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Feds award $2.4 million to fund pregnancy exposure hotline, counseling
The MotherToBaby network, which provides free education and counseling about drug exposure during pregnancy, is getting a funding infusion, thanks to a $2.4-million federal grant.
The money is part of a 2-year cooperative agreement between the Health Resources and Services Administration’s Maternal and Child Health Bureau and the Organization of Teratology Information Specialists, which operates the MotherToBaby network.
The new money will allow the nonprofit group to expand access to a number of its services, including its toll-free hotline, website, and in-person counseling program.
The MotherToBaby network includes 14 sites at universities and hospitals around the United States where women can receive free, evidence-based, personalized risk assessments related to their exposure to a number of prescription and over-the-counter drugs during pregnancy and breastfeeding. The toll-free hotline (1-866-626-6847) connects women and health care providers to teratogen information specialists, while the website includes fact sheets on medications and other exposures.
“Before this funding opportunity, we were in danger of closing some of the services providing critical exposure counseling to health care providers and the general public,” Dr. Kenneth Lyons Jones, a past president of MotherToBaby, said in an interview. “Not only does the funding from HRSA make it possible for our 14 services to continue providing free and in-depth personalized risk assessments, but also to conduct even more outreach efforts across all 50 states.”
The group plans to use the funding specifically to reach out to women in Spanish-speaking communities. They estimate that more than 100,000 women and their health care providers seek information about birth-defect prevention from MotherToBaby each year. With the new federal support, they are hoping to increase that number two-fold over the next 2 years, Dr. Jones said.
On Twitter @maryellenny
The MotherToBaby network, which provides free education and counseling about drug exposure during pregnancy, is getting a funding infusion, thanks to a $2.4-million federal grant.
The money is part of a 2-year cooperative agreement between the Health Resources and Services Administration’s Maternal and Child Health Bureau and the Organization of Teratology Information Specialists, which operates the MotherToBaby network.
The new money will allow the nonprofit group to expand access to a number of its services, including its toll-free hotline, website, and in-person counseling program.
The MotherToBaby network includes 14 sites at universities and hospitals around the United States where women can receive free, evidence-based, personalized risk assessments related to their exposure to a number of prescription and over-the-counter drugs during pregnancy and breastfeeding. The toll-free hotline (1-866-626-6847) connects women and health care providers to teratogen information specialists, while the website includes fact sheets on medications and other exposures.
“Before this funding opportunity, we were in danger of closing some of the services providing critical exposure counseling to health care providers and the general public,” Dr. Kenneth Lyons Jones, a past president of MotherToBaby, said in an interview. “Not only does the funding from HRSA make it possible for our 14 services to continue providing free and in-depth personalized risk assessments, but also to conduct even more outreach efforts across all 50 states.”
The group plans to use the funding specifically to reach out to women in Spanish-speaking communities. They estimate that more than 100,000 women and their health care providers seek information about birth-defect prevention from MotherToBaby each year. With the new federal support, they are hoping to increase that number two-fold over the next 2 years, Dr. Jones said.
On Twitter @maryellenny
The MotherToBaby network, which provides free education and counseling about drug exposure during pregnancy, is getting a funding infusion, thanks to a $2.4-million federal grant.
The money is part of a 2-year cooperative agreement between the Health Resources and Services Administration’s Maternal and Child Health Bureau and the Organization of Teratology Information Specialists, which operates the MotherToBaby network.
The new money will allow the nonprofit group to expand access to a number of its services, including its toll-free hotline, website, and in-person counseling program.
The MotherToBaby network includes 14 sites at universities and hospitals around the United States where women can receive free, evidence-based, personalized risk assessments related to their exposure to a number of prescription and over-the-counter drugs during pregnancy and breastfeeding. The toll-free hotline (1-866-626-6847) connects women and health care providers to teratogen information specialists, while the website includes fact sheets on medications and other exposures.
“Before this funding opportunity, we were in danger of closing some of the services providing critical exposure counseling to health care providers and the general public,” Dr. Kenneth Lyons Jones, a past president of MotherToBaby, said in an interview. “Not only does the funding from HRSA make it possible for our 14 services to continue providing free and in-depth personalized risk assessments, but also to conduct even more outreach efforts across all 50 states.”
The group plans to use the funding specifically to reach out to women in Spanish-speaking communities. They estimate that more than 100,000 women and their health care providers seek information about birth-defect prevention from MotherToBaby each year. With the new federal support, they are hoping to increase that number two-fold over the next 2 years, Dr. Jones said.
On Twitter @maryellenny
Pregnancy outcomes similar in kidney transplant patients, despite age
Pregnancy outcomes were similar for women who underwent kidney transplants in childhood and those who received transplants as adults, according to findings published Feb. 2 in JAMA Pediatrics.
Live births occurred in 76% of pregnancies in women who received kidney transplants as children, compared with 77% of pregnancies among women who received transplants as adults, wrote Melanie L. Wyld and her colleagues from Sydney Medical School in Australia.
The study examined a total of 101 pregnancies in 66 women who received transplants before age 18 years, and 626 pregnancies in 401 women who were adults at the time of transplant.
Mean gestational age and prematurity incidence were also similar in the two groups, with child-transplant recipients having a mean gestational age of 35 weeks, and adult-transplant recipients having a mean gestational age of 36 weeks.
Incidence of prematurity was 45% in child-transplant mothers and 53% in adult-transplant mothers, the researchers reported.
“To our knowledge, this study is the first to look at pregnancy outcomes for women who received a kidney transplant as a child,” the researchers wrote. These results should “provide comfort to such mothers and their physicians that their early onset of kidney failure and longer period of posttransplant exposure to immunosuppression do not adversely affect their pregnancy outcomes,” they added.
Read the full article at: JAMA Pediatr. 2015;169(2):e143626. (doi:10.1001/jamapediatrics.2014.3626).
Pregnancy outcomes were similar for women who underwent kidney transplants in childhood and those who received transplants as adults, according to findings published Feb. 2 in JAMA Pediatrics.
Live births occurred in 76% of pregnancies in women who received kidney transplants as children, compared with 77% of pregnancies among women who received transplants as adults, wrote Melanie L. Wyld and her colleagues from Sydney Medical School in Australia.
The study examined a total of 101 pregnancies in 66 women who received transplants before age 18 years, and 626 pregnancies in 401 women who were adults at the time of transplant.
Mean gestational age and prematurity incidence were also similar in the two groups, with child-transplant recipients having a mean gestational age of 35 weeks, and adult-transplant recipients having a mean gestational age of 36 weeks.
Incidence of prematurity was 45% in child-transplant mothers and 53% in adult-transplant mothers, the researchers reported.
“To our knowledge, this study is the first to look at pregnancy outcomes for women who received a kidney transplant as a child,” the researchers wrote. These results should “provide comfort to such mothers and their physicians that their early onset of kidney failure and longer period of posttransplant exposure to immunosuppression do not adversely affect their pregnancy outcomes,” they added.
Read the full article at: JAMA Pediatr. 2015;169(2):e143626. (doi:10.1001/jamapediatrics.2014.3626).
Pregnancy outcomes were similar for women who underwent kidney transplants in childhood and those who received transplants as adults, according to findings published Feb. 2 in JAMA Pediatrics.
Live births occurred in 76% of pregnancies in women who received kidney transplants as children, compared with 77% of pregnancies among women who received transplants as adults, wrote Melanie L. Wyld and her colleagues from Sydney Medical School in Australia.
The study examined a total of 101 pregnancies in 66 women who received transplants before age 18 years, and 626 pregnancies in 401 women who were adults at the time of transplant.
Mean gestational age and prematurity incidence were also similar in the two groups, with child-transplant recipients having a mean gestational age of 35 weeks, and adult-transplant recipients having a mean gestational age of 36 weeks.
Incidence of prematurity was 45% in child-transplant mothers and 53% in adult-transplant mothers, the researchers reported.
“To our knowledge, this study is the first to look at pregnancy outcomes for women who received a kidney transplant as a child,” the researchers wrote. These results should “provide comfort to such mothers and their physicians that their early onset of kidney failure and longer period of posttransplant exposure to immunosuppression do not adversely affect their pregnancy outcomes,” they added.
Read the full article at: JAMA Pediatr. 2015;169(2):e143626. (doi:10.1001/jamapediatrics.2014.3626).
First EDition: News for and about the practice of Emergency Medicine
Magnesium given at stroke onset didn’t improve functional outcomes
BY MICHELE G. SULLIVAN
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial.
The drug did not shift functional outcomes at 3 months in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.
Vitals Key clinical point: Magnesium infusion soon after stroke onset did not improve functional outcomes at 3 months. Major finding: At 3 months, a little more than half of the magnesium and placebo groups had a modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower. Data source: The randomized, placebo-controlled FAST-MAG trial of 1,700 patients with suspected stroke. Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study. |
At 3 months, a little more than half of each group had a modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).
The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions while en route to a hospital in an emergency vehicle.
In animal models of stroke, magnesium sulfate has been shown to exert vasodilatory and direct neuroprotective and glioprotective effects, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors.
Slow transport of magnesium across the blood-brain barrier may explain why FAST-MAG didn’t replicate these earlier findings. Magnesium levels in the cerebrospinal fluid peak 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Despite a rapid increase in serum levels, brain tissue levels may not have risen quickly enough to yield a benefit, the researchers speculated.
Glucose level may predict mortality in acute heart failure
BY MARY ANN MOON
FROM THE EUROPEAN HEART JOURNAL
Blood glucose level may predict 30-day mortality in adults who present with acute heart failure, regardless of whether the patients have preexisting diabetes, based on a study by Dr. Maneesh Sud of the University of Toronto and his associates.
Hyperglycemia occurs in up to 40% of acute heart failure patients. If prognostic, blood glucose levels at ED presentation “may serve as a screen to identify high-risk patients who warrant formal testing for diabetes, allowing for prompt referral to prevent further morbidity and mortality,” the researchers said.
Vitals Key clinical point: A high glucose level at presentation for acute heart failure may identify patients at increased risk for death within 30 days. Major finding: Regardless of a preexisting diagnosis of diabetes, risk of death at 30 days was about 1.5 times higher in acute heart failure patients who had blood glucose levels exceeding 11.1 mmol/L at presentation in the emergency department. Data source: A secondary analysis of data from two population-based cohorts comprising 16,524 patients. Disclosures: This study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Ontario. Dr. Sud and his associates reported having no relevant financial disclosures. |
The researchers analyzed data from two large population-based cohorts of patients hospitalized for acute HF during a 3-year period. Of the 16,524 patients, 44% had preexisting diabetes (Eur. Heart J. 2015 [doi:10.1093/eurheartj/ehu462].
Among patients with established diabetes, a blood glucose level exceeding 11.1 mmol/L was associated with significantly increased all-cause 30-day mortality with a hazard ratio (HR) of 1.48. Among patients without established diabetes, a blood glucose level exceeding 6.1 mmol/L increased all-cause 30-day mortality with an HR of 1.26; that risk rose in a dose-dependent fashion with increasing glucose levels and reached 1.5 at the level of 11.1 mmol/L.
In severe trauma, 1:1:1 transfusion protocol linked to less exsanguination
BY MARY ANN MOON
FROM JAMA
Among profoundly injured trauma patients with major bleeding, early (24 hour) and late (30 day) mortality were similar between those who received transfusions of plasma, platelets, and red blood cells in a 1:1:1 ratio and those who received transfusions in a 1:1:2 ratio in a phase III clinical trial of 680 adults.
Transfusion protocols for such patients have been “predominantly guided by tradition rather than evidence from large, multicenter randomized trials,” said Dr. John B. Holcomb of the Center for Translational Injury Research, University of Texas Health Science Center, Houston, and his associates in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial. In the last decade, many clinicians changed over to the 1:1:1 ratio because it is more balanced and more closely replicates the ratio present in whole blood than does the traditional 1:1:2 ratio.
Vitals Key clinical point: In severe trauma patients with major bleeding, increasing the ratio of red blood cells did not improve early and late mortality. Major finding: At 24 hours, mortality was 12.7% in the group given a 1:1:1 ratio of plasma to platelets to red blood cells and 17% in the 1:1:2 group; at 30 days, mortality 22.4% in the 1:1:1 group and 26.1% 1:1:2 group. Data source: A phase III multicenter partially blinded, randomized trial comparing two strategies for hemorrhage control in 680 profoundly injured adults treated during a 16-month period. Disclosures: This study was supported by the U.S. National Heart, Lung, and Blood Institute, the U.S. Department of Defense, Defense Research and Development Canada, and the Canadian Institutes of Health Research-Institute of Circulatory and Respiratory Health. Dr. Holcomb reported having no financial disclosures; two associates reported ties to TEM International, CSL Behring, and Decision Health. |
The researchers described the study as the first multicenter randomized trial to use approved blood products to compare the two transfusion ratios with mortality as the primary end point. The 680 adults enrolled in the study were treated for severe injury with major bleeding during a 16-month period at 12 Level 1 trauma centers in North America.
Overall 24-hour mortality was not significantly different, at 12.7% in the 1:1:1 group and 17% in the 1:1:2 group, and 30-day mortality also was not significantly different at 22.4% and 26.1%, respectively. However, exsanguination, the predominant cause of death within 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs. 14.6%), and significantly more patients in the 1:1:1 group achieved anatomic homeostasis (86.1% vs. 78.1%). Thus, clinicians “should consider using a 1:1:1 transfusion protocol,” Dr. Holcomb and his associates said (JAMA 2015 Feb. 3 [doi:10.10001/jama.2015.12]).
There also were no significant differences between the two study groups in 23 complications, including transfusion-related complications. “Despite significant concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications, such as acute respiratory distress syndrome, multiple organ failure, infection, venous thromboembolism, and sepsis, no differences were detected between the two treatment groups,” the researchers noted.
Stress tests in ED lead to unneeded cardiac interventions
BY NICOLA GARRETT
FROM JAMA INTERNAL MEDICINE
Noninvasive testing in the emergency department of patients who have chest pain and have not had a myocardial infarction can result in overdiagnosis and unnecessary interventions, based on the results of a retrospective analysis.
After 6 months of follow-up, 0.33% of 421,774 privately insured patients who presented to the emergency department (ED) with chest pain were hospitalized with an MI. There was no difference in the rate of MIs in patients who did and did not undergo exercise and stress electrocardiography, myocardial perfusion scintigraphy (MPS), or coronary CT angiography, Dr. Andrew. J. Foy of Penn State Milton S. Hershey Medical Center in Hershey, Pa., and his colleagues reported in an article published online in JAMA Internal Medicine (2015 Jan. 26 [doi:10.1001/jamainternmed.2014.7657]).
Vitals Key clinical point: Guidelines for treatment of chest pain in low-risk patients in the emergency department may need revision, as noninvasive testing of these patients may be leading to unneeded interventions. Major finding: An unnecessary catheterization is performed in 1 of every 27 patients who undergo myocardial perfusion scintigraphy instead of an initial strategy of no testing. Data source: A retrospective analysis of health insurance claims data. Disclosures: The researchers reported having no conflicts of interest. |
However, interventions were increased without a concomitant reduction in MI in patients who underwent tests in the ED. “Overdiagnosis is a legitimate concern in this patient population,” the study authors wrote.
Using data from the analysis, the researchers estimated that an unnecessary catheterization is performed in 1 of every 27 patients who undergo MPS instead of an initial strategy of no testing.
“When viewed in the broader context of the approximately 6 million ED visits for a chief symptom of chest pain, for every 100,000 patients who undergo MPS instead of an initial strategy of no testing, approximately 3,700 patients will undergo an unnecessary catheterization,” they wrote.
New treatment options outlined for acute-onset, severe hypertension in pregnancy
BY NICOLA GARRETT
FROM OBSTETRICS AND GYNECOLOGY
The American College of Obstetricians and Gynecologists has added nifedipine as a first-line treatment for acute-onset severe hypertension during pregnancy and the postpartum period in an updated opinion from its Committee on Obstetric Practice.
The update, released on Jan. 22, points to studies showing that women who received oral nifedipine had their blood pressure lowered more quickly than with either intravenous labetalol or hydralazine – the traditional first-line treatments – and had a significant increase in urine output. Concerns about neuromuscular blockade and severe hypotension with the use of nifedipine and magnesium sulphate were not borne out in a large review, the committee members wrote, but they advised careful monitoring since both drugs are calcium antagonists.
The committee opinion includes model order sets for the use of labetalol, hydralazine, and nifedipine for the initial management of acute onset severe hypertension in women who are pregnant or post partum with preeclampsia or eclampsia (Obstet. Gynecol. 2015;125:521-5).
While all three medications are appropriate in treating hypertensive emergencies during pregnancy, each drug has adverse effects.
For instance, parenteral hydralazine can increase the risk of maternal hypotension. Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease, or heart failure. Nifedipine has been associated with increased maternal heart rate and overshoot hypotension.
“Patients may respond to one drug and not another,” the committee noted.
The ACOG committee also called for standardized clinical guidelines for the management of patients with preeclampsia and eclampsia.
“With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications,” they wrote. “Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency.”
The committee recommended checklists as one tool to help standardize the use of guidelines.
“Drip-and-ship” thrombolysis remains common for ischemic stroke
BY MICHELE G. SULLIVAN
AT THE INTERNATIONAL STROKE CONFERENCE
NASHVILLE, TENN. – About 25% of patients with ischemic stroke who receive thrombolytic therapy get it in the field before hospital transfer with the “drip-and-ship” paradigm. While there were only modest differences in clinical outcomes between these patients and those treated when admitted to an emergency department, drip-and-ship may actually increase the overall use of tissue plasminogen activator (TPA), Dr. Kevin N. Sheth said at the International Stroke Conference, sponsored by the American Heart Association.
The retrospective analysis, which was simultaneously published in Stroke (2015 Feb. 11 [doi:10.1161/STROKEAHA.114.007506]), plumbed the Get With the Guidelines registry for data to describe trends in the use of TPA and drip-and-ship administration across the United States over time. The study involved 1,440 hospitals and 44,667 patients who had an ischemic stroke during 2003-2010 and received TPA. Of these, 10,475 (23.5%) received it in the field before optional admission and within 3 hours of symptom onset.
Vitals Key clinical point: The rate of thrombolysis for ischemic stroke via drip-and-ship has remained steady over the past 12 years. Major finding: About a quarter of ischemic stroke patients eligible for TPA are getting it in the field, via the “drip-and-ship” paradigm. Data source: A retrospective study comprising 44,667 patients with ischemic stroke. Disclosures: Dr. Sheth is a member of the Get with the Guidelines (GWTG) Stroke Clinical Workgroup, and he is a coinvestigator and executive committee member for Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals (GAMES-RP), a phase II trial to prevent swelling in patients with large stroke, funded by Remedy Pharmaceuticals. |
Baseline characteristics were similar between the treatment groups. The patients’ mean age was 70 years, and the sex distribution was evenly split. More than 75% of each group was white.
The National Institutes of Health Stroke Scale (NIHSS) score was significantly higher among those who presented for hospital treatment (12.9 vs. 11). However, these patients were seen before TPA administration, while the drip-and-ship group had already been treated, a temporal difference that could have accounted for the score finding, cautioned Dr. Sheth, director of the neuroscience ICU and chief of clinical research at Yale University, New Haven, Conn.
In hospitals that employed drip-and-ship, there were significantly higher rates of stroke patients treated each year as well as more beds. Those hospitals also were more often teaching facilities and were designated as a primary stroke center.
Drip-and-ship frequency remained fairly steady over the study period – about 25% of all eligible patients had it in both 2003 and 2010. Among those treated at the hospital, the frequency of TPA administration within 3 hours of stroke onset rose sharply over the study period, from about 11% in 2003 to 25% in 2010. In contrast, the percentage of timely thrombolysis in drip-and-ship patients moved very little, from about 5% to 9% over the same period.
Overall inpatient mortality was 10%, but was slightly higher among drip-and-ship patients (10.93% vs. 9.67). Symptomatic intracranial hemorrhage occurred in 5.79% of those treated via drip-and-ship and 5.22% of those treated in the hospital. Nearly the same percentage of patients were discharged walking independently (38.4% vs. 38.8%) and discharged home (40.3% vs. 40.6%).
Among the hospital-treated patients, fewer than 4% (1,200) underwent endovascular therapy; this occurred in 707 (7%) of drip-and-ship patients. Those who got endovascular treatment had higher median NIHSS scores at TPA administration than did those who did not (17 vs. 12, respectively). Endovascular treatment was significantly associated with higher mortality (20% vs. 10%) and intracranial hemorrhage (11% vs. 5%).
In a multivariate analysis that adjusted for NIHSS score, in-hospital mortality was significantly more likely in drip-and-ship patients (odds ratio, 1.23). Those patients also were significantly less likely to be independently walking at discharge (OR, 0.66) or discharge to home (OR, 0.66). Intracranial hemorrhage was significantly more likely in drip-and-ship patients (OR, 1.4), as was a hospital stay of longer than 4 days (OR, 1.20).
“These are very modest differences clinically,” Dr. Sheth said, adding that selection bias or unmeasured confounding could have influenced the findings.
Three trials cement embolectomy for acute ischemic stroke
BY MITCHEL L. ZOLER
NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.
The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.
Vitals Key clinical point: Results from three randomized, controlled trials confirmed the safety and dramatic efficacy of endovascular embolectomy for selected patients with acute, ischemic stroke. Major finding: In SWIFT PRIME, a 90-day modified Rankin Scale score of 0-2 occurred in 60% of patients treated with thrombolysis plus embolectomy and 36% of patients treated with thrombolysis only. Data source: SWIFT PRIME, a prospective, multicenter randomized trial that enrolled 195 patients at 39 centers in the United States and Europe. Disclosures: SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures. |
All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.
With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.
“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.
“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.
In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).
But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.
The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.
“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.
“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.
The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.
“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.
The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).
The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).
SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.
On Twitter @mitchelzoler
Views on the News
Results warrant embolectomy scale-up
Many U.S. centers have interventionalists who already perform endovascular treatments within intracerebral arteries, but the issue is can they do this form of embolectomy in the high-quality, highly-reliable, rapid way that it was done in these trials? Stent-retriever catheters are relatively straightforward to use by operators who are experienced doing vascular procedures in the brain, but they don’t deliver this treatment by themselves. You need a team that is focused on doing it quickly, and that will be the kind of training we’ll need to roll out this treatment broadly. We achieved it for stroke thrombolytic treatment through the Target Stroke program (JAMA 2014;311:1632-40), so we know that we can achieve this sort of goal. Delivering embolectomy requires more people and more technology than thrombolysis, but it is not rocket science; it just needs a system.
Embolectomy will not replace routine thrombolysis treatment; it will piggyback on top of it. The percentage of patients with a proximal occlusion in a large artery is relatively small. The results we have seen suggest that using embolectomy plus thrombolysis has no adverse-effect downside, compared with thrombolysis alone. Once routine use of embolectomy becomes established, we can directly compare catheter treatment only against combined embolectomy and thrombolysis. My impression today is that what we’d compare is transporting stroke patients directly to a center that can perform embolectomy against taking patients to the closest center that can treat them with thrombolysis and then transporting them to the center that performs embolectomy.
The results of these three new studies plus the previously-reported results from MR CLEAN are not exactly a game changer, because many centers were already performing embolectomy but in a limited way. Now we have the data to give us confidence to do it routinely and to know which patients to select for embolectomy. Because many centers are already doing this, it will not take 5 years to diffuse the technology. Embolectomy is already a treatment cited in the guidelines, but now it will be a level 1A recommendation.
The significance of the new reports is that they will have a dramatic impact on public health systems and in the triage of patients with stroke. It will affect how patients get triaged, and will allow us to identify which patients should go to which centers. I believe we will soon develop clinical examination tools that will allow prehospital providers to discern patients with mild strokes who can go to the nearest center that can administer thrombolysis and which patients need to go to comprehensive centers that can perform embolectomy. We now need to do what we did for thrombolysis, and help centers develop the expertise to do embolectomy as a team and to shave minutes off the delivery at every step of the process. It’s clear that it is the time from stroke onset to getting the artery open that is the key to improved patient outcomes.
If I have my way, we will launch later this year a big effort to focus on improving embolectomy delivery. Now that we know for certain that it works we need to turn the crank and make sure that as many patients as possible who qualify get this treatment.
Dr. Lee H. Schwamm is professor of neurology at Harvard Medical School, and director of acute stroke services at Massachusetts General Hospital, both in Boston. He is a consultant to Penumbra and has received research support from Genentech. He made these comments in an interview.
Magnesium given at stroke onset didn’t improve functional outcomes
BY MICHELE G. SULLIVAN
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial.
The drug did not shift functional outcomes at 3 months in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.
Vitals Key clinical point: Magnesium infusion soon after stroke onset did not improve functional outcomes at 3 months. Major finding: At 3 months, a little more than half of the magnesium and placebo groups had a modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower. Data source: The randomized, placebo-controlled FAST-MAG trial of 1,700 patients with suspected stroke. Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study. |
At 3 months, a little more than half of each group had a modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).
The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions while en route to a hospital in an emergency vehicle.
In animal models of stroke, magnesium sulfate has been shown to exert vasodilatory and direct neuroprotective and glioprotective effects, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors.
Slow transport of magnesium across the blood-brain barrier may explain why FAST-MAG didn’t replicate these earlier findings. Magnesium levels in the cerebrospinal fluid peak 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Despite a rapid increase in serum levels, brain tissue levels may not have risen quickly enough to yield a benefit, the researchers speculated.
Glucose level may predict mortality in acute heart failure
BY MARY ANN MOON
FROM THE EUROPEAN HEART JOURNAL
Blood glucose level may predict 30-day mortality in adults who present with acute heart failure, regardless of whether the patients have preexisting diabetes, based on a study by Dr. Maneesh Sud of the University of Toronto and his associates.
Hyperglycemia occurs in up to 40% of acute heart failure patients. If prognostic, blood glucose levels at ED presentation “may serve as a screen to identify high-risk patients who warrant formal testing for diabetes, allowing for prompt referral to prevent further morbidity and mortality,” the researchers said.
Vitals Key clinical point: A high glucose level at presentation for acute heart failure may identify patients at increased risk for death within 30 days. Major finding: Regardless of a preexisting diagnosis of diabetes, risk of death at 30 days was about 1.5 times higher in acute heart failure patients who had blood glucose levels exceeding 11.1 mmol/L at presentation in the emergency department. Data source: A secondary analysis of data from two population-based cohorts comprising 16,524 patients. Disclosures: This study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Ontario. Dr. Sud and his associates reported having no relevant financial disclosures. |
The researchers analyzed data from two large population-based cohorts of patients hospitalized for acute HF during a 3-year period. Of the 16,524 patients, 44% had preexisting diabetes (Eur. Heart J. 2015 [doi:10.1093/eurheartj/ehu462].
Among patients with established diabetes, a blood glucose level exceeding 11.1 mmol/L was associated with significantly increased all-cause 30-day mortality with a hazard ratio (HR) of 1.48. Among patients without established diabetes, a blood glucose level exceeding 6.1 mmol/L increased all-cause 30-day mortality with an HR of 1.26; that risk rose in a dose-dependent fashion with increasing glucose levels and reached 1.5 at the level of 11.1 mmol/L.
In severe trauma, 1:1:1 transfusion protocol linked to less exsanguination
BY MARY ANN MOON
FROM JAMA
Among profoundly injured trauma patients with major bleeding, early (24 hour) and late (30 day) mortality were similar between those who received transfusions of plasma, platelets, and red blood cells in a 1:1:1 ratio and those who received transfusions in a 1:1:2 ratio in a phase III clinical trial of 680 adults.
Transfusion protocols for such patients have been “predominantly guided by tradition rather than evidence from large, multicenter randomized trials,” said Dr. John B. Holcomb of the Center for Translational Injury Research, University of Texas Health Science Center, Houston, and his associates in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial. In the last decade, many clinicians changed over to the 1:1:1 ratio because it is more balanced and more closely replicates the ratio present in whole blood than does the traditional 1:1:2 ratio.
Vitals Key clinical point: In severe trauma patients with major bleeding, increasing the ratio of red blood cells did not improve early and late mortality. Major finding: At 24 hours, mortality was 12.7% in the group given a 1:1:1 ratio of plasma to platelets to red blood cells and 17% in the 1:1:2 group; at 30 days, mortality 22.4% in the 1:1:1 group and 26.1% 1:1:2 group. Data source: A phase III multicenter partially blinded, randomized trial comparing two strategies for hemorrhage control in 680 profoundly injured adults treated during a 16-month period. Disclosures: This study was supported by the U.S. National Heart, Lung, and Blood Institute, the U.S. Department of Defense, Defense Research and Development Canada, and the Canadian Institutes of Health Research-Institute of Circulatory and Respiratory Health. Dr. Holcomb reported having no financial disclosures; two associates reported ties to TEM International, CSL Behring, and Decision Health. |
The researchers described the study as the first multicenter randomized trial to use approved blood products to compare the two transfusion ratios with mortality as the primary end point. The 680 adults enrolled in the study were treated for severe injury with major bleeding during a 16-month period at 12 Level 1 trauma centers in North America.
Overall 24-hour mortality was not significantly different, at 12.7% in the 1:1:1 group and 17% in the 1:1:2 group, and 30-day mortality also was not significantly different at 22.4% and 26.1%, respectively. However, exsanguination, the predominant cause of death within 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs. 14.6%), and significantly more patients in the 1:1:1 group achieved anatomic homeostasis (86.1% vs. 78.1%). Thus, clinicians “should consider using a 1:1:1 transfusion protocol,” Dr. Holcomb and his associates said (JAMA 2015 Feb. 3 [doi:10.10001/jama.2015.12]).
There also were no significant differences between the two study groups in 23 complications, including transfusion-related complications. “Despite significant concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications, such as acute respiratory distress syndrome, multiple organ failure, infection, venous thromboembolism, and sepsis, no differences were detected between the two treatment groups,” the researchers noted.
Stress tests in ED lead to unneeded cardiac interventions
BY NICOLA GARRETT
FROM JAMA INTERNAL MEDICINE
Noninvasive testing in the emergency department of patients who have chest pain and have not had a myocardial infarction can result in overdiagnosis and unnecessary interventions, based on the results of a retrospective analysis.
After 6 months of follow-up, 0.33% of 421,774 privately insured patients who presented to the emergency department (ED) with chest pain were hospitalized with an MI. There was no difference in the rate of MIs in patients who did and did not undergo exercise and stress electrocardiography, myocardial perfusion scintigraphy (MPS), or coronary CT angiography, Dr. Andrew. J. Foy of Penn State Milton S. Hershey Medical Center in Hershey, Pa., and his colleagues reported in an article published online in JAMA Internal Medicine (2015 Jan. 26 [doi:10.1001/jamainternmed.2014.7657]).
Vitals Key clinical point: Guidelines for treatment of chest pain in low-risk patients in the emergency department may need revision, as noninvasive testing of these patients may be leading to unneeded interventions. Major finding: An unnecessary catheterization is performed in 1 of every 27 patients who undergo myocardial perfusion scintigraphy instead of an initial strategy of no testing. Data source: A retrospective analysis of health insurance claims data. Disclosures: The researchers reported having no conflicts of interest. |
However, interventions were increased without a concomitant reduction in MI in patients who underwent tests in the ED. “Overdiagnosis is a legitimate concern in this patient population,” the study authors wrote.
Using data from the analysis, the researchers estimated that an unnecessary catheterization is performed in 1 of every 27 patients who undergo MPS instead of an initial strategy of no testing.
“When viewed in the broader context of the approximately 6 million ED visits for a chief symptom of chest pain, for every 100,000 patients who undergo MPS instead of an initial strategy of no testing, approximately 3,700 patients will undergo an unnecessary catheterization,” they wrote.
New treatment options outlined for acute-onset, severe hypertension in pregnancy
BY NICOLA GARRETT
FROM OBSTETRICS AND GYNECOLOGY
The American College of Obstetricians and Gynecologists has added nifedipine as a first-line treatment for acute-onset severe hypertension during pregnancy and the postpartum period in an updated opinion from its Committee on Obstetric Practice.
The update, released on Jan. 22, points to studies showing that women who received oral nifedipine had their blood pressure lowered more quickly than with either intravenous labetalol or hydralazine – the traditional first-line treatments – and had a significant increase in urine output. Concerns about neuromuscular blockade and severe hypotension with the use of nifedipine and magnesium sulphate were not borne out in a large review, the committee members wrote, but they advised careful monitoring since both drugs are calcium antagonists.
The committee opinion includes model order sets for the use of labetalol, hydralazine, and nifedipine for the initial management of acute onset severe hypertension in women who are pregnant or post partum with preeclampsia or eclampsia (Obstet. Gynecol. 2015;125:521-5).
While all three medications are appropriate in treating hypertensive emergencies during pregnancy, each drug has adverse effects.
For instance, parenteral hydralazine can increase the risk of maternal hypotension. Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease, or heart failure. Nifedipine has been associated with increased maternal heart rate and overshoot hypotension.
“Patients may respond to one drug and not another,” the committee noted.
The ACOG committee also called for standardized clinical guidelines for the management of patients with preeclampsia and eclampsia.
“With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications,” they wrote. “Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency.”
The committee recommended checklists as one tool to help standardize the use of guidelines.
“Drip-and-ship” thrombolysis remains common for ischemic stroke
BY MICHELE G. SULLIVAN
AT THE INTERNATIONAL STROKE CONFERENCE
NASHVILLE, TENN. – About 25% of patients with ischemic stroke who receive thrombolytic therapy get it in the field before hospital transfer with the “drip-and-ship” paradigm. While there were only modest differences in clinical outcomes between these patients and those treated when admitted to an emergency department, drip-and-ship may actually increase the overall use of tissue plasminogen activator (TPA), Dr. Kevin N. Sheth said at the International Stroke Conference, sponsored by the American Heart Association.
The retrospective analysis, which was simultaneously published in Stroke (2015 Feb. 11 [doi:10.1161/STROKEAHA.114.007506]), plumbed the Get With the Guidelines registry for data to describe trends in the use of TPA and drip-and-ship administration across the United States over time. The study involved 1,440 hospitals and 44,667 patients who had an ischemic stroke during 2003-2010 and received TPA. Of these, 10,475 (23.5%) received it in the field before optional admission and within 3 hours of symptom onset.
Vitals Key clinical point: The rate of thrombolysis for ischemic stroke via drip-and-ship has remained steady over the past 12 years. Major finding: About a quarter of ischemic stroke patients eligible for TPA are getting it in the field, via the “drip-and-ship” paradigm. Data source: A retrospective study comprising 44,667 patients with ischemic stroke. Disclosures: Dr. Sheth is a member of the Get with the Guidelines (GWTG) Stroke Clinical Workgroup, and he is a coinvestigator and executive committee member for Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals (GAMES-RP), a phase II trial to prevent swelling in patients with large stroke, funded by Remedy Pharmaceuticals. |
Baseline characteristics were similar between the treatment groups. The patients’ mean age was 70 years, and the sex distribution was evenly split. More than 75% of each group was white.
The National Institutes of Health Stroke Scale (NIHSS) score was significantly higher among those who presented for hospital treatment (12.9 vs. 11). However, these patients were seen before TPA administration, while the drip-and-ship group had already been treated, a temporal difference that could have accounted for the score finding, cautioned Dr. Sheth, director of the neuroscience ICU and chief of clinical research at Yale University, New Haven, Conn.
In hospitals that employed drip-and-ship, there were significantly higher rates of stroke patients treated each year as well as more beds. Those hospitals also were more often teaching facilities and were designated as a primary stroke center.
Drip-and-ship frequency remained fairly steady over the study period – about 25% of all eligible patients had it in both 2003 and 2010. Among those treated at the hospital, the frequency of TPA administration within 3 hours of stroke onset rose sharply over the study period, from about 11% in 2003 to 25% in 2010. In contrast, the percentage of timely thrombolysis in drip-and-ship patients moved very little, from about 5% to 9% over the same period.
Overall inpatient mortality was 10%, but was slightly higher among drip-and-ship patients (10.93% vs. 9.67). Symptomatic intracranial hemorrhage occurred in 5.79% of those treated via drip-and-ship and 5.22% of those treated in the hospital. Nearly the same percentage of patients were discharged walking independently (38.4% vs. 38.8%) and discharged home (40.3% vs. 40.6%).
Among the hospital-treated patients, fewer than 4% (1,200) underwent endovascular therapy; this occurred in 707 (7%) of drip-and-ship patients. Those who got endovascular treatment had higher median NIHSS scores at TPA administration than did those who did not (17 vs. 12, respectively). Endovascular treatment was significantly associated with higher mortality (20% vs. 10%) and intracranial hemorrhage (11% vs. 5%).
In a multivariate analysis that adjusted for NIHSS score, in-hospital mortality was significantly more likely in drip-and-ship patients (odds ratio, 1.23). Those patients also were significantly less likely to be independently walking at discharge (OR, 0.66) or discharge to home (OR, 0.66). Intracranial hemorrhage was significantly more likely in drip-and-ship patients (OR, 1.4), as was a hospital stay of longer than 4 days (OR, 1.20).
“These are very modest differences clinically,” Dr. Sheth said, adding that selection bias or unmeasured confounding could have influenced the findings.
Three trials cement embolectomy for acute ischemic stroke
BY MITCHEL L. ZOLER
NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.
The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.
Vitals Key clinical point: Results from three randomized, controlled trials confirmed the safety and dramatic efficacy of endovascular embolectomy for selected patients with acute, ischemic stroke. Major finding: In SWIFT PRIME, a 90-day modified Rankin Scale score of 0-2 occurred in 60% of patients treated with thrombolysis plus embolectomy and 36% of patients treated with thrombolysis only. Data source: SWIFT PRIME, a prospective, multicenter randomized trial that enrolled 195 patients at 39 centers in the United States and Europe. Disclosures: SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures. |
All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.
With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.
“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.
“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.
In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).
But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.
The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.
“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.
“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.
The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.
“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.
The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).
The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).
SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.
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Views on the News
Results warrant embolectomy scale-up
Many U.S. centers have interventionalists who already perform endovascular treatments within intracerebral arteries, but the issue is can they do this form of embolectomy in the high-quality, highly-reliable, rapid way that it was done in these trials? Stent-retriever catheters are relatively straightforward to use by operators who are experienced doing vascular procedures in the brain, but they don’t deliver this treatment by themselves. You need a team that is focused on doing it quickly, and that will be the kind of training we’ll need to roll out this treatment broadly. We achieved it for stroke thrombolytic treatment through the Target Stroke program (JAMA 2014;311:1632-40), so we know that we can achieve this sort of goal. Delivering embolectomy requires more people and more technology than thrombolysis, but it is not rocket science; it just needs a system.
Embolectomy will not replace routine thrombolysis treatment; it will piggyback on top of it. The percentage of patients with a proximal occlusion in a large artery is relatively small. The results we have seen suggest that using embolectomy plus thrombolysis has no adverse-effect downside, compared with thrombolysis alone. Once routine use of embolectomy becomes established, we can directly compare catheter treatment only against combined embolectomy and thrombolysis. My impression today is that what we’d compare is transporting stroke patients directly to a center that can perform embolectomy against taking patients to the closest center that can treat them with thrombolysis and then transporting them to the center that performs embolectomy.
The results of these three new studies plus the previously-reported results from MR CLEAN are not exactly a game changer, because many centers were already performing embolectomy but in a limited way. Now we have the data to give us confidence to do it routinely and to know which patients to select for embolectomy. Because many centers are already doing this, it will not take 5 years to diffuse the technology. Embolectomy is already a treatment cited in the guidelines, but now it will be a level 1A recommendation.
The significance of the new reports is that they will have a dramatic impact on public health systems and in the triage of patients with stroke. It will affect how patients get triaged, and will allow us to identify which patients should go to which centers. I believe we will soon develop clinical examination tools that will allow prehospital providers to discern patients with mild strokes who can go to the nearest center that can administer thrombolysis and which patients need to go to comprehensive centers that can perform embolectomy. We now need to do what we did for thrombolysis, and help centers develop the expertise to do embolectomy as a team and to shave minutes off the delivery at every step of the process. It’s clear that it is the time from stroke onset to getting the artery open that is the key to improved patient outcomes.
If I have my way, we will launch later this year a big effort to focus on improving embolectomy delivery. Now that we know for certain that it works we need to turn the crank and make sure that as many patients as possible who qualify get this treatment.
Dr. Lee H. Schwamm is professor of neurology at Harvard Medical School, and director of acute stroke services at Massachusetts General Hospital, both in Boston. He is a consultant to Penumbra and has received research support from Genentech. He made these comments in an interview.
Magnesium given at stroke onset didn’t improve functional outcomes
BY MICHELE G. SULLIVAN
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Magnesium sulfate infused within 2 hours of stroke symptom onset failed to improve clinical outcomes, according to results from the randomized, placebo-controlled Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial.
The drug did not shift functional outcomes at 3 months in FAST-MAG to a more favorable distribution nor, in secondary endpoints, did it change outcome scores as measured by the modified Rankin Scale or National Institutes of Health Stroke Scale.
Vitals Key clinical point: Magnesium infusion soon after stroke onset did not improve functional outcomes at 3 months. Major finding: At 3 months, a little more than half of the magnesium and placebo groups had a modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower. Data source: The randomized, placebo-controlled FAST-MAG trial of 1,700 patients with suspected stroke. Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke. Dr. Saver has served as an unpaid consultant on a number of trials conducted by pharmaceutical companies. He had no other financial declarations with regard to the FAST-MAG study. |
At 3 months, a little more than half of each group had a modified Rankin Scale score of 2 or lower and about 65% of each group had a National Institutes of Health Stroke Scale score of 8 or lower, both of which indicate good functional recovery. About 15% of each group had died, Dr. Jeffrey L. Saver and his colleagues reported (N. Engl. J. Med. 2015;372:528-36).
The trial randomized 1,700 patients with suspected ischemic stroke to either magnesium sulfate or placebo infusions while en route to a hospital in an emergency vehicle.
In animal models of stroke, magnesium sulfate has been shown to exert vasodilatory and direct neuroprotective and glioprotective effects, said Dr. Saver, director of the clinical stroke program at the University of California, Los Angeles, and his coauthors.
Slow transport of magnesium across the blood-brain barrier may explain why FAST-MAG didn’t replicate these earlier findings. Magnesium levels in the cerebrospinal fluid peak 4 hours after parenteral administration in the presence of an intact blood-brain barrier and more quickly in regions of focal ischemia where the blood-brain barrier is disrupted. Despite a rapid increase in serum levels, brain tissue levels may not have risen quickly enough to yield a benefit, the researchers speculated.
Glucose level may predict mortality in acute heart failure
BY MARY ANN MOON
FROM THE EUROPEAN HEART JOURNAL
Blood glucose level may predict 30-day mortality in adults who present with acute heart failure, regardless of whether the patients have preexisting diabetes, based on a study by Dr. Maneesh Sud of the University of Toronto and his associates.
Hyperglycemia occurs in up to 40% of acute heart failure patients. If prognostic, blood glucose levels at ED presentation “may serve as a screen to identify high-risk patients who warrant formal testing for diabetes, allowing for prompt referral to prevent further morbidity and mortality,” the researchers said.
Vitals Key clinical point: A high glucose level at presentation for acute heart failure may identify patients at increased risk for death within 30 days. Major finding: Regardless of a preexisting diagnosis of diabetes, risk of death at 30 days was about 1.5 times higher in acute heart failure patients who had blood glucose levels exceeding 11.1 mmol/L at presentation in the emergency department. Data source: A secondary analysis of data from two population-based cohorts comprising 16,524 patients. Disclosures: This study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Ontario. Dr. Sud and his associates reported having no relevant financial disclosures. |
The researchers analyzed data from two large population-based cohorts of patients hospitalized for acute HF during a 3-year period. Of the 16,524 patients, 44% had preexisting diabetes (Eur. Heart J. 2015 [doi:10.1093/eurheartj/ehu462].
Among patients with established diabetes, a blood glucose level exceeding 11.1 mmol/L was associated with significantly increased all-cause 30-day mortality with a hazard ratio (HR) of 1.48. Among patients without established diabetes, a blood glucose level exceeding 6.1 mmol/L increased all-cause 30-day mortality with an HR of 1.26; that risk rose in a dose-dependent fashion with increasing glucose levels and reached 1.5 at the level of 11.1 mmol/L.
In severe trauma, 1:1:1 transfusion protocol linked to less exsanguination
BY MARY ANN MOON
FROM JAMA
Among profoundly injured trauma patients with major bleeding, early (24 hour) and late (30 day) mortality were similar between those who received transfusions of plasma, platelets, and red blood cells in a 1:1:1 ratio and those who received transfusions in a 1:1:2 ratio in a phase III clinical trial of 680 adults.
Transfusion protocols for such patients have been “predominantly guided by tradition rather than evidence from large, multicenter randomized trials,” said Dr. John B. Holcomb of the Center for Translational Injury Research, University of Texas Health Science Center, Houston, and his associates in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial. In the last decade, many clinicians changed over to the 1:1:1 ratio because it is more balanced and more closely replicates the ratio present in whole blood than does the traditional 1:1:2 ratio.
Vitals Key clinical point: In severe trauma patients with major bleeding, increasing the ratio of red blood cells did not improve early and late mortality. Major finding: At 24 hours, mortality was 12.7% in the group given a 1:1:1 ratio of plasma to platelets to red blood cells and 17% in the 1:1:2 group; at 30 days, mortality 22.4% in the 1:1:1 group and 26.1% 1:1:2 group. Data source: A phase III multicenter partially blinded, randomized trial comparing two strategies for hemorrhage control in 680 profoundly injured adults treated during a 16-month period. Disclosures: This study was supported by the U.S. National Heart, Lung, and Blood Institute, the U.S. Department of Defense, Defense Research and Development Canada, and the Canadian Institutes of Health Research-Institute of Circulatory and Respiratory Health. Dr. Holcomb reported having no financial disclosures; two associates reported ties to TEM International, CSL Behring, and Decision Health. |
The researchers described the study as the first multicenter randomized trial to use approved blood products to compare the two transfusion ratios with mortality as the primary end point. The 680 adults enrolled in the study were treated for severe injury with major bleeding during a 16-month period at 12 Level 1 trauma centers in North America.
Overall 24-hour mortality was not significantly different, at 12.7% in the 1:1:1 group and 17% in the 1:1:2 group, and 30-day mortality also was not significantly different at 22.4% and 26.1%, respectively. However, exsanguination, the predominant cause of death within 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs. 14.6%), and significantly more patients in the 1:1:1 group achieved anatomic homeostasis (86.1% vs. 78.1%). Thus, clinicians “should consider using a 1:1:1 transfusion protocol,” Dr. Holcomb and his associates said (JAMA 2015 Feb. 3 [doi:10.10001/jama.2015.12]).
There also were no significant differences between the two study groups in 23 complications, including transfusion-related complications. “Despite significant concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications, such as acute respiratory distress syndrome, multiple organ failure, infection, venous thromboembolism, and sepsis, no differences were detected between the two treatment groups,” the researchers noted.
Stress tests in ED lead to unneeded cardiac interventions
BY NICOLA GARRETT
FROM JAMA INTERNAL MEDICINE
Noninvasive testing in the emergency department of patients who have chest pain and have not had a myocardial infarction can result in overdiagnosis and unnecessary interventions, based on the results of a retrospective analysis.
After 6 months of follow-up, 0.33% of 421,774 privately insured patients who presented to the emergency department (ED) with chest pain were hospitalized with an MI. There was no difference in the rate of MIs in patients who did and did not undergo exercise and stress electrocardiography, myocardial perfusion scintigraphy (MPS), or coronary CT angiography, Dr. Andrew. J. Foy of Penn State Milton S. Hershey Medical Center in Hershey, Pa., and his colleagues reported in an article published online in JAMA Internal Medicine (2015 Jan. 26 [doi:10.1001/jamainternmed.2014.7657]).
Vitals Key clinical point: Guidelines for treatment of chest pain in low-risk patients in the emergency department may need revision, as noninvasive testing of these patients may be leading to unneeded interventions. Major finding: An unnecessary catheterization is performed in 1 of every 27 patients who undergo myocardial perfusion scintigraphy instead of an initial strategy of no testing. Data source: A retrospective analysis of health insurance claims data. Disclosures: The researchers reported having no conflicts of interest. |
However, interventions were increased without a concomitant reduction in MI in patients who underwent tests in the ED. “Overdiagnosis is a legitimate concern in this patient population,” the study authors wrote.
Using data from the analysis, the researchers estimated that an unnecessary catheterization is performed in 1 of every 27 patients who undergo MPS instead of an initial strategy of no testing.
“When viewed in the broader context of the approximately 6 million ED visits for a chief symptom of chest pain, for every 100,000 patients who undergo MPS instead of an initial strategy of no testing, approximately 3,700 patients will undergo an unnecessary catheterization,” they wrote.
New treatment options outlined for acute-onset, severe hypertension in pregnancy
BY NICOLA GARRETT
FROM OBSTETRICS AND GYNECOLOGY
The American College of Obstetricians and Gynecologists has added nifedipine as a first-line treatment for acute-onset severe hypertension during pregnancy and the postpartum period in an updated opinion from its Committee on Obstetric Practice.
The update, released on Jan. 22, points to studies showing that women who received oral nifedipine had their blood pressure lowered more quickly than with either intravenous labetalol or hydralazine – the traditional first-line treatments – and had a significant increase in urine output. Concerns about neuromuscular blockade and severe hypotension with the use of nifedipine and magnesium sulphate were not borne out in a large review, the committee members wrote, but they advised careful monitoring since both drugs are calcium antagonists.
The committee opinion includes model order sets for the use of labetalol, hydralazine, and nifedipine for the initial management of acute onset severe hypertension in women who are pregnant or post partum with preeclampsia or eclampsia (Obstet. Gynecol. 2015;125:521-5).
While all three medications are appropriate in treating hypertensive emergencies during pregnancy, each drug has adverse effects.
For instance, parenteral hydralazine can increase the risk of maternal hypotension. Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease, or heart failure. Nifedipine has been associated with increased maternal heart rate and overshoot hypotension.
“Patients may respond to one drug and not another,” the committee noted.
The ACOG committee also called for standardized clinical guidelines for the management of patients with preeclampsia and eclampsia.
“With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications,” they wrote. “Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency.”
The committee recommended checklists as one tool to help standardize the use of guidelines.
“Drip-and-ship” thrombolysis remains common for ischemic stroke
BY MICHELE G. SULLIVAN
AT THE INTERNATIONAL STROKE CONFERENCE
NASHVILLE, TENN. – About 25% of patients with ischemic stroke who receive thrombolytic therapy get it in the field before hospital transfer with the “drip-and-ship” paradigm. While there were only modest differences in clinical outcomes between these patients and those treated when admitted to an emergency department, drip-and-ship may actually increase the overall use of tissue plasminogen activator (TPA), Dr. Kevin N. Sheth said at the International Stroke Conference, sponsored by the American Heart Association.
The retrospective analysis, which was simultaneously published in Stroke (2015 Feb. 11 [doi:10.1161/STROKEAHA.114.007506]), plumbed the Get With the Guidelines registry for data to describe trends in the use of TPA and drip-and-ship administration across the United States over time. The study involved 1,440 hospitals and 44,667 patients who had an ischemic stroke during 2003-2010 and received TPA. Of these, 10,475 (23.5%) received it in the field before optional admission and within 3 hours of symptom onset.
Vitals Key clinical point: The rate of thrombolysis for ischemic stroke via drip-and-ship has remained steady over the past 12 years. Major finding: About a quarter of ischemic stroke patients eligible for TPA are getting it in the field, via the “drip-and-ship” paradigm. Data source: A retrospective study comprising 44,667 patients with ischemic stroke. Disclosures: Dr. Sheth is a member of the Get with the Guidelines (GWTG) Stroke Clinical Workgroup, and he is a coinvestigator and executive committee member for Glyburide Advantage in Malignant Edema and Stroke-Remedy Pharmaceuticals (GAMES-RP), a phase II trial to prevent swelling in patients with large stroke, funded by Remedy Pharmaceuticals. |
Baseline characteristics were similar between the treatment groups. The patients’ mean age was 70 years, and the sex distribution was evenly split. More than 75% of each group was white.
The National Institutes of Health Stroke Scale (NIHSS) score was significantly higher among those who presented for hospital treatment (12.9 vs. 11). However, these patients were seen before TPA administration, while the drip-and-ship group had already been treated, a temporal difference that could have accounted for the score finding, cautioned Dr. Sheth, director of the neuroscience ICU and chief of clinical research at Yale University, New Haven, Conn.
In hospitals that employed drip-and-ship, there were significantly higher rates of stroke patients treated each year as well as more beds. Those hospitals also were more often teaching facilities and were designated as a primary stroke center.
Drip-and-ship frequency remained fairly steady over the study period – about 25% of all eligible patients had it in both 2003 and 2010. Among those treated at the hospital, the frequency of TPA administration within 3 hours of stroke onset rose sharply over the study period, from about 11% in 2003 to 25% in 2010. In contrast, the percentage of timely thrombolysis in drip-and-ship patients moved very little, from about 5% to 9% over the same period.
Overall inpatient mortality was 10%, but was slightly higher among drip-and-ship patients (10.93% vs. 9.67). Symptomatic intracranial hemorrhage occurred in 5.79% of those treated via drip-and-ship and 5.22% of those treated in the hospital. Nearly the same percentage of patients were discharged walking independently (38.4% vs. 38.8%) and discharged home (40.3% vs. 40.6%).
Among the hospital-treated patients, fewer than 4% (1,200) underwent endovascular therapy; this occurred in 707 (7%) of drip-and-ship patients. Those who got endovascular treatment had higher median NIHSS scores at TPA administration than did those who did not (17 vs. 12, respectively). Endovascular treatment was significantly associated with higher mortality (20% vs. 10%) and intracranial hemorrhage (11% vs. 5%).
In a multivariate analysis that adjusted for NIHSS score, in-hospital mortality was significantly more likely in drip-and-ship patients (odds ratio, 1.23). Those patients also were significantly less likely to be independently walking at discharge (OR, 0.66) or discharge to home (OR, 0.66). Intracranial hemorrhage was significantly more likely in drip-and-ship patients (OR, 1.4), as was a hospital stay of longer than 4 days (OR, 1.20).
“These are very modest differences clinically,” Dr. Sheth said, adding that selection bias or unmeasured confounding could have influenced the findings.
Three trials cement embolectomy for acute ischemic stroke
BY MITCHEL L. ZOLER
NASHVILLE, TENN. – Treatment of selected patients with acute ischemic stroke underwent a dramatic, sudden shift with reports from three randomized, controlled trials that showed substantial added benefit and no incremental risk with the use of catheter-based embolic retrieval to open blocked intracerebral arteries when performed on top of standard thrombolytic therapy.
The three studies, each run independently and based in different countries, supported the results first reported last October and published online in December (N. Engl. J. Med. 2015;372:11-20) from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) study. These were the first contemporary trial results to show a jump in functional outcomes with use of a stent retriever catheter to pluck out the occluding embolus from an artery in the stroke patient’s brain to restore normal blood flow.
Vitals Key clinical point: Results from three randomized, controlled trials confirmed the safety and dramatic efficacy of endovascular embolectomy for selected patients with acute, ischemic stroke. Major finding: In SWIFT PRIME, a 90-day modified Rankin Scale score of 0-2 occurred in 60% of patients treated with thrombolysis plus embolectomy and 36% of patients treated with thrombolysis only. Data source: SWIFT PRIME, a prospective, multicenter randomized trial that enrolled 195 patients at 39 centers in the United States and Europe. Disclosures: SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures. |
All three of the newly-reported studies stopped before reaching their prespecified enrollment levels because of overwhelming evidence for embolectomy’s incremental efficacy.
With four reports from prospective, randomized trials showing similar benefits and no added harm to patients, experts at the International Stroke Conference uniformly anointed catheter-based embolectomy the new standard of care for the small percentage of acute, ischemic-stroke patients who present with proximal, large-artery obstructions and also match the other strict clinical and imaging inclusion and exclusion criteria used in the studies.
“Starting now, in patients with an acute ischemic stroke due to proximal vessel occlusion, rapid endovascular treatment using a retrieval stent is the standard of care,” Dr. Mayank Goyal declared from the plenary-session podium. He is a professor of diagnostic imaging at the University of Calgary (Canada) and an investigator in two of the three trials presented at the conference, which was sponsored by the American Heart Association.
“Today the world changed. We are now in a new era, the era of highly-effective intravascular recanalization therapy,” said Dr. Jeffrey L. Saver, professor of neurology and director of the Stroke Center at the University of California, Los Angeles, and lead investigator for one of the new studies.
In three of the four studies, the researchers did not report specific numbers on how selective they were in focusing in on the ischemic stroke patients most likely to benefit from this treatment, but the one study that did, EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial), run at nine Australian centers and one in New Zealand, showed the extensive winnowing that occurred. Of 7,796 patients with an acute ischemic stroke who initially presented, 1,044 (13%) were eligible to receive thrombolytic therapy (alteplase in this study). And from among these 1,044 patients, a mere 70 – less than 1% of the initial group – were deemed eligible for randomization into the embolectomy trial. The top three reasons for exclusion of patients who qualified for thrombolytic treatment from the trial was an absence of a major-vessel occlusion (45% of the excluded patients), presentation outside of the times when enrollment personnel were available (22%), and poor premorbid function (16%).
But subgroup analyses in three of the four studies (EXTEND-IA with a total of 70 patients was too small for subgroup analyses) showed no subgroup of patients who failed to benefit from embolectomy, including elderly patients who in some cases were nonagenarians.
The unusual confluence of having four major trials showing remarkably consistent results meant that the stroke experts gathered at the meeting focused their attention not on whether stent retrievers should now be widely and routinely used in appropriate patients but instead on how this technology will roll out worldwide.
“From here on out we are obligated to treat patients with this technology at centers that can do this, and we are obligated to have more centers that can provide it,” said Dr. Kyra J. Becker, professor of neurology and neurological surgery and codirector of the Stroke Center at the University of Washington, Seattle. Dr. Becker had no involvement in any of the stent retriever trials. “I had been a doubter of this technology,” primarily because results reported at the International Stroke Conference a couple of years ago failed to prove the efficacy of clot retrieval in ischemic stroke patients, she noted. “Our ability to select appropriate patients and do it in a timely fashion hadn’t gotten to where it had to be until now,” Dr. Becker said in an interview.
“We only enrolled patients with blockages, we treated them quickly, and we used much better devices to open their arteries,” Dr. Saver added, explaining why the new studies succeeded when earlier studies had not.
The trial led by Dr. Saver, SWIFT-PRIME (SOLITAIRE™ FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), enrolled 195 patients at 39 sites in the United States and in Europe. At 90 days after treatment, 59 patients (60%) among those treated with thrombolysis plus embolectomy had a modified Rankin Scale score of 0-2, compared with 33 patients (36%) among those treated only with thrombolysis (in this trial intravenous treatment with tissue plasminogen activator), a highly significant difference for the study’s primary endpoint.
“For every two and half patients treated, one more patient had a better disability outcome, and for every four patients treated, one more patient was independent at long-term follow-up,” Dr. Saver said. Safety measures were similar among patients in the study’s two arms.
The EXTEND-IA results showed a 90-day modified Rankin Scale score of 0-2 in 52% of the embolectomy patients, compared with 28% of those treated only with thrombolysis. The study’s co–primary endpoints were median level of reperfusion at 24 hours after treatment, 100% with embolectomy and 37% with thrombolysis only, and early neurologic recovery, defined as at least an 8-point drop from the baseline in the National Institutes of Health Stroke Scale score or a score of 0 or 1 when assessed 3 days after treatment. Patients met this second endpoint at an 80% rate with embolectomy and a 37% rate with thrombolysis only. Results of EXTEND-IA appeared in an article published online concurrently with the meeting report (N. Engl J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414792]).
The third, and largest, of the three studies presented at the conference, ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times), enrolled 316 patients at 11 centers in Canada, 6 in the United States, 3 in South Korea, and 1 in Ireland. After 90 days, 53% of patients in the embolectomy arm had achieved a modified Rankin Scale score of 0-2, this study’s primary endpoint, compared with 29% of patients in the thrombolysis-only arm (treatment with alteplase). These results also appeared in an article published online concurrently with the conference report (N. Engl. J. Med. 2015 Feb. 11 [doi:10.1056/NEJMoa1414905]).
SWIFT PRIME was sponsored by Covidien, which markets the stent retriever used in the study. Dr. Saver and Dr. Goyal are consultants to Covidien. EXTEND-IA used stent retrievers provided by Covidien. ESCAPE received a grant from Covidien. Dr. Becker had no relevant disclosures.
On Twitter @mitchelzoler
Views on the News
Results warrant embolectomy scale-up
Many U.S. centers have interventionalists who already perform endovascular treatments within intracerebral arteries, but the issue is can they do this form of embolectomy in the high-quality, highly-reliable, rapid way that it was done in these trials? Stent-retriever catheters are relatively straightforward to use by operators who are experienced doing vascular procedures in the brain, but they don’t deliver this treatment by themselves. You need a team that is focused on doing it quickly, and that will be the kind of training we’ll need to roll out this treatment broadly. We achieved it for stroke thrombolytic treatment through the Target Stroke program (JAMA 2014;311:1632-40), so we know that we can achieve this sort of goal. Delivering embolectomy requires more people and more technology than thrombolysis, but it is not rocket science; it just needs a system.
Embolectomy will not replace routine thrombolysis treatment; it will piggyback on top of it. The percentage of patients with a proximal occlusion in a large artery is relatively small. The results we have seen suggest that using embolectomy plus thrombolysis has no adverse-effect downside, compared with thrombolysis alone. Once routine use of embolectomy becomes established, we can directly compare catheter treatment only against combined embolectomy and thrombolysis. My impression today is that what we’d compare is transporting stroke patients directly to a center that can perform embolectomy against taking patients to the closest center that can treat them with thrombolysis and then transporting them to the center that performs embolectomy.
The results of these three new studies plus the previously-reported results from MR CLEAN are not exactly a game changer, because many centers were already performing embolectomy but in a limited way. Now we have the data to give us confidence to do it routinely and to know which patients to select for embolectomy. Because many centers are already doing this, it will not take 5 years to diffuse the technology. Embolectomy is already a treatment cited in the guidelines, but now it will be a level 1A recommendation.
The significance of the new reports is that they will have a dramatic impact on public health systems and in the triage of patients with stroke. It will affect how patients get triaged, and will allow us to identify which patients should go to which centers. I believe we will soon develop clinical examination tools that will allow prehospital providers to discern patients with mild strokes who can go to the nearest center that can administer thrombolysis and which patients need to go to comprehensive centers that can perform embolectomy. We now need to do what we did for thrombolysis, and help centers develop the expertise to do embolectomy as a team and to shave minutes off the delivery at every step of the process. It’s clear that it is the time from stroke onset to getting the artery open that is the key to improved patient outcomes.
If I have my way, we will launch later this year a big effort to focus on improving embolectomy delivery. Now that we know for certain that it works we need to turn the crank and make sure that as many patients as possible who qualify get this treatment.
Dr. Lee H. Schwamm is professor of neurology at Harvard Medical School, and director of acute stroke services at Massachusetts General Hospital, both in Boston. He is a consultant to Penumbra and has received research support from Genentech. He made these comments in an interview.
Does a second course of antenatal corticosteroids offer benefit in the setting of preterm PROM?
Gyamfi-Bannerman and Son report their secondary analysis of a randomized controlled trial (RCT) conducted through the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal-Fetal Medicine Units Network. The aim of the parent RCT was to determine whether antenatal administration of magnesium sulfate decreases the rate of cerebral palsy or death in children delivered preterm. More than 80% of the women enrolled in this RCT had preterm PROM. Of these women, 98% were given antenatal corticosteroids for fetal maturation, and 9% received two courses. This aspect of the RCT provided an opportunity for Gyamfi-Bannerman and Son to study the comparative effects of one course versus two courses of ACS in the setting of preterm PROM.
Background of the study
Concern about the declining efficacy of ACS when the interval between administration and delivery exceeds 7 days prompted several randomized trials exploring the safety and efficacy of multiple ACS courses. Multiple courses were ultimately deemed to be inadvisable because of an association with reduced birth weight and neonatal head circumference.1,2 However, the unfavorable effects of ACS on anthropometrics was observed when more than three courses were administered, leaving open the possibility of giving only one additional course when needed as a “rescue” dose. Indeed, the use of a single rescue course of ACS in women with intact membranes had a favorable impact on neonatal respiratory function in two RCTs.3,4
The best available evidence (Level 1) demonstrates that the use of a single course of ACS in preterm PROM does not increase the risk of neonatal or maternal infection even in the setting of prolonged rupture of membranes.5 However, pregnant women with preterm PROM were excluded from trials of repetitive ACS dosing because earlier observational studies had suggested that they would experience a substantially increased risk of infectious morbidity when three or more courses of ACS are given.6–8 What remained debatable on a scientific level was whether a single rescue dose of ACS in women with preterm PROM would be safe and beneficial.
Findings of the analysis
Compared with a single course of ACS, exposure to two courses did not influence the rate of neonatal sepsis or chorioamnionitis. As reassuring as that finding may be, the study found no benefit for the additional course, although it was powered to do so. There was no difference in the rates of respiratory distress syndrome between the study groups.
The findings of Gyamfi-Bannerman and Son replicate those of a subgroup analysis of women in an RCT comparing weekly and single-course ACS.9 In that study, weekly courses of ACS in women with preterm PROM did not improve neonatal outcomes beyond what was achieved with single-course therapy. Similar findings have been reported by the Cochrane database.10
Ruptured versus intact membranes: When is the benefit of ACS greater?
The improvement in neonatal outcomes observed with ACS in pregnancies complicated by preterm PROM is not as pronounced as it is in gestations with intact membranes. In preterm PROM, fetuses reportedly are stressed by the presence of intrauterine inflammation or infection, or both, which accelerates lung maturity by encouraging the secretion of endogenous corticosteroids, resulting in the production of surfactant and eliminating the potential benefit of exogenous ACS.11 This theoretical consideration has not been verified in a systematic analysis of accumulated data,5 and the administration of a single course of ACS in preterm PROM now has been shown clearly to improve neonatal outcomes.12 As Gyamfi-Bannerman and Son demonstrate, the same cannot be said about the administration of a rescue dose of ACS.
Strengths and limitations of the trial
Gyamfi-Bannerman and Son did not address the same interaction as the parent study. The exposure of interest was ACS, an event that occurred in a manner unrelated to the randomization for magnesium sulfate administration. Therefore, the outcome data are no longer randomized in nature, and the study becomes a retrospective cohort analysis.
Gyamfi-Bannerman and Son recognize the limitations of such a study, especially the lack of standardization in the intervention (exact timing of intervention or type of formulation). As with any nonrandomized experiment, the potential for unintended systematic bias is present.
This study, in particular, was subject to “survivor bias,” as reflected in the significantly different intervals between membrane rupture and delivery in the two groups.
What this evidence means for practice
We must always remain cautious about basing policy or clinical decisions on cohort studies. It has been argued that basing a change in clinical practice on the findings of subgroup analyses is a deviation from fundamental scientific truth.13 Such findings should be regarded as hypothesis testing only and considered exploratory in nature.
This study’s abstract conclusion that there is a lack of association between a second dose of ACS and neonatal sepsis should not be regarded as justification to use a rescue course of ACS in women with preterm PROM. We recommend that such a practice be avoided outside the context of an approved research protocol.
— Kathleen M. Antony, MD, and Alex C. Vidaeff, MD, MPH
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
1. Wapner RJ, Sorokin Y, Thom EA, et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol. 2006;195(3):633–642.
2. Murphy KE, Hannah ME, Willan AR, et al; MACS Collaborative Group. Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS): a randomized controlled trial. Lancet. 2008;372(9656):2143–2151.
3. Garite TJ, Kurtzman, Maurel K, et al. Impact of a “rescue course” of antenatal corticosteroids: a multicenter randomized placebo-controlled trial. Am J Obstet Gynecol. 2009;200(3):248.e1–e9.
4. McEvoy C, Schilling D, Peters D, et al. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. Am J Obstet Gynecol. 2010;202(6):544.e1–e9.
5. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454.
6. Rotmensch S, Vishne TH, Celentano C, et al. Maternal infectious morbidity following multiple courses of betamethasone. J Infect. 1999;39(1):49–54.
7. Vermillion ST, Soper DE, Chasedunn-Roark J. Neonatal sepsis after betamethasone administration to patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 1999;181(2):320–327.
8. Yang SH, Choi SJ, Roh CR, et al. Multiple courses of antenatal corticosteroid therapy in patients with preterm premature rupture of membranes. J Perinat Med. 2004;32(1):42–48.
9. Lee MJ, Davies J, Guinn D, et al. Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes. Obstet Gynecol. 2004;103(2):274–281.
10. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2011;(6):CD003935.
11. Lyon A. Chronic lung disease of prematurity. The role of intrauterine infection. Eur J Pediatr. 2000;159(11):798–802.
12. Vidaeff AC, Ramin SM. Antenatal corticosteroids after preterm premature rupture of membranes. Clin Obstet Gynecol. 2011;54(2):337–343.
13. Bailar JC. How to distort the scientific record without actually lying: truth, and the arts of science. Eur J Oncol. 2006;11(4):217–224.
Gyamfi-Bannerman and Son report their secondary analysis of a randomized controlled trial (RCT) conducted through the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal-Fetal Medicine Units Network. The aim of the parent RCT was to determine whether antenatal administration of magnesium sulfate decreases the rate of cerebral palsy or death in children delivered preterm. More than 80% of the women enrolled in this RCT had preterm PROM. Of these women, 98% were given antenatal corticosteroids for fetal maturation, and 9% received two courses. This aspect of the RCT provided an opportunity for Gyamfi-Bannerman and Son to study the comparative effects of one course versus two courses of ACS in the setting of preterm PROM.
Background of the study
Concern about the declining efficacy of ACS when the interval between administration and delivery exceeds 7 days prompted several randomized trials exploring the safety and efficacy of multiple ACS courses. Multiple courses were ultimately deemed to be inadvisable because of an association with reduced birth weight and neonatal head circumference.1,2 However, the unfavorable effects of ACS on anthropometrics was observed when more than three courses were administered, leaving open the possibility of giving only one additional course when needed as a “rescue” dose. Indeed, the use of a single rescue course of ACS in women with intact membranes had a favorable impact on neonatal respiratory function in two RCTs.3,4
The best available evidence (Level 1) demonstrates that the use of a single course of ACS in preterm PROM does not increase the risk of neonatal or maternal infection even in the setting of prolonged rupture of membranes.5 However, pregnant women with preterm PROM were excluded from trials of repetitive ACS dosing because earlier observational studies had suggested that they would experience a substantially increased risk of infectious morbidity when three or more courses of ACS are given.6–8 What remained debatable on a scientific level was whether a single rescue dose of ACS in women with preterm PROM would be safe and beneficial.
Findings of the analysis
Compared with a single course of ACS, exposure to two courses did not influence the rate of neonatal sepsis or chorioamnionitis. As reassuring as that finding may be, the study found no benefit for the additional course, although it was powered to do so. There was no difference in the rates of respiratory distress syndrome between the study groups.
The findings of Gyamfi-Bannerman and Son replicate those of a subgroup analysis of women in an RCT comparing weekly and single-course ACS.9 In that study, weekly courses of ACS in women with preterm PROM did not improve neonatal outcomes beyond what was achieved with single-course therapy. Similar findings have been reported by the Cochrane database.10
Ruptured versus intact membranes: When is the benefit of ACS greater?
The improvement in neonatal outcomes observed with ACS in pregnancies complicated by preterm PROM is not as pronounced as it is in gestations with intact membranes. In preterm PROM, fetuses reportedly are stressed by the presence of intrauterine inflammation or infection, or both, which accelerates lung maturity by encouraging the secretion of endogenous corticosteroids, resulting in the production of surfactant and eliminating the potential benefit of exogenous ACS.11 This theoretical consideration has not been verified in a systematic analysis of accumulated data,5 and the administration of a single course of ACS in preterm PROM now has been shown clearly to improve neonatal outcomes.12 As Gyamfi-Bannerman and Son demonstrate, the same cannot be said about the administration of a rescue dose of ACS.
Strengths and limitations of the trial
Gyamfi-Bannerman and Son did not address the same interaction as the parent study. The exposure of interest was ACS, an event that occurred in a manner unrelated to the randomization for magnesium sulfate administration. Therefore, the outcome data are no longer randomized in nature, and the study becomes a retrospective cohort analysis.
Gyamfi-Bannerman and Son recognize the limitations of such a study, especially the lack of standardization in the intervention (exact timing of intervention or type of formulation). As with any nonrandomized experiment, the potential for unintended systematic bias is present.
This study, in particular, was subject to “survivor bias,” as reflected in the significantly different intervals between membrane rupture and delivery in the two groups.
What this evidence means for practice
We must always remain cautious about basing policy or clinical decisions on cohort studies. It has been argued that basing a change in clinical practice on the findings of subgroup analyses is a deviation from fundamental scientific truth.13 Such findings should be regarded as hypothesis testing only and considered exploratory in nature.
This study’s abstract conclusion that there is a lack of association between a second dose of ACS and neonatal sepsis should not be regarded as justification to use a rescue course of ACS in women with preterm PROM. We recommend that such a practice be avoided outside the context of an approved research protocol.
— Kathleen M. Antony, MD, and Alex C. Vidaeff, MD, MPH
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Gyamfi-Bannerman and Son report their secondary analysis of a randomized controlled trial (RCT) conducted through the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Maternal-Fetal Medicine Units Network. The aim of the parent RCT was to determine whether antenatal administration of magnesium sulfate decreases the rate of cerebral palsy or death in children delivered preterm. More than 80% of the women enrolled in this RCT had preterm PROM. Of these women, 98% were given antenatal corticosteroids for fetal maturation, and 9% received two courses. This aspect of the RCT provided an opportunity for Gyamfi-Bannerman and Son to study the comparative effects of one course versus two courses of ACS in the setting of preterm PROM.
Background of the study
Concern about the declining efficacy of ACS when the interval between administration and delivery exceeds 7 days prompted several randomized trials exploring the safety and efficacy of multiple ACS courses. Multiple courses were ultimately deemed to be inadvisable because of an association with reduced birth weight and neonatal head circumference.1,2 However, the unfavorable effects of ACS on anthropometrics was observed when more than three courses were administered, leaving open the possibility of giving only one additional course when needed as a “rescue” dose. Indeed, the use of a single rescue course of ACS in women with intact membranes had a favorable impact on neonatal respiratory function in two RCTs.3,4
The best available evidence (Level 1) demonstrates that the use of a single course of ACS in preterm PROM does not increase the risk of neonatal or maternal infection even in the setting of prolonged rupture of membranes.5 However, pregnant women with preterm PROM were excluded from trials of repetitive ACS dosing because earlier observational studies had suggested that they would experience a substantially increased risk of infectious morbidity when three or more courses of ACS are given.6–8 What remained debatable on a scientific level was whether a single rescue dose of ACS in women with preterm PROM would be safe and beneficial.
Findings of the analysis
Compared with a single course of ACS, exposure to two courses did not influence the rate of neonatal sepsis or chorioamnionitis. As reassuring as that finding may be, the study found no benefit for the additional course, although it was powered to do so. There was no difference in the rates of respiratory distress syndrome between the study groups.
The findings of Gyamfi-Bannerman and Son replicate those of a subgroup analysis of women in an RCT comparing weekly and single-course ACS.9 In that study, weekly courses of ACS in women with preterm PROM did not improve neonatal outcomes beyond what was achieved with single-course therapy. Similar findings have been reported by the Cochrane database.10
Ruptured versus intact membranes: When is the benefit of ACS greater?
The improvement in neonatal outcomes observed with ACS in pregnancies complicated by preterm PROM is not as pronounced as it is in gestations with intact membranes. In preterm PROM, fetuses reportedly are stressed by the presence of intrauterine inflammation or infection, or both, which accelerates lung maturity by encouraging the secretion of endogenous corticosteroids, resulting in the production of surfactant and eliminating the potential benefit of exogenous ACS.11 This theoretical consideration has not been verified in a systematic analysis of accumulated data,5 and the administration of a single course of ACS in preterm PROM now has been shown clearly to improve neonatal outcomes.12 As Gyamfi-Bannerman and Son demonstrate, the same cannot be said about the administration of a rescue dose of ACS.
Strengths and limitations of the trial
Gyamfi-Bannerman and Son did not address the same interaction as the parent study. The exposure of interest was ACS, an event that occurred in a manner unrelated to the randomization for magnesium sulfate administration. Therefore, the outcome data are no longer randomized in nature, and the study becomes a retrospective cohort analysis.
Gyamfi-Bannerman and Son recognize the limitations of such a study, especially the lack of standardization in the intervention (exact timing of intervention or type of formulation). As with any nonrandomized experiment, the potential for unintended systematic bias is present.
This study, in particular, was subject to “survivor bias,” as reflected in the significantly different intervals between membrane rupture and delivery in the two groups.
What this evidence means for practice
We must always remain cautious about basing policy or clinical decisions on cohort studies. It has been argued that basing a change in clinical practice on the findings of subgroup analyses is a deviation from fundamental scientific truth.13 Such findings should be regarded as hypothesis testing only and considered exploratory in nature.
This study’s abstract conclusion that there is a lack of association between a second dose of ACS and neonatal sepsis should not be regarded as justification to use a rescue course of ACS in women with preterm PROM. We recommend that such a practice be avoided outside the context of an approved research protocol.
— Kathleen M. Antony, MD, and Alex C. Vidaeff, MD, MPH
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
1. Wapner RJ, Sorokin Y, Thom EA, et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol. 2006;195(3):633–642.
2. Murphy KE, Hannah ME, Willan AR, et al; MACS Collaborative Group. Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS): a randomized controlled trial. Lancet. 2008;372(9656):2143–2151.
3. Garite TJ, Kurtzman, Maurel K, et al. Impact of a “rescue course” of antenatal corticosteroids: a multicenter randomized placebo-controlled trial. Am J Obstet Gynecol. 2009;200(3):248.e1–e9.
4. McEvoy C, Schilling D, Peters D, et al. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. Am J Obstet Gynecol. 2010;202(6):544.e1–e9.
5. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454.
6. Rotmensch S, Vishne TH, Celentano C, et al. Maternal infectious morbidity following multiple courses of betamethasone. J Infect. 1999;39(1):49–54.
7. Vermillion ST, Soper DE, Chasedunn-Roark J. Neonatal sepsis after betamethasone administration to patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 1999;181(2):320–327.
8. Yang SH, Choi SJ, Roh CR, et al. Multiple courses of antenatal corticosteroid therapy in patients with preterm premature rupture of membranes. J Perinat Med. 2004;32(1):42–48.
9. Lee MJ, Davies J, Guinn D, et al. Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes. Obstet Gynecol. 2004;103(2):274–281.
10. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2011;(6):CD003935.
11. Lyon A. Chronic lung disease of prematurity. The role of intrauterine infection. Eur J Pediatr. 2000;159(11):798–802.
12. Vidaeff AC, Ramin SM. Antenatal corticosteroids after preterm premature rupture of membranes. Clin Obstet Gynecol. 2011;54(2):337–343.
13. Bailar JC. How to distort the scientific record without actually lying: truth, and the arts of science. Eur J Oncol. 2006;11(4):217–224.
1. Wapner RJ, Sorokin Y, Thom EA, et al. Single versus weekly courses of antenatal corticosteroids: evaluation of safety and efficacy. Am J Obstet Gynecol. 2006;195(3):633–642.
2. Murphy KE, Hannah ME, Willan AR, et al; MACS Collaborative Group. Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS): a randomized controlled trial. Lancet. 2008;372(9656):2143–2151.
3. Garite TJ, Kurtzman, Maurel K, et al. Impact of a “rescue course” of antenatal corticosteroids: a multicenter randomized placebo-controlled trial. Am J Obstet Gynecol. 2009;200(3):248.e1–e9.
4. McEvoy C, Schilling D, Peters D, et al. Respiratory compliance in preterm infants after a single rescue course of antenatal steroids: a randomized controlled trial. Am J Obstet Gynecol. 2010;202(6):544.e1–e9.
5. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454.
6. Rotmensch S, Vishne TH, Celentano C, et al. Maternal infectious morbidity following multiple courses of betamethasone. J Infect. 1999;39(1):49–54.
7. Vermillion ST, Soper DE, Chasedunn-Roark J. Neonatal sepsis after betamethasone administration to patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 1999;181(2):320–327.
8. Yang SH, Choi SJ, Roh CR, et al. Multiple courses of antenatal corticosteroid therapy in patients with preterm premature rupture of membranes. J Perinat Med. 2004;32(1):42–48.
9. Lee MJ, Davies J, Guinn D, et al. Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes. Obstet Gynecol. 2004;103(2):274–281.
10. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2011;(6):CD003935.
11. Lyon A. Chronic lung disease of prematurity. The role of intrauterine infection. Eur J Pediatr. 2000;159(11):798–802.
12. Vidaeff AC, Ramin SM. Antenatal corticosteroids after preterm premature rupture of membranes. Clin Obstet Gynecol. 2011;54(2):337–343.
13. Bailar JC. How to distort the scientific record without actually lying: truth, and the arts of science. Eur J Oncol. 2006;11(4):217–224.
Optimal pharmacologic treatment of nausea and vomiting of pregnancy
CASE: Pregnant patient seeks medication for her NVP
A 23-year-old G1P0 woman at 9 weeks’ gestation presents to your office with nausea and vomiting that is interfering with work. She has tried many changes in her daily habits. She has tried eating small, frequent meals; snacking on nuts and crackers; using lemon-scented products; and avoiding coffee and strong odors. Following an evaluation you diagnose nausea and vomiting of pregnancy (NVP). She asks, “Is there a medication for my nausea that is safe for my baby?”
Nausea with or without vomiting is a common problem for pregnant women between 6 and 14 weeks of gestation. In one study, nausea with or without vomiting was reported by 69% of patients and resulted in pharmacologic treatment in 15%.1 In a Cochrane review of NVP, investigators analyzed 37 trials involving treatments such as acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, vitamin B6, and antiemetic medications. The authors concluded, “There is a lack of high-quality evidence to support any particular intervention.”2 Clinicians are challenged to effectively treat the symptoms of NVP and simultaneously to minimize the risk that the fetus will be exposed to a teratogen during the first trimester, a vulnerable period in organ development.
In this editorial, I briefly review nonpharmacologic options for NVP, but focus on current pharmacologic treatments. Of those available to ObGyns, what is the best first-choice treatment given recent and accumulated data regarding associated congenital anomalies?
Nonpharmacologic treatment
Although the authors of the Cochrane review did not identify high-quality evidence to support nonpharmacologic interventions, results of multiple randomized trials have demonstrated that ginger is effective in reducing pregnancy-associated nausea and vomiting.3 Ginger treatment is recommended at doses of 250 mg in capsules or syrup four times daily.
First-line pharmacologic treatment: Doxylamine plus pyridoxine
The US Food and Drug Administration (FDA) has approved the combination of doxylamine plus pyridoxine (vitamin B6) in a delayed-release formulation for treatment of NVP (Diclegis). Doxylamine is an antihistamine that blocks H1-receptor sites in the chemoreceptor trigger zone. It also diminishes vestibular stimulation and depresses labyrinthine activity through central anticholinergic activity. Its elimination half-life is 10 to 12 hours (Lexicomp). Each tablet contains doxylamine 10 mg and pyridoxine 10 mg. The starting dose is 2 tablets at bedtime.
If the woman has persistent symptoms, a third tablet is added, to be taken in the morning. If symptoms continue, a fourth tablet is recommended to be taken in the afternoon. In a large, randomized clinical trial, doxylamine-pyridoxine treatment reduced nausea, vomiting, and retching and improved perceived quality of life compared with placebo.4 The FDA assigned doxylamine-pyridoxine pregnancy category A because of the extensive evidence that it does not cause an increase in fetal malformations.5,6
If the delayed-release doxylamine-pyridoxine formulation (Diclegis) is not available to the patient, alternative formulations of doxylamine and pyridoxine can be prescribed. Pyridoxine is widely available over the counter as 25-mg tablets, and one tablet can be prescribed two or three times daily. Doxylamine is available as a chewable prescription medicine in 5-mg tablets (Aldex AN) and two tablets can be prescribed two or three times daily. Doxylamine is also available as a 25-mg over-the-counter tablet in Unisom SleepTabs. One-half tablet can be prescribed two or three times daily. The patient should be alerted that Unisom SleepGels contain diphenhydramine, not doxylamine.
Second-line pharmacologic treatment
Metoclopramide Metoclopramide is a dopamine antagonist. It enhances upper gastrointestinal motility, accelerates gastric emptying, and increases lower esophageal sphincter tone. At higher doses it blocks serotonin receptors in the chemoreceptor trigger zone. Its elimination half-life is 5 to 6 hours (Lexicomp). There are no large, randomized, placebo-controlled trials of oral metoclopramide for the treatment of nausea and vomiting of early pregnancy.
I am recommending metoclopramide as a second-line treatment for NVP because it appears to be effective and is not known to be associated with an increased risk of congenital malformations. Metoclopramide is widely used to prevent and treat intraoperative and postoperative nausea associated with cesarean delivery.7 In addition, intravenous (IV) metoclopramide is commonly used to treat women hospitalized with hyperemesis gravidarum. Results of randomized clinical trials demonstrate that when used to treat hyperemesis gravidarum, IV metoclopramide (10 mg every 8 hours) has similar efficacy to IV ondansetron (4 mg every 8 hours)8 and IV promethazine (25 mg every 8 hours).9 When using metoclopramide as an oral treatment for NVP, 10 mg every 8 hours is a commonly recommended regimen.
The FDA has assigned metoclopramide to pregnancy category B, which indicates that there is no evidence of fetal risk. Studies from Israel and Denmark show that metoclopramide is not associated with an increased risk of congenital malformations. In the study from Israel, among 3,458 infants born to women who had filled a prescription for metoclopramide during the first trimester of pregnancy, there was no increase in major congenital malformations, low birth weight, preterm delivery, or perinatal death.10 In the study from Denmark, among 28,486 infants born to mothers who had filled a prescription for metoclopramide in the first trimester there was no increase in congenital malformations or any of 20 individual categories of malformations, including neural tube defects, transposition of the great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip or palate, anorectal atresia/stenosis, or limb reduction.11 The results of these two large studies are reassuring that metoclopramide is not associated with an increased risk of congenital malformations.
Metoclopramide can cause tardive dyskinesia, a serious movement disorder that may be irreversible with discontinuation of the drug. This risk increases with dose and length of treatment. The FDA recommends that clinicians avoid the use of metoclopramide for more than 12 weeks.
Third-line pharmacologic treatment: Ondansetron
In the United States ondansetron is commonly used to treat NVP.12 The drug is a selective 5-HT3 antagonist that blocks serotonin action in the central nervous system chemoreceptor trigger zone. The elimination half-life of ondansetron is 3 to 6 hours (Lexicomp).
The frequent use of ondansetron may be due, in part, to the perception that it is a very effective antiemetic. For example, in one small clinical trial, ondansetron 4 mg every 8 hours was reported to be superior to a combination of pyridoxine 25 mg every 8 hours plus doxylamine 12.5 mg every 8 hours.13 (Note that the pyridoxine and doxylamine tablets used in this trial were not in a combination delayed-release formulation.) I am recommending ondansetron as a third-line treatment for NVP because, although it is effective, it may be associated with an increased risk of fetal cardiac anomalies.
Is ondansetron associated with cardiac malformations?
The FDA has assigned ondansetron to pregnancy category B; however, there is concern that it may be associated with congenital heart defects. In a recent study of 1,349 infants born to Swedish women who had filled a prescription for ondansetron in early pregnancy, a significantly increased risk of cardiovascular defect (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.04−2.14) and cardiac septum defect (OR, 2.05; 95% CI, 1.19−3.28) was reported.14 The cardiac anomalies were mostly atrial septal or ventricular septal defects.
In a second study, reported as an abstract, authors analyzed congenital malformations in 1,248 infants born to Danish women who filled a prescription for ondansetron in early pregnancy. These authors also found an increased risk of a congenital heart malformation (OR, 2.0; 95% CI, 1.3−3.1).15
A US case-control study showed an association between ondansetron use and cleft palate.1 The Swedish14 and Danish15 studies reported above did not find an association between ondansetron use and cleft palate.
The FDA issued a warning in June 2012 that at a dose of 32 mg, administered intravenously, ondansetron may prolong the QT interval and result in a potentially fatal heart arrhythmia, torsades de pointes.16 In the announcement the FDA did not alter the recommendations for oral dosing because there is no strong evidence that oral dosing is associated with clinically significant arrhythmias. Authors of a recent systematic review concluded that IV administration of large doses of ondansetron may cause cardiac arrhythmias, especially in patients with cardiac disease and those taking other drugs that prolong the QT interval, but that a single oral dose of ondansetron does not have a significant risk of causing an arrhythmia.17
Health Canada18 has advised that many commonly prescribed medications increase serotonin activity. When multiple drugs that each increase serotonin activity are prescribed in combination, the risk of serotonin syndrome is increased. Serotonin syndrome results in hyperthermia, agitation, tachycardia, and muscle twitching and can be fatal. Ondansetron was specifically mentioned in the Health Canada warning, but a search of the literature revealed very few reported cases of ondansetron being implicated in the serotonin syndrome.19
My bottom-line recommendations
NVP is a common obstetric problem. When oral pharmacologic therapy is indicated, first-line treatment should be with the FDA-approved combination of doxylamine-pyridoxine because it is both effective and associated with no known increased risk of congenital malformations. An effective second-line agent is metoclopramide. Based on very limited data, metoclopramide appears effective and is not associated with an increased risk of congenital malformations. However, it is not FDA approved for treatment of NVP. Ondansetron appears to be effective but its use in early pregnancy may be associated with congenital anomalies. Consequently, ondansetron should not be used to treat NVP unless first- and second-line treatments have been ineffective to treat the patient’s symptoms.
INSTANT POLL
Which of the following pharmacologic treatments of nausea with or without vomiting during pregnancy is your first-line medication choice?
• Ondansetron
• Metoclopramide
• Doxylamine-pyridoxine
• Meclizine Promethazine
• Trimethobenzamide
Visit the Quick Poll on the homepage, give your answer, and then see how other ObGyns have answered.
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
1. Anderka M, Mitchell AA, Louik C, Werler MMA, Hernandez-Diaz S, Rasmussen SA; National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012;94(1):22–30.
2. Matthews A, Haas Dm, O’Mathuna DP, Dowswell T, Doyle M. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2014;(3):CD007575.
3. Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005;105(4):849–856.
4. Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;203(6):571.e1–7.
5. Einarson TR, Leeder JS, Koren G. A method for meta-analysis of epidemiologic studies. Drug Intell Clin Pharm. 1988;22(10):813–824.
6. McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects. I. A meta-analysis of the epidemiologic studies. Teratology. 1994;50(1):27–37.
7. Mishriky BM, Habib AS. Metoclopramide for nausea and vomiting prophylaxis during and after cesarean delivery: a systematic review and meta-analysis. Br J Anaesth. 2012;108(3):374–383.
8. Abas MN, Tan PC, Azmi N, Omar SZ. Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1272–1279.
9. Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010;115(5):975–981.
10. Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med. 2009;360(24):2528–2535.
11. Pasternak B, Svanstrom H, Molgaard-Nielsen D, Melbye M, Hviid A. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA. 2013;310(15):1601–1611.
12. Koren G. Treating morning sickness in the United States—changes in prescribing are needed. Am J Obstet Gynecol. 2014;211(6):602–606.
13. Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SH. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy : a randomized controlled trial. Obstet Gynecol. 2014;124(4):735–742.
14. Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 2014;50:134–137.
15. Andersen JT, Jimenez-Solem E, Andersen NL, Poulsen HE. Ondansetron use in early pregnancy and the risk of congenital malformations—a registry based nationwide cohort study. Abstract presented at: 29th International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 25–28, 2013; Montreal, Canada. Abstract 25, Pregnancy Session 1. Pharmacoepidemiol Drug Saf. 2013;22(suppl 1):13–14.
16. US Food and Drug Administration. Ondansetron (Zofran) IV: drug safety communication - QT prolongation. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310219.htm. Published June 29, 2012. Accessed December 26, 2014.
17. Freedman SB, Uleryk E, Rumantir M, Finkelstein Y. Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med. 2014;64(1):19–25.
18. Health Canada. Canadian Adverse Reaction Newsletter. 2003;13(3). http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v13n3-eng.php. Published June 24, 2003. Accessed December 26, 2014.
19. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT3 antagonist agents. Psychosomatics. 2001;42(3):258–260.
Robert L. Barbieri, MD
Dr. Barbieri is Editor in Chief, OBG Management; Chair, Obstetrics and Gynecology, at Brigham and Women’s Hospital, Boston, Massachusetts; and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School, Boston.
Dr. Barbieri reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Dr. Barbieri is Editor in Chief, OBG Management; Chair, Obstetrics and Gynecology, at Brigham and Women’s Hospital, Boston, Massachusetts; and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School, Boston.
Dr. Barbieri reports no financial relationships relevant to this article.
Robert L. Barbieri, MD
Dr. Barbieri is Editor in Chief, OBG Management; Chair, Obstetrics and Gynecology, at Brigham and Women’s Hospital, Boston, Massachusetts; and Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School, Boston.
Dr. Barbieri reports no financial relationships relevant to this article.
CASE: Pregnant patient seeks medication for her NVP
A 23-year-old G1P0 woman at 9 weeks’ gestation presents to your office with nausea and vomiting that is interfering with work. She has tried many changes in her daily habits. She has tried eating small, frequent meals; snacking on nuts and crackers; using lemon-scented products; and avoiding coffee and strong odors. Following an evaluation you diagnose nausea and vomiting of pregnancy (NVP). She asks, “Is there a medication for my nausea that is safe for my baby?”
Nausea with or without vomiting is a common problem for pregnant women between 6 and 14 weeks of gestation. In one study, nausea with or without vomiting was reported by 69% of patients and resulted in pharmacologic treatment in 15%.1 In a Cochrane review of NVP, investigators analyzed 37 trials involving treatments such as acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, vitamin B6, and antiemetic medications. The authors concluded, “There is a lack of high-quality evidence to support any particular intervention.”2 Clinicians are challenged to effectively treat the symptoms of NVP and simultaneously to minimize the risk that the fetus will be exposed to a teratogen during the first trimester, a vulnerable period in organ development.
In this editorial, I briefly review nonpharmacologic options for NVP, but focus on current pharmacologic treatments. Of those available to ObGyns, what is the best first-choice treatment given recent and accumulated data regarding associated congenital anomalies?
Nonpharmacologic treatment
Although the authors of the Cochrane review did not identify high-quality evidence to support nonpharmacologic interventions, results of multiple randomized trials have demonstrated that ginger is effective in reducing pregnancy-associated nausea and vomiting.3 Ginger treatment is recommended at doses of 250 mg in capsules or syrup four times daily.
First-line pharmacologic treatment: Doxylamine plus pyridoxine
The US Food and Drug Administration (FDA) has approved the combination of doxylamine plus pyridoxine (vitamin B6) in a delayed-release formulation for treatment of NVP (Diclegis). Doxylamine is an antihistamine that blocks H1-receptor sites in the chemoreceptor trigger zone. It also diminishes vestibular stimulation and depresses labyrinthine activity through central anticholinergic activity. Its elimination half-life is 10 to 12 hours (Lexicomp). Each tablet contains doxylamine 10 mg and pyridoxine 10 mg. The starting dose is 2 tablets at bedtime.
If the woman has persistent symptoms, a third tablet is added, to be taken in the morning. If symptoms continue, a fourth tablet is recommended to be taken in the afternoon. In a large, randomized clinical trial, doxylamine-pyridoxine treatment reduced nausea, vomiting, and retching and improved perceived quality of life compared with placebo.4 The FDA assigned doxylamine-pyridoxine pregnancy category A because of the extensive evidence that it does not cause an increase in fetal malformations.5,6
If the delayed-release doxylamine-pyridoxine formulation (Diclegis) is not available to the patient, alternative formulations of doxylamine and pyridoxine can be prescribed. Pyridoxine is widely available over the counter as 25-mg tablets, and one tablet can be prescribed two or three times daily. Doxylamine is available as a chewable prescription medicine in 5-mg tablets (Aldex AN) and two tablets can be prescribed two or three times daily. Doxylamine is also available as a 25-mg over-the-counter tablet in Unisom SleepTabs. One-half tablet can be prescribed two or three times daily. The patient should be alerted that Unisom SleepGels contain diphenhydramine, not doxylamine.
Second-line pharmacologic treatment
Metoclopramide Metoclopramide is a dopamine antagonist. It enhances upper gastrointestinal motility, accelerates gastric emptying, and increases lower esophageal sphincter tone. At higher doses it blocks serotonin receptors in the chemoreceptor trigger zone. Its elimination half-life is 5 to 6 hours (Lexicomp). There are no large, randomized, placebo-controlled trials of oral metoclopramide for the treatment of nausea and vomiting of early pregnancy.
I am recommending metoclopramide as a second-line treatment for NVP because it appears to be effective and is not known to be associated with an increased risk of congenital malformations. Metoclopramide is widely used to prevent and treat intraoperative and postoperative nausea associated with cesarean delivery.7 In addition, intravenous (IV) metoclopramide is commonly used to treat women hospitalized with hyperemesis gravidarum. Results of randomized clinical trials demonstrate that when used to treat hyperemesis gravidarum, IV metoclopramide (10 mg every 8 hours) has similar efficacy to IV ondansetron (4 mg every 8 hours)8 and IV promethazine (25 mg every 8 hours).9 When using metoclopramide as an oral treatment for NVP, 10 mg every 8 hours is a commonly recommended regimen.
The FDA has assigned metoclopramide to pregnancy category B, which indicates that there is no evidence of fetal risk. Studies from Israel and Denmark show that metoclopramide is not associated with an increased risk of congenital malformations. In the study from Israel, among 3,458 infants born to women who had filled a prescription for metoclopramide during the first trimester of pregnancy, there was no increase in major congenital malformations, low birth weight, preterm delivery, or perinatal death.10 In the study from Denmark, among 28,486 infants born to mothers who had filled a prescription for metoclopramide in the first trimester there was no increase in congenital malformations or any of 20 individual categories of malformations, including neural tube defects, transposition of the great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip or palate, anorectal atresia/stenosis, or limb reduction.11 The results of these two large studies are reassuring that metoclopramide is not associated with an increased risk of congenital malformations.
Metoclopramide can cause tardive dyskinesia, a serious movement disorder that may be irreversible with discontinuation of the drug. This risk increases with dose and length of treatment. The FDA recommends that clinicians avoid the use of metoclopramide for more than 12 weeks.
Third-line pharmacologic treatment: Ondansetron
In the United States ondansetron is commonly used to treat NVP.12 The drug is a selective 5-HT3 antagonist that blocks serotonin action in the central nervous system chemoreceptor trigger zone. The elimination half-life of ondansetron is 3 to 6 hours (Lexicomp).
The frequent use of ondansetron may be due, in part, to the perception that it is a very effective antiemetic. For example, in one small clinical trial, ondansetron 4 mg every 8 hours was reported to be superior to a combination of pyridoxine 25 mg every 8 hours plus doxylamine 12.5 mg every 8 hours.13 (Note that the pyridoxine and doxylamine tablets used in this trial were not in a combination delayed-release formulation.) I am recommending ondansetron as a third-line treatment for NVP because, although it is effective, it may be associated with an increased risk of fetal cardiac anomalies.
Is ondansetron associated with cardiac malformations?
The FDA has assigned ondansetron to pregnancy category B; however, there is concern that it may be associated with congenital heart defects. In a recent study of 1,349 infants born to Swedish women who had filled a prescription for ondansetron in early pregnancy, a significantly increased risk of cardiovascular defect (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.04−2.14) and cardiac septum defect (OR, 2.05; 95% CI, 1.19−3.28) was reported.14 The cardiac anomalies were mostly atrial septal or ventricular septal defects.
In a second study, reported as an abstract, authors analyzed congenital malformations in 1,248 infants born to Danish women who filled a prescription for ondansetron in early pregnancy. These authors also found an increased risk of a congenital heart malformation (OR, 2.0; 95% CI, 1.3−3.1).15
A US case-control study showed an association between ondansetron use and cleft palate.1 The Swedish14 and Danish15 studies reported above did not find an association between ondansetron use and cleft palate.
The FDA issued a warning in June 2012 that at a dose of 32 mg, administered intravenously, ondansetron may prolong the QT interval and result in a potentially fatal heart arrhythmia, torsades de pointes.16 In the announcement the FDA did not alter the recommendations for oral dosing because there is no strong evidence that oral dosing is associated with clinically significant arrhythmias. Authors of a recent systematic review concluded that IV administration of large doses of ondansetron may cause cardiac arrhythmias, especially in patients with cardiac disease and those taking other drugs that prolong the QT interval, but that a single oral dose of ondansetron does not have a significant risk of causing an arrhythmia.17
Health Canada18 has advised that many commonly prescribed medications increase serotonin activity. When multiple drugs that each increase serotonin activity are prescribed in combination, the risk of serotonin syndrome is increased. Serotonin syndrome results in hyperthermia, agitation, tachycardia, and muscle twitching and can be fatal. Ondansetron was specifically mentioned in the Health Canada warning, but a search of the literature revealed very few reported cases of ondansetron being implicated in the serotonin syndrome.19
My bottom-line recommendations
NVP is a common obstetric problem. When oral pharmacologic therapy is indicated, first-line treatment should be with the FDA-approved combination of doxylamine-pyridoxine because it is both effective and associated with no known increased risk of congenital malformations. An effective second-line agent is metoclopramide. Based on very limited data, metoclopramide appears effective and is not associated with an increased risk of congenital malformations. However, it is not FDA approved for treatment of NVP. Ondansetron appears to be effective but its use in early pregnancy may be associated with congenital anomalies. Consequently, ondansetron should not be used to treat NVP unless first- and second-line treatments have been ineffective to treat the patient’s symptoms.
INSTANT POLL
Which of the following pharmacologic treatments of nausea with or without vomiting during pregnancy is your first-line medication choice?
• Ondansetron
• Metoclopramide
• Doxylamine-pyridoxine
• Meclizine Promethazine
• Trimethobenzamide
Visit the Quick Poll on the homepage, give your answer, and then see how other ObGyns have answered.
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
CASE: Pregnant patient seeks medication for her NVP
A 23-year-old G1P0 woman at 9 weeks’ gestation presents to your office with nausea and vomiting that is interfering with work. She has tried many changes in her daily habits. She has tried eating small, frequent meals; snacking on nuts and crackers; using lemon-scented products; and avoiding coffee and strong odors. Following an evaluation you diagnose nausea and vomiting of pregnancy (NVP). She asks, “Is there a medication for my nausea that is safe for my baby?”
Nausea with or without vomiting is a common problem for pregnant women between 6 and 14 weeks of gestation. In one study, nausea with or without vomiting was reported by 69% of patients and resulted in pharmacologic treatment in 15%.1 In a Cochrane review of NVP, investigators analyzed 37 trials involving treatments such as acupressure, acustimulation, acupuncture, ginger, chamomile, lemon oil, vitamin B6, and antiemetic medications. The authors concluded, “There is a lack of high-quality evidence to support any particular intervention.”2 Clinicians are challenged to effectively treat the symptoms of NVP and simultaneously to minimize the risk that the fetus will be exposed to a teratogen during the first trimester, a vulnerable period in organ development.
In this editorial, I briefly review nonpharmacologic options for NVP, but focus on current pharmacologic treatments. Of those available to ObGyns, what is the best first-choice treatment given recent and accumulated data regarding associated congenital anomalies?
Nonpharmacologic treatment
Although the authors of the Cochrane review did not identify high-quality evidence to support nonpharmacologic interventions, results of multiple randomized trials have demonstrated that ginger is effective in reducing pregnancy-associated nausea and vomiting.3 Ginger treatment is recommended at doses of 250 mg in capsules or syrup four times daily.
First-line pharmacologic treatment: Doxylamine plus pyridoxine
The US Food and Drug Administration (FDA) has approved the combination of doxylamine plus pyridoxine (vitamin B6) in a delayed-release formulation for treatment of NVP (Diclegis). Doxylamine is an antihistamine that blocks H1-receptor sites in the chemoreceptor trigger zone. It also diminishes vestibular stimulation and depresses labyrinthine activity through central anticholinergic activity. Its elimination half-life is 10 to 12 hours (Lexicomp). Each tablet contains doxylamine 10 mg and pyridoxine 10 mg. The starting dose is 2 tablets at bedtime.
If the woman has persistent symptoms, a third tablet is added, to be taken in the morning. If symptoms continue, a fourth tablet is recommended to be taken in the afternoon. In a large, randomized clinical trial, doxylamine-pyridoxine treatment reduced nausea, vomiting, and retching and improved perceived quality of life compared with placebo.4 The FDA assigned doxylamine-pyridoxine pregnancy category A because of the extensive evidence that it does not cause an increase in fetal malformations.5,6
If the delayed-release doxylamine-pyridoxine formulation (Diclegis) is not available to the patient, alternative formulations of doxylamine and pyridoxine can be prescribed. Pyridoxine is widely available over the counter as 25-mg tablets, and one tablet can be prescribed two or three times daily. Doxylamine is available as a chewable prescription medicine in 5-mg tablets (Aldex AN) and two tablets can be prescribed two or three times daily. Doxylamine is also available as a 25-mg over-the-counter tablet in Unisom SleepTabs. One-half tablet can be prescribed two or three times daily. The patient should be alerted that Unisom SleepGels contain diphenhydramine, not doxylamine.
Second-line pharmacologic treatment
Metoclopramide Metoclopramide is a dopamine antagonist. It enhances upper gastrointestinal motility, accelerates gastric emptying, and increases lower esophageal sphincter tone. At higher doses it blocks serotonin receptors in the chemoreceptor trigger zone. Its elimination half-life is 5 to 6 hours (Lexicomp). There are no large, randomized, placebo-controlled trials of oral metoclopramide for the treatment of nausea and vomiting of early pregnancy.
I am recommending metoclopramide as a second-line treatment for NVP because it appears to be effective and is not known to be associated with an increased risk of congenital malformations. Metoclopramide is widely used to prevent and treat intraoperative and postoperative nausea associated with cesarean delivery.7 In addition, intravenous (IV) metoclopramide is commonly used to treat women hospitalized with hyperemesis gravidarum. Results of randomized clinical trials demonstrate that when used to treat hyperemesis gravidarum, IV metoclopramide (10 mg every 8 hours) has similar efficacy to IV ondansetron (4 mg every 8 hours)8 and IV promethazine (25 mg every 8 hours).9 When using metoclopramide as an oral treatment for NVP, 10 mg every 8 hours is a commonly recommended regimen.
The FDA has assigned metoclopramide to pregnancy category B, which indicates that there is no evidence of fetal risk. Studies from Israel and Denmark show that metoclopramide is not associated with an increased risk of congenital malformations. In the study from Israel, among 3,458 infants born to women who had filled a prescription for metoclopramide during the first trimester of pregnancy, there was no increase in major congenital malformations, low birth weight, preterm delivery, or perinatal death.10 In the study from Denmark, among 28,486 infants born to mothers who had filled a prescription for metoclopramide in the first trimester there was no increase in congenital malformations or any of 20 individual categories of malformations, including neural tube defects, transposition of the great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip or palate, anorectal atresia/stenosis, or limb reduction.11 The results of these two large studies are reassuring that metoclopramide is not associated with an increased risk of congenital malformations.
Metoclopramide can cause tardive dyskinesia, a serious movement disorder that may be irreversible with discontinuation of the drug. This risk increases with dose and length of treatment. The FDA recommends that clinicians avoid the use of metoclopramide for more than 12 weeks.
Third-line pharmacologic treatment: Ondansetron
In the United States ondansetron is commonly used to treat NVP.12 The drug is a selective 5-HT3 antagonist that blocks serotonin action in the central nervous system chemoreceptor trigger zone. The elimination half-life of ondansetron is 3 to 6 hours (Lexicomp).
The frequent use of ondansetron may be due, in part, to the perception that it is a very effective antiemetic. For example, in one small clinical trial, ondansetron 4 mg every 8 hours was reported to be superior to a combination of pyridoxine 25 mg every 8 hours plus doxylamine 12.5 mg every 8 hours.13 (Note that the pyridoxine and doxylamine tablets used in this trial were not in a combination delayed-release formulation.) I am recommending ondansetron as a third-line treatment for NVP because, although it is effective, it may be associated with an increased risk of fetal cardiac anomalies.
Is ondansetron associated with cardiac malformations?
The FDA has assigned ondansetron to pregnancy category B; however, there is concern that it may be associated with congenital heart defects. In a recent study of 1,349 infants born to Swedish women who had filled a prescription for ondansetron in early pregnancy, a significantly increased risk of cardiovascular defect (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.04−2.14) and cardiac septum defect (OR, 2.05; 95% CI, 1.19−3.28) was reported.14 The cardiac anomalies were mostly atrial septal or ventricular septal defects.
In a second study, reported as an abstract, authors analyzed congenital malformations in 1,248 infants born to Danish women who filled a prescription for ondansetron in early pregnancy. These authors also found an increased risk of a congenital heart malformation (OR, 2.0; 95% CI, 1.3−3.1).15
A US case-control study showed an association between ondansetron use and cleft palate.1 The Swedish14 and Danish15 studies reported above did not find an association between ondansetron use and cleft palate.
The FDA issued a warning in June 2012 that at a dose of 32 mg, administered intravenously, ondansetron may prolong the QT interval and result in a potentially fatal heart arrhythmia, torsades de pointes.16 In the announcement the FDA did not alter the recommendations for oral dosing because there is no strong evidence that oral dosing is associated with clinically significant arrhythmias. Authors of a recent systematic review concluded that IV administration of large doses of ondansetron may cause cardiac arrhythmias, especially in patients with cardiac disease and those taking other drugs that prolong the QT interval, but that a single oral dose of ondansetron does not have a significant risk of causing an arrhythmia.17
Health Canada18 has advised that many commonly prescribed medications increase serotonin activity. When multiple drugs that each increase serotonin activity are prescribed in combination, the risk of serotonin syndrome is increased. Serotonin syndrome results in hyperthermia, agitation, tachycardia, and muscle twitching and can be fatal. Ondansetron was specifically mentioned in the Health Canada warning, but a search of the literature revealed very few reported cases of ondansetron being implicated in the serotonin syndrome.19
My bottom-line recommendations
NVP is a common obstetric problem. When oral pharmacologic therapy is indicated, first-line treatment should be with the FDA-approved combination of doxylamine-pyridoxine because it is both effective and associated with no known increased risk of congenital malformations. An effective second-line agent is metoclopramide. Based on very limited data, metoclopramide appears effective and is not associated with an increased risk of congenital malformations. However, it is not FDA approved for treatment of NVP. Ondansetron appears to be effective but its use in early pregnancy may be associated with congenital anomalies. Consequently, ondansetron should not be used to treat NVP unless first- and second-line treatments have been ineffective to treat the patient’s symptoms.
INSTANT POLL
Which of the following pharmacologic treatments of nausea with or without vomiting during pregnancy is your first-line medication choice?
• Ondansetron
• Metoclopramide
• Doxylamine-pyridoxine
• Meclizine Promethazine
• Trimethobenzamide
Visit the Quick Poll on the homepage, give your answer, and then see how other ObGyns have answered.
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
1. Anderka M, Mitchell AA, Louik C, Werler MMA, Hernandez-Diaz S, Rasmussen SA; National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012;94(1):22–30.
2. Matthews A, Haas Dm, O’Mathuna DP, Dowswell T, Doyle M. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2014;(3):CD007575.
3. Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005;105(4):849–856.
4. Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;203(6):571.e1–7.
5. Einarson TR, Leeder JS, Koren G. A method for meta-analysis of epidemiologic studies. Drug Intell Clin Pharm. 1988;22(10):813–824.
6. McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects. I. A meta-analysis of the epidemiologic studies. Teratology. 1994;50(1):27–37.
7. Mishriky BM, Habib AS. Metoclopramide for nausea and vomiting prophylaxis during and after cesarean delivery: a systematic review and meta-analysis. Br J Anaesth. 2012;108(3):374–383.
8. Abas MN, Tan PC, Azmi N, Omar SZ. Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1272–1279.
9. Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010;115(5):975–981.
10. Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med. 2009;360(24):2528–2535.
11. Pasternak B, Svanstrom H, Molgaard-Nielsen D, Melbye M, Hviid A. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA. 2013;310(15):1601–1611.
12. Koren G. Treating morning sickness in the United States—changes in prescribing are needed. Am J Obstet Gynecol. 2014;211(6):602–606.
13. Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SH. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy : a randomized controlled trial. Obstet Gynecol. 2014;124(4):735–742.
14. Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 2014;50:134–137.
15. Andersen JT, Jimenez-Solem E, Andersen NL, Poulsen HE. Ondansetron use in early pregnancy and the risk of congenital malformations—a registry based nationwide cohort study. Abstract presented at: 29th International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 25–28, 2013; Montreal, Canada. Abstract 25, Pregnancy Session 1. Pharmacoepidemiol Drug Saf. 2013;22(suppl 1):13–14.
16. US Food and Drug Administration. Ondansetron (Zofran) IV: drug safety communication - QT prolongation. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310219.htm. Published June 29, 2012. Accessed December 26, 2014.
17. Freedman SB, Uleryk E, Rumantir M, Finkelstein Y. Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med. 2014;64(1):19–25.
18. Health Canada. Canadian Adverse Reaction Newsletter. 2003;13(3). http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v13n3-eng.php. Published June 24, 2003. Accessed December 26, 2014.
19. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT3 antagonist agents. Psychosomatics. 2001;42(3):258–260.
1. Anderka M, Mitchell AA, Louik C, Werler MMA, Hernandez-Diaz S, Rasmussen SA; National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012;94(1):22–30.
2. Matthews A, Haas Dm, O’Mathuna DP, Dowswell T, Doyle M. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2014;(3):CD007575.
3. Borrelli F, Capasso R, Aviello G, Pittler MH, Izzo AA. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005;105(4):849–856.
4. Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;203(6):571.e1–7.
5. Einarson TR, Leeder JS, Koren G. A method for meta-analysis of epidemiologic studies. Drug Intell Clin Pharm. 1988;22(10):813–824.
6. McKeigue PM, Lamm SH, Linn S, Kutcher JS. Bendectin and birth defects. I. A meta-analysis of the epidemiologic studies. Teratology. 1994;50(1):27–37.
7. Mishriky BM, Habib AS. Metoclopramide for nausea and vomiting prophylaxis during and after cesarean delivery: a systematic review and meta-analysis. Br J Anaesth. 2012;108(3):374–383.
8. Abas MN, Tan PC, Azmi N, Omar SZ. Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1272–1279.
9. Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010;115(5):975–981.
10. Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med. 2009;360(24):2528–2535.
11. Pasternak B, Svanstrom H, Molgaard-Nielsen D, Melbye M, Hviid A. Metoclopramide in pregnancy and risk of major congenital malformations and fetal death. JAMA. 2013;310(15):1601–1611.
12. Koren G. Treating morning sickness in the United States—changes in prescribing are needed. Am J Obstet Gynecol. 2014;211(6):602–606.
13. Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SH. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy : a randomized controlled trial. Obstet Gynecol. 2014;124(4):735–742.
14. Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 2014;50:134–137.
15. Andersen JT, Jimenez-Solem E, Andersen NL, Poulsen HE. Ondansetron use in early pregnancy and the risk of congenital malformations—a registry based nationwide cohort study. Abstract presented at: 29th International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 25–28, 2013; Montreal, Canada. Abstract 25, Pregnancy Session 1. Pharmacoepidemiol Drug Saf. 2013;22(suppl 1):13–14.
16. US Food and Drug Administration. Ondansetron (Zofran) IV: drug safety communication - QT prolongation. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310219.htm. Published June 29, 2012. Accessed December 26, 2014.
17. Freedman SB, Uleryk E, Rumantir M, Finkelstein Y. Ondansetron and the risk of cardiac arrhythmias: a systematic review and postmarketing analysis. Ann Emerg Med. 2014;64(1):19–25.
18. Health Canada. Canadian Adverse Reaction Newsletter. 2003;13(3). http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v13n3-eng.php. Published June 24, 2003. Accessed December 26, 2014.
19. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT3 antagonist agents. Psychosomatics. 2001;42(3):258–260.
Negligence during cord blood sampling? Child has CP
Negligence during cord blood sampling? Child has CP
A woman’s first child was treated for neonatal alloimmune thrombocytopenia (NAIT) after birth. When prenatal testing identified NAIT in her second child, the mother received twice-weekly immunoglobulin injections to increase the fetus’ platelet count.
At 33 weeks’ gestation, percutaneous umbilical blood sampling (PUBS) was undertaken by a maternal-fetal medicine (MFM) specialist to check the baby’s platelet count and inject additional platelets. During the procedure, the mother’s blood pressure dropped from 122/80 to 80/40 mm Hg. The fetal heart rate dropped from 120–130 bpm to 65 bpm. An emergency cesarean delivery was performed.
At birth, the baby had seizures and respiratory distress secondary to perinatal asphyxia. She has severe spastic quadriplegic cerebral palsy. At age 9 years, she has been hospitalized for multiple complications, underwent tendon-release procedures on both legs, and receives occupational and physical therapy. She cannot speak, needs a feeding tube, is wheelchair bound, and requires 24-hour nursing care.
PARENTS’ CLAIM The MFM was not adequately trained to perform PUBS and did not use continuous ultrasound guidance during the procedure. She was negligent in attempting to insert the needle into the umbilical cord multiple times. She failed to recognize fetal distress. The anesthesiologist only told the MFM that the patient was hypotensive, not that the patient’s blood pressure never returned to baseline.
defendants’ DEFENSE The mother was part of a NAIT study, and the procedure was properly performed under the guidelines of that study. A sonographer constantly monitored the fetal heart rate. The anesthesiologist claimed that proper actions were taken in response to low blood pressure; there was no requirement to communicate more information to the MFM. The child’s hypoxia was due to placental abruption. The estimated cost of the life-care plan for the child is $5 to $10 million.
VERDICT A $15 million Indiana verdict was returned against the medical center that employed the anesthesiologist, but was reduced to $1,250,000 by the state cap. A defense verdict was returned for the MFM.
Woman dies from cervical cancer: $2.33M
When a woman had an abnormal Pap smear in 2001, her gynecologist did not order a repeat test, but told the patient to return in 3 months. The patient did not see the gynecologist again until 2007. At that time, her Pap smear was normal, but she was experiencing symptoms. The gynecologist did not order further testing.
In 2009, the patient was found to have advanced cervical cancer. She died 2 years later at age 48.
ESTATE’S CLAIM The second Pap smear was incorrectly interpreted. Further testing should have been ordered in 2001 and 2007.
DEFENDANTS’ DEFENSE The laboratory and patient’s estate settled for a confidential amount before the trial commenced. The gynecologist denied negligence. He claimed the patient was at fault for not returning to see him, as recommended.
VERDICT A New Jersey jury found the gynecologist 40% at fault, the laboratory 50% at fault, and the patient 10% at fault. A gross verdict of $2.33 million was returned.
Was it HELLP syndrome?
By her prenatal visit at 33 weeks’ gestation, a mother had gained 59 lb during her pregnancy. Three days later, she went to the emergency department (ED). The fetus had died.
PARENT’S CLAIM The ObGyn failed to intervene when the mother was gaining excessive weight. The mother had HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); timely diagnosis could have avoided fetal demise.
DEFENDANTS’ DEFENSE Fetal demise could not have been diagnosed or prevented. The cause of the mother’s illness was never fully identified.
VERDICT A Tennessee defense verdict was returned.
Vesicovaginal fistula after hysterectomy
A woman underwent a hysterectomy performed by her ObGyn. A week later, during a postoperative visit, the ObGyn detected a bladder injury and related vesicovaginal fistula. He attempted a repair, but it failed. Eventually, successful repair surgery was performed by a urologist.
PATIENT’S CLAIM The ObGyn only should have used sharp dissection during the hysterectomy, as opposed to a combination of sharp and blunt dissection, due to dense adhesions that had developed after earlier abdominal surgery. Because the ObGyn had never repaired a vesicovaginal fistula before, he should have requested the assistance of a urologist or urogynecologist. A peritoneal flap should have been used during the initial repair.
PHYSICIAN’S DEFENSE Referral to a urologist or urogynecologist had been offered to the patient, but was refused (no record of this was found in the patient’s file). There was no negligence in the attempted repair.
VERDICT A $387,000 Virginia verdict was returned.
Did she really need that hysterectomy?
A 31-year-old woman went to the ED with sudden, severe abdominal pain. The radiologist noted that the patient’s appendix could not be visualized on computed tomography (CT) because it was behind the cecum. A general surgeon interpreted the report as ruling out appendicitis, made a diagnosis of pelvic inflammatory disease, and requested a gynecologic consult. An ObGyn sent his nurse practitioner to see the patient in the ED. The patient was discharged and instructed to follow up with the ObGyn.
When the patient’s condition worsened 2 days later, she returned to the ED. The ObGyn performed laparoscopic exploratory surgery. When he could not find the appendix, he called the general surgeon. The surgeon was in his car, and told the ObGyn that it was unnecessary to visualize the appendix; the ObGyn could complete the surgery. The patient was again discharged without a firm diagnosis. She was readmitted to the hospital several hours after discharge and treated for sepsis.
She was in and out of the hospital several times during the next 7 weeks until the ObGyn told her that the only way to cure her pain was to perform a partial hysterectomy. He scheduled a concurrent prophylactic appendectomy by the general surgeon. At surgery, the surgeon found and removed a burst appendix. The ObGyn then performed a hysterectomy, although he had been present during the appendectomy.
PATIENT’S CLAIM Any general surgeon could have come into the operating room during exploratory surgery to assist in ruling out appendicitis; there were other general surgeons available at the hospital. The ObGyn was negligent in performing the hysterectomy after the surgeon had performed the appendectomy.
PHYSICIAN’S DEFENSE The general surgeon died before the case could be deposed. The ObGyn admitted that the removal of the burst appendix resolved the patient’s medical problems; her uterus had not been damaged by sepsis.
VERDICT A $350,000 Michigan settlement was reached.
Erb’s palsy: $1.7M net award
At 38 weeks’ gestation, a mother went to the local ED reporting shortness of breath. She was transferred to a university medical center where a chest x-ray revealed what was thought to be pneumonia or a pulmonary embolism. The decision was made to induce labor. During vaginal delivery, shoulder dystocia was encountered.
The 3-year-old child has Erb’s palsy and, despite treatment and therapy, does not have full use of her left arm and shoulder.
PARENTS’ CLAIM Maneuvers undertaken to relieve shoulder dystocia were not properly performed, injuring the baby. A cesarean delivery should have been performed because of the mother’s condition.
DEFENDANTS’ DEFENSE Proper maneuvers were used. There was no medical necessity for emergency cesarean delivery.
VERDICT A $3 million Maryland verdict was returned. After state caps and recalculation of a lost-wages claim from the mother due to jury error, the net award was $1.7 million.
Was nonreassuring fetal heart rate ignored?
In her third trimester, a 20-year-old woman was admitted to the hospital for observation, which included fetal heart-rate monitoring.
After 2 days, the patient began to bleed vaginally, and the nurses called the ObGyn. When he came to the hospital, he performed emergency cesarean delivery. The fetus was stillborn.
PATIENT’S CLAIM The nurses failed to inform the ObGyn when nonreassuring fetal heart-rate monitoring results were first evident. The ObGyn did not come to the hospital immediately after being told about the vaginal bleeding. The surgical team was not ready when it was time for the cesarean delivery.
DEFENDANTS’ DEFENSE The case was tried against the hospital that employed the nurses and ObGyn. The hospital claimed that fetal demise was caused by a sudden placental abruption. The nurses’ actions were appropriate. The hospital faulted the ObGyn for not coming to the hospital when summoned by the nurses.
VERDICT A $100,000 Louisiana verdict was returned. The jury found the ObGyn 99% at fault and the hospital 1% at fault. The patient was awarded $100,000 from the Patient’s Compensation Fund; the hospital paid $1,000.
Patient says wrong ovary was removed
A woman saw her ObGyn (Dr. A) because of lower abdominal pain. Dr. A performed laparoscopic right salpingo-oophorectomy.
A tumor on the left ovary was found 5 months later, and a second operation was performed by another ObGyn (Dr. B) with Dr. A’s assistance. During this surgery, the patient’s sigmoid colon was injured; a fistula developed and a third operation was required to repair the colon.
PATIENT’S CLAIM The initial plan was to remove the left ovary. When Dr. Aremoved the right ovary instead of the left, the patient experienced sudden onset of menopause; the left ovary was nonfunctional. Dr. B was negligent in injuring the sigmoid colon.
PHYSICIANS’ DEFENSE Dr. B was released from the case because colon injury is a known complication of the procedure. Dr. A claimed that the radiologic film of the mass was misleading, and that the ovary he removed was diseased.
VERDICT A Virginia defense verdict was returned.
Second pregnancy ends in injury after shoulder dystocia
A mother told her new ObGyn that, during the birth of her first child a few years earlier, shoulder dystocia had been encountered. Although the baby was born unharmed, her prior ObGyn had recommended that she undergo cesarean delivery for future pregnancies. During the second pregnancy, the mother and new ObGyn discussed the possibility of a trial of labor and vaginal delivery.
When the mother went into labor at 37 weeks’ gestation, the ObGyn believed the child was of normal weight and proceeded with a vaginal delivery. When shoulder dystocia was encountered, various maneuvers were performed. Birth occurred 5 minutes later using moderate traction.
The child showed no signs of life at birth; Apgar scores were 0 for more than 14 minutes. The newborn was sent to the neonatal intensive care unit and later airlifted to another hospital. He had hypoxic ischemic encephalopathy and a C5–C6 brachial plexus injury.
Additional testing revealed that he has neurocognitive deficits including attention deficit hyperactivity disorder and executive function disabilities.
Parents’ claim The ObGyn was negligent in failing to fully explain the risks of vaginal delivery, failing to recommend cesarean delivery based on the patient’s history and prior physician’s recommendation. The ObGyn failed to perform ultrasonography when the mother was admitted to the hospital; such imaging would have revealed that the fetus was larger than her first baby, mandating cesarean delivery. The ObGyn failed to perform an episiotomy after dystocia was encountered, and he applied excessive traction during dystocial maneuvers.
PHYSICIAN’S DEFENSE The mother was extensively counseled on the risks of vaginal delivery, but the ObGyn admitted that he did not recommend a cesarean delivery. Ultrasonography would have had no benefit. The use of moderate traction was necessary to prevent severe brain damage or death. The child’s current deficits are not related to his birth.
VERDICT The hospital settled for $85,000 before the trial began. An Illinois defense verdict was returned for the ObGyn.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Negligence during cord blood sampling? Child has CP
A woman’s first child was treated for neonatal alloimmune thrombocytopenia (NAIT) after birth. When prenatal testing identified NAIT in her second child, the mother received twice-weekly immunoglobulin injections to increase the fetus’ platelet count.
At 33 weeks’ gestation, percutaneous umbilical blood sampling (PUBS) was undertaken by a maternal-fetal medicine (MFM) specialist to check the baby’s platelet count and inject additional platelets. During the procedure, the mother’s blood pressure dropped from 122/80 to 80/40 mm Hg. The fetal heart rate dropped from 120–130 bpm to 65 bpm. An emergency cesarean delivery was performed.
At birth, the baby had seizures and respiratory distress secondary to perinatal asphyxia. She has severe spastic quadriplegic cerebral palsy. At age 9 years, she has been hospitalized for multiple complications, underwent tendon-release procedures on both legs, and receives occupational and physical therapy. She cannot speak, needs a feeding tube, is wheelchair bound, and requires 24-hour nursing care.
PARENTS’ CLAIM The MFM was not adequately trained to perform PUBS and did not use continuous ultrasound guidance during the procedure. She was negligent in attempting to insert the needle into the umbilical cord multiple times. She failed to recognize fetal distress. The anesthesiologist only told the MFM that the patient was hypotensive, not that the patient’s blood pressure never returned to baseline.
defendants’ DEFENSE The mother was part of a NAIT study, and the procedure was properly performed under the guidelines of that study. A sonographer constantly monitored the fetal heart rate. The anesthesiologist claimed that proper actions were taken in response to low blood pressure; there was no requirement to communicate more information to the MFM. The child’s hypoxia was due to placental abruption. The estimated cost of the life-care plan for the child is $5 to $10 million.
VERDICT A $15 million Indiana verdict was returned against the medical center that employed the anesthesiologist, but was reduced to $1,250,000 by the state cap. A defense verdict was returned for the MFM.
Woman dies from cervical cancer: $2.33M
When a woman had an abnormal Pap smear in 2001, her gynecologist did not order a repeat test, but told the patient to return in 3 months. The patient did not see the gynecologist again until 2007. At that time, her Pap smear was normal, but she was experiencing symptoms. The gynecologist did not order further testing.
In 2009, the patient was found to have advanced cervical cancer. She died 2 years later at age 48.
ESTATE’S CLAIM The second Pap smear was incorrectly interpreted. Further testing should have been ordered in 2001 and 2007.
DEFENDANTS’ DEFENSE The laboratory and patient’s estate settled for a confidential amount before the trial commenced. The gynecologist denied negligence. He claimed the patient was at fault for not returning to see him, as recommended.
VERDICT A New Jersey jury found the gynecologist 40% at fault, the laboratory 50% at fault, and the patient 10% at fault. A gross verdict of $2.33 million was returned.
Was it HELLP syndrome?
By her prenatal visit at 33 weeks’ gestation, a mother had gained 59 lb during her pregnancy. Three days later, she went to the emergency department (ED). The fetus had died.
PARENT’S CLAIM The ObGyn failed to intervene when the mother was gaining excessive weight. The mother had HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); timely diagnosis could have avoided fetal demise.
DEFENDANTS’ DEFENSE Fetal demise could not have been diagnosed or prevented. The cause of the mother’s illness was never fully identified.
VERDICT A Tennessee defense verdict was returned.
Vesicovaginal fistula after hysterectomy
A woman underwent a hysterectomy performed by her ObGyn. A week later, during a postoperative visit, the ObGyn detected a bladder injury and related vesicovaginal fistula. He attempted a repair, but it failed. Eventually, successful repair surgery was performed by a urologist.
PATIENT’S CLAIM The ObGyn only should have used sharp dissection during the hysterectomy, as opposed to a combination of sharp and blunt dissection, due to dense adhesions that had developed after earlier abdominal surgery. Because the ObGyn had never repaired a vesicovaginal fistula before, he should have requested the assistance of a urologist or urogynecologist. A peritoneal flap should have been used during the initial repair.
PHYSICIAN’S DEFENSE Referral to a urologist or urogynecologist had been offered to the patient, but was refused (no record of this was found in the patient’s file). There was no negligence in the attempted repair.
VERDICT A $387,000 Virginia verdict was returned.
Did she really need that hysterectomy?
A 31-year-old woman went to the ED with sudden, severe abdominal pain. The radiologist noted that the patient’s appendix could not be visualized on computed tomography (CT) because it was behind the cecum. A general surgeon interpreted the report as ruling out appendicitis, made a diagnosis of pelvic inflammatory disease, and requested a gynecologic consult. An ObGyn sent his nurse practitioner to see the patient in the ED. The patient was discharged and instructed to follow up with the ObGyn.
When the patient’s condition worsened 2 days later, she returned to the ED. The ObGyn performed laparoscopic exploratory surgery. When he could not find the appendix, he called the general surgeon. The surgeon was in his car, and told the ObGyn that it was unnecessary to visualize the appendix; the ObGyn could complete the surgery. The patient was again discharged without a firm diagnosis. She was readmitted to the hospital several hours after discharge and treated for sepsis.
She was in and out of the hospital several times during the next 7 weeks until the ObGyn told her that the only way to cure her pain was to perform a partial hysterectomy. He scheduled a concurrent prophylactic appendectomy by the general surgeon. At surgery, the surgeon found and removed a burst appendix. The ObGyn then performed a hysterectomy, although he had been present during the appendectomy.
PATIENT’S CLAIM Any general surgeon could have come into the operating room during exploratory surgery to assist in ruling out appendicitis; there were other general surgeons available at the hospital. The ObGyn was negligent in performing the hysterectomy after the surgeon had performed the appendectomy.
PHYSICIAN’S DEFENSE The general surgeon died before the case could be deposed. The ObGyn admitted that the removal of the burst appendix resolved the patient’s medical problems; her uterus had not been damaged by sepsis.
VERDICT A $350,000 Michigan settlement was reached.
Erb’s palsy: $1.7M net award
At 38 weeks’ gestation, a mother went to the local ED reporting shortness of breath. She was transferred to a university medical center where a chest x-ray revealed what was thought to be pneumonia or a pulmonary embolism. The decision was made to induce labor. During vaginal delivery, shoulder dystocia was encountered.
The 3-year-old child has Erb’s palsy and, despite treatment and therapy, does not have full use of her left arm and shoulder.
PARENTS’ CLAIM Maneuvers undertaken to relieve shoulder dystocia were not properly performed, injuring the baby. A cesarean delivery should have been performed because of the mother’s condition.
DEFENDANTS’ DEFENSE Proper maneuvers were used. There was no medical necessity for emergency cesarean delivery.
VERDICT A $3 million Maryland verdict was returned. After state caps and recalculation of a lost-wages claim from the mother due to jury error, the net award was $1.7 million.
Was nonreassuring fetal heart rate ignored?
In her third trimester, a 20-year-old woman was admitted to the hospital for observation, which included fetal heart-rate monitoring.
After 2 days, the patient began to bleed vaginally, and the nurses called the ObGyn. When he came to the hospital, he performed emergency cesarean delivery. The fetus was stillborn.
PATIENT’S CLAIM The nurses failed to inform the ObGyn when nonreassuring fetal heart-rate monitoring results were first evident. The ObGyn did not come to the hospital immediately after being told about the vaginal bleeding. The surgical team was not ready when it was time for the cesarean delivery.
DEFENDANTS’ DEFENSE The case was tried against the hospital that employed the nurses and ObGyn. The hospital claimed that fetal demise was caused by a sudden placental abruption. The nurses’ actions were appropriate. The hospital faulted the ObGyn for not coming to the hospital when summoned by the nurses.
VERDICT A $100,000 Louisiana verdict was returned. The jury found the ObGyn 99% at fault and the hospital 1% at fault. The patient was awarded $100,000 from the Patient’s Compensation Fund; the hospital paid $1,000.
Patient says wrong ovary was removed
A woman saw her ObGyn (Dr. A) because of lower abdominal pain. Dr. A performed laparoscopic right salpingo-oophorectomy.
A tumor on the left ovary was found 5 months later, and a second operation was performed by another ObGyn (Dr. B) with Dr. A’s assistance. During this surgery, the patient’s sigmoid colon was injured; a fistula developed and a third operation was required to repair the colon.
PATIENT’S CLAIM The initial plan was to remove the left ovary. When Dr. Aremoved the right ovary instead of the left, the patient experienced sudden onset of menopause; the left ovary was nonfunctional. Dr. B was negligent in injuring the sigmoid colon.
PHYSICIANS’ DEFENSE Dr. B was released from the case because colon injury is a known complication of the procedure. Dr. A claimed that the radiologic film of the mass was misleading, and that the ovary he removed was diseased.
VERDICT A Virginia defense verdict was returned.
Second pregnancy ends in injury after shoulder dystocia
A mother told her new ObGyn that, during the birth of her first child a few years earlier, shoulder dystocia had been encountered. Although the baby was born unharmed, her prior ObGyn had recommended that she undergo cesarean delivery for future pregnancies. During the second pregnancy, the mother and new ObGyn discussed the possibility of a trial of labor and vaginal delivery.
When the mother went into labor at 37 weeks’ gestation, the ObGyn believed the child was of normal weight and proceeded with a vaginal delivery. When shoulder dystocia was encountered, various maneuvers were performed. Birth occurred 5 minutes later using moderate traction.
The child showed no signs of life at birth; Apgar scores were 0 for more than 14 minutes. The newborn was sent to the neonatal intensive care unit and later airlifted to another hospital. He had hypoxic ischemic encephalopathy and a C5–C6 brachial plexus injury.
Additional testing revealed that he has neurocognitive deficits including attention deficit hyperactivity disorder and executive function disabilities.
Parents’ claim The ObGyn was negligent in failing to fully explain the risks of vaginal delivery, failing to recommend cesarean delivery based on the patient’s history and prior physician’s recommendation. The ObGyn failed to perform ultrasonography when the mother was admitted to the hospital; such imaging would have revealed that the fetus was larger than her first baby, mandating cesarean delivery. The ObGyn failed to perform an episiotomy after dystocia was encountered, and he applied excessive traction during dystocial maneuvers.
PHYSICIAN’S DEFENSE The mother was extensively counseled on the risks of vaginal delivery, but the ObGyn admitted that he did not recommend a cesarean delivery. Ultrasonography would have had no benefit. The use of moderate traction was necessary to prevent severe brain damage or death. The child’s current deficits are not related to his birth.
VERDICT The hospital settled for $85,000 before the trial began. An Illinois defense verdict was returned for the ObGyn.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
Negligence during cord blood sampling? Child has CP
A woman’s first child was treated for neonatal alloimmune thrombocytopenia (NAIT) after birth. When prenatal testing identified NAIT in her second child, the mother received twice-weekly immunoglobulin injections to increase the fetus’ platelet count.
At 33 weeks’ gestation, percutaneous umbilical blood sampling (PUBS) was undertaken by a maternal-fetal medicine (MFM) specialist to check the baby’s platelet count and inject additional platelets. During the procedure, the mother’s blood pressure dropped from 122/80 to 80/40 mm Hg. The fetal heart rate dropped from 120–130 bpm to 65 bpm. An emergency cesarean delivery was performed.
At birth, the baby had seizures and respiratory distress secondary to perinatal asphyxia. She has severe spastic quadriplegic cerebral palsy. At age 9 years, she has been hospitalized for multiple complications, underwent tendon-release procedures on both legs, and receives occupational and physical therapy. She cannot speak, needs a feeding tube, is wheelchair bound, and requires 24-hour nursing care.
PARENTS’ CLAIM The MFM was not adequately trained to perform PUBS and did not use continuous ultrasound guidance during the procedure. She was negligent in attempting to insert the needle into the umbilical cord multiple times. She failed to recognize fetal distress. The anesthesiologist only told the MFM that the patient was hypotensive, not that the patient’s blood pressure never returned to baseline.
defendants’ DEFENSE The mother was part of a NAIT study, and the procedure was properly performed under the guidelines of that study. A sonographer constantly monitored the fetal heart rate. The anesthesiologist claimed that proper actions were taken in response to low blood pressure; there was no requirement to communicate more information to the MFM. The child’s hypoxia was due to placental abruption. The estimated cost of the life-care plan for the child is $5 to $10 million.
VERDICT A $15 million Indiana verdict was returned against the medical center that employed the anesthesiologist, but was reduced to $1,250,000 by the state cap. A defense verdict was returned for the MFM.
Woman dies from cervical cancer: $2.33M
When a woman had an abnormal Pap smear in 2001, her gynecologist did not order a repeat test, but told the patient to return in 3 months. The patient did not see the gynecologist again until 2007. At that time, her Pap smear was normal, but she was experiencing symptoms. The gynecologist did not order further testing.
In 2009, the patient was found to have advanced cervical cancer. She died 2 years later at age 48.
ESTATE’S CLAIM The second Pap smear was incorrectly interpreted. Further testing should have been ordered in 2001 and 2007.
DEFENDANTS’ DEFENSE The laboratory and patient’s estate settled for a confidential amount before the trial commenced. The gynecologist denied negligence. He claimed the patient was at fault for not returning to see him, as recommended.
VERDICT A New Jersey jury found the gynecologist 40% at fault, the laboratory 50% at fault, and the patient 10% at fault. A gross verdict of $2.33 million was returned.
Was it HELLP syndrome?
By her prenatal visit at 33 weeks’ gestation, a mother had gained 59 lb during her pregnancy. Three days later, she went to the emergency department (ED). The fetus had died.
PARENT’S CLAIM The ObGyn failed to intervene when the mother was gaining excessive weight. The mother had HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); timely diagnosis could have avoided fetal demise.
DEFENDANTS’ DEFENSE Fetal demise could not have been diagnosed or prevented. The cause of the mother’s illness was never fully identified.
VERDICT A Tennessee defense verdict was returned.
Vesicovaginal fistula after hysterectomy
A woman underwent a hysterectomy performed by her ObGyn. A week later, during a postoperative visit, the ObGyn detected a bladder injury and related vesicovaginal fistula. He attempted a repair, but it failed. Eventually, successful repair surgery was performed by a urologist.
PATIENT’S CLAIM The ObGyn only should have used sharp dissection during the hysterectomy, as opposed to a combination of sharp and blunt dissection, due to dense adhesions that had developed after earlier abdominal surgery. Because the ObGyn had never repaired a vesicovaginal fistula before, he should have requested the assistance of a urologist or urogynecologist. A peritoneal flap should have been used during the initial repair.
PHYSICIAN’S DEFENSE Referral to a urologist or urogynecologist had been offered to the patient, but was refused (no record of this was found in the patient’s file). There was no negligence in the attempted repair.
VERDICT A $387,000 Virginia verdict was returned.
Did she really need that hysterectomy?
A 31-year-old woman went to the ED with sudden, severe abdominal pain. The radiologist noted that the patient’s appendix could not be visualized on computed tomography (CT) because it was behind the cecum. A general surgeon interpreted the report as ruling out appendicitis, made a diagnosis of pelvic inflammatory disease, and requested a gynecologic consult. An ObGyn sent his nurse practitioner to see the patient in the ED. The patient was discharged and instructed to follow up with the ObGyn.
When the patient’s condition worsened 2 days later, she returned to the ED. The ObGyn performed laparoscopic exploratory surgery. When he could not find the appendix, he called the general surgeon. The surgeon was in his car, and told the ObGyn that it was unnecessary to visualize the appendix; the ObGyn could complete the surgery. The patient was again discharged without a firm diagnosis. She was readmitted to the hospital several hours after discharge and treated for sepsis.
She was in and out of the hospital several times during the next 7 weeks until the ObGyn told her that the only way to cure her pain was to perform a partial hysterectomy. He scheduled a concurrent prophylactic appendectomy by the general surgeon. At surgery, the surgeon found and removed a burst appendix. The ObGyn then performed a hysterectomy, although he had been present during the appendectomy.
PATIENT’S CLAIM Any general surgeon could have come into the operating room during exploratory surgery to assist in ruling out appendicitis; there were other general surgeons available at the hospital. The ObGyn was negligent in performing the hysterectomy after the surgeon had performed the appendectomy.
PHYSICIAN’S DEFENSE The general surgeon died before the case could be deposed. The ObGyn admitted that the removal of the burst appendix resolved the patient’s medical problems; her uterus had not been damaged by sepsis.
VERDICT A $350,000 Michigan settlement was reached.
Erb’s palsy: $1.7M net award
At 38 weeks’ gestation, a mother went to the local ED reporting shortness of breath. She was transferred to a university medical center where a chest x-ray revealed what was thought to be pneumonia or a pulmonary embolism. The decision was made to induce labor. During vaginal delivery, shoulder dystocia was encountered.
The 3-year-old child has Erb’s palsy and, despite treatment and therapy, does not have full use of her left arm and shoulder.
PARENTS’ CLAIM Maneuvers undertaken to relieve shoulder dystocia were not properly performed, injuring the baby. A cesarean delivery should have been performed because of the mother’s condition.
DEFENDANTS’ DEFENSE Proper maneuvers were used. There was no medical necessity for emergency cesarean delivery.
VERDICT A $3 million Maryland verdict was returned. After state caps and recalculation of a lost-wages claim from the mother due to jury error, the net award was $1.7 million.
Was nonreassuring fetal heart rate ignored?
In her third trimester, a 20-year-old woman was admitted to the hospital for observation, which included fetal heart-rate monitoring.
After 2 days, the patient began to bleed vaginally, and the nurses called the ObGyn. When he came to the hospital, he performed emergency cesarean delivery. The fetus was stillborn.
PATIENT’S CLAIM The nurses failed to inform the ObGyn when nonreassuring fetal heart-rate monitoring results were first evident. The ObGyn did not come to the hospital immediately after being told about the vaginal bleeding. The surgical team was not ready when it was time for the cesarean delivery.
DEFENDANTS’ DEFENSE The case was tried against the hospital that employed the nurses and ObGyn. The hospital claimed that fetal demise was caused by a sudden placental abruption. The nurses’ actions were appropriate. The hospital faulted the ObGyn for not coming to the hospital when summoned by the nurses.
VERDICT A $100,000 Louisiana verdict was returned. The jury found the ObGyn 99% at fault and the hospital 1% at fault. The patient was awarded $100,000 from the Patient’s Compensation Fund; the hospital paid $1,000.
Patient says wrong ovary was removed
A woman saw her ObGyn (Dr. A) because of lower abdominal pain. Dr. A performed laparoscopic right salpingo-oophorectomy.
A tumor on the left ovary was found 5 months later, and a second operation was performed by another ObGyn (Dr. B) with Dr. A’s assistance. During this surgery, the patient’s sigmoid colon was injured; a fistula developed and a third operation was required to repair the colon.
PATIENT’S CLAIM The initial plan was to remove the left ovary. When Dr. Aremoved the right ovary instead of the left, the patient experienced sudden onset of menopause; the left ovary was nonfunctional. Dr. B was negligent in injuring the sigmoid colon.
PHYSICIANS’ DEFENSE Dr. B was released from the case because colon injury is a known complication of the procedure. Dr. A claimed that the radiologic film of the mass was misleading, and that the ovary he removed was diseased.
VERDICT A Virginia defense verdict was returned.
Second pregnancy ends in injury after shoulder dystocia
A mother told her new ObGyn that, during the birth of her first child a few years earlier, shoulder dystocia had been encountered. Although the baby was born unharmed, her prior ObGyn had recommended that she undergo cesarean delivery for future pregnancies. During the second pregnancy, the mother and new ObGyn discussed the possibility of a trial of labor and vaginal delivery.
When the mother went into labor at 37 weeks’ gestation, the ObGyn believed the child was of normal weight and proceeded with a vaginal delivery. When shoulder dystocia was encountered, various maneuvers were performed. Birth occurred 5 minutes later using moderate traction.
The child showed no signs of life at birth; Apgar scores were 0 for more than 14 minutes. The newborn was sent to the neonatal intensive care unit and later airlifted to another hospital. He had hypoxic ischemic encephalopathy and a C5–C6 brachial plexus injury.
Additional testing revealed that he has neurocognitive deficits including attention deficit hyperactivity disorder and executive function disabilities.
Parents’ claim The ObGyn was negligent in failing to fully explain the risks of vaginal delivery, failing to recommend cesarean delivery based on the patient’s history and prior physician’s recommendation. The ObGyn failed to perform ultrasonography when the mother was admitted to the hospital; such imaging would have revealed that the fetus was larger than her first baby, mandating cesarean delivery. The ObGyn failed to perform an episiotomy after dystocia was encountered, and he applied excessive traction during dystocial maneuvers.
PHYSICIAN’S DEFENSE The mother was extensively counseled on the risks of vaginal delivery, but the ObGyn admitted that he did not recommend a cesarean delivery. Ultrasonography would have had no benefit. The use of moderate traction was necessary to prevent severe brain damage or death. The child’s current deficits are not related to his birth.
VERDICT The hospital settled for $85,000 before the trial began. An Illinois defense verdict was returned for the ObGyn.
These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.
Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.
IN THIS ARTICLE
-Woman dies from cervical cancer: $2.33M
-Was it HELLP syndrome?
-Vesicovaginal fistula after hysterectomy
-Did she really need that hysterectomy?
-Erb’s palsy: $1.7M net award
-Was nonreassuring fetal heart rate ignored?
-Patient says wrong ovary was removed
-Second pregnancy ends in injury after shoulder dystocia
Tight hypertension control in pregnancy not tied to better outcomes
Rates of adverse perinatal outcomes were no different between women who achieved tight control of mild to moderate hypertension during pregnancy and those who achieved less tight control in an international randomized trial.
The findings, published Jan. 29 in the New England Journal of Medicine, showed no significant differences in a composite of pregnancy loss (including miscarriage, ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high-level neonatal care exceeding 48 hours between women with tight control (30.7%) and less tight control (31.4%). There were also no significant differences in serious maternal complications between the two levels of hypertension control.
The results come from the Control of Hypertension in Pregnancy Study (CHIPS), a randomized trial that assessed perinatal outcomes in 986 hypertensive pregnant women treated at 94 sites during a 3-year period.
The appropriate blood pressure targets for women with nonsevere hypertension during pregnancy have been hotly debated, with some research indicating that tight control yields maternal benefits and other studies suggesting it causes problems for the fetus, including poor fetal growth. However, most of the relevant randomized, controlled trials have been small or of moderate or poor quality, according to the CHIPS researchers.
Meanwhile, international guidelines for nonsevere hypertension during pregnancy vary, recommending either less tight control or tight control.
With CHIPS, the researchers are hoping to settle some of the controversy by directly comparing perinatal and maternal outcomes for tight versus less tight control of nonproteinuric, nonsevere hypertension in pregnancy.
“Our trial is substantially larger than previous trials that have examined the effects of lower versus higher blood pressure targets during pregnancy,” Dr. Laura A. Magee of the British Columbia Women’s Hospital and Health Centre in Vancouver and her colleagues wrote (N. Engl. J. Med. 2015;372:407-17).
The study participants, who had nonproteinuric hypertension that was either preexisting or developed during gestation, were randomly assigned to a tight diastolic blood pressure target of 85 mm Hg (489 women) or a less tight target of 100 mm Hg (497 women). Adherence to antihypertensive therapy was similar between the two groups at approximately 74%, and blood pressure was higher throughout pregnancy in the group with less tight control, according to the study.
CHIPS also showed no significant between-group differences in other perinatal outcomes, such as the frequency of newborns who were small for gestational age and respiratory complications and treatment. Further, there were no significant differences in the secondary outcome of serious maternal complications, and no maternal deaths in either group. However, the rate of severe hypertension was higher among women with less tight blood pressure control (40.6% versus 27.5%), though there was no corresponding increase in stroke or transient ischemic attack.
The current study showed that tight control of hypertension conferred no apparent benefits to the fetus and only a moderate benefit (a lower rate of progression to severe hypertension) for the mother.
It does, however, provide valuable reassurance that tight control, as targeted in this study, does not carry major risks for the fetus or newborn.
Dr. Caren G. Solomon and Dr. Michael F. Greene of the department of obstetrics and gynecology at Massachusetts General Hospital, Boston, made these comments in an accompanying editorial (N. Engl. J. Med. 2015;372:475-6). They reported having no relevant financial disclosures.
The current study showed that tight control of hypertension conferred no apparent benefits to the fetus and only a moderate benefit (a lower rate of progression to severe hypertension) for the mother.
It does, however, provide valuable reassurance that tight control, as targeted in this study, does not carry major risks for the fetus or newborn.
Dr. Caren G. Solomon and Dr. Michael F. Greene of the department of obstetrics and gynecology at Massachusetts General Hospital, Boston, made these comments in an accompanying editorial (N. Engl. J. Med. 2015;372:475-6). They reported having no relevant financial disclosures.
The current study showed that tight control of hypertension conferred no apparent benefits to the fetus and only a moderate benefit (a lower rate of progression to severe hypertension) for the mother.
It does, however, provide valuable reassurance that tight control, as targeted in this study, does not carry major risks for the fetus or newborn.
Dr. Caren G. Solomon and Dr. Michael F. Greene of the department of obstetrics and gynecology at Massachusetts General Hospital, Boston, made these comments in an accompanying editorial (N. Engl. J. Med. 2015;372:475-6). They reported having no relevant financial disclosures.
Rates of adverse perinatal outcomes were no different between women who achieved tight control of mild to moderate hypertension during pregnancy and those who achieved less tight control in an international randomized trial.
The findings, published Jan. 29 in the New England Journal of Medicine, showed no significant differences in a composite of pregnancy loss (including miscarriage, ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high-level neonatal care exceeding 48 hours between women with tight control (30.7%) and less tight control (31.4%). There were also no significant differences in serious maternal complications between the two levels of hypertension control.
The results come from the Control of Hypertension in Pregnancy Study (CHIPS), a randomized trial that assessed perinatal outcomes in 986 hypertensive pregnant women treated at 94 sites during a 3-year period.
The appropriate blood pressure targets for women with nonsevere hypertension during pregnancy have been hotly debated, with some research indicating that tight control yields maternal benefits and other studies suggesting it causes problems for the fetus, including poor fetal growth. However, most of the relevant randomized, controlled trials have been small or of moderate or poor quality, according to the CHIPS researchers.
Meanwhile, international guidelines for nonsevere hypertension during pregnancy vary, recommending either less tight control or tight control.
With CHIPS, the researchers are hoping to settle some of the controversy by directly comparing perinatal and maternal outcomes for tight versus less tight control of nonproteinuric, nonsevere hypertension in pregnancy.
“Our trial is substantially larger than previous trials that have examined the effects of lower versus higher blood pressure targets during pregnancy,” Dr. Laura A. Magee of the British Columbia Women’s Hospital and Health Centre in Vancouver and her colleagues wrote (N. Engl. J. Med. 2015;372:407-17).
The study participants, who had nonproteinuric hypertension that was either preexisting or developed during gestation, were randomly assigned to a tight diastolic blood pressure target of 85 mm Hg (489 women) or a less tight target of 100 mm Hg (497 women). Adherence to antihypertensive therapy was similar between the two groups at approximately 74%, and blood pressure was higher throughout pregnancy in the group with less tight control, according to the study.
CHIPS also showed no significant between-group differences in other perinatal outcomes, such as the frequency of newborns who were small for gestational age and respiratory complications and treatment. Further, there were no significant differences in the secondary outcome of serious maternal complications, and no maternal deaths in either group. However, the rate of severe hypertension was higher among women with less tight blood pressure control (40.6% versus 27.5%), though there was no corresponding increase in stroke or transient ischemic attack.
Rates of adverse perinatal outcomes were no different between women who achieved tight control of mild to moderate hypertension during pregnancy and those who achieved less tight control in an international randomized trial.
The findings, published Jan. 29 in the New England Journal of Medicine, showed no significant differences in a composite of pregnancy loss (including miscarriage, ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high-level neonatal care exceeding 48 hours between women with tight control (30.7%) and less tight control (31.4%). There were also no significant differences in serious maternal complications between the two levels of hypertension control.
The results come from the Control of Hypertension in Pregnancy Study (CHIPS), a randomized trial that assessed perinatal outcomes in 986 hypertensive pregnant women treated at 94 sites during a 3-year period.
The appropriate blood pressure targets for women with nonsevere hypertension during pregnancy have been hotly debated, with some research indicating that tight control yields maternal benefits and other studies suggesting it causes problems for the fetus, including poor fetal growth. However, most of the relevant randomized, controlled trials have been small or of moderate or poor quality, according to the CHIPS researchers.
Meanwhile, international guidelines for nonsevere hypertension during pregnancy vary, recommending either less tight control or tight control.
With CHIPS, the researchers are hoping to settle some of the controversy by directly comparing perinatal and maternal outcomes for tight versus less tight control of nonproteinuric, nonsevere hypertension in pregnancy.
“Our trial is substantially larger than previous trials that have examined the effects of lower versus higher blood pressure targets during pregnancy,” Dr. Laura A. Magee of the British Columbia Women’s Hospital and Health Centre in Vancouver and her colleagues wrote (N. Engl. J. Med. 2015;372:407-17).
The study participants, who had nonproteinuric hypertension that was either preexisting or developed during gestation, were randomly assigned to a tight diastolic blood pressure target of 85 mm Hg (489 women) or a less tight target of 100 mm Hg (497 women). Adherence to antihypertensive therapy was similar between the two groups at approximately 74%, and blood pressure was higher throughout pregnancy in the group with less tight control, according to the study.
CHIPS also showed no significant between-group differences in other perinatal outcomes, such as the frequency of newborns who were small for gestational age and respiratory complications and treatment. Further, there were no significant differences in the secondary outcome of serious maternal complications, and no maternal deaths in either group. However, the rate of severe hypertension was higher among women with less tight blood pressure control (40.6% versus 27.5%), though there was no corresponding increase in stroke or transient ischemic attack.
Key clinical point: The rates of pregnancy loss, high-level neonatal care, and maternal complications were no different, regardless of whether mild to moderate hypertension was tightly controlled or less tightly controlled during pregnancy.
Major finding: The rate of the primary outcome – a composite of pregnancy loss or high-level neonatal care exceeding 48 hours – was not significantly different between women with tight control of hypertension (30.7%) and less tight control (31.4%).
Data source: The international randomized, controlled Control of Hypertension in Pregnancy Study involving 986 pregnant women at 94 medical centers who had nonsevere, nonproteinuric hypertension.
Disclosures: CHIPS was supported by the Canadian Institutes of Health Research. Dr. Magee reported having no financial disclosures; one of her associates reported receiving consulting fees and research support from Alere International.
Use of NIPT reduces invasive testing at one medical center
Following the introduction of noninvasive prenatal testing (NIPT) at the Maine Medical Center in Portland, the number of invasive prenatal diagnostic procedures decreased.
In a retrospective study, Joseph R. Wax, MD, and colleagues gathered statistics on the rates of genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection among women who were at increased risk for aneuploidy. These rates were compared before and after the availability of NIPT.
The study included 1,046 women who underwent NIPT between June 1, 2012, and February 1, 2013, as well as 1,464 women who would have been eligible for NIPT if it had been available between December 1, 2010, and November 30, 2011. All women were aged 35 years or older and had ultrasound findings suggestive of increased risk of aneuploidy, a positive aneuploidy screen, prior trisomic fetus, or parental balanced translocation with increased risk for trisomy 13 or 21. One laboratory performed NIPT after patients received genetic counseling. The two groups were compared by maternal demographics, aneuploidy risk factors, rates of genetic counseling, invasive diagnostic procedures, and trisomy 21 detection.1
Results of the study
A total of 33 fetuses with trisomy 21 were identified by positive aneuploidy screening. After the introduction of NIPT, genetic counseling for aneuploidy risk increased (adjusted odds ratio [aOR], 1.77; P <.0001). However, the overall use of invasive diagnostic testing (aOR, 0.42; P <.0001), including amniocentesis (aOR, 0.37, P <.0001), decreased, although the prenatal diagnosis of trisomy 21 remained similar (88% vs 100%; P = .86).1
Dr. Wax and colleagues concluded that, “NIPT in clinical practice uses more genetic counseling resources but requires significantly fewer invasive procedures to maintain the detection rates of trisomy 21.”1
Reference
1. Wax JR, Cartin A, Chard R, Lucas FL, Pinette MG. Noninvasive prenatal testing: Impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection. J Clinic Ultrasound. 2015;43(1):1–6.
Following the introduction of noninvasive prenatal testing (NIPT) at the Maine Medical Center in Portland, the number of invasive prenatal diagnostic procedures decreased.
In a retrospective study, Joseph R. Wax, MD, and colleagues gathered statistics on the rates of genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection among women who were at increased risk for aneuploidy. These rates were compared before and after the availability of NIPT.
The study included 1,046 women who underwent NIPT between June 1, 2012, and February 1, 2013, as well as 1,464 women who would have been eligible for NIPT if it had been available between December 1, 2010, and November 30, 2011. All women were aged 35 years or older and had ultrasound findings suggestive of increased risk of aneuploidy, a positive aneuploidy screen, prior trisomic fetus, or parental balanced translocation with increased risk for trisomy 13 or 21. One laboratory performed NIPT after patients received genetic counseling. The two groups were compared by maternal demographics, aneuploidy risk factors, rates of genetic counseling, invasive diagnostic procedures, and trisomy 21 detection.1
Results of the study
A total of 33 fetuses with trisomy 21 were identified by positive aneuploidy screening. After the introduction of NIPT, genetic counseling for aneuploidy risk increased (adjusted odds ratio [aOR], 1.77; P <.0001). However, the overall use of invasive diagnostic testing (aOR, 0.42; P <.0001), including amniocentesis (aOR, 0.37, P <.0001), decreased, although the prenatal diagnosis of trisomy 21 remained similar (88% vs 100%; P = .86).1
Dr. Wax and colleagues concluded that, “NIPT in clinical practice uses more genetic counseling resources but requires significantly fewer invasive procedures to maintain the detection rates of trisomy 21.”1
Following the introduction of noninvasive prenatal testing (NIPT) at the Maine Medical Center in Portland, the number of invasive prenatal diagnostic procedures decreased.
In a retrospective study, Joseph R. Wax, MD, and colleagues gathered statistics on the rates of genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection among women who were at increased risk for aneuploidy. These rates were compared before and after the availability of NIPT.
The study included 1,046 women who underwent NIPT between June 1, 2012, and February 1, 2013, as well as 1,464 women who would have been eligible for NIPT if it had been available between December 1, 2010, and November 30, 2011. All women were aged 35 years or older and had ultrasound findings suggestive of increased risk of aneuploidy, a positive aneuploidy screen, prior trisomic fetus, or parental balanced translocation with increased risk for trisomy 13 or 21. One laboratory performed NIPT after patients received genetic counseling. The two groups were compared by maternal demographics, aneuploidy risk factors, rates of genetic counseling, invasive diagnostic procedures, and trisomy 21 detection.1
Results of the study
A total of 33 fetuses with trisomy 21 were identified by positive aneuploidy screening. After the introduction of NIPT, genetic counseling for aneuploidy risk increased (adjusted odds ratio [aOR], 1.77; P <.0001). However, the overall use of invasive diagnostic testing (aOR, 0.42; P <.0001), including amniocentesis (aOR, 0.37, P <.0001), decreased, although the prenatal diagnosis of trisomy 21 remained similar (88% vs 100%; P = .86).1
Dr. Wax and colleagues concluded that, “NIPT in clinical practice uses more genetic counseling resources but requires significantly fewer invasive procedures to maintain the detection rates of trisomy 21.”1
Reference
1. Wax JR, Cartin A, Chard R, Lucas FL, Pinette MG. Noninvasive prenatal testing: Impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection. J Clinic Ultrasound. 2015;43(1):1–6.
Reference
1. Wax JR, Cartin A, Chard R, Lucas FL, Pinette MG. Noninvasive prenatal testing: Impact on genetic counseling, invasive prenatal diagnosis, and trisomy 21 detection. J Clinic Ultrasound. 2015;43(1):1–6.
High interferon levels related to preeclampsia in pregnant lupus patients
Pregnant women with systemic lupus erythematosus and elevated levels of interferon-alpha are more likely to develop preeclampsia, according to a small study by Dr. Danieli Andrade and her associates.
A total of 28 systemic lupus erythematosus (SLE) patients with uncomplicated pregnancies did not have elevated interferon-alpha (IFN-alpha) levels, while another 28 SLE patients with preeclampsia who were matched for age and gender/ethnicity did. However, nonautoimmune pregnant women who developed preeclampsia also did not experience elevated IFN-alpha. SLE patients with preeclampsia and elevated levels of IFN-alpha had minimal amounts of an antiangiogenic growth factor, even though an excess of that antiangiogenic growth factor is usually associated with preeclampsia in SLE pregnancies.
In a related editorial, Dr. Ana Cerdeira and Dr. Ravi Thadhani theorize how IFN-alpha could cause the endothelial system to be more sensitive to the antiangiogenic growth factor, so that even slightly elevated levels of the antiangiogenic growth factor could cause preeclampsia. They also agree with the study authors on the relevance of the findings and how elevated IFN-alpha levels could be used to risk stratify SLE pregnancies.
Read the full article at Arthritis & Rheumatology (doi:10.1002/art.39029) and the editorial at doi:10.1002/art.39028.
Pregnant women with systemic lupus erythematosus and elevated levels of interferon-alpha are more likely to develop preeclampsia, according to a small study by Dr. Danieli Andrade and her associates.
A total of 28 systemic lupus erythematosus (SLE) patients with uncomplicated pregnancies did not have elevated interferon-alpha (IFN-alpha) levels, while another 28 SLE patients with preeclampsia who were matched for age and gender/ethnicity did. However, nonautoimmune pregnant women who developed preeclampsia also did not experience elevated IFN-alpha. SLE patients with preeclampsia and elevated levels of IFN-alpha had minimal amounts of an antiangiogenic growth factor, even though an excess of that antiangiogenic growth factor is usually associated with preeclampsia in SLE pregnancies.
In a related editorial, Dr. Ana Cerdeira and Dr. Ravi Thadhani theorize how IFN-alpha could cause the endothelial system to be more sensitive to the antiangiogenic growth factor, so that even slightly elevated levels of the antiangiogenic growth factor could cause preeclampsia. They also agree with the study authors on the relevance of the findings and how elevated IFN-alpha levels could be used to risk stratify SLE pregnancies.
Read the full article at Arthritis & Rheumatology (doi:10.1002/art.39029) and the editorial at doi:10.1002/art.39028.
Pregnant women with systemic lupus erythematosus and elevated levels of interferon-alpha are more likely to develop preeclampsia, according to a small study by Dr. Danieli Andrade and her associates.
A total of 28 systemic lupus erythematosus (SLE) patients with uncomplicated pregnancies did not have elevated interferon-alpha (IFN-alpha) levels, while another 28 SLE patients with preeclampsia who were matched for age and gender/ethnicity did. However, nonautoimmune pregnant women who developed preeclampsia also did not experience elevated IFN-alpha. SLE patients with preeclampsia and elevated levels of IFN-alpha had minimal amounts of an antiangiogenic growth factor, even though an excess of that antiangiogenic growth factor is usually associated with preeclampsia in SLE pregnancies.
In a related editorial, Dr. Ana Cerdeira and Dr. Ravi Thadhani theorize how IFN-alpha could cause the endothelial system to be more sensitive to the antiangiogenic growth factor, so that even slightly elevated levels of the antiangiogenic growth factor could cause preeclampsia. They also agree with the study authors on the relevance of the findings and how elevated IFN-alpha levels could be used to risk stratify SLE pregnancies.
Read the full article at Arthritis & Rheumatology (doi:10.1002/art.39029) and the editorial at doi:10.1002/art.39028.
ACOG outlines new treatment options for hypertensive emergencies in pregnancy
The American College of Obstetricians and Gynecologists has added nifedipine as a first-line treatment for acute-onset severe hypertension during pregnancy and the postpartum period in an updated opinion from its Committee on Obstetric Practice.
The update, released on Jan. 22, points to studies showing that women who received oral nifedipine had their blood pressure lowered more quickly than with either intravenous labetalol or hydralazine – the traditional first-line treatments – and had a significant increase in urine output. Concerns about neuromuscular blockade and severe hypotension with the use of nifedipine and magnesium sulphate were not borne out in a large review, the committee members wrote, but they advised careful monitoring since both drugs are calcium antagonists.
The committee opinion includes model order sets for the use of labetalol, hydralazine, and nifedipine for the initial management of acute onset severe hypertension in women who are pregnant or post partum with preeclampsia or eclampsia (Obstet. Gynecol. 2015;125:521-5).
While all three medications are appropriate in treating hypertensive emergencies during pregnancy, each drug has adverse effects.
For instance, parenteral hydralazine can increase the risk of maternal hypotension. Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease, or heart failure. Nifedipine has been associated with increased maternal heart rate and overshoot hypotension.
“Patients may respond to one drug and not another,” the committee noted.
The ACOG committee also called for standardized clinical guidelines for the management of patients with preeclampsia and eclampsia.
“With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications,” they wrote. “Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency.”
The committee recommended checklists as one tool to help standardize the use of guidelines.
The American College of Obstetricians and Gynecologists has added nifedipine as a first-line treatment for acute-onset severe hypertension during pregnancy and the postpartum period in an updated opinion from its Committee on Obstetric Practice.
The update, released on Jan. 22, points to studies showing that women who received oral nifedipine had their blood pressure lowered more quickly than with either intravenous labetalol or hydralazine – the traditional first-line treatments – and had a significant increase in urine output. Concerns about neuromuscular blockade and severe hypotension with the use of nifedipine and magnesium sulphate were not borne out in a large review, the committee members wrote, but they advised careful monitoring since both drugs are calcium antagonists.
The committee opinion includes model order sets for the use of labetalol, hydralazine, and nifedipine for the initial management of acute onset severe hypertension in women who are pregnant or post partum with preeclampsia or eclampsia (Obstet. Gynecol. 2015;125:521-5).
While all three medications are appropriate in treating hypertensive emergencies during pregnancy, each drug has adverse effects.
For instance, parenteral hydralazine can increase the risk of maternal hypotension. Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease, or heart failure. Nifedipine has been associated with increased maternal heart rate and overshoot hypotension.
“Patients may respond to one drug and not another,” the committee noted.
The ACOG committee also called for standardized clinical guidelines for the management of patients with preeclampsia and eclampsia.
“With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications,” they wrote. “Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency.”
The committee recommended checklists as one tool to help standardize the use of guidelines.
The American College of Obstetricians and Gynecologists has added nifedipine as a first-line treatment for acute-onset severe hypertension during pregnancy and the postpartum period in an updated opinion from its Committee on Obstetric Practice.
The update, released on Jan. 22, points to studies showing that women who received oral nifedipine had their blood pressure lowered more quickly than with either intravenous labetalol or hydralazine – the traditional first-line treatments – and had a significant increase in urine output. Concerns about neuromuscular blockade and severe hypotension with the use of nifedipine and magnesium sulphate were not borne out in a large review, the committee members wrote, but they advised careful monitoring since both drugs are calcium antagonists.
The committee opinion includes model order sets for the use of labetalol, hydralazine, and nifedipine for the initial management of acute onset severe hypertension in women who are pregnant or post partum with preeclampsia or eclampsia (Obstet. Gynecol. 2015;125:521-5).
While all three medications are appropriate in treating hypertensive emergencies during pregnancy, each drug has adverse effects.
For instance, parenteral hydralazine can increase the risk of maternal hypotension. Parenteral labetalol may cause neonatal bradycardia and should be avoided in women with asthma, heart disease, or heart failure. Nifedipine has been associated with increased maternal heart rate and overshoot hypotension.
“Patients may respond to one drug and not another,” the committee noted.
The ACOG committee also called for standardized clinical guidelines for the management of patients with preeclampsia and eclampsia.
“With the advent of pregnancy hypertension guidelines in the United Kingdom, care of maternity patients with preeclampsia or eclampsia improved significantly and maternal mortality rates decreased because of a reduction in cerebral and respiratory complications,” they wrote. “Individuals and institutions should have mechanisms in place to initiate the prompt administration of medication when a patient presents with a hypertensive emergency.”
The committee recommended checklists as one tool to help standardize the use of guidelines.
FROM OBSTETRICS AND GYNECOLOGY