior history of estrogen-related or unprovoked VTE, being a carrier of severe inherited thrombophilia (homozygotes for factor V Leiden or factor II G20210A variants, double heterozygotes, or persons with antithrombin, protein C, or protein S deficiencies), and the presence of antiphospholipid (aPL) antibodies.¹¹ Women with systemic lupus erythematosus, diabetes, sickle cell disease, and heart disease also have a high risk for VTE during pregnancy.¹² Other risk factors predisposing to thrombosis include black ethnicity, smoking, operative procedures, conception after assisted reproductive techniques, high body mass index, antepartum immobilization, severe preeclampsia, advanced age and parity, and a family history of VTE.¹³ A prospective cohort study of 1,297,037 pregnancies and related puerperium identified the following risk factors for thrombosis: hospitalization, infection, hyperemesis, multiple pregnancies, preeclampsia, obesity, cesarean section, major postpartum hemorrhage, intrauterine growth restriction, and fetal death.¹⁴ Risk factors identified in an Agency for Healthcare Research and Quality study include: age 35 or older, black ethnicity, lupus, sickle cell disease, heart disease, postpartum infection, and transfusion.¹⁵ The combination of more than one risk factor increases the risk for VTE. All these factors have to be considered when deciding on prophylactic or therapeutic anticoagulation therapy in pregnancy. In addition, the risks of anticoagulation, including bruising, bleeding, and other side effects (eg, reduced bone mineral density with therapeutic-dose unfractionated heparin), allergic reactions, and rarely thrombocytopenia, must be considered.

EVALUATION AND DIAGNOSIS

CASE PRESENTATION I

A 31-year-old woman G1P0 at 10 weeks’ gestation with no personal or family history of thrombosis presents with acute onset of shortness of breath and left-sided chest pain that awoke her the morning of presentation. Her vital signs are significant for a heart rate of 106 beats/min, respiration rate of 22 breaths/min, blood pressure of 105/76 mm Hg, and pulse oximetry of 98% on room air. The patient denies previous exposure to oral contraceptives. She does not smoke. She reports that she had noticed left calf pain and swelling, which worsened with walking after a 4-hour drive 2 days prior.

• What is the approach to diagnosis of thromboembolism in pregnant patients?

DEEP VEIN THROMBOSIS

Although a clinical diagnosis of DVT in pregnancy is unreliable, a history and physical examination are necessary to exclude other diagnoses and to assess the likelihood of thrombosis. Unfortunately, studies of the accuracy of history and physical examination for detecting DVT and PE have not included pregnant patients. In most pregnant patients with clinically suspected DVT, the diagnosis is not confirmed. Other causes of leg pain and swelling are not uncommon during pregnancy and include cellulitis, ruptured Baker’s cyst, or muscular pain.

A cross-sectional study described the derivation of the LEFt clinical decision rule, which relies on 3 variables in pregnant women with suspected DVT: left leg presentation (L), ≥ 2 cm calf circumference difference (E for edema), and first trimester presentation (Ft). If none of these variables is present, the negative predictive value is 100%.¹⁶ A validation study suggested that a negative LEFt rule accurately identifies pregnant women in whom the risk for confirmed DVT appears to be very low. The rule should not be used as an individual test for excluding DVT during pregnancy, but could be applied in a diagnostic approach in association with D-dimer measurement and compression ultrasonography (CUS); however, it has not been prospectively validated for safety and efficacy.¹⁷ In a study of 149 consecutive pregnant women with suspected DVT, a whole-blood agglutination D-dimer had a sensitivity of 100% and specificity of 60%.¹⁸ A 2006 systematic review found only 4 diagnostic studies of VTE in pregnancy in the literature. One of these studies showed that a combination of a negative CUS and normal D-dimer can accurately exclude DVT.¹⁹

Serial CUS is necessary for pregnant women with a high clinical suspicion of DVT but a negative initial investigation. In a study of 221 pregnant women in whom DVT was clinically suspected, 16 women (7.2%) were diagnosed with DVT by initial CUS, and none were diagnosed with DVT onserial testing.²⁰ During follow-up (≥ 3 months), 6 of the 205 women with normal serial CUS results presented with symptoms of DVT, PE, or both, and 1 of them was diagnosed with DVT and PE. The sensitivity of serial CUS with Doppler imaging was 94.1% (95% confidence interval [CI] 69.2% to 99.7%), and the negative predictive value was 99.5% (95% CI 96.9% to 100%).²⁰ All ultrasounds undertaken for investigation of pregnancy-associated DVT should include imaging of the iliac veins if there is a high index of suspicion and the CUS is negative for femoral DVT. Serial CUS with Doppler imaging of the iliac vein performed over a 7-day period excludes DVT in symptomatic pregnant women.²⁰ Repeat CUS may be done 2 to 4 days and 6 to 8 days after the initial scan.

Ileofemoral vein thrombosis accounts for approximately 90% of proximal thromboses in pregnancy, occurring most often in the left lower extremity.²⁰ The incidence of isolated iliac vein thrombosis in pregnancy is low, but when it does occur, delay in diagnosis can lead to significant morbidity. Therefore, for women with suspected isolated iliac vein thrombosis in whom CUS is negative or nondiagnostic, magnetic resonance direct thrombus imaging (MRDTI) should be performed.²¹ Patients with iliac vein thrombosis may present with unexplained inguinal, pelvic, or abdominal pain, which may be accompanied by back pain, and they usually present with swelling of the entire leg. MRDTI does not require gadolinium contrast and its accuracy appears to be similar to that of venography for iliac vein thrombi in the nonpregnant population.²¹ Exposure to gadolinium during pregnancy is associated with an increased risk for rheumatologic, inflammatory, or infiltrative skin conditions and stillbirth or neonatal death.²²

Ovarian vein thrombosis is a rare but serious diagnosis. It occurs mostly in the postpartum period, mainly after cesarean delivery, and usually affects the right ovarian vein. The diagnosis is confirmed by ultrasound, computed tomography (CT), or magnetic resonance imaging.²³

PULMONARY EMBOLISM

PE is more difficult to diagnose than DVT, particularly because clinical signs of PE are unreliable in the pregnant patient. The mortality rate of untreated PE is high, ranging from 18% to 38%, and approximately one-third of patients with untreated thromboembolic disease develop recurrent embolism.²⁴ Studies have reported a PE prevalence between 1.4% and 4.2% in pregnant women with suspected clinical diagnosis of PE.²⁵

The clinical presentation of PE and associated laboratory testing results may be subtler in pregnant than in nonpregnant patients. Arterial blood gases (ABG) may show hypoxemia or hypocapnia. The ABG in pregnancy has a sensitivity of 76.9%, specificity of 20.2%, and negative and positive predictive values of 80% and 11.5% for PE, respectively.²⁶ The alveolar-arterial oxygen gradient is a poor screening test for PE during pregnancy and postpartum. A retrospective chart review of 17 pregnant women with documented PE showed that 58% had normal alveolar-arterial gradients.²⁷ Therefore, in a pregnant woman with a history suspicious for PE, objective imaging studies should be performed even if the patient has normal ABG.

The 2011 guidelines from the American Thoracic Society (ATS) and the Society of Thoracic Radiology (STR) recommend against using D-dimer to diagnose PE in pregnancy.²⁸ In addition, lower extremity CUS should only be performed as the first diagnostic imaging procedure if the patient has signs or symptoms of DVT. Instead, the ATS/STR guidelines recommend a plain radiograph of the chest as the first imaging test. If the chest radiograph is normal, a ventilation/perfusion scan (V/Q) scan is preferred over CT pulmonary angiography (CTPA). Diagnostic accuracy of the V/Q scan may be superior to CTPA in pregnancy, and it is preferable because of the lower prevalence of indeterminate V/Q scan in pregnant women.²⁹ Moreover, there is lower radiation exposure to the maternal breast and lung tissue with a V/Q scan than with CTPA. CTPA confers lower fetal radiation doses than V/Q scans (0.03–0.66 mGy versus 0.32–0.74 mGy, respectively) but higher total body maternal radiation (4–16 mSv versus 1–2.5 mSv).³⁰ A quantitative approach to lung scan interpretation, based on the distribution histogram of V/Q ratios, may be helpful in categorizing patients with suspected PE.²⁸ A study of 121 suspected episodes of PE in 120 pregnant women showed that 104 women with normal or nondiagnostic scans did not develop subsequent episodes of VTE during a mean follow-up period of 20 months.³¹

If the baseline chest radiograph is abnormal in a pregnant woman with clinical suspicion of PE, a CTPA should be performed. As noted, fetal radiation doses for CTPA examinations in which the fetus is not directly imaged are minimal. If CTPA is recommended for the diagnosis of PE, the patient should be informed that radiation to the breast may increase her baseline risk for breast cancer. The ATS guidelines state that “given the lack of evidence documenting clear superiority of any one diagnostic test, the values and preferences of a patient and her physician likely will and should determine the final choice and sequence of tests performed.”²⁸

CASE I CONTINUED

Upon presentation to the emergency department, the circumference of the patient’s left leg is not significantly greater than that of her right leg, and her leg pain has resolved. Bilateral CUS is negative for proximal or distal DVT. Chest radiograph shows an opacification of her left lower lobe. CTPA shows bilateral segmental and subsegmental lower lobe pulmonary emboli.

• How does risk for VTE change throughout pregnancy?

Women are at increased risk for VTE throughout the entire pregnancy, starting from conception, but mainly during the postpartum period. A Danish historical controlled cohort study of 819,751 pregnant women (ages 15–49 years) over a 10-year period identified 727 women with VTE. The absolute risk for VTE per 10,000 pregnancy-years increased from 4.1 (95% CI 3.2 to 5.2) during weeks 1 to 11 to 59.0 (95% CI 46.1 to 76.4) in week 40 and decreased in the postpartum period from 60 (95% CI 47.2 to 76.4) during the first week after birth to 2.1 during weeks 9–12 after birth (95% CI 1.1 to 4.2).³² This study showed that the risk of VTE increases throughout pregnancy and reaches its maximum during the peripartum period and is not significantly increased after 6 weeks post-delivery. In a retrospective cross-over cohort study of 1,687,930 women in California who delivered their first newborn, an elevated risk of VTE persisted until at least 12 weeks after delivery. However, the absolute increase in risk after 6 weeks postpartum was low.³³

CASE 1 CONCLUSION

The patient is started on anticoagulation therapy and carefully monitored during the remainder of the pregnancy and postpartum period. Anticoagulation is discontinued 6 weeks after delivery.

TREATMENT

ANTICOAGULATION THERAPY

The treatment of VTE can be lifesaving. In a study comparing 35 patients with PE randomly assigned to treatment with anticoagulants versus no treatment, 5 of 19 patients in the untreated group died from PE and an additional 5 had nonfatal recurrences, as compared with none in the treated group.²⁴ Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are both safe and effective anticoagulants during pregnancy as neither crosses the placenta. In a review of 186 reports of fetal and infant outcomes following anticoagulant therapy during pregnancy in 1325 pregnancies, outcomes in UFH-treated patients were similar to those in the normal population after excluding pregnancies with comorbid conditions independently associated with adverse outcomes.³⁴ A 2005 systematic review of LMWH for prophylaxis and treatment of VTE during pregnancy included 64 studies of 277 pregnancies. There were no maternal deaths, live births resulted from 94.7% of the pregnancies, VTE or arterial thrombosis occurred in 0.86%, and significant bleeding occurred in 1.98%.³⁵

The standard UFH regimen is an initial bolus of 5000 units subcutaneously and 17,500 units every 12 hours, with dose adjustment made based on a mid-interval activated partial thromboplastin time (aPTT).³⁶ Although still controversial, it has been suggested that the anti-Xa assay with a mid-dosing interval target of 0.3 to 0.7 U/mL is a more reliable measure of therapeutic UFH activity than the aPTT, as the aPTT response is suppressed due to a pregnancy-related increase in factor VIII. LMWH is dosed based on weight; regimens are enoxaparin 1 mg/kg subcutaneously twice daily or 1.5 mg/kg subcutaneously once daily, and dalteparin 100 units/kg every 12 hours or 150 units/kg daily.

A 2017 Cochrane review of the effect of LMWH compared with UFH for the treatment of VTE in the nonpregnant setting included 23 studies with 9587 patients. Thrombotic complications (odds ratio [OR] 0.70 [CI 0.57 to 0.85]) and major hemorrhage (OR 0.58 [CI 0.40 to 0.83]) were lower in patients receiving LMWH, with a trend toward lower mortality.³⁷ In addition, the incidence of bleeding complications in patients treated with subcutaneous LMWH versus intravenous heparin was compared in a 2012 systematic review of 27 randomized controlled trials with a total of 28,637 patients. In patients treated with LMWH, there was a nonstatistically significant lower incidence of major bleeding events (OR 0.79 [95% CI 0.60 to 1.04]) and a statistically significant reduction in bleeding risk (OR 0.68 [95% CI 0.47 to 1.00]) compared to patients treated with UFH.³⁸ Additionally, a trial comparing the use of standard UFH versus LMWH found a significantly lower incidence of thrombocytopenia in patients treated with LMWH.^39,40 Overall, LMWH is more effective at decreasing both thrombotic and bleeding complications, and the risk for osteoporosis is lower with LMWH. Based on these results, the American College of Chest Physicians (ACCP) recommends LMWH as the first-line treatment for VTE in pregnancy.⁴¹

In specific clinical situations, such as patients with renal dysfunction with creatinine clearance (CrCl) less than 30 mL/min, UFH is indicated. In a study of 103 pregnancies in 93 women given anti-coagulation during pregnancy, 89.3% received UFH. There were no maternal deaths, and fetal demise occurred in 8 pregnancies (7.8%) at a median of 14 weeks’ gestation. There were 2 episodes of PE (1.9%) and 2 major bleeding events requiring transfusion (1.9%).⁴² UFH costs much less than LMWH, and therefore UFH remains an important, inexpensive, and efficacious anticoagulant option for pregnant women who require anticoagulation and cannot afford LMWH.⁴³

Due to the physiologic changes associated with pregnancy, LMWH and UFH dosages may need to be adjusted. An observational study of 20 pregnant women with acute VTE found no recurrent VTE or major bleeding after treatment with dalteparin. Dalteparin doses approximately 10% to 20% higher than those recommended in nonpregnant women were required to reach therapeutic target anti-Xa activity.⁴⁴

Caution Regarding Oral Anticoagulants

Due to its teratogenicity, warfarin is not a first-line anticoagulation option. It is strictly contraindicated during the first trimester during organogenesis, and its use during pregnancy is restricted to women with mechanical heart valves. Warfarin crosses the placenta and has been associated with nasal hypoplasia, stippled epiphyses, and growth restriction, particularly between 6 to 9 weeks’ gestation. Every effort should be made to substitute UFH or LMWH for warfarin between 6 and 12 weeks of gestation. The bridging process should begin as early in the gestational age as possible due to the long half-life of warfarin.⁴⁵ When used later in gestation, warfarin has been associated with fetal hemorrhage and central nervous system abnormalities. Other complications from use during the second and third trimesters include microcephaly, blindness, deafness, and fetal growth restriction.^46,47 Its use also increases the risk for abortion and fetal death in utero.^48–50

The direct oral anticoagulants (DOACs) are not approved for use in pregnancy. Although there are limited anecdotal reports of DOAC use in pregnancy,⁵¹ there is preclinical evidence of placental transfer with the DOACs rivaroxaban and apixaban (direct Xa inhibitors) and the oral thrombin inhibitor dabigatran, thus increasing the risk to the fetus.^52–54 Edoxaban, another direct Xa inhibitor, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It should be discontinued in nursing mothers.⁵⁵

THROMBOLYSIS

Fetal as well as maternal survival is dependent on adequate maternal perfusion and oxygenation. The risk of death from PE is significant, with a cross-sectional study of 58 patients with acute, massive PE showing a 55% mortality rate.⁵⁶ Thus, pregnancy is not an absolute contraindication to mechanical or systemic (recombinant tissue plasminogen activator or streptokinase) thrombolysis in an unstable patient at high risk for death.^57–59 There are no major studies of this approach, although a small review of 13 cases using systemic thrombolysis showed no increased risk of maternal mortality.⁵⁸ Thrombolysis should be considered for appropriate indications in pregnant patients as it would be in nonpregnant patients. However, caution is required when drawing conclusions regarding maternal and fetal safety, given the lack of controlled clinical trials including pregnant women.

SURGICAL PULMONARY EMBOLECTOMY

Surgical pulmonary embolectomy is an important therapeutic and potentially life-saving option in women presenting with massive PE in the immediate postpartum period. Because of the risk of massive uterine bleeding immediately postpartum, thrombolytic therapy should not be used.⁶⁰

INFERIOR VENA CAVA FILTER

Placement of an inferior vena cava (IVC) filter is indicated in patients who have an acute VTE with absolute contraindications for anticoagulation. In addition, it can be considered in patients with extensive ileofemoral venous thrombosis within 2 weeks prior to expected delivery.⁶¹ In a systematic review of 44 studies of IVC filters placed in pregnant patients, the IVC filter complication rate was 8.87% and the failure-to-retrieve rate was 11.25%.⁶² The complication rate is similar to that found in the nonpregnant population. Thus, IVC filters may be used when appropriately indicated and should be removed as soon as clinically feasible.

RECURRENT THROMBOSIS AND THROMBOPHILIAS

CASE PRESENTATION 2

A 34-year-old pregnant woman G1P0 at 38 weeks’ gestation presents with a painful, swollen left calf that is associated with difficulty on walking; the circumference of the left calf is 2 cm greater than that of the right. She has no shortness of breath or chest pain. She has a prior history of distal right lower extremity DVT while on combined oral contraceptives. Her mother also has a history of DVT while bedbound during a prolonged hospitalization at an older age. CUS is negative, and the patient is discharged home. However, 24 hours later she returns to the hospital with worsening swelling and pain in her left leg. Magnetic resonance venography demonstrates a large left external iliac and common iliac DVT. She is admitted and is started on UFH, and a retrievable IVC filter is placed in anticipation of delivery.

• What is the risk for VTE recurrence during pregnancy?

A personal and family history of VTE should be obtained when evaluating pregnant patients. A retrospective study of 109 women with prior history of VTE showed recurrence rates per patient-year of 10.9% during pregnancy and 3.7% in the nonpregnant period; the relative risk of recurrent VTE during pregnancy was 3.5 (95% CI 1.6 to 7.8).⁶³ Two large European retrospective cohort studies of VTE in pregnancy showed that the recurrence rate of VTE in women with a history of thrombosis is around 6% during pregnancy, equally distributed among trimesters. The highest incidence of recurrence was in the postpartum period, ranging from 8.3% to 10%.⁶⁴ The recurrence risk during pregnancy in women with a history of a single episode of VTE was 2.4% antepartum (95% CI 0.2% to 6.9%).⁶⁵ These risks may be lower in women without thrombophilia or with a temporary risk factor associated with their previous thromboembolic event.⁶⁵ Recurrence risk is higher if the previous VTE was estrogen-related, either due to pregnancy or through hormonal contraception (10%), than if the previous VTE was non-estrogen-related (2.7%).^64,66

The timing of the case patient’s presentation is consistent with reports of increased risk of VTE during the peripartum period. Her prior history of estrogen-related DVT is concerning for a risk of recurrence, particularly during pregnancy. A retrospective cohort study of 1104 women with previous VTE, 88 of whom became pregnant without receiving thromboprophylaxis, showed that the overall rate of VTE recurrence was 5.8% (95% CI 3.0% to 10.6%) and 8.3% (95% CI 4.5% to 14.6%) during pregnancy and postpartum, respectively. The risk of VTE recurrence was absent if the first VTE was related to a transient risk factor other than pregnancy, postpartum period, or hormonal contraception.⁶⁷ However, the recurrence rate of VTE in women with prior unprovoked VTE and/or thrombophilia has been reported as 5.9% (95% CI 1.2% to 16.2%).⁶⁵ The presence of an underlying hypercoagulable state can increase the recurrence risk by 25% to 50%, depending on the disorder.⁶⁸ A retrospective cohort study of 270 pregnancies in 105 carriers of factor V Leiden, identified because of a symptomatic relative with the factor V Leiden mutation, found a VTE risk (mostly in the postpartum period) of 6.4% for heterozygous women, 16.7% for homozygous women, 20% for double heterozygous women, and 1.2% for noncarriers.⁶⁹

• Should the patient be screened for a thrombophilia disorder?

Half of all index thromboses in patients with thrombophilia occur in association with an additional risk factor. In women of child-bearing age, pregnancy, the postpartum period, and the use of combined hormonal contraception are all risk factors for VTE. A 2010 guideline from the British hematology community recommended testing for thrombophilia in women with prior VTE secondary to a minor provoking factor before or during pregnancy, but not testing women with unprovoked VTE (who would receive prophylaxis regardless) or those with VTE secondary to a major provoking factor (who would not require prophylaxis).⁷⁰ Indications to screen for aPL antibodies include: women with (1) 3 unexplained recurrent first-trimester pregnancy losses or 1 second or third trimester fetal loss of morphologically normal fetuses; (2) severe preeclampsia; (3) intrauterine growth restriction; or (4) premature labor (< 34 weeks’ gestation).^71,72

CASE 2 CONCLUSION

The patient is subsequently screened for inherited thrombophilia disorders and is found to be heterozygous for factor V Leiden.

CASE PRESENTATION 3

A 25-year-old woman is diagnosed with antiphospholipid syndrome (APS) during her second pregnancy when she experiences fetal loss during her second trimester. Pathologic examination of the placenta reveals infarcts. Laboratory evaluation reveals positive high-titer anticardiolipin and anti-beta-2 glycoprotein 1 antibodies (IgG isotype) and lupus anticoagulant on 2 separate occasions 12 weeks apart. In a subsequent pregnancy, she is started on prophylactic LMWH and daily low-dose aspirin (81 mg). At 36 weeks’ gestation, she presents with a blood pressure of 210/104 mm Hg and a platelet count of 94,000 cells/µL. She is diagnosed with preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and is induced for early delivery. About 2 weeks after vaginal delivery, she notices shortness of breath and chest pain. A CTPA demonstrates a right lower lobe lobar defect consistent with a PE. Her anticoagulation is increased to therapeutic dosage LMWH.

• To what extent does thrombophilia increase the risk for VTE in pregnancy?

Approximately 50% of pregnancy-related VTEs are associated with inherited thrombophilia. A systematic review of 79 studies, in which 9 studies (n = 2526 patients) assessed the risk of VTE associated with inherited thrombophilia in pregnancy, revealed that the odds ratio for individuals with thrombophilia to develop VTE ranged from 0.74 to 34.40.⁷³ Although women with thrombophilia have an increased relative risk of developing VTE in pregnancy, the absolute risk of VTE remains low (Table 1).^41,73,74

• How is APS managed in pregnant patients?

Women with history of recurrent early pregnancy loss (< 10 weeks’ gestation) related to the presence of aPL antibodies are managed with low-dose aspirin and prophylactic-dose UFH or LMWH. This treatment increases the rate of subsequent successful pregnancy outcomes and reduces the risk for thrombosis. A 2010 systematic review and meta-analysis of UFH plus low-dose aspirin compared with low-dose aspirin alone in patients with APS and recurrent pregnancy loss included 5 trials and 334 patients. Patients receiving dual therapy had higher rates of live births (74.3%; relative risk [RR] 1.30 [CI 1.04 to 1.63]) compared to the aspirin-only group (55.8%).⁷⁵ A 2009 randomized controlled trial compared low-dose aspirin to low-dose aspirin plus LMWH in women with recurrent pregnancy loss and either aPL antibodies, antinuclear antibody, or inherited thrombophilia. The study was stopped early after 4 years and found no difference in rates of live births between the groups (77.8% versus 79.1%).⁷⁶ However, a randomized case-control trial of women with aPL antibodies and recurrent miscarriage found a 72% live birth rate in 47 women randomly assigned to low-dose aspirin and LMWH.⁷⁷ A 2012 guideline from the American College of Chest Physicians (ACCP) recommends that women with aPL antibodies with a history of 3 or more pregnancy losses receive low-dose aspirin plus prophylactic-dose LMWH or UFH.⁷⁸ A 2014 systematic review and meta-analysis showed that the combination of low-dose aspirin and UFH resulted in a higher live-birth rate than aspirin alone in 803 women with APS (RR 1.54 [95% CI 1.25 to 1.89]).⁷⁹ Further large randomized controlled trials are needed to confirm optimal management of recurrent miscarriage and aPL antibodies.

The addition of prednisone to aspirin, heparin, or both has shown no benefits in pregnant women with aPL antibodies. Indeed, prolonged use of steroids may cause serious pregnancy complications, such as prematurity and hypertension.^80–83 Intravenous infusions of immunoglobulin (IVIG) have not been shown to be superior to heparin and aspirin. This finding was confirmed in a multicenter clinical trial that tested the effects of IVIG compared with LMWH plus low-dose aspirin for the treatment of women with aPL antibodies and recurrent miscarriage. The rate of live-birth was 72.5% in the group treated with heparin plus low-dose aspirin compared with 39.5% in the IVIG group.⁸⁴

Preeclampsia and HELLP syndrome complicated the case patient’s pregnancy even though she was being treated with prophylactic-dose LMWH and low-dose aspirin, the current standard of care for pregnant women with APS (UFH can be used as well). It is important to note that complications may still occur despite standard treatment. Indeed, PE is more common in the postpartum than in the antepartum period. Prompt diagnosis is paramount to initiate the appropriate treatment; in this case the dose of LMWH was increased from prophylactic to therapeutic dose. However, additional therapeutic modalities are necessary to improve outcomes. A randomized controlled trial comparing standard of care with or without hydroxychloroquine is under way to address this issue.

PROPHYLAXIS

CASE PRESENTATION 4

A 34-year-old woman G1P0 at 6 weeks’ gestation with a past medical history of a proximal lower extremity DVT while on oral contraception is treated with warfarin anticoagulation for 6 months. Her obstetrician consults the hematologist to advise regarding antithrombotic management during this pregnancy.

• What is the approach to prophylaxis in women at high risk for pregnancy-associated VTE?

All women at high risk for pregnancy-associated VTE should be counseled about the signs and symptoms of DVT or PE during preconception and pregnancy and have a plan developed should these symptoms arise. The ACCP guidelines on antithrombotic therapy outline recommendations ranging from clinical vigilance to prophylactic and intermediate-dose anticoagulation, depending on the risk for VTE recurrence, based on the personal and family history of VTE and type of thrombophilia (Table 2).⁷⁸ These recommendations range from grade 2B to 2C.

For women with a history of estrogen-related VTE, single unprovoked VTE, or recurrent unprovoked VTE not on chronic anticoagulation, antepartum and postpartum pharmacologic thromboprophylaxis with either prophylactic or intermediate-dose LMWH is recommended (grade 2C). In patients with prior history of provoked VTE (non-estrogen related), antepartum clinical vigilance and postpartum pharmacologic thromboprophylaxis is recommended (grade 2C, 2B).

In asymptomatic pregnant women who are homozygote carriers for factor V Leiden or prothrombin G20210A variants and have a positive family history of thrombosis, antepartum and postpartum pharmacologic thromboprophylaxis is recommended (grade 2B). In asymptomatic homozygote carriers of factor V Leiden or prothrombin G20210A variants with no family history of thrombosis and women with all other thrombophilias with a positive family history of thrombosis, postpartum pharmacologic thromboprophylaxis is indicated (grade 2B and 2C, respectively). For women with confirmed APS and clinical criteria of obstetric APS with recurrent pregnancy loss, antepartum thromboprophylaxis with LMWH and low-dose aspirin is recommended (grade 1B). For pregnant women with all other thrombophilias with no personal or family history of thrombosis, clinical vigilance is suggested (grade 2 C).⁷⁸

As an alternative to LMWH, vitamin K antagonists (VKA) such as warfarin can be used for postpartum thromboprophylaxis; in patients with protein C or S deficiency, due to the risk of warfarin-induced skin necrosis, a rapid-onset anticoagulant must be concomitantly administered. Warfarin and LMWH are safe anticoagulants during lactation, but there are no clinical data on the effects of the DOACs on infants during lactation. Data from animal studies indicate that DOACs are secreted into breast milk.⁸⁵

• What risks are associated with anticoagulant therapy in pregnancy?

VKAs cross the placenta and can cause teratogenicity, pregnancy loss, fetal bleeding, and neurodevelopmental deficits. Therefore, discontinuation of VKAs prior to the sixth week of gestation is necessary to avoid warfarin embryopathy. DOACs have been shown to readily cross the placenta but with unknown human reproductive risks. Fondaparinux, a synthetic pentasaccharide, crosses the placenta in small quantities. Though there are reports of the successful use of fondaparinux in pregnancy, there is limited reported experience of its use in the first trimester.⁸⁶

The risk for bleeding with anticoagulation is notably acceptable. In a case-control study of 88 pregnant women receiving therapeutic-dose anticoagulation, the risk of postpartum hemorrhage (PPH) after vaginal delivery was 30% in those who received LMWH anticoagulation versus 18% in those who did not (OR 1.9 [95% CI 1.1 to 3.5]).⁸⁷ However, the risk for severe PPH (≥ 500 mL) was similar (5.6% versus 5.0%; OR 1.1 [95% CI 0.4 to 3.6]). The risk for PPH after cesarean section was 12% in LMWH users versus 4% in LMWH non-users (OR 2.9 [95% CI 0.5 to 19.4]). The risk for PPH associated with delivery within 24 hours after the last dose of LMWH was 1.2 times higher (95% CI 0.4 to 3.6) compared to a longer interval. Therefore, therapeutic LMWH increases the risk for blood loss after vaginal delivery, but not the risk for severe PPH. The risk for PPH is influenced by the interval between the last dose of LMWH and delivery. Of note in this study, per the institution’s protocol, the anticoagulation was stopped with signs of labor or determination of need for delivery. The risk for blood loss may be mitigated in more planned delivery scenarios.⁸⁷

CASE 4 CONTINUED

The patient is placed on prophylactic-dose LMWH with good tolerance and delivers at 39 weeks' gestation via caesarian section due to nonprogression of labor. Postpartum she is restarted on prophylactic-dose anticoagulation with LMWH. Two weeks after discharge from the hospital, she presents with right calf pain and mild shortness of breath. On physical exam, her leg circumferences are equal. A D-dimer assay is 3375 ng/mL (normal 0–229). CUS of the right leg shows a complete occlusive DVT of the mid-distal superficial femoral and popliteal veins and partially occlusive acute DVT of the right posterior tibial and peroneal veins. CTPA reveals a right lower lobe PE. Because she had developed VTE despite prophylactic LMWH, her anticoagulation is changed to therapeutic dose. She is treated with anticoagulation with LMWH for a total of 3 months, after which a repeat CUS shows no residual thrombosis.

• What is the recommended dosing of heparin and LMWH during pregnancy?

A prospective study of 14 pregnant women receiving UFH prophylaxis found that a prophylactic dose of 5000 units twice a day was inadequate to achieve prophylactic heparin levels in any patient in the second or third trimester.⁸⁸ Similar to treatment dosage, there is no consensus evidence for prophylactic dosing, and dosage recommendations are based on expert opinion. In a retrospective study of 25 pregnant women on intermediate-dose UFH, the mean UFH dose required to achieve a target anti-factor Xa level of 0.1 to 0.3 units/mL was 236.9 units/kg/day.⁸⁹ However, the use of anti-factor Xa levels for monitoring is controversial as there is no data to support a difference in outcomes with its use in prophylactic or therapeutic dosing.

The timing of the previous VTE history is important when deciding on the anticoagulant dose in pregnancy. In pregnant women with a VTE that occurred within the previous 4 to 6 weeks, full-dose anticoagulation with LMWH should be considered; an intermediate dose (three-fourths of a therapeutic dose) may be used if the thrombotic episode occurred more than 6 weeks earlier but still within a year. Prophylactic dosing may be sufficient if the episode occurred more than a year earlier.⁹⁰ A clinical trial (High-Low) is under way to explore the optimal dose of LMWH in pregnant women with prior history of VTE who are not on chronic anticoagulation therapy.⁹¹

• How is anticoagulation therapy managed in the peripartum period?

Neuraxial anesthesia during active labor while on anticoagulation increases the risk for central nervous system bleeding. Therefore, if spontaneous labor occurs in women on therapeutic dose anticoagulation, neuraxial anesthesia cannot be used. However, in the event of elective induction of labor or caesarean section, neuroaxial anesthesia may be performed 12 hours after the administration of the last prophylactic dose of LMWH or 24 hours after the last therapeutic dose of LMWH. Intravenous UFH should be stopped for 6 hours before induction of labor with a confirmed normal aPTT before placement of neuraxial anesthesia. There is no contraindication for using neuraxial anesthesia during subcutaneous standard UFH at total doses of 10,000 units daily. The risk of spinal hematoma with larger daily subcutaneous doses is unclear; therefore, a documented normal aPTT must be obtained before placement of neuroaxial anesthesia.

Postpartum, reinitiation of prophylactic-dose LMWH should be delayed for at least 12 hours after the removal of an epidural catheter. Therapeutic-dose LMWH should be administered no earlier than 24 hours after neuraxial anesthesia, providing that proper hemostasis is achieved. In the absence of persistent bleeding, if no regional anesthesia was used, LMWH may be resumed 12 hours after delivery.⁹² Anticoagulation with either LMWH or warfarin is recommended for at least 6 to 12 weeks postpartum.³³

COUNSELING

Patients should be advised to manage controllable risk factors, including avoiding prolonged immobilization, avoiding excessive weight gain in pregnancy, and stopping smoking. Periods of immobilization tend to cause reduced blood flow (stasis), which predisposes to thrombosis. In a systematic review of records of all patients with confirmed PE after arrival at Charles de Gaulle airport in Paris during a 13-year period, women had a higher risk of PE after a long-distance flight than men, with an estimated incidence of 0.61 per million passengers versus 0.20, respectively; the incidence reached 7.24 and 2.35 cases, respectively, in passengers traveling more than 10,000 kilometers.^93,94

The risk of air travel-related thrombosis in pregnant women is estimated to be between 0.03% and 0.1%. Physicians must decide on an individual basis how to prevent travel-related thrombosis in their pregnant patients. In most passengers, prevention can be limited to encouraging exercise, avoidance of long sleeping periods, and not using a window seat. Women at high risk for VTE, such as women with a prior history of VTE who are not on anticoagulation or women with known asymptomatic thrombophilia or other risk factors for thrombosis such as obesity, may benefit from a short period (1–3 days) of LMWH starting 2 hours before a long-distance flight.⁹⁵

Activation of the coagulation system has been demonstrated in cigarette smokers.⁹⁶ Heavy smoking was found to be a significant risk factor for VTE in a cross-sectional analysis of 2404 men and women.⁹⁷ An increased risk for thrombosis during pregnancy is seen in cigarette smokers^15,98 and is enhanced with the concomitant use of illicit drugs.⁹⁹ Other obstetric complications associated with smoking and illicit drug use during pregnancy include preterm labor, spontaneous abortion, perinatal death, low birth weight, and abruption placenta. The efficacy of nicotine replacement therapy in pregnancy is uncertain.¹⁰⁰ Recommendations are to advise patients to stop smoking, obtain psychosocial counseling, and utilize adjunctive therapies, which have been shown to have some effect on abstinence rates.¹⁰¹

CONCLUSION

Women are at increased risk for VTE during pregnancy and the postpartum period. Awareness of risk factors and the signs and symptoms of VTE is paramount. Prompt diagnosis and treatment is mandatory to decrease complications of VTE. LMWH is the mainstay treatment of VTE in pregnancy, as it does not cross the placenta. Both LMWH and warfarin are safe during lactation. Close communication among the patient, obstetrician, hematologist, anesthesiologist, and neonatologist is crucial to optimize the care of these patients.

INTRODUCTION

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading nonobstetric cause of maternal death in the United States and in developed countries.^1,2 During pregnancy, the risk for VTE increases four- to six-fold, and although the risk is present throughout pregnancy, the mother is at highest risk immediately postpartum.^3–5

VTE risk is increased due to physiologic and anatomic changes that occur in pregnancy. These changes include hypercoagulability, progesterone-induced venous stasis, decreased venous outflow, compression of the inferior vena cava and pelvic veins by the expanding uterus, and decreased mobility. The hypercoagulability of pregnancy is due to increased levels of coagulation factors I (fibrinogen), VII, VIII, and X, and von Willebrand factor; decreased free protein S, a natural anticoagulant; acquired resistance to activated protein C; and decreased fibrinolysis due to increased levels of plasminogen activator inhibitor-1 and -2.^6,7 These changes confer increased hemostasis to the mother for delivery but also place her at higher risk for thrombosis.

A review of the literature found that more than 70% of pregnancy-associated DVTs are located in the ileofemoral region, as compared with approximately 9% in non-pregnant patients.⁸ The proximal location is associated with a higher risk for post-thrombotic syndrome and embolization as compared with calf DVTs.⁹ Proximal postnatal thrombosis, smoking, and older age are independent predictors of the development of post-thrombotic syndrome.¹⁰

RISK FACTORS

Clinical risk factors that increase the risk for VTE during pregnancy include a prior history of estrogen-related or unprovoked VTE, being a carrier of severe inherited thrombophilia (homozygotes for factor V Leiden or factor II G20210A variants, double heterozygotes, or persons with antithrombin, protein C, or protein S deficiencies), and the presence of antiphospholipid (aPL) antibodies.¹¹ Women with systemic lupus erythematosus, diabetes, sickle cell disease, and heart disease also have a high risk for VTE during pregnancy.¹² Other risk factors predisposing to thrombosis include black ethnicity, smoking, operative procedures, conception after assisted reproductive techniques, high body mass index, antepartum immobilization, severe preeclampsia, advanced age and parity, and a family history of VTE.¹³ A prospective cohort study of 1,297,037 pregnancies and related puerperium identified the following risk factors for thrombosis: hospitalization, infection, hyperemesis, multiple pregnancies, preeclampsia, obesity, cesarean section, major postpartum hemorrhage, intrauterine growth restriction, and fetal death.¹⁴ Risk factors identified in an Agency for Healthcare Research and Quality study include: age 35 or older, black ethnicity, lupus, sickle cell disease, heart disease, postpartum infection, and transfusion.¹⁵ The combination of more than one risk factor increases the risk for VTE. All these factors have to be considered when deciding on prophylactic or therapeutic anticoagulation therapy in pregnancy. In addition, the risks of anticoagulation, including bruising, bleeding, and other side effects (eg, reduced bone mineral density with therapeutic-dose unfractionated heparin), allergic reactions, and rarely thrombocytopenia, must be considered.

EVALUATION AND DIAGNOSIS

CASE PRESENTATION I

A 31-year-old woman G1P0 at 10 weeks’ gestation with no personal or family history of thrombosis presents with acute onset of shortness of breath and left-sided chest pain that awoke her the morning of presentation. Her vital signs are significant for a heart rate of 106 beats/min, respiration rate of 22 breaths/min, blood pressure of 105/76 mm Hg, and pulse oximetry of 98% on room air. The patient denies previous exposure to oral contraceptives. She does not smoke. She reports that she had noticed left calf pain and swelling, which worsened with walking after a 4-hour drive 2 days prior.

• What is the approach to diagnosis of thromboembolism in pregnant patients?

DEEP VEIN THROMBOSIS

Although a clinical diagnosis of DVT in pregnancy is unreliable, a history and physical examination are necessary to exclude other diagnoses and to assess the likelihood of thrombosis. Unfortunately, studies of the accuracy of history and physical examination for detecting DVT and PE have not included pregnant patients. In most pregnant patients with clinically suspected DVT, the diagnosis is not confirmed. Other causes of leg pain and swelling are not uncommon during pregnancy and include cellulitis, ruptured Baker’s cyst, or muscular pain.

A cross-sectional study described the derivation of the LEFt clinical decision rule, which relies on 3 variables in pregnant women with suspected DVT: left leg presentation (L), ≥ 2 cm calf circumference difference (E for edema), and first trimester presentation (Ft). If none of these variables is present, the negative predictive value is 100%.¹⁶ A validation study suggested that a negative LEFt rule accurately identifies pregnant women in whom the risk for confirmed DVT appears to be very low. The rule should not be used as an individual test for excluding DVT during pregnancy, but could be applied in a diagnostic approach in association with D-dimer measurement and compression ultrasonography (CUS); however, it has not been prospectively validated for safety and efficacy.¹⁷ In a study of 149 consecutive pregnant women with suspected DVT, a whole-blood agglutination D-dimer had a sensitivity of 100% and specificity of 60%.¹⁸ A 2006 systematic review found only 4 diagnostic studies of VTE in pregnancy in the literature. One of these studies showed that a combination of a negative CUS and normal D-dimer can accurately exclude DVT.¹⁹

Serial CUS is necessary for pregnant women with a high clinical suspicion of DVT but a negative initial investigation. In a study of 221 pregnant women in whom DVT was clinically suspected, 16 women (7.2%) were diagnosed with DVT by initial CUS, and none were diagnosed with DVT onserial testing.²⁰ During follow-up (≥ 3 months), 6 of the 205 women with normal serial CUS results presented with symptoms of DVT, PE, or both, and 1 of them was diagnosed with DVT and PE. The sensitivity of serial CUS with Doppler imaging was 94.1% (95% confidence interval [CI] 69.2% to 99.7%), and the negative predictive value was 99.5% (95% CI 96.9% to 100%).²⁰ All ultrasounds undertaken for investigation of pregnancy-associated DVT should include imaging of the iliac veins if there is a high index of suspicion and the CUS is negative for femoral DVT. Serial CUS with Doppler imaging of the iliac vein performed over a 7-day period excludes DVT in symptomatic pregnant women.²⁰ Repeat CUS may be done 2 to 4 days and 6 to 8 days after the initial scan.

Ileofemoral vein thrombosis accounts for approximately 90% of proximal thromboses in pregnancy, occurring most often in the left lower extremity.²⁰ The incidence of isolated iliac vein thrombosis in pregnancy is low, but when it does occur, delay in diagnosis can lead to significant morbidity. Therefore, for women with suspected isolated iliac vein thrombosis in whom CUS is negative or nondiagnostic, magnetic resonance direct thrombus imaging (MRDTI) should be performed.²¹ Patients with iliac vein thrombosis may present with unexplained inguinal, pelvic, or abdominal pain, which may be accompanied by back pain, and they usually present with swelling of the entire leg. MRDTI does not require gadolinium contrast and its accuracy appears to be similar to that of venography for iliac vein thrombi in the nonpregnant population.²¹ Exposure to gadolinium during pregnancy is associated with an increased risk for rheumatologic, inflammatory, or infiltrative skin conditions and stillbirth or neonatal death.²²

Ovarian vein thrombosis is a rare but serious diagnosis. It occurs mostly in the postpartum period, mainly after cesarean delivery, and usually affects the right ovarian vein. The diagnosis is confirmed by ultrasound, computed tomography (CT), or magnetic resonance imaging.²³

PULMONARY EMBOLISM