Clinical Review

Ectopic pregnancy is a significant health risk to women during their childbearing years; approximately 6% of all pregnancy-related deaths are due to ectopic pregnancy.^1-3 Some 1% to 2% of all pregnancies in the United States each year—approximately 100,000 cases—are ectopic, with an estimated annual cost of care approaching $1.1 billion.⁴ The incidence of ectopic pregnancy has increased in the past 20 years; in one analysis, ectopic pregnancy was diagnosed in 18% of women who presented to an emergency department (ED) with first trimester vaginal bleeding, abdominal pain, or both.⁵ This growing prevalence is attributed to a number of factors, including the sensitivity of current diagnostic methods in detecting early ectopic pregnancy, the greater incidence of salpingitis, and the growing use of assisted reproductive technologies.^2,6

While the number of ectopic pregnancies is on the rise, the proportion of patients requiring hospitalization for surgical treatment of ectopic pregnancy has decreased significantly. Today, for appropriate patients, many clinicians manage ectopic pregnancy on an outpatient basis using the drug methotrexate.⁶

In this article, we will present an overview of the current status of medical management of ectopic pregnancy, along with a case study. The case study describes a patient diagnosed with an unruptured ectopic pregnancy who was managed medically with methotrexate. It illustrates how, with early diagnosis, clinicians can intervene to make medical management an effective treatment option in selected situations.

On the next page: Diagnosis and case continuation >>

DIAGNOSIS
There is some variation in the presentation of women experiencing ectopic pregnancy; this may be due to differences in the pathologic mechanisms of ectopic pregnancy. Patients may be asymptomatic, hemodynamically compromised, or somewhere in between.³ Typical clinical signs include abdominal pain, amenorrhea, and vaginal bleeding. Approximately 40% to 50% of patients present with vaginal bleeding, 50% may have a palpable adnexal mass, and 75% may have abdominal tenderness.³ Only about 50% of women with ectopic pregnancies present with these typical symptoms.³

The patient may also experience common symptoms of early pregnancy, such as nausea, fatigue, and breast fullness. Worrisome signs and symptoms, including abdominal guarding, hypotension, tachycardia, shock, shoulder pain from peritoneal irritation, dizziness, fever, and vomiting, may also be present.^3,7 Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at presentation, which is highly suggestive of rupture.³    

Risk factors
Risk factors for ectopic pregnancy include pre­vious ectopic pregnancy; previous tubal procedures; history of sexually transmitted disease or genital infections; infertility; use of assisted reproductive technology; previous abdominal or pelvic surgery; smoking; pelvic inflammatory disease; exposure in utero to diethylstilbestrol; and previous intra­uterine device use.^2,5,7,8 Knowledge of these risk factors can help identify a patient with an ectopic pregnancy.

The diagnosis of ectopic pregnancy is most certainly a clinical challenge. The differential diagnosis is based upon history and physical findings; the list can be lengthy if both vaginal bleeding and abdominal pain (nonspecific symptoms common in women who miscarry) are present.⁷ Prompt completion of diagnostic testing is critical in making a definitive diagnosis. Possible diagnoses are listed in Table 1.

CASE Upon examination, the patient appeared comfortable and relaxed, and there were no signs of distress. Blood pressure was 100/65 mm Hg, pulse rate was 72 beats/min, and temperature was 99.0°F. There was no tenderness upon abdominal examination. Pelvic examination revealed a small amount of brown vaginal discharge but no active bleeding or pooled blood, clots, or tissue. The cervical os was closed, and positive Chadwick sign was present. Bimanual examination revealed no cervical motion tenderness. The uterus was soft, mobile, and nontender, and consistent in size with a gestation at eight weeks. There were no palpable adnexa, ovaries, or masses. There was no pain with bimanual examination and no evidence of tenderness at the posterior fornix. The remainder of the physical examination was unremarkable.

It is important to note that examination results in the case patient are not unusual in a woman with a small, unruptured ectopic pregnancy. All findings were normal except for the scant brown vaginal discharge. Abdominal and adnexal tenderness are common, as is a palpable adnexal mass; but absence of a detectable mass does not exclude ectopic pregnancy.¹ Pathologic findings may include severe abdominal tenderness and pain, significant vaginal bleeding, passage of clots, tachycardia, and orthostatic hypotension.

Diagnostic workup
Laboratory tests are critical to making an accurate diagnosis for women whose history and physical examination results are consistent with ectopic pregnancy. Assessment for ectopic pregnancy should include a urine pregnancy test, transvaginal ultrasound, measurement of serum ß-human chorionic gonadotropin (ß-hCG) level, and occasionally, diagnostic curettage.¹ Once the diagnosis is confirmed, a complete blood count (CBC) is necessary to assess anemia and platelet functioning. Coagulation tests may be required for worrisome bleeding. Blood type, Rh status, and antibody screen are also necessary to determine whether a patient who is Rh D-negative will require Rh immune globulin. See Table 2 for the patient’s laboratory test results.

In a patient with a ß-hCG level greater than the discriminatory cutoff value of 1,500 to 1,800 mIU/mL, the level above which an intrauterine gestational sac is visible on transvaginal ultrasound in a normal pregnancy, an empty uterus is considered an ectopic pregnancy until proven otherwise.³ In a definite intrauterine pregnancy of about six weeks’ gestation, transvaginal ultrasound reveals a gestational sac that contains a yolk sac and a fetal pole.³

CASE The patient’s presenting symptoms, combined with a positive pregnancy test, ß-hCG level of 1,850 mIU/mL, and a complex adnexal mass in the right fallopian tube, were highly suggestive of an un­ruptured ectopic pregnancy (see Table 3 for the patient’s transvaginal ultrasound findings). There was also a secondary finding of a corpus luteum cyst. Other diagnoses were ruled out, and the patient was diagnosed with an unruptured ectopic pregnancy.

On the next page: Treatment >>

TREATMENT
A patient with an ectopic pregnancy who presents with pain and hemodynamic instability should be referred immediately for appropriate surgical care.⁷ Otherwise, once the diagnosis of ectopic pregnancy is confirmed, the patient should be referred to an obstetric specialist. Treatments for ectopic pregnancy include expectant management and surgery—which will be discussed briefly—and medical management, which is the focus of this review.⁵

Expectant management
Most ectopic pregnancies are diagnosed early as a result of accurate, minimally invasive and noninvasive diagnostic tools and greater awareness of risk factors. Since the natural course of early ectopic pregnancy is often self-limited, eventually resulting in tubal abortion or reabsorption, expectant management is a viable option.⁹

This treatment option may be considered if the patient is asymptomatic; ß-hCG is < 200 mIU/mL; the ectopic mass is < 3 cm; and no fetal heartbeat is present.^1,2 With this approach, patients must be willing to accept the risk for tubal rupture and agree to close monitoring of ß-hCG levels. The ß-hCG level must be measured every 24 to 48 hours in order to determine if it is declining adequately, plateauing, or increasing.^2,5

Surgery
For the hemodynamically unstable patient, the treatment decision is relatively straightforward. Optimal treatment for a ruptured ectopic pregnancy is immediate surgery, which may include salpingostomy or salpingectomy.¹⁰ Surgery may also be considered for hemodynamically stable patients with nonruptured ectopic pregnancies; in addition to her clinical presentation, overall management may be driven by a patient’s preferences.⁵ Salpingostomy and salpingectomy can be performed either laparoscopically or via laparotomy, depending on the specific situation.

Medical management
The use of methotrexate for the management of unruptured ectopic pregnancy was introduced in the early 1980s.¹¹ Initially, protocols called for multiple doses administered during the course of an inpatient stay. Further research led to revised treatment recommendations and today, medical management most often consists of a single dose of methotrexate with outpatient follow-up.³

Methotrexate is a folic acid antagonist often used as an antimetabolite chemotherapeutic agent. In ectopic pregnancy, it inhibits growth of the rapidly dividing trophoblastic cells and ultimately ends the pregnancy.² Outcomes of medical management are comparable to those of surgical treatment, including the potential for future normal pregnancies.^2,5

An analysis of US trends in ectopic pregnancy management from 2002-2007 revealed that the use of methotrexate increased from 11.1% to 35.1% during that time, while the use of surgical approaches declined from 90% to 65%.¹⁰ Medical management of ectopic pregnancy eliminates the costs of surgery, anesthesia, and hospitalization and avoids potential complications of surgery and anesthesia.

Appropriate candidates
A hemodynamically stable patient with a confirmed or high clinical suspicion of ectopic pregnancy, an unruptured mass, no active bleeding, and low ­ß-hCG levels (< 5,000 mIU/mL) can be considered for methotrexate therapy.^2,3,9 It is critical that medically managed patients be willing and able to adhere to all follow-up appointments.⁹ Before initiating treatment, normal serum creatinine and transaminase levels should be confirmed, and there should be no evidence of significant anemia, leukopenia, or thrombocytopenia.² To detect any adverse effects of methotrexate on renal, hepatic, and hematologic functioning, these tests are repeated one week after administration.²

Contraindications
Contraindications to methotrexate treatment include breastfeeding, immunodeficiency, alcoholism, alcoholic liver disease or other chronic liver disease, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia), known sensitivity to methotrexate, active pulmonary disease, peptic ulcer, and hepatic, renal, or hematologic dysfunction. Relative contraindications are a gestational sac larger than 3.5 cm and embryonic cardiac motion.²

On the next page: Patient education >>

PATIENT EDUCATION AND INFORMED CONSENT
A diagnosis of unruptured ectopic pregnancy requires patient education about the condition and its treatment options. The clinician should explain what an ectopic pregnancy is and distinguish between unruptured and ruptured. A discussion of the benefits and risks of each treatment option for which the patient is an appropriate candidate, as well as what to anticipate during treatment, is needed. Emotional support for impending pregnancy loss should also be provided.

For patients who choose medical management, education includes methotrexate-specific information and written instructions to follow after methotrexate administration. Patients must be instructed about the use of safety precautions after treatment (eg, the toilet should be double-flushed with the lid closed during the first 72 hours after treatment to prevent exposing others to methotrexate in urine and stool), the need for adherence to follow-up visits, and warning signs of a possible rupture.⁵ These warning signs are listed in Table 4.

The most common adverse effects of methotrexate are gastrointestinal (nausea, vomiting, stomatitis). Patients should be advised to avoid alcohol, NSAIDs, folic acid supplements, excessive sun exposure (due to photosensitivity), strenuous exercise, and sexual intercourse until ß-hCG has returned to nonpregnant levels. Other adverse effects may include a temporary elevation in liver enzymes and rarely, alopecia. Abdominal pain may occur a few days after methotrexate administration, likely from the cytotoxic effects of the drug on the trophoblastic tissue.

Informed consent is required prior to methotrexate administration. The patient must be advised of the potential risks of medical management with methotrexate, including rupture of the ectopic pregnancy during treatment, inadvertent administration of methotrexate in the presence of an early intrauterine embryo, allergic reaction to methotrexate, and methotrexate-induced pneumonitis.⁵

CASE After lengthy discussion of the treatment options, the patient chose medical management with methotrexate. She verbalized her understanding of the teaching provided and signed an informed consent document.

METHOTREXATE REGIMENS
Protocols for single-dose, two-dose, and fixed multidose methotrexate regimens are described in the medical literature, according to a 2008 American Congress of Obstetricians and Gynecologists practice bulletin.² A 2013 practice committee opinion of the American Society for Reproductive Medicine (ASRM) indicates that single-dose and multiple-dose regimens are used most often.¹²

With methotrexate treatment, complete resolution of ectopic pregnancy usually occurs in two to three weeks but may require up to six to eight weeks, depending on how high the ß-hCG level is when treatment begins.¹²

Single-dose
In the single-dose regimen, an intramuscular (IM) injection of methotrexate 50 mg/m² is administered on day 1. The ß-hCG levels are measured on days 4 and 7 after administration; a decrease of at least 15% in the ß-hCG level should be observed. The ­ß-hCG level is then measured weekly until it reaches < 2 mIU/mL or is undetectable.² If the level does not decline, a repeat dose of methotrexate can be given, with measurement of ß-hCG on days 4 and 7 after the repeat dose. If the ß-hCG level fails to decrease, additional methotrexate or surgical intervention should be considered.

The single-dose regimen is more frequently used and is most successful when ß-hCG levels are low (< 5,000 mIU/mL), the ectopic mass is small
(< 3.5 cm), and embryonic cardiac activity is not observed on ultrasound.^2,3 Patients with ß-hCG levels > 5,000 mIU/mL may be appropriate candidates for additional doses of methotrexate.² In fact, the single-dose protocol provides for repeat doses of methotrexate if the ß-hCG level is not decreasing adequately.¹²

Multiple-dose
With the multiple-dose regimen, methotrexate 1 mg/kg IM is administered on days 1, 3, 5, and 7; on days 2, 4, 6, and 8, the patient receives leucovorin (folinic acid) 0.1 mg/kg IM. The ß-hCG level is measured on days methotrexate is administered; once the minimum 15% decline is observed, ß-hCG is measured weekly until a nonpregnant level is reached.¹²

CASE The patient was referred to an obstetrics clinic and reported for all scheduled follow-up appointments. She was discharged from care after a full reduction in her ß-hCG to nonpregnant levels. While at the clinic, the patient was referred to social services for psychosocial counseling.

CONCLUSION
Ectopic implantation is a serious complication that may occur during the first trimester of pregnancy. Worldwide, it is the leading cause of maternal death in the first trimester. For women who meet specific criteria, outpatient treatment of early ectopic pregnancy with methotrexate avoids surgery and decreases the overall cost of care. Medical management and conservative surgical management offer the patient comparable outcomes for tubal patency preservation and risk for ectopic pregnancy ­recurrence.¹¹

REFERENCES
1. Lozeau AM, Potter B. Diagnosis and management of ectopic pregnancy. Am Fam Physician. 2005;72(9):1707-1714.

2. American Congress of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479-1485.

3. Sepilian VP, Wood E. Ectopic pregnancy. http://emedicine.medscape.com/article/2041923-overview. Medscape. Accessed June 19, 2014.

4. Stein JC, Wang R, Adler N, et al. Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: a meta-analysis. Ann Emerg Med. 2010;56(6):674-683.

5. Murtaza UI, Ortmann MJ, Mando-Vandrick J, Lee ASD. Management of first-trimester complications in the emergency department. Am J Health Syst Pharm. 2013;70(2):99-111.

6. Sewell CA, Cundiff GW. Trends for inpatient treatment of tubal pregnancy in Maryland. Am J Obstet Gynecol. 2002;186(3):404-408.

7. Nama V, Manyonda I. Tubal ectopic pregnancy: diagnosis and management. Arch Gynecol Obstet. 2009;279(4):443-453.

8. Barnhart KT, Sammel MD, Gracia CR, et al. Risk factors for ectopic pregnancy in women with symptomatic first-trimester pregnancies. Fertil Steril. 2006;86(1):36-43.

9. Hajenius PJ, Mol F, Mol BW, et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev. 2007;(1):CD000324.

10. Hoover KW, Tao G, Kent CK. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol. 2010;115(3): 495-502.

11. Autry A. Medical treatment of ectopic pregnancy: is there something new? Obstet Gynecol. 2013;122(4):733.

12. The Practice Committee of the American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril. 2013;100(3):638-644.

Ectopic pregnancy is a significant health risk to women during their childbearing years; approximately 6% of all pregnancy-related deaths are due to ectopic pregnancy.^1-3 Some 1% to 2% of all pregnancies in the United States each year—approximately 100,000 cases—are ectopic, with an estimated annual cost of care approaching $1.1 billion.⁴ The incidence of ectopic pregnancy has increased in the past 20 years; in one analysis, ectopic pregnancy was diagnosed in 18% of women who presented to an emergency department (ED) with first trimester vaginal bleeding, abdominal pain, or both.⁵ This growing prevalence is attributed to a number of factors, including the sensitivity of current diagnostic methods in detecting early ectopic pregnancy, the greater incidence of salpingitis, and the growing use of assisted reproductive technologies.^2,6

While the number of ectopic pregnancies is on the rise, the proportion of patients requiring hospitalization for surgical treatment of ectopic pregnancy has decreased significantly. Today, for appropriate patients, many clinicians manage ectopic pregnancy on an outpatient basis using the drug methotrexate.⁶

In this article, we will present an overview of the current status of medical management of ectopic pregnancy, along with a case study. The case study describes a patient diagnosed with an unruptured ectopic pregnancy who was managed medically with methotrexate. It illustrates how, with early diagnosis, clinicians can intervene to make medical management an effective treatment option in selected situations.

On the next page: Diagnosis and case continuation >>

DIAGNOSIS
There is some variation in the presentation of women experiencing ectopic pregnancy; this may be due to differences in the pathologic mechanisms of ectopic pregnancy. Patients may be asymptomatic, hemodynamically compromised, or somewhere in between.³ Typical clinical signs include abdominal pain, amenorrhea, and vaginal bleeding. Approximately 40% to 50% of patients present with vaginal bleeding, 50% may have a palpable adnexal mass, and 75% may have abdominal tenderness.³ Only about 50% of women with ectopic pregnancies present with these typical symptoms.³

The patient may also experience common symptoms of early pregnancy, such as nausea, fatigue, and breast fullness. Worrisome signs and symptoms, including abdominal guarding, hypotension, tachycardia, shock, shoulder pain from peritoneal irritation, dizziness, fever, and vomiting, may also be present.^3,7 Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at presentation, which is highly suggestive of rupture.³    

Risk factors
Risk factors for ectopic pregnancy include pre­vious ectopic pregnancy; previous tubal procedures; history of sexually transmitted disease or genital infections; infertility; use of assisted reproductive technology; previous abdominal or pelvic surgery; smoking; pelvic inflammatory disease; exposure in utero to diethylstilbestrol; and previous intra­uterine device use.^2,5,7,8 Knowledge of these risk factors can help identify a patient with an ectopic pregnancy.

The diagnosis of ectopic pregnancy is most certainly a clinical challenge. The differential diagnosis is based upon history and physical findings; the list can be lengthy if both vaginal bleeding and abdominal pain (nonspecific symptoms common in women who miscarry) are present.⁷ Prompt completion of diagnostic testing is critical in making a definitive diagnosis. Possible diagnoses are listed in Table 1.

CASE Upon examination, the patient appeared comfortable and relaxed, and there were no signs of distress. Blood pressure was 100/65 mm Hg, pulse rate was 72 beats/min, and temperature was 99.0°F. There was no tenderness upon abdominal examination. Pelvic examination revealed a small amount of brown vaginal discharge but no active bleeding or pooled blood, clots, or tissue. The cervical os was closed, and positive Chadwick sign was present. Bimanual examination revealed no cervical motion tenderness. The uterus was soft, mobile, and nontender, and consistent in size with a gestation at eight weeks. There were no palpable adnexa, ovaries, or masses. There was no pain with bimanual examination and no evidence of tenderness at the posterior fornix. The remainder of the physical examination was unremarkable.

It is important to note that examination results in the case patient are not unusual in a woman with a small, unruptured ectopic pregnancy. All findings were normal except for the scant brown vaginal discharge. Abdominal and adnexal tenderness are common, as is a palpable adnexal mass; but absence of a detectable mass does not exclude ectopic pregnancy.¹ Pathologic findings may include severe abdominal tenderness and pain, significant vaginal bleeding, passage of clots, tachycardia, and orthostatic hypotension.

Diagnostic workup
Laboratory tests are critical to making an accurate diagnosis for women whose history and physical examination results are consistent with ectopic pregnancy. Assessment for ectopic pregnancy should include a urine pregnancy test, transvaginal ultrasound, measurement of serum ß-human chorionic gonadotropin (ß-hCG) level, and occasionally, diagnostic curettage.¹ Once the diagnosis is confirmed, a complete blood count (CBC) is necessary to assess anemia and platelet functioning. Coagulation tests may be required for worrisome bleeding. Blood type, Rh status, and antibody screen are also necessary to determine whether a patient who is Rh D-negative will require Rh immune globulin. See Table 2 for the patient’s laboratory test results.

In a patient with a ß-hCG level greater than the discriminatory cutoff value of 1,500 to 1,800 mIU/mL, the level above which an intrauterine gestational sac is visible on transvaginal ultrasound in a normal pregnancy, an empty uterus is considered an ectopic pregnancy until proven otherwise.³ In a definite intrauterine pregnancy of about six weeks’ gestation, transvaginal ultrasound reveals a gestational sac that contains a yolk sac and a fetal pole.³

CASE The patient’s presenting symptoms, combined with a positive pregnancy test, ß-hCG level of 1,850 mIU/mL, and a complex adnexal mass in the right fallopian tube, were highly suggestive of an un­ruptured ectopic pregnancy (see Table 3 for the patient’s transvaginal ultrasound findings). There was also a secondary finding of a corpus luteum cyst. Other diagnoses were ruled out, and the patient was diagnosed with an unruptured ectopic pregnancy.

On the next page: Treatment >>

TREATMENT
A patient with an ectopic pregnancy who presents with pain and hemodynamic instability should be referred immediately for appropriate surgical care.⁷ Otherwise, once the diagnosis of ectopic pregnancy is confirmed, the patient should be referred to an obstetric specialist. Treatments for ectopic pregnancy include expectant management and surgery—which will be discussed briefly—and medical management, which is the focus of this review.⁵

Expectant management
Most ectopic pregnancies are diagnosed early as a result of accurate, minimally invasive and noninvasive diagnostic tools and greater awareness of risk factors. Since the natural course of early ectopic pregnancy is often self-limited, eventually resulting in tubal abortion or reabsorption, expectant management is a viable option.⁹

This treatment option may be considered if the patient is asymptomatic; ß-hCG is < 200 mIU/mL; the ectopic mass is < 3 cm; and no fetal heartbeat is present.^1,2 With this approach, patients must be willing to accept the risk for tubal rupture and agree to close monitoring of ß-hCG levels. The ß-hCG level must be measured every 24 to 48 hours in order to determine if it is declining adequately, plateauing, or increasing.^2,5

Surgery
For the hemodynamically unstable patient, the treatment decision is relatively straightforward. Optimal treatment for a ruptured ectopic pregnancy is immediate surgery, which may include salpingostomy or salpingectomy.¹⁰ Surgery may also be considered for hemodynamically stable patients with nonruptured ectopic pregnancies; in addition to her clinical presentation, overall management may be driven by a patient’s preferences.⁵ Salpingostomy and salpingectomy can be performed either laparoscopically or via laparotomy, depending on the specific situation.

Medical management
The use of methotrexate for the management of unruptured ectopic pregnancy was introduced in the early 1980s.¹¹ Initially, protocols called for multiple doses administered during the course of an inpatient stay. Further research led to revised treatment recommendations and today, medical management most often consists of a single dose of methotrexate with outpatient follow-up.³

Methotrexate is a folic acid antagonist often used as an antimetabolite chemotherapeutic agent. In ectopic pregnancy, it inhibits growth of the rapidly dividing trophoblastic cells and ultimately ends the pregnancy.² Outcomes of medical management are comparable to those of surgical treatment, including the potential for future normal pregnancies.^2,5

An analysis of US trends in ectopic pregnancy management from 2002-2007 revealed that the use of methotrexate increased from 11.1% to 35.1% during that time, while the use of surgical approaches declined from 90% to 65%.¹⁰ Medical management of ectopic pregnancy eliminates the costs of surgery, anesthesia, and hospitalization and avoids potential complications of surgery and anesthesia.

Appropriate candidates
A hemodynamically stable patient with a confirmed or high clinical suspicion of ectopic pregnancy, an unruptured mass, no active bleeding, and low ­ß-hCG levels (< 5,000 mIU/mL) can be considered for methotrexate therapy.^2,3,9 It is critical that medically managed patients be willing and able to adhere to all follow-up appointments.⁹ Before initiating treatment, normal serum creatinine and transaminase levels should be confirmed, and there should be no evidence of significant anemia, leukopenia, or thrombocytopenia.² To detect any adverse effects of methotrexate on renal, hepatic, and hematologic functioning, these tests are repeated one week after administration.²

Contraindications
Contraindications to methotrexate treatment include breastfeeding, immunodeficiency, alcoholism, alcoholic liver disease or other chronic liver disease, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia), known sensitivity to methotrexate, active pulmonary disease, peptic ulcer, and hepatic, renal, or hematologic dysfunction. Relative contraindications are a gestational sac larger than 3.5 cm and embryonic cardiac motion.²

On the next page: Patient education >>

PATIENT EDUCATION AND INFORMED CONSENT
A diagnosis of unruptured ectopic pregnancy requires patient education about the condition and its treatment options. The clinician should explain what an ectopic pregnancy is and distinguish between unruptured and ruptured. A discussion of the benefits and risks of each treatment option for which the patient is an appropriate candidate, as well as what to anticipate during treatment, is needed. Emotional support for impending pregnancy loss should also be provided.

For patients who choose medical management, education includes methotrexate-specific information and written instructions to follow after methotrexate administration. Patients must be instructed about the use of safety precautions after treatment (eg, the toilet should be double-flushed with the lid closed during the first 72 hours after treatment to prevent exposing others to methotrexate in urine and stool), the need for adherence to follow-up visits, and warning signs of a possible rupture.⁵ These warning signs are listed in Table 4.

The most common adverse effects of methotrexate are gastrointestinal (nausea, vomiting, stomatitis). Patients should be advised to avoid alcohol, NSAIDs, folic acid supplements, excessive sun exposure (due to photosensitivity), strenuous exercise, and sexual intercourse until ß-hCG has returned to nonpregnant levels. Other adverse effects may include a temporary elevation in liver enzymes and rarely, alopecia. Abdominal pain may occur a few days after methotrexate administration, likely from the cytotoxic effects of the drug on the trophoblastic tissue.

Informed consent is required prior to methotrexate administration. The patient must be advised of the potential risks of medical management with methotrexate, including rupture of the ectopic pregnancy during treatment, inadvertent administration of methotrexate in the presence of an early intrauterine embryo, allergic reaction to methotrexate, and methotrexate-induced pneumonitis.⁵

CASE After lengthy discussion of the treatment options, the patient chose medical management with methotrexate. She verbalized her understanding of the teaching provided and signed an informed consent document.

METHOTREXATE REGIMENS
Protocols for single-dose, two-dose, and fixed multidose methotrexate regimens are described in the medical literature, according to a 2008 American Congress of Obstetricians and Gynecologists practice bulletin.² A 2013 practice committee opinion of the American Society for Reproductive Medicine (ASRM) indicates that single-dose and multiple-dose regimens are used most often.¹²

With methotrexate treatment, complete resolution of ectopic pregnancy usually occurs in two to three weeks but may require up to six to eight weeks, depending on how high the ß-hCG level is when treatment begins.¹²

Single-dose
In the single-dose regimen, an intramuscular (IM) injection of methotrexate 50 mg/m² is administered on day 1. The ß-hCG levels are measured on days 4 and 7 after administration; a decrease of at least 15% in the ß-hCG level should be observed. The ­ß-hCG level is then measured weekly until it reaches < 2 mIU/mL or is undetectable.² If the level does not decline, a repeat dose of methotrexate can be given, with measurement of ß-hCG on days 4 and 7 after the repeat dose. If the ß-hCG level fails to decrease, additional methotrexate or surgical intervention should be considered.

The single-dose regimen is more frequently used and is most successful when ß-hCG levels are low (< 5,000 mIU/mL), the ectopic mass is small
(< 3.5 cm), and embryonic cardiac activity is not observed on ultrasound.^2,3 Patients with ß-hCG levels > 5,000 mIU/mL may be appropriate candidates for additional doses of methotrexate.² In fact, the single-dose protocol provides for repeat doses of methotrexate if the ß-hCG level is not decreasing adequately.¹²

Multiple-dose
With the multiple-dose regimen, methotrexate 1 mg/kg IM is administered on days 1, 3, 5, and 7; on days 2, 4, 6, and 8, the patient receives leucovorin (folinic acid) 0.1 mg/kg IM. The ß-hCG level is measured on days methotrexate is administered; once the minimum 15% decline is observed, ß-hCG is measured weekly until a nonpregnant level is reached.¹²

CASE The patient was referred to an obstetrics clinic and reported for all scheduled follow-up appointments. She was discharged from care after a full reduction in her ß-hCG to nonpregnant levels. While at the clinic, the patient was referred to social services for psychosocial counseling.

CONCLUSION
Ectopic implantation is a serious complication that may occur during the first trimester of pregnancy. Worldwide, it is the leading cause of maternal death in the first trimester. For women who meet specific criteria, outpatient treatment of early ectopic pregnancy with methotrexate avoids surgery and decreases the overall cost of care. Medical management and conservative surgical management offer the patient comparable outcomes for tubal patency preservation and risk for ectopic pregnancy ­recurrence.¹¹

REFERENCES
1. Lozeau AM, Potter B. Diagnosis and management of ectopic pregnancy. Am Fam Physician. 2005;72(9):1707-1714.

2. American Congress of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479-1485.

3. Sepilian VP, Wood E. Ectopic pregnancy. http://emedicine.medscape.com/article/2041923-overview. Medscape. Accessed June 19, 2014.

4. Stein JC, Wang R, Adler N, et al. Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: a meta-analysis. Ann Emerg Med. 2010;56(6):674-683.

5. Murtaza UI, Ortmann MJ, Mando-Vandrick J, Lee ASD. Management of first-trimester complications in the emergency department. Am J Health Syst Pharm. 2013;70(2):99-111.

6. Sewell CA, Cundiff GW. Trends for inpatient treatment of tubal pregnancy in Maryland. Am J Obstet Gynecol. 2002;186(3):404-408.

7. Nama V, Manyonda I. Tubal ectopic pregnancy: diagnosis and management. Arch Gynecol Obstet. 2009;279(4):443-453.

8. Barnhart KT, Sammel MD, Gracia CR, et al. Risk factors for ectopic pregnancy in women with symptomatic first-trimester pregnancies. Fertil Steril. 2006;86(1):36-43.

9. Hajenius PJ, Mol F, Mol BW, et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev. 2007;(1):CD000324.

10. Hoover KW, Tao G, Kent CK. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol. 2010;115(3): 495-502.

11. Autry A. Medical treatment of ectopic pregnancy: is there something new? Obstet Gynecol. 2013;122(4):733.

12. The Practice Committee of the American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril. 2013;100(3):638-644.

Ectopic pregnancy is a significant health risk to women during their childbearing years; approximately 6% of all pregnancy-related deaths are due to ectopic pregnancy.^1-3 Some 1% to 2% of all pregnancies in the United States each year—approximately 100,000 cases—are ectopic, with an estimated annual cost of care approaching $1.1 billion.⁴ The incidence of ectopic pregnancy has increased in the past 20 years; in one analysis, ectopic pregnancy was diagnosed in 18% of women who presented to an emergency department (ED) with first trimester vaginal bleeding, abdominal pain, or both.⁵ This growing prevalence is attributed to a number of factors, including the sensitivity of current diagnostic methods in detecting early ectopic pregnancy, the greater incidence of salpingitis, and the growing use of assisted reproductive technologies.^2,6

While the number of ectopic pregnancies is on the rise, the proportion of patients requiring hospitalization for surgical treatment of ectopic pregnancy has decreased significantly. Today, for appropriate patients, many clinicians manage ectopic pregnancy on an outpatient basis using the drug methotrexate.⁶

In this article, we will present an overview of the current status of medical management of ectopic pregnancy, along with a case study. The case study describes a patient diagnosed with an unruptured ectopic pregnancy who was managed medically with methotrexate. It illustrates how, with early diagnosis, clinicians can intervene to make medical management an effective treatment option in selected situations.

On the next page: Diagnosis and case continuation >>

DIAGNOSIS
There is some variation in the presentation of women experiencing ectopic pregnancy; this may be due to differences in the pathologic mechanisms of ectopic pregnancy. Patients may be asymptomatic, hemodynamically compromised, or somewhere in between.³ Typical clinical signs include abdominal pain, amenorrhea, and vaginal bleeding. Approximately 40% to 50% of patients present with vaginal bleeding, 50% may have a palpable adnexal mass, and 75% may have abdominal tenderness.³ Only about 50% of women with ectopic pregnancies present with these typical symptoms.³

The patient may also experience common symptoms of early pregnancy, such as nausea, fatigue, and breast fullness. Worrisome signs and symptoms, including abdominal guarding, hypotension, tachycardia, shock, shoulder pain from peritoneal irritation, dizziness, fever, and vomiting, may also be present.^3,7 Approximately 20% of patients with ectopic pregnancies are hemodynamically compromised at presentation, which is highly suggestive of rupture.³    

Risk factors
Risk factors for ectopic pregnancy include pre­vious ectopic pregnancy; previous tubal procedures; history of sexually transmitted disease or genital infections; infertility; use of assisted reproductive technology; previous abdominal or pelvic surgery; smoking; pelvic inflammatory disease; exposure in utero to diethylstilbestrol; and previous intra­uterine device use.^2,5,7,8 Knowledge of these risk factors can help identify a patient with an ectopic pregnancy.

The diagnosis of ectopic pregnancy is most certainly a clinical challenge. The differential diagnosis is based upon history and physical findings; the list can be lengthy if both vaginal bleeding and abdominal pain (nonspecific symptoms common in women who miscarry) are present.⁷ Prompt completion of diagnostic testing is critical in making a definitive diagnosis. Possible diagnoses are listed in Table 1.

CASE Upon examination, the patient appeared comfortable and relaxed, and there were no signs of distress. Blood pressure was 100/65 mm Hg, pulse rate was 72 beats/min, and temperature was 99.0°F. There was no tenderness upon abdominal examination. Pelvic examination revealed a small amount of brown vaginal discharge but no active bleeding or pooled blood, clots, or tissue. The cervical os was closed, and positive Chadwick sign was present. Bimanual examination revealed no cervical motion tenderness. The uterus was soft, mobile, and nontender, and consistent in size with a gestation at eight weeks. There were no palpable adnexa, ovaries, or masses. There was no pain with bimanual examination and no evidence of tenderness at the posterior fornix. The remainder of the physical examination was unremarkable.

It is important to note that examination results in the case patient are not unusual in a woman with a small, unruptured ectopic pregnancy. All findings were normal except for the scant brown vaginal discharge. Abdominal and adnexal tenderness are common, as is a palpable adnexal mass; but absence of a detectable mass does not exclude ectopic pregnancy.¹ Pathologic findings may include severe abdominal tenderness and pain, significant vaginal bleeding, passage of clots, tachycardia, and orthostatic hypotension.

Diagnostic workup
Laboratory tests are critical to making an accurate diagnosis for women whose history and physical examination results are consistent with ectopic pregnancy. Assessment for ectopic pregnancy should include a urine pregnancy test, transvaginal ultrasound, measurement of serum ß-human chorionic gonadotropin (ß-hCG) level, and occasionally, diagnostic curettage.¹ Once the diagnosis is confirmed, a complete blood count (CBC) is necessary to assess anemia and platelet functioning. Coagulation tests may be required for worrisome bleeding. Blood type, Rh status, and antibody screen are also necessary to determine whether a patient who is Rh D-negative will require Rh immune globulin. See Table 2 for the patient’s laboratory test results.

In a patient with a ß-hCG level greater than the discriminatory cutoff value of 1,500 to 1,800 mIU/mL, the level above which an intrauterine gestational sac is visible on transvaginal ultrasound in a normal pregnancy, an empty uterus is considered an ectopic pregnancy until proven otherwise.³ In a definite intrauterine pregnancy of about six weeks’ gestation, transvaginal ultrasound reveals a gestational sac that contains a yolk sac and a fetal pole.³

CASE The patient’s presenting symptoms, combined with a positive pregnancy test, ß-hCG level of 1,850 mIU/mL, and a complex adnexal mass in the right fallopian tube, were highly suggestive of an un­ruptured ectopic pregnancy (see Table 3 for the patient’s transvaginal ultrasound findings). There was also a secondary finding of a corpus luteum cyst. Other diagnoses were ruled out, and the patient was diagnosed with an unruptured ectopic pregnancy.

On the next page: Treatment >>

TREATMENT
A patient with an ectopic pregnancy who presents with pain and hemodynamic instability should be referred immediately for appropriate surgical care.⁷ Otherwise, once the diagnosis of ectopic pregnancy is confirmed, the patient should be referred to an obstetric specialist. Treatments for ectopic pregnancy include expectant management and surgery—which will be discussed briefly—and medical management, which is the focus of this review.⁵

Expectant management
Most ectopic pregnancies are diagnosed early as a result of accurate, minimally invasive and noninvasive diagnostic tools and greater awareness of risk factors. Since the natural course of early ectopic pregnancy is often self-limited, eventually resulting in tubal abortion or reabsorption, expectant management is a viable option.⁹

This treatment option may be considered if the patient is asymptomatic; ß-hCG is < 200 mIU/mL; the ectopic mass is < 3 cm; and no fetal heartbeat is present.^1,2 With this approach, patients must be willing to accept the risk for tubal rupture and agree to close monitoring of ß-hCG levels. The ß-hCG level must be measured every 24 to 48 hours in order to determine if it is declining adequately, plateauing, or increasing.^2,5

Surgery
For the hemodynamically unstable patient, the treatment decision is relatively straightforward. Optimal treatment for a ruptured ectopic pregnancy is immediate surgery, which may include salpingostomy or salpingectomy.¹⁰ Surgery may also be considered for hemodynamically stable patients with nonruptured ectopic pregnancies; in addition to her clinical presentation, overall management may be driven by a patient’s preferences.⁵ Salpingostomy and salpingectomy can be performed either laparoscopically or via laparotomy, depending on the specific situation.

Medical management
The use of methotrexate for the management of unruptured ectopic pregnancy was introduced in the early 1980s.¹¹ Initially, protocols called for multiple doses administered during the course of an inpatient stay. Further research led to revised treatment recommendations and today, medical management most often consists of a single dose of methotrexate with outpatient follow-up.³

Methotrexate is a folic acid antagonist often used as an antimetabolite chemotherapeutic agent. In ectopic pregnancy, it inhibits growth of the rapidly dividing trophoblastic cells and ultimately ends the pregnancy.² Outcomes of medical management are comparable to those of surgical treatment, including the potential for future normal pregnancies.^2,5

An analysis of US trends in ectopic pregnancy management from 2002-2007 revealed that the use of methotrexate increased from 11.1% to 35.1% during that time, while the use of surgical approaches declined from 90% to 65%.¹⁰ Medical management of ectopic pregnancy eliminates the costs of surgery, anesthesia, and hospitalization and avoids potential complications of surgery and anesthesia.

Appropriate candidates
A hemodynamically stable patient with a confirmed or high clinical suspicion of ectopic pregnancy, an unruptured mass, no active bleeding, and low ­ß-hCG levels (< 5,000 mIU/mL) can be considered for methotrexate therapy.^2,3,9 It is critical that medically managed patients be willing and able to adhere to all follow-up appointments.⁹ Before initiating treatment, normal serum creatinine and transaminase levels should be confirmed, and there should be no evidence of significant anemia, leukopenia, or thrombocytopenia.² To detect any adverse effects of methotrexate on renal, hepatic, and hematologic functioning, these tests are repeated one week after administration.²

Contraindications
Contraindications to methotrexate treatment include breastfeeding, immunodeficiency, alcoholism, alcoholic liver disease or other chronic liver disease, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia), known sensitivity to methotrexate, active pulmonary disease, peptic ulcer, and hepatic, renal, or hematologic dysfunction. Relative contraindications are a gestational sac larger than 3.5 cm and embryonic cardiac motion.²

On the next page: Patient education >>

PATIENT EDUCATION AND INFORMED CONSENT
A diagnosis of unruptured ectopic pregnancy requires patient education about the condition and its treatment options. The clinician should explain what an ectopic pregnancy is and distinguish between unruptured and ruptured. A discussion of the benefits and risks of each treatment option for which the patient is an appropriate candidate, as well as what to anticipate during treatment, is needed. Emotional support for impending pregnancy loss should also be provided.

For patients who choose medical management, education includes methotrexate-specific information and written instructions to follow after methotrexate administration. Patients must be instructed about the use of safety precautions after treatment (eg, the toilet should be double-flushed with the lid closed during the first 72 hours after treatment to prevent exposing others to methotrexate in urine and stool), the need for adherence to follow-up visits, and warning signs of a possible rupture.⁵ These warning signs are listed in Table 4.

The most common adverse effects of methotrexate are gastrointestinal (nausea, vomiting, stomatitis). Patients should be advised to avoid alcohol, NSAIDs, folic acid supplements, excessive sun exposure (due to photosensitivity), strenuous exercise, and sexual intercourse until ß-hCG has returned to nonpregnant levels. Other adverse effects may include a temporary elevation in liver enzymes and rarely, alopecia. Abdominal pain may occur a few days after methotrexate administration, likely from the cytotoxic effects of the drug on the trophoblastic tissue.

Informed consent is required prior to methotrexate administration. The patient must be advised of the potential risks of medical management with methotrexate, including rupture of the ectopic pregnancy during treatment, inadvertent administration of methotrexate in the presence of an early intrauterine embryo, allergic reaction to methotrexate, and methotrexate-induced pneumonitis.⁵

CASE After lengthy discussion of the treatment options, the patient chose medical management with methotrexate. She verbalized her understanding of the teaching provided and signed an informed consent document.

METHOTREXATE REGIMENS
Protocols for single-dose, two-dose, and fixed multidose methotrexate regimens are described in the medical literature, according to a 2008 American Congress of Obstetricians and Gynecologists practice bulletin.² A 2013 practice committee opinion of the American Society for Reproductive Medicine (ASRM) indicates that single-dose and multiple-dose regimens are used most often.¹²

With methotrexate treatment, complete resolution of ectopic pregnancy usually occurs in two to three weeks but may require up to six to eight weeks, depending on how high the ß-hCG level is when treatment begins.¹²

Single-dose
In the single-dose regimen, an intramuscular (IM) injection of methotrexate 50 mg/m² is administered on day 1. The ß-hCG levels are measured on days 4 and 7 after administration; a decrease of at least 15% in the ß-hCG level should be observed. The ­ß-hCG level is then measured weekly until it reaches < 2 mIU/mL or is undetectable.² If the level does not decline, a repeat dose of methotrexate can be given, with measurement of ß-hCG on days 4 and 7 after the repeat dose. If the ß-hCG level fails to decrease, additional methotrexate or surgical intervention should be considered.

The single-dose regimen is more frequently used and is most successful when ß-hCG levels are low (< 5,000 mIU/mL), the ectopic mass is small
(< 3.5 cm), and embryonic cardiac activity is not observed on ultrasound.^2,3 Patients with ß-hCG levels > 5,000 mIU/mL may be appropriate candidates for additional doses of methotrexate.² In fact, the single-dose protocol provides for repeat doses of methotrexate if the ß-hCG level is not decreasing adequately.¹²

Multiple-dose
With the multiple-dose regimen, methotrexate 1 mg/kg IM is administered on days 1, 3, 5, and 7; on days 2, 4, 6, and 8, the patient receives leucovorin (folinic acid) 0.1 mg/kg IM. The ß-hCG level is measured on days methotrexate is administered; once the minimum 15% decline is observed, ß-hCG is measured weekly until a nonpregnant level is reached.¹²

CASE The patient was referred to an obstetrics clinic and reported for all scheduled follow-up appointments. She was discharged from care after a full reduction in her ß-hCG to nonpregnant levels. While at the clinic, the patient was referred to social services for psychosocial counseling.

CONCLUSION
Ectopic implantation is a serious complication that may occur during the first trimester of pregnancy. Worldwide, it is the leading cause of maternal death in the first trimester. For women who meet specific criteria, outpatient treatment of early ectopic pregnancy with methotrexate avoids surgery and decreases the overall cost of care. Medical management and conservative surgical management offer the patient comparable outcomes for tubal patency preservation and risk for ectopic pregnancy ­recurrence.¹¹

REFERENCES
1. Lozeau AM, Potter B. Diagnosis and management of ectopic pregnancy. Am Fam Physician. 2005;72(9):1707-1714.

2. American Congress of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: medical management of ectopic pregnancy. Obstet Gynecol. 2008;111(6):1479-1485.

3. Sepilian VP, Wood E. Ectopic pregnancy. http://emedicine.medscape.com/article/2041923-overview. Medscape. Accessed June 19, 2014.

4. Stein JC, Wang R, Adler N, et al. Emergency physician ultrasonography for evaluating patients at risk for ectopic pregnancy: a meta-analysis. Ann Emerg Med. 2010;56(6):674-683.

5. Murtaza UI, Ortmann MJ, Mando-Vandrick J, Lee ASD. Management of first-trimester complications in the emergency department. Am J Health Syst Pharm. 2013;70(2):99-111.

6. Sewell CA, Cundiff GW. Trends for inpatient treatment of tubal pregnancy in Maryland. Am J Obstet Gynecol. 2002;186(3):404-408.

7. Nama V, Manyonda I. Tubal ectopic pregnancy: diagnosis and management. Arch Gynecol Obstet. 2009;279(4):443-453.

8. Barnhart KT, Sammel MD, Gracia CR, et al. Risk factors for ectopic pregnancy in women with symptomatic first-trimester pregnancies. Fertil Steril. 2006;86(1):36-43.

9. Hajenius PJ, Mol F, Mol BW, et al. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev. 2007;(1):CD000324.

10. Hoover KW, Tao G, Kent CK. Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol. 2010;115(3): 495-502.

11. Autry A. Medical treatment of ectopic pregnancy: is there something new? Obstet Gynecol. 2013;122(4):733.

12. The Practice Committee of the American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril. 2013;100(3):638-644.

There are many reports in the medical and dental literature of complications arising from a routine delivery of dental care. One complication can include physical injury from swallowing or aspirating foreign objects.¹ However, a review of such literature presents a scarcity of documented instances and no long-term evaluation of the aforementioned events.^2,3

This report presents the case of a patient who aspirated a hex driver tool during a procedure to place a crown on a dental implant. The aspirated object was subsequently removed through flexible fiberoptic bronchoscopy without complications.

Case Report

An 83-year-old man was referred to the Pulmonary and Critical Care Department of the VA Caribbean Healthcare System in San Juan, Puerto Rico, after a hex driver tool was lost during a procedure to place a crown on a dental implant, performed under topical anesthesia. It was first thought that the patient swallowed the hex driver, since he never experienced or complained of coughing or shortness of breath. A chest radiograph revealed a metal object lying within the right main stem bronchus, for which the patient was referred to the Pulmonary and Critical Care Department (Figure 1).

The patient’s past medical history was remarkable for hypertension and hypercholesterolemia. Outpatient medications included hydrochlorothiazide, simvastatin, aspirin, felodipine, and lorazepam. He had no previous history of dysphagia or neurologic disease. A physical examination revealed expiratory and inspiratory wheezing localized to the right lower lobe without associated rhonchi or crackles. No distress, shortness of breath, or coughing was noted.

A flexible fiberoptic bronchoscopy was performed under conscious sedation with 3 mg of IV midazolam and topical anesthesia with nebulized 4% lidocaine. No mucosal edema, hyperemia, or structural damage was noted during direct visualization of both the right and left bronchopulmonary segments. A metallic object was visualized at the entrance of the right lower lobe. The foreign object had irregular borders, providing multiple edges that made it suitable to be embraced (Figure 2).

Using a radial jaw single-use biopsy forceps 1.8 mm, the physician clinched and retrieved the object through the bronchoscope. The object was retrieved on the same day of the dental procedure almost 5 hours after it was aspirated. The patient tolerated the procedure well; no coughing, oxygen desaturation, or bleeding occurred during the procedure.

After a few hours of observation, a postprocedural radiograph confirmed the removal of the foreign body without evidence of pneumothorax. The patient was discharged, and 24 hours after the incident remained asymptomatic without chest pain, cough, hemoptysis, sputum production, or fever.

Discussion

Foreign-body aspiration and inadvertent swallowing remains underrecognized by clinicians. In the U.S., more than 2,700 people, including more than 300 children, die of foreign-body aspiration each year.^4,5 Aspiration or ingestion of a foreign body during a dental procedure is serious and potentially fatal.⁶ Some of the consequences of an aspirated object are complete or partial airway obstruction, respiratory distress and failure, pneumothorax, and hemorrhage.⁷ In addition, inadvertent aspiration of foreign objects in asymptomatic patients may not be evident for months, resulting in late complications as postobstructive pneumonia, bronchiectasis, or lung abscess.⁸ Early recognition and diagnosis of these events are crucial to prevent complications.

Accidental aspiration of foreign objects during dental procedures is not as common as is swallowing. In the normal population, the foreign object enters the gastrointestinal tract in about 92.5% of the time, and the tracheobronchial tree in 7.5% of these instances.

A 10-year review done at the School of Dentistry of the University of North Carolina reported 36 incidents of lost instruments during dental procedures. In only 1 case, an object was aspirated, 25 of the 36 cases were secondary to ingestion, and in the remaining 10 incidents, swallowing or aspiration was ruled out by radiography or after the object’s removal from the patient’s mouth.² Previous reviews about foreign-body aspiration in adults have reported dental appliances as the second most commonly aspirated foreign objects.⁴ Of all aspirated objects, the most common site of impaction is the right lower lobe; however, aspiration has been reported in all pulmonary lobes.⁶

Available literature recognizes that impaction of aspirated objects occurred in 56% of instances within the right lower lobe and 33% in the left lower lobe.^7,9 Identification of risk factors for aspiration is important for any patient who will undergo dental procedures, such as advanced age (ie, elderly patients may have a decreased gag reflex); neurologic conditions, such as stroke; dementia and other degenerative diseases; the use of topical anesthesia; and altered states of consciousness associated with the use of IV sedation.^1,2

The key sign that most dentists recognize when patients aspirate an object during a dental procedure is coughing. It has been reported that coughing resulting from aspiration of foreign objects may range from mild to severe. In this case, the patient was completely asymptomatic during the procedure. The only clue of possible object aspiration was the reported tool loss by the dentist. It is important to always examine, account for, and review all equipment used during dental procedures. Assessment for any lost objects or missing parts of instruments should be done promptly with a high degree of suspicion for possible swallowing or aspiration if an object is missing.

It has been recommended to use a gauze throat screen and rubber dam and to avoid a supine position during a procedure, among other techniques, to minimize risk of ingestion or aspiration.² Imaging studies should be used for further evaluation of the patient; however, some instruments, such as dental pieces and impression material, may not be identified by plain films. In those cases, further evaluation with more sophisticated imaging techniques, such as computed tomography (CT), should be considered.^1-10

In a previous case report of a patient who aspirated a third molar during a dental procedure, a chest film failed to identify it. A chest CT was performed, and the object showed in the right main stem bronchus. In another instance, aspiration of impression material in a 45-year-old man was not observed by chest radiography. In this case, the history of coughing and respiratory symptoms days after the procedure pointed toward aspiration of an object as the culprit, with subsequent identification and removal by flexible fiberoptic bronchoscopy.^1-11

Bronchoscopy is the treatment of choice for extraction of aspirated foreign bodies; however, there is still a debate about whether to use flexible or rigid bronchoscopy. The decision is usually made based on the object size, localization, medical facility, and personnel expertise. The rigid bronchoscope has the advantages of offering better control and visualization of the airway and easier use of removal instruments. Its primary disadvantage is that the procedure needs to be done in the operating room under general anesthesia. Flexible fiberoptic bronchoscopy done under conscious sedation and topical anesthesia may be as effective as rigid bronchoscopy and even superior in the case of smaller and more distal impacted objects.^10-14

In this case, flexible fiberoptic bronchoscopy was used successfully for the removal of the foreign object. Biopsy forceps were used to grasp the object and retrieve it from the airway without complication.

Conclusion

Aspiration of foreign objects during a dental procedure is a potential life-threatening complication. A high-level of suspicion is needed for early diagnosis and referral of the patient for extraction of the object and further avoidance of complications. Flexible fiberoptic bronchoscopy is a feasible procedure for removal of objects within the airway. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc. , the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

There are many reports in the medical and dental literature of complications arising from a routine delivery of dental care. One complication can include physical injury from swallowing or aspirating foreign objects.¹ However, a review of such literature presents a scarcity of documented instances and no long-term evaluation of the aforementioned events.^2,3

This report presents the case of a patient who aspirated a hex driver tool during a procedure to place a crown on a dental implant. The aspirated object was subsequently removed through flexible fiberoptic bronchoscopy without complications.

Case Report

An 83-year-old man was referred to the Pulmonary and Critical Care Department of the VA Caribbean Healthcare System in San Juan, Puerto Rico, after a hex driver tool was lost during a procedure to place a crown on a dental implant, performed under topical anesthesia. It was first thought that the patient swallowed the hex driver, since he never experienced or complained of coughing or shortness of breath. A chest radiograph revealed a metal object lying within the right main stem bronchus, for which the patient was referred to the Pulmonary and Critical Care Department (Figure 1).

The patient’s past medical history was remarkable for hypertension and hypercholesterolemia. Outpatient medications included hydrochlorothiazide, simvastatin, aspirin, felodipine, and lorazepam. He had no previous history of dysphagia or neurologic disease. A physical examination revealed expiratory and inspiratory wheezing localized to the right lower lobe without associated rhonchi or crackles. No distress, shortness of breath, or coughing was noted.

A flexible fiberoptic bronchoscopy was performed under conscious sedation with 3 mg of IV midazolam and topical anesthesia with nebulized 4% lidocaine. No mucosal edema, hyperemia, or structural damage was noted during direct visualization of both the right and left bronchopulmonary segments. A metallic object was visualized at the entrance of the right lower lobe. The foreign object had irregular borders, providing multiple edges that made it suitable to be embraced (Figure 2).

Using a radial jaw single-use biopsy forceps 1.8 mm, the physician clinched and retrieved the object through the bronchoscope. The object was retrieved on the same day of the dental procedure almost 5 hours after it was aspirated. The patient tolerated the procedure well; no coughing, oxygen desaturation, or bleeding occurred during the procedure.

After a few hours of observation, a postprocedural radiograph confirmed the removal of the foreign body without evidence of pneumothorax. The patient was discharged, and 24 hours after the incident remained asymptomatic without chest pain, cough, hemoptysis, sputum production, or fever.

Discussion

Foreign-body aspiration and inadvertent swallowing remains underrecognized by clinicians. In the U.S., more than 2,700 people, including more than 300 children, die of foreign-body aspiration each year.^4,5 Aspiration or ingestion of a foreign body during a dental procedure is serious and potentially fatal.⁶ Some of the consequences of an aspirated object are complete or partial airway obstruction, respiratory distress and failure, pneumothorax, and hemorrhage.⁷ In addition, inadvertent aspiration of foreign objects in asymptomatic patients may not be evident for months, resulting in late complications as postobstructive pneumonia, bronchiectasis, or lung abscess.⁸ Early recognition and diagnosis of these events are crucial to prevent complications.

Accidental aspiration of foreign objects during dental procedures is not as common as is swallowing. In the normal population, the foreign object enters the gastrointestinal tract in about 92.5% of the time, and the tracheobronchial tree in 7.5% of these instances.

A 10-year review done at the School of Dentistry of the University of North Carolina reported 36 incidents of lost instruments during dental procedures. In only 1 case, an object was aspirated, 25 of the 36 cases were secondary to ingestion, and in the remaining 10 incidents, swallowing or aspiration was ruled out by radiography or after the object’s removal from the patient’s mouth.² Previous reviews about foreign-body aspiration in adults have reported dental appliances as the second most commonly aspirated foreign objects.⁴ Of all aspirated objects, the most common site of impaction is the right lower lobe; however, aspiration has been reported in all pulmonary lobes.⁶

Available literature recognizes that impaction of aspirated objects occurred in 56% of instances within the right lower lobe and 33% in the left lower lobe.^7,9 Identification of risk factors for aspiration is important for any patient who will undergo dental procedures, such as advanced age (ie, elderly patients may have a decreased gag reflex); neurologic conditions, such as stroke; dementia and other degenerative diseases; the use of topical anesthesia; and altered states of consciousness associated with the use of IV sedation.^1,2

The key sign that most dentists recognize when patients aspirate an object during a dental procedure is coughing. It has been reported that coughing resulting from aspiration of foreign objects may range from mild to severe. In this case, the patient was completely asymptomatic during the procedure. The only clue of possible object aspiration was the reported tool loss by the dentist. It is important to always examine, account for, and review all equipment used during dental procedures. Assessment for any lost objects or missing parts of instruments should be done promptly with a high degree of suspicion for possible swallowing or aspiration if an object is missing.

It has been recommended to use a gauze throat screen and rubber dam and to avoid a supine position during a procedure, among other techniques, to minimize risk of ingestion or aspiration.² Imaging studies should be used for further evaluation of the patient; however, some instruments, such as dental pieces and impression material, may not be identified by plain films. In those cases, further evaluation with more sophisticated imaging techniques, such as computed tomography (CT), should be considered.^1-10

In a previous case report of a patient who aspirated a third molar during a dental procedure, a chest film failed to identify it. A chest CT was performed, and the object showed in the right main stem bronchus. In another instance, aspiration of impression material in a 45-year-old man was not observed by chest radiography. In this case, the history of coughing and respiratory symptoms days after the procedure pointed toward aspiration of an object as the culprit, with subsequent identification and removal by flexible fiberoptic bronchoscopy.^1-11

Bronchoscopy is the treatment of choice for extraction of aspirated foreign bodies; however, there is still a debate about whether to use flexible or rigid bronchoscopy. The decision is usually made based on the object size, localization, medical facility, and personnel expertise. The rigid bronchoscope has the advantages of offering better control and visualization of the airway and easier use of removal instruments. Its primary disadvantage is that the procedure needs to be done in the operating room under general anesthesia. Flexible fiberoptic bronchoscopy done under conscious sedation and topical anesthesia may be as effective as rigid bronchoscopy and even superior in the case of smaller and more distal impacted objects.^10-14

In this case, flexible fiberoptic bronchoscopy was used successfully for the removal of the foreign object. Biopsy forceps were used to grasp the object and retrieve it from the airway without complication.

Conclusion

Aspiration of foreign objects during a dental procedure is a potential life-threatening complication. A high-level of suspicion is needed for early diagnosis and referral of the patient for extraction of the object and further avoidance of complications. Flexible fiberoptic bronchoscopy is a feasible procedure for removal of objects within the airway. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc. , the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

There are many reports in the medical and dental literature of complications arising from a routine delivery of dental care. One complication can include physical injury from swallowing or aspirating foreign objects.¹ However, a review of such literature presents a scarcity of documented instances and no long-term evaluation of the aforementioned events.^2,3

This report presents the case of a patient who aspirated a hex driver tool during a procedure to place a crown on a dental implant. The aspirated object was subsequently removed through flexible fiberoptic bronchoscopy without complications.

Case Report

An 83-year-old man was referred to the Pulmonary and Critical Care Department of the VA Caribbean Healthcare System in San Juan, Puerto Rico, after a hex driver tool was lost during a procedure to place a crown on a dental implant, performed under topical anesthesia. It was first thought that the patient swallowed the hex driver, since he never experienced or complained of coughing or shortness of breath. A chest radiograph revealed a metal object lying within the right main stem bronchus, for which the patient was referred to the Pulmonary and Critical Care Department (Figure 1).

The patient’s past medical history was remarkable for hypertension and hypercholesterolemia. Outpatient medications included hydrochlorothiazide, simvastatin, aspirin, felodipine, and lorazepam. He had no previous history of dysphagia or neurologic disease. A physical examination revealed expiratory and inspiratory wheezing localized to the right lower lobe without associated rhonchi or crackles. No distress, shortness of breath, or coughing was noted.

A flexible fiberoptic bronchoscopy was performed under conscious sedation with 3 mg of IV midazolam and topical anesthesia with nebulized 4% lidocaine. No mucosal edema, hyperemia, or structural damage was noted during direct visualization of both the right and left bronchopulmonary segments. A metallic object was visualized at the entrance of the right lower lobe. The foreign object had irregular borders, providing multiple edges that made it suitable to be embraced (Figure 2).

Using a radial jaw single-use biopsy forceps 1.8 mm, the physician clinched and retrieved the object through the bronchoscope. The object was retrieved on the same day of the dental procedure almost 5 hours after it was aspirated. The patient tolerated the procedure well; no coughing, oxygen desaturation, or bleeding occurred during the procedure.

After a few hours of observation, a postprocedural radiograph confirmed the removal of the foreign body without evidence of pneumothorax. The patient was discharged, and 24 hours after the incident remained asymptomatic without chest pain, cough, hemoptysis, sputum production, or fever.

Discussion

Foreign-body aspiration and inadvertent swallowing remains underrecognized by clinicians. In the U.S., more than 2,700 people, including more than 300 children, die of foreign-body aspiration each year.^4,5 Aspiration or ingestion of a foreign body during a dental procedure is serious and potentially fatal.⁶ Some of the consequences of an aspirated object are complete or partial airway obstruction, respiratory distress and failure, pneumothorax, and hemorrhage.⁷ In addition, inadvertent aspiration of foreign objects in asymptomatic patients may not be evident for months, resulting in late complications as postobstructive pneumonia, bronchiectasis, or lung abscess.⁸ Early recognition and diagnosis of these events are crucial to prevent complications.

Accidental aspiration of foreign objects during dental procedures is not as common as is swallowing. In the normal population, the foreign object enters the gastrointestinal tract in about 92.5% of the time, and the tracheobronchial tree in 7.5% of these instances.

A 10-year review done at the School of Dentistry of the University of North Carolina reported 36 incidents of lost instruments during dental procedures. In only 1 case, an object was aspirated, 25 of the 36 cases were secondary to ingestion, and in the remaining 10 incidents, swallowing or aspiration was ruled out by radiography or after the object’s removal from the patient’s mouth.² Previous reviews about foreign-body aspiration in adults have reported dental appliances as the second most commonly aspirated foreign objects.⁴ Of all aspirated objects, the most common site of impaction is the right lower lobe; however, aspiration has been reported in all pulmonary lobes.⁶

Available literature recognizes that impaction of aspirated objects occurred in 56% of instances within the right lower lobe and 33% in the left lower lobe.^7,9 Identification of risk factors for aspiration is important for any patient who will undergo dental procedures, such as advanced age (ie, elderly patients may have a decreased gag reflex); neurologic conditions, such as stroke; dementia and other degenerative diseases; the use of topical anesthesia; and altered states of consciousness associated with the use of IV sedation.^1,2

The key sign that most dentists recognize when patients aspirate an object during a dental procedure is coughing. It has been reported that coughing resulting from aspiration of foreign objects may range from mild to severe. In this case, the patient was completely asymptomatic during the procedure. The only clue of possible object aspiration was the reported tool loss by the dentist. It is important to always examine, account for, and review all equipment used during dental procedures. Assessment for any lost objects or missing parts of instruments should be done promptly with a high degree of suspicion for possible swallowing or aspiration if an object is missing.

It has been recommended to use a gauze throat screen and rubber dam and to avoid a supine position during a procedure, among other techniques, to minimize risk of ingestion or aspiration.² Imaging studies should be used for further evaluation of the patient; however, some instruments, such as dental pieces and impression material, may not be identified by plain films. In those cases, further evaluation with more sophisticated imaging techniques, such as computed tomography (CT), should be considered.^1-10

In a previous case report of a patient who aspirated a third molar during a dental procedure, a chest film failed to identify it. A chest CT was performed, and the object showed in the right main stem bronchus. In another instance, aspiration of impression material in a 45-year-old man was not observed by chest radiography. In this case, the history of coughing and respiratory symptoms days after the procedure pointed toward aspiration of an object as the culprit, with subsequent identification and removal by flexible fiberoptic bronchoscopy.^1-11

Bronchoscopy is the treatment of choice for extraction of aspirated foreign bodies; however, there is still a debate about whether to use flexible or rigid bronchoscopy. The decision is usually made based on the object size, localization, medical facility, and personnel expertise. The rigid bronchoscope has the advantages of offering better control and visualization of the airway and easier use of removal instruments. Its primary disadvantage is that the procedure needs to be done in the operating room under general anesthesia. Flexible fiberoptic bronchoscopy done under conscious sedation and topical anesthesia may be as effective as rigid bronchoscopy and even superior in the case of smaller and more distal impacted objects.^10-14

In this case, flexible fiberoptic bronchoscopy was used successfully for the removal of the foreign object. Biopsy forceps were used to grasp the object and retrieve it from the airway without complication.

Conclusion

Aspiration of foreign objects during a dental procedure is a potential life-threatening complication. A high-level of suspicion is needed for early diagnosis and referral of the patient for extraction of the object and further avoidance of complications. Flexible fiberoptic bronchoscopy is a feasible procedure for removal of objects within the airway. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc. , the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Obstructive sleep apnea (OSA) is recognized primarily as a problem of the upper airway. Although narrowing or actual obstruction of the airway during the night can be found in only 1 or 2 areas of the upper airway, most often sleep apnea involves the entire pharyngeal upper airway passages. Three regions are considered to be of major concern: the nasal cavity region, the retropalatal region, and the retrolingual region. As the level of these 3 regions descends, the volume of tissue from the nose to the base of the tongue increases significantly. This leads to increased difficulty treating OSA with each descending region as well as to a lower success rate overall. Sometimes, the problem causing OSA is limited to only 1 region but may involve 2 or even all 3 regions.¹

Continuous positive airway pressure (CPAP) therapy and other positive airway pressure (PAP) therapies have been considered a safe and effective treatment for OSA. Unfortunately, compliance rates, even among patients who use it to successfully eliminate their symptoms, can vary from 50% to 70%. Complaints about using CPAP and other PAP therapies range from skin irritation, discomfort to the nose or nasal passages, and eye problems to claustrophobia from wearing a mask. Patients who are unable or unwilling to use CPAP therapy can be candidates for surgical treatment of OSA.²

This article discusses surgical options for adult patients who have OSA who choose not to use CPAP therapy, the reasons to perform surgery for adults who have OSA, and the desired outcomes of surgery for OSA with a focus on minimally invasive procedures. Interventions for pediatric patients are not addressed.

Treatment Options          

Treatments other than CPAP can help lessen the severity of OSA. Noninvasive treatments include weight loss, positional treatment (avoiding sleeping on one’s back), and oral appliances. Practice parameters from the American Academy of Sleep Medicine (AASM) for the treatment of OSA include dietary weight loss in addition to the primary therapy. An improvement in the apnea-hypopnea index (AHI) may occur with dietary weight loss.³

Major weight loss through the use of bariatric surgery has been shown to be effective in treating OSA and obesity hypoventilation syndrome (OHS), which is defined as daytime hypercapnia and hypoxemia (PaCO₂ > 45 mm Hg and PaO₂ < 70 mm Hg at sea level) in an obese patient (body mass index [BMI] > 30 kg/m²) with sleep-disordered breathing in the absence of any other cause of hypoventilation.⁴ Some individuals may have both conditions. However, CPAP therapy should not be discontinued even when major weight loss occurs until repeat polysomnography has been performed. Major weight loss may cure OHS and help improve the severity of OSA but will not totally resolve the condition.⁴ According to Woodson, sleep apnea in patients who are morbidly obese may be different from traditional OSA as rapid eye movement (REM), REM-related apneas, and hypoventilation occur more often in this population. Although weight loss is strongly recommended for patients with OSA, bariatric surgery is not recommended as the sole treatment for traditional OSA.⁵

Positional therapy, wherein the patient avoids the supine position, can be effective as a secondary or supplemental therapy in addition to treatment with CPAP. Guidelines recommend this primarily for individuals who have a lower AHI when in the nonsupine position than when lying on their backs. Patients who benefit from positional therapy tend to be younger, less obese, and with a less severe condition. The AASM practice parameter was based on 3 level II studies—randomized trials with high alpha and beta levels.⁶ One of the level II studies compared supine with an upright position, stating: “Because not all patients normalize AHI when non-supine, the committee’s opinion is that correction of OSA by position should be documented with an appropriate test.” Special pillows have been described in 2 papers reviewed by AASM, which seemed to improve OSA.⁶

The AASM guidelines state that oral appliances are indicated for some patients, although they are not as efficacious in treating OSA as CPAP therapy. Oral appliances are recommended for patients with mild to moderate OSA who have not responded to CPAP therapy, cannot tolerate CPAP therapy, are not appropriate for treatment with CPAP for some reason, or fail treatment with CPAP along with other behavioral measures, such as weight loss or positional therapy.⁶  

In addition, the AASM guidelines recommend that patients with severe OSA, “should have an initial trial of nasal CPAP because greater effectiveness has been shown with this intervention than with the use of oral appliances. Upper airway surgery (including tonsillectomy and adenoidectomy, craniofacial operations, and tracheostomy) may also supersede use of oral appliances in patients for whom these operations are predicted to be highly effective in treating sleep apnea.”⁶

Nasal expiratory positive end pressure (EPAP) devices may be helpful in treating OSA in some patients. These devices contain a mechanical valve with very low inspiratory resistance but high expiratory resistance. The device has an adhesive and is applied by the patient to create a seal. Exhalation causes a high expiratory resistance that splints the upper airway open. This increases the resistance of the airway to close on inspiration.⁷ An EPAP device is recommended for potential use in mild to moderate OSA for patients who either have an intolerance to CPAP therapy or have failed to respond to it.⁸            

Finally, there are major surgeries performed by oral surgeons that can benefit some patients with OSA. One of these is maxillomandibular advancement (MMA). According to the AASM practice parameter: MMA “involves simultaneous advancement of the maxilla and mandible through sagittal split osteotomies. It provides enlargement of the retrolingual airway and some advancement of the retropalatal airway.”⁹ It is indicated as a surgical treatment for patients with severe OSA who are either unwilling or do not tolerate CPAP treatment. These individuals would not benefit from an oral appliance (recommended for mild to moderate OSA) or would find it undesirable.⁹

There is also stepwise or multilevel surgery (MLS) that can be performed. These include a number of combined procedures, which address multiple sites with narrowing in the upper airway. Frequently, MLS will consist of
2 phases: the first involves use of the uvulopalatopharyngoplasty (UPPP) procedure “and or genioglossus advancement and hyoid myotomy (GAHM). The second phase surgeries consist of utilizing maxillary and mandibular advancement osteotomy (MMO), offered to those failing Phase I surgeries.”⁹

OSA Surgical Procedures

Tracheostomies are first estimated to have been performed in 2000 BC.¹⁰ Performing a tracheostomy to bypass the upper airway was used in the 1960s and 1970s for the treatment of OSA and for many years was the only treatment available for people with Pickwickian syndrome (OHS) and nocturnal upper airway obstruction. The procedure was generally not tolerated or accepted by patients, even though it improved their quality of life and added to their life expectancy. Once CPAP treatment proved successful for OSA, tracheostomy has rarely been necessary.¹¹

Uvulopalatopharyngoplasty surgery was introduced in 1981. The aim of this surgery is to decrease snoring and treat OSA by removing obstructive tissues, enlarging the cross-sectional portion of the upper airway, and bypassing the upper airway. Tissue that is removed includes the tonsils, uvula, and the distal portion of the soft palate.¹²

Woodson considers surgery for OSA to be the third-line of treatment. The first-line treatment would be CPAP therapy, and second-line therapy would include oral appliances to enlarge the airway or retain the tongue (if the individual has no dentition). The intent of surgery falls into 3 categories: curative, salvage, and ancillary.

In a chronic disease such as OSA, “many may question whether a cure exists.” Instead of eliminating OSA, the curative intent is definitively to reduce symptoms and disease morbidity for long periods. The criteria for defining a responder or cure to surgery for OSA are found in Table 1.⁵

Surgery for salvage aims at treating patients who have failed CPAP therapy. Successful treatment with the intent of salvage can occur with a lessening of disease severity, including morbidity and mortality, but not necessarily totally eliminating the symptoms. Finally, ancillary surgery for OSA aims to combine a surgical procedure with the first-line therapy (positive pressure) to add an additional therapeutic benefit. The combination of CPAP and ancillary procedures may be of the most benefit to patients with OSA.⁵

As mentioned previously, the AASM has developed practice parameters for the treatment of OSA, including surgery. Desired outcomes of treatment for OSA include the resolution of symptoms and clinical signs, normalization of the quality of sleep, AHI, and levels of oxyhemoglobin saturation. It is recognized that normalization of the AHI may not reverse all the components of OSA, and up to 22% of patients continue to have residual hypersomnia with CPAP therapy.⁹

Despite this, most studies that show significant benefits in lowering cardiovascular risk, mortality rates, symptoms, and neurocognitive effects have also shown significant reductions in the AHI.⁹ Therefore, the AASM puts a high value on treating OSA with the goal of normalization of the AHI. There exists a lack of quality studies and good evidence regarding the effectiveness of surgical procedures of the upper airway as treatment for OSA. Despite this, the AASM recommendation is that “all reasonable treatment alternatives for OSA be discussed in a manner that allows the patient to make an informed decision.”⁹

Types of OSA Surgeries

Surgery for OSA can be divided into 2 categories, invasive surgery and minimally invasive surgery (Table 2). Invasive surgeries for OSA have a higher risk of complications and postoperative pain.⁹

Invasive Surgery
The UPPP surgery is perhaps the best-known invasive procedure for treating OSA. A meta-analysis of 15 studies on UPPP outcomes found overall improvement in AHI of 33% but with postoperative AHI remaining elevated at an average of 29.8 events per hour.¹³

Adverse effects for the procedure include changes in taste, dysphagia, nasal regurgitation, and voice alterations. Seven of the 15 studies reported at least 1 death following the UPPP procedure. The effects of UPPP surgery on systemic and cardiovascular sequelae of OSA are not fully known and need to be further researched. ¹³

Another invasive procedure that is similar to the UPPP is the laser-assisted uvulopalatoplasty (LAUP) procedure. First reported in 1990, LAUP was developed as a procedure to eliminate snoring and was found to be effective. Other studies have been conducted since then, but there are inconsistencies in the specific types of procedures performed and a lack of detailed data analysis.

Adverse effects of the LAUP procedure include minor bleeding, globus sensation, local infection, minor dysphagia and dysphonia, and transient velopharyngeal insufficiency.¹⁴ However, studies have also shown that about one-quarter of the participants developed persistent dysphagia or mild to moderate scar fibrosis. Postoperative swelling can reduce an already narrow airway, and the use of sedatives or narcotics can make this problem worse. Some studies have noted structural changes following this procedure that lower airway resistance, resulting in the collapse of the upper airway and the narrowing of the airway during inhalation with worsening OSA.^13,14

Practice parameters for the LAUP procedure were developed by the AASM in 1994. The AASM recommended against using LAUP to treat OSA (and other sleep-related breathing disorders) and against substituting LAUP for UPPP surgery. The AASM also suggested criteria for choosing candidates for LAUP and urged that patients be given full information about the procedure and a preoperative evaluation from their provider.^5,14

Minimally Invasive Surgery
Radiofrequency surgery and soft palate implants are considered minimally invasive procedures, according to the criteria established in a study by Maurer.¹¹ Various nasal surgeries (eg, septoplasty, adenoidectomy, and polyp removal) could also be considered minimally invasive and are often performed in patients with OSA to improve tolerance of CPAP by improving the ability to breathe nasally. However, nasal surgery with improvement of nasal breathing has not been found to have a significant impact on adults who have OSA. An advantage of nasal surgery is that some studies have shown longer use of CPAP therapy, up to 2 hours longer per night.⁵

With radiofrequency of the tongue base, high-frequency radio waves, either monopolar or bipolar, are used to coagulate the interstitial tissue at the base of the tongue. This, in turn, leads to necrosis and scarring, which then leads to stiffening of the tissue and in some cases, volume reduction. The surgeon controls the temperature to avoid overdosing and tissue carbonization. A number of lesions are produced during a session and the number of sessions necessary for full treatment varies per surgeon and the technical system used in procedures.

Although radiofrequency ablation (RFA) has been used on the tonsils and soft palate, RFA is currently available only to patients with OSA on the tongue base. A reduction in AHI of 33% on average was achieved in a review of 6 studies, and the reduction was stable over a 2-year period.¹¹ The average presurgery AHI was 39.5, and the average postsurgery AHI was 28.7. In this same review, the average Epworth Sleepiness Scale (ESS) (a commonly used subjective tool to measure levels of daytime sleepiness) score was 10.4 presurgery and 4.5 postsurgery.¹¹

A Chinese study looked at complications from RFA of the tongue base. According to the abstract (the article was written in Chinese), 1 patient (n = 193) developed a fatal arrhythmia. The authors’ recommendation was for close monitoring after surgery until the swelling subsided.¹⁵

With soft palate implants, small cylinders of woven polyester (“polyethylene terephthalate, commonly marketed as Dacron polyester”) yarn, 18 mm long by 2 mm diameter, are inserted at the junction of the hard palate and soft palate. Placed into the proximal soft palate tissue, these implants are designed to stiffen the soft palate “through fibrotic tissue encapsulation and tissue ingrowth over time.” Many patients with only snoring or mild to moderate OSA have found improvement with this procedure. Improved reduction of snoring was found in 1 study (n = 79), which looked at the use of Pillar implants to reduce snoring (Figure 1). This reduction of snoring occurred in patients with lower AHI levels before the procedure.¹⁶ Mauer reviewed 3 studies of the palatal implants and found a pooled reduction of 26% in AHI after placement.¹¹

Criteria for Surgery

The mechanism that causes collapse of a patient’s airway will vary from one person to the next. Variables include age, body weight, anatomy, and body position. Thus, different findings will require different surgical techniques, and there is no one-size-fits-all surgery for OSA.¹¹

A thorough physical examination of the upper airway is important. Maurer recommends considering the use of videoendoscopy under sedation, which allows a view of the mechanism and site of obstruction, with pressure catheters inserted to collect data. This procedure was developed in the 1990s to improve the analysis of obstruction within the upper airway. Unfortunately, the data are unclear about whether this aids in the surgical outcome.¹¹ Powell stated that sleep endoscopy is currently considered investigational because medication-induced sleep may differ from natural sleep without medication.¹

Nasopharyngoscopy, using fiberoptics, and lateral cephalometric analysis have been used for several years as primary diagnostic tools for patients being considered for a surgical procedure for OSA. Some new imaging procedures (eg, 3-D imaging coupled with advanced software programs) have been developed that may be helpful to assess regions that are constricted as well as provide a more exact measurement of the airway from the nose to the larynx.¹

Risks and Complications of Surgery
The higher risk of anesthesia-related complications during or after surgery related to OSA is one reason that surgery is usually considered to be the third-line of treatment. Patients with OSA commonly have hypertension and other cardiovascular disease, which adds to the risk of anesthesia-related complications. Patients who have anatomical abnormalities of the jaw or portions of the upper airway will also be at a higher risk. Initial intubation and providing anesthesia during procedures may be more difficult for patients with these jaw or airway abnormalities. Postsurgical pain management with opioids contributes to the higher rate of apnea. After extubation, the incidence of apnea has been found to be higher in the population with OSA as well.¹⁷

A study published in 2001 used a case-control matched population methodology to examine patients who were undergoing elective surgeries for either hip or knee joint replacements. Significant differences in overall complication rates were found among the patients with OSA (n = 101) compared with those of the control group (n = 101). These differences were not related to the type of anesthesia, narcotic use after surgery, or the type of operation performed. The OSA group had a significantly higher number of patients who required higher flow rates of oxygen postoperatively and for a longer period. Serious complications, including the reintubation of 2  patients and unplanned intensive care unit (ICU) transfers, were noted in the patients with OSA (24%) compared with the control group (P = .004). The mean length of hospital stay was significantly longer for patients with OSA (6.8 + 2.8 days) compared with those in the control group (5.1 + 4.1 days, P = .007).¹⁸

The OSA group in the aforementioned study was divided into 2 types during this investigation: one group (n = 36) included patients undiagnosed with OSA until after their surgery (mean 1.8 years); the other group (n = 65) had a confirmed diagnosis at the time of surgery. All 36 in the first group and 32 from the second group with diagnosed OSA did not use CPAP therapy at home; a total of 68 patients (67.3%) who had not received therapy before the surgery. The 33 patients with diagnosed OSA (32.7%) who did use CPAP therapy before surgery had lower complication rates, including shorter hospital stays (6.0 + 2.1 days) compared with their counterparts with untreated OSA (7.2 + 3.1 days). The authors surmised that there might be a carryover protective effect at least for the first postoperative day.¹⁸

A retrospective study examined patients with OSA who had outpatient surgical procedures performed under either major regional anesthesia (central neuraxial) or general anesthesia. The study looked at the first outpatient surgical procedure for the patient with OSA following the diagnosis except for otorhinolaryngologic surgeries, which were excluded from the study. The 234 patients with OSA were then matched to the same number of control patients who had also had outpatient surgical procedures (excluding the otorhinolaryngologic procedures). The researchers noted a higher incidence of endotracheal intubation in the OSA group (79.9% vs 73.9% in the control group, P = .017).

The OSA group was less likely to have a laryngeal mask airway used during surgery for their airway management (5.1% vs 10.7% in the control group, P = .017). The only significantly different complication between the 2 groups was unplanned admissions to an ICU in the postoperative period (although numbers/percentages were not listed in the article). However, there was no difference in the overall unplanned hospital admission rate between the 2 groups. One limitation to this study was that the control group had not been tested for OSA, and therefore, it was possible that some in the control group might have had undiagnosed OSA.¹⁹

It is recommended that the surgeon and anesthesiologist ask about a diagnosis of OSA or sleep apnea symptoms during the preanesthesia assessment for any surgery. The provider performing the preoperative physical examination should pay attention to the circumference of the neck, chin-throat length, Mallampati classification, mandible position, and BMI. Any findings that suggest undiagnosed OSA should prompt further evaluation before any elective surgery.

Those who are at risk of OSA anesthesia-related complications should be offered regional anesthesia if possible. It is undesirable to premedicate with sedatives or opioids for this population. The sniffing position during surgery has been found to reduce the collapsibility of the airway and improve its dimensions. All patients who use CPAP therapy at home should have this therapy available for use in the recovery room with the lateral position preferred.¹⁷

Outpatient surgery using sedation and local anesthetics can also be a higher risk for patients with OSA. The unprotected, potentially problematic airway is still a serious concern. Patients requiring short procedures may do well with titrated sedation if well positioned and appropriately selected for this before the procedure. Clinicians must be prepared to handle any complications that occur. One complication that occurs commonly in obese patients related to a smaller functional residual capacity is rapid oxygen desaturation.¹⁷

A Chinese study evaluated complications in patients who had received tongue base reduction through RFA. Complications, both intraoperative and postoperative, included hematoma of the tongue base, bleeding, altered taste, an abscess at the base of the tongue, speech dysfunction, numbness, and deviation of the tongue extension movement. One cardiac death occurred 37 hours following surgery related to swelling of the tongue base and pain, which aggravated sleep apnea and nocturnal hypoxemia and induced a fatal arrhythmia.¹⁵

The Future of OSA Treatments

Research is underway to evaluate the effectiveness of an implanted system to stimulate the hypoglossal nerve with the intent of activating the upper airway musculature. A small study of 8 patients found improvement in the degree of upper airway collapsibility and the severity of OSA. Continued research on the device is focusing on the parameters for the nerve stimulation. The criteria for patient selection are also being established.²⁰

Another study of hypoglossal nerve stimulation (HNS) evaluated 21 patients who were unable to tolerate CPAP therapy. The researchers found significant improvement in AHI (43.1 + 17.5 to 19.5 + 16.7); Functional Outcomes of Sleep Questionnaire (14.4 + 2.0 to 16.7 + 2.2); ESS (12.1 + 4.7 to 8.1 + 4.4); Beck Depression Inventory (15.8 + 9.0 to 9.7 + 7.6); and the Calgary Sleep Apnea Quality of Life Index (3.2 + 1.0 to 4.9 to 4.9 + 1.3). The researchers concluded HNS decreased OSA-related symptoms and the severity of OSA.²¹ At least one of these devices, the Inspire device, has been approved for use in Europe (Figure 2).²² In addition, the FDA has approve the Inspire Upper Airway Stimulation therapy for use in a subset of patients with moderate to severe OSA who are unable to use CPAP.²³

A recent study investigated the effect of HNS on the severity of OSA among patients who had moderate to severe OSA and had not had a response to CPAP therapy. The HNS was associated with significant improvement in reducing the frequency of respiratory events. The median AHI at 12 months decreased from 29.3 events per hour to 9.0 events per hour (P < .001), and the number of times per hour of sleep that the blood oxygen level dropped by ≥ 4% from the baseline (oxygen desaturation index score) decreased from 25.4 to 7.4 events per hour (P < .001).²⁴

Another area being studied is the development of a device to advance the tongue. Forty-two patients had mandibular bone anchors inserted with a flexible tether connected to a surgically inserted anchor in the posterior tongue. Unfortunately, 31% of the participants developed tissue anchor barb fractures that were asymptomatic and detected through radiography. At this time, the failure rate does not warrant clinical use. However, some patients showed significant improvement in multiple measures for sleep apnea, and more research is ongoing with the device.²⁵

Similarly, a surgically inserted tongue pin that connects to an oral device during sleep has been studied. This pin prevents the tongue from moving back and obstructing the upper airway. Polysomnographies were performed both before and after and showed an increased rate of apnea in the 10 subjects. Visualization with magnetic resonance imaging showed that the upper airway was not kept open by this fixation device. Additional research with a modified design for the device is recommended.²⁶     

Reshaping of the epiglottis using a CO₂ laser has been studied with cadaver specimens. The researchers believe scar formation following the reshaping would aid in retraction of the epiglottis anteriorly. Studies with animals are being conducted with different laser types. Future studies involving selected patients with OSA who have epiglottis malformations would be the next step.²⁷

More studies about both minimally invasive and invasive surgeries for OSA are needed. There are many unanswered questions, including the timing of follow-up assessments, how long to observe a patient after surgery, whether the use of multilevel surgery affects the rate of relapse, and what are the best follow-up tools to use. Research needs to be performed in diverse populations, including gender, race/ethnicity, and age groups. Complications of surgical procedures need to be studied and clarified over both short- and long-term periods.⁹

Conclusions

Although there have been some successes in using surgical procedures to treat OSA, CPAP therapy remains the first-line treatment. Invasive surgeries have higher rates of complications and risks than do those of minimally invasive procedures. There are also additional risks related to the use of anesthesia both during and after surgery. Referrals for surgery should include information about a diagnosis of OSA, and patients should be instructed to discuss this with the anesthesiologist or certified nurse anesthetist.

With careful selection by the surgeon and sleep providers, patients who do not tolerate CPAP therapy or respond to other noninvasive interventions can benefit from a surgical procedure. Minimally invasive surgeries are less risky for the patient and should be considered. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

WEB EXCLUSIVE CASE STUDY

A Physical Examination of the Upper Airway by an Ear, Nose, and Throat Physician

Obstructive sleep apnea (OSA) is recognized primarily as a problem of the upper airway. Although narrowing or actual obstruction of the airway during the night can be found in only 1 or 2 areas of the upper airway, most often sleep apnea involves the entire pharyngeal upper airway passages. Three regions are considered to be of major concern: the nasal cavity region, the retropalatal region, and the retrolingual region. As the level of these 3 regions descends, the volume of tissue from the nose to the base of the tongue increases significantly. This leads to increased difficulty treating OSA with each descending region as well as to a lower success rate overall. Sometimes, the problem causing OSA is limited to only 1 region but may involve 2 or even all 3 regions.¹

Continuous positive airway pressure (CPAP) therapy and other positive airway pressure (PAP) therapies have been considered a safe and effective treatment for OSA. Unfortunately, compliance rates, even among patients who use it to successfully eliminate their symptoms, can vary from 50% to 70%. Complaints about using CPAP and other PAP therapies range from skin irritation, discomfort to the nose or nasal passages, and eye problems to claustrophobia from wearing a mask. Patients who are unable or unwilling to use CPAP therapy can be candidates for surgical treatment of OSA.²

This article discusses surgical options for adult patients who have OSA who choose not to use CPAP therapy, the reasons to perform surgery for adults who have OSA, and the desired outcomes of surgery for OSA with a focus on minimally invasive procedures. Interventions for pediatric patients are not addressed.

Treatment Options          

Treatments other than CPAP can help lessen the severity of OSA. Noninvasive treatments include weight loss, positional treatment (avoiding sleeping on one’s back), and oral appliances. Practice parameters from the American Academy of Sleep Medicine (AASM) for the treatment of OSA include dietary weight loss in addition to the primary therapy. An improvement in the apnea-hypopnea index (AHI) may occur with dietary weight loss.³

Major weight loss through the use of bariatric surgery has been shown to be effective in treating OSA and obesity hypoventilation syndrome (OHS), which is defined as daytime hypercapnia and hypoxemia (PaCO₂ > 45 mm Hg and PaO₂ < 70 mm Hg at sea level) in an obese patient (body mass index [BMI] > 30 kg/m²) with sleep-disordered breathing in the absence of any other cause of hypoventilation.⁴ Some individuals may have both conditions. However, CPAP therapy should not be discontinued even when major weight loss occurs until repeat polysomnography has been performed. Major weight loss may cure OHS and help improve the severity of OSA but will not totally resolve the condition.⁴ According to Woodson, sleep apnea in patients who are morbidly obese may be different from traditional OSA as rapid eye movement (REM), REM-related apneas, and hypoventilation occur more often in this population. Although weight loss is strongly recommended for patients with OSA, bariatric surgery is not recommended as the sole treatment for traditional OSA.⁵

Positional therapy, wherein the patient avoids the supine position, can be effective as a secondary or supplemental therapy in addition to treatment with CPAP. Guidelines recommend this primarily for individuals who have a lower AHI when in the nonsupine position than when lying on their backs. Patients who benefit from positional therapy tend to be younger, less obese, and with a less severe condition. The AASM practice parameter was based on 3 level II studies—randomized trials with high alpha and beta levels.⁶ One of the level II studies compared supine with an upright position, stating: “Because not all patients normalize AHI when non-supine, the committee’s opinion is that correction of OSA by position should be documented with an appropriate test.” Special pillows have been described in 2 papers reviewed by AASM, which seemed to improve OSA.⁶

The AASM guidelines state that oral appliances are indicated for some patients, although they are not as efficacious in treating OSA as CPAP therapy. Oral appliances are recommended for patients with mild to moderate OSA who have not responded to CPAP therapy, cannot tolerate CPAP therapy, are not appropriate for treatment with CPAP for some reason, or fail treatment with CPAP along with other behavioral measures, such as weight loss or positional therapy.⁶  

In addition, the AASM guidelines recommend that patients with severe OSA, “should have an initial trial of nasal CPAP because greater effectiveness has been shown with this intervention than with the use of oral appliances. Upper airway surgery (including tonsillectomy and adenoidectomy, craniofacial operations, and tracheostomy) may also supersede use of oral appliances in patients for whom these operations are predicted to be highly effective in treating sleep apnea.”⁶

Nasal expiratory positive end pressure (EPAP) devices may be helpful in treating OSA in some patients. These devices contain a mechanical valve with very low inspiratory resistance but high expiratory resistance. The device has an adhesive and is applied by the patient to create a seal. Exhalation causes a high expiratory resistance that splints the upper airway open. This increases the resistance of the airway to close on inspiration.⁷ An EPAP device is recommended for potential use in mild to moderate OSA for patients who either have an intolerance to CPAP therapy or have failed to respond to it.⁸            

Finally, there are major surgeries performed by oral surgeons that can benefit some patients with OSA. One of these is maxillomandibular advancement (MMA). According to the AASM practice parameter: MMA “involves simultaneous advancement of the maxilla and mandible through sagittal split osteotomies. It provides enlargement of the retrolingual airway and some advancement of the retropalatal airway.”⁹ It is indicated as a surgical treatment for patients with severe OSA who are either unwilling or do not tolerate CPAP treatment. These individuals would not benefit from an oral appliance (recommended for mild to moderate OSA) or would find it undesirable.⁹

There is also stepwise or multilevel surgery (MLS) that can be performed. These include a number of combined procedures, which address multiple sites with narrowing in the upper airway. Frequently, MLS will consist of
2 phases: the first involves use of the uvulopalatopharyngoplasty (UPPP) procedure “and or genioglossus advancement and hyoid myotomy (GAHM). The second phase surgeries consist of utilizing maxillary and mandibular advancement osteotomy (MMO), offered to those failing Phase I surgeries.”⁹

OSA Surgical Procedures

Tracheostomies are first estimated to have been performed in 2000 BC.¹⁰ Performing a tracheostomy to bypass the upper airway was used in the 1960s and 1970s for the treatment of OSA and for many years was the only treatment available for people with Pickwickian syndrome (OHS) and nocturnal upper airway obstruction. The procedure was generally not tolerated or accepted by patients, even though it improved their quality of life and added to their life expectancy. Once CPAP treatment proved successful for OSA, tracheostomy has rarely been necessary.¹¹

Uvulopalatopharyngoplasty surgery was introduced in 1981. The aim of this surgery is to decrease snoring and treat OSA by removing obstructive tissues, enlarging the cross-sectional portion of the upper airway, and bypassing the upper airway. Tissue that is removed includes the tonsils, uvula, and the distal portion of the soft palate.¹²

Woodson considers surgery for OSA to be the third-line of treatment. The first-line treatment would be CPAP therapy, and second-line therapy would include oral appliances to enlarge the airway or retain the tongue (if the individual has no dentition). The intent of surgery falls into 3 categories: curative, salvage, and ancillary.

In a chronic disease such as OSA, “many may question whether a cure exists.” Instead of eliminating OSA, the curative intent is definitively to reduce symptoms and disease morbidity for long periods. The criteria for defining a responder or cure to surgery for OSA are found in Table 1.⁵

Surgery for salvage aims at treating patients who have failed CPAP therapy. Successful treatment with the intent of salvage can occur with a lessening of disease severity, including morbidity and mortality, but not necessarily totally eliminating the symptoms. Finally, ancillary surgery for OSA aims to combine a surgical procedure with the first-line therapy (positive pressure) to add an additional therapeutic benefit. The combination of CPAP and ancillary procedures may be of the most benefit to patients with OSA.⁵

As mentioned previously, the AASM has developed practice parameters for the treatment of OSA, including surgery. Desired outcomes of treatment for OSA include the resolution of symptoms and clinical signs, normalization of the quality of sleep, AHI, and levels of oxyhemoglobin saturation. It is recognized that normalization of the AHI may not reverse all the components of OSA, and up to 22% of patients continue to have residual hypersomnia with CPAP therapy.⁹

Despite this, most studies that show significant benefits in lowering cardiovascular risk, mortality rates, symptoms, and neurocognitive effects have also shown significant reductions in the AHI.⁹ Therefore, the AASM puts a high value on treating OSA with the goal of normalization of the AHI. There exists a lack of quality studies and good evidence regarding the effectiveness of surgical procedures of the upper airway as treatment for OSA. Despite this, the AASM recommendation is that “all reasonable treatment alternatives for OSA be discussed in a manner that allows the patient to make an informed decision.”⁹

Types of OSA Surgeries

Surgery for OSA can be divided into 2 categories, invasive surgery and minimally invasive surgery (Table 2). Invasive surgeries for OSA have a higher risk of complications and postoperative pain.⁹

Invasive Surgery
The UPPP surgery is perhaps the best-known invasive procedure for treating OSA. A meta-analysis of 15 studies on UPPP outcomes found overall improvement in AHI of 33% but with postoperative AHI remaining elevated at an average of 29.8 events per hour.¹³

Adverse effects for the procedure include changes in taste, dysphagia, nasal regurgitation, and voice alterations. Seven of the 15 studies reported at least 1 death following the UPPP procedure. The effects of UPPP surgery on systemic and cardiovascular sequelae of OSA are not fully known and need to be further researched. ¹³

Another invasive procedure that is similar to the UPPP is the laser-assisted uvulopalatoplasty (LAUP) procedure. First reported in 1990, LAUP was developed as a procedure to eliminate snoring and was found to be effective. Other studies have been conducted since then, but there are inconsistencies in the specific types of procedures performed and a lack of detailed data analysis.

Adverse effects of the LAUP procedure include minor bleeding, globus sensation, local infection, minor dysphagia and dysphonia, and transient velopharyngeal insufficiency.¹⁴ However, studies have also shown that about one-quarter of the participants developed persistent dysphagia or mild to moderate scar fibrosis. Postoperative swelling can reduce an already narrow airway, and the use of sedatives or narcotics can make this problem worse. Some studies have noted structural changes following this procedure that lower airway resistance, resulting in the collapse of the upper airway and the narrowing of the airway during inhalation with worsening OSA.^13,14

Practice parameters for the LAUP procedure were developed by the AASM in 1994. The AASM recommended against using LAUP to treat OSA (and other sleep-related breathing disorders) and against substituting LAUP for UPPP surgery. The AASM also suggested criteria for choosing candidates for LAUP and urged that patients be given full information about the procedure and a preoperative evaluation from their provider.^5,14

Minimally Invasive Surgery
Radiofrequency surgery and soft palate implants are considered minimally invasive procedures, according to the criteria established in a study by Maurer.¹¹ Various nasal surgeries (eg, septoplasty, adenoidectomy, and polyp removal) could also be considered minimally invasive and are often performed in patients with OSA to improve tolerance of CPAP by improving the ability to breathe nasally. However, nasal surgery with improvement of nasal breathing has not been found to have a significant impact on adults who have OSA. An advantage of nasal surgery is that some studies have shown longer use of CPAP therapy, up to 2 hours longer per night.⁵

With radiofrequency of the tongue base, high-frequency radio waves, either monopolar or bipolar, are used to coagulate the interstitial tissue at the base of the tongue. This, in turn, leads to necrosis and scarring, which then leads to stiffening of the tissue and in some cases, volume reduction. The surgeon controls the temperature to avoid overdosing and tissue carbonization. A number of lesions are produced during a session and the number of sessions necessary for full treatment varies per surgeon and the technical system used in procedures.

Although radiofrequency ablation (RFA) has been used on the tonsils and soft palate, RFA is currently available only to patients with OSA on the tongue base. A reduction in AHI of 33% on average was achieved in a review of 6 studies, and the reduction was stable over a 2-year period.¹¹ The average presurgery AHI was 39.5, and the average postsurgery AHI was 28.7. In this same review, the average Epworth Sleepiness Scale (ESS) (a commonly used subjective tool to measure levels of daytime sleepiness) score was 10.4 presurgery and 4.5 postsurgery.¹¹

A Chinese study looked at complications from RFA of the tongue base. According to the abstract (the article was written in Chinese), 1 patient (n = 193) developed a fatal arrhythmia. The authors’ recommendation was for close monitoring after surgery until the swelling subsided.¹⁵

With soft palate implants, small cylinders of woven polyester (“polyethylene terephthalate, commonly marketed as Dacron polyester”) yarn, 18 mm long by 2 mm diameter, are inserted at the junction of the hard palate and soft palate. Placed into the proximal soft palate tissue, these implants are designed to stiffen the soft palate “through fibrotic tissue encapsulation and tissue ingrowth over time.” Many patients with only snoring or mild to moderate OSA have found improvement with this procedure. Improved reduction of snoring was found in 1 study (n = 79), which looked at the use of Pillar implants to reduce snoring (Figure 1). This reduction of snoring occurred in patients with lower AHI levels before the procedure.¹⁶ Mauer reviewed 3 studies of the palatal implants and found a pooled reduction of 26% in AHI after placement.¹¹

Criteria for Surgery

The mechanism that causes collapse of a patient’s airway will vary from one person to the next. Variables include age, body weight, anatomy, and body position. Thus, different findings will require different surgical techniques, and there is no one-size-fits-all surgery for OSA.¹¹

A thorough physical examination of the upper airway is important. Maurer recommends considering the use of videoendoscopy under sedation, which allows a view of the mechanism and site of obstruction, with pressure catheters inserted to collect data. This procedure was developed in the 1990s to improve the analysis of obstruction within the upper airway. Unfortunately, the data are unclear about whether this aids in the surgical outcome.¹¹ Powell stated that sleep endoscopy is currently considered investigational because medication-induced sleep may differ from natural sleep without medication.¹

Nasopharyngoscopy, using fiberoptics, and lateral cephalometric analysis have been used for several years as primary diagnostic tools for patients being considered for a surgical procedure for OSA. Some new imaging procedures (eg, 3-D imaging coupled with advanced software programs) have been developed that may be helpful to assess regions that are constricted as well as provide a more exact measurement of the airway from the nose to the larynx.¹

Risks and Complications of Surgery
The higher risk of anesthesia-related complications during or after surgery related to OSA is one reason that surgery is usually considered to be the third-line of treatment. Patients with OSA commonly have hypertension and other cardiovascular disease, which adds to the risk of anesthesia-related complications. Patients who have anatomical abnormalities of the jaw or portions of the upper airway will also be at a higher risk. Initial intubation and providing anesthesia during procedures may be more difficult for patients with these jaw or airway abnormalities. Postsurgical pain management with opioids contributes to the higher rate of apnea. After extubation, the incidence of apnea has been found to be higher in the population with OSA as well.¹⁷

A study published in 2001 used a case-control matched population methodology to examine patients who were undergoing elective surgeries for either hip or knee joint replacements. Significant differences in overall complication rates were found among the patients with OSA (n = 101) compared with those of the control group (n = 101). These differences were not related to the type of anesthesia, narcotic use after surgery, or the type of operation performed. The OSA group had a significantly higher number of patients who required higher flow rates of oxygen postoperatively and for a longer period. Serious complications, including the reintubation of 2  patients and unplanned intensive care unit (ICU) transfers, were noted in the patients with OSA (24%) compared with the control group (P = .004). The mean length of hospital stay was significantly longer for patients with OSA (6.8 + 2.8 days) compared with those in the control group (5.1 + 4.1 days, P = .007).¹⁸

The OSA group in the aforementioned study was divided into 2 types during this investigation: one group (n = 36) included patients undiagnosed with OSA until after their surgery (mean 1.8 years); the other group (n = 65) had a confirmed diagnosis at the time of surgery. All 36 in the first group and 32 from the second group with diagnosed OSA did not use CPAP therapy at home; a total of 68 patients (67.3%) who had not received therapy before the surgery. The 33 patients with diagnosed OSA (32.7%) who did use CPAP therapy before surgery had lower complication rates, including shorter hospital stays (6.0 + 2.1 days) compared with their counterparts with untreated OSA (7.2 + 3.1 days). The authors surmised that there might be a carryover protective effect at least for the first postoperative day.¹⁸

A retrospective study examined patients with OSA who had outpatient surgical procedures performed under either major regional anesthesia (central neuraxial) or general anesthesia. The study looked at the first outpatient surgical procedure for the patient with OSA following the diagnosis except for otorhinolaryngologic surgeries, which were excluded from the study. The 234 patients with OSA were then matched to the same number of control patients who had also had outpatient surgical procedures (excluding the otorhinolaryngologic procedures). The researchers noted a higher incidence of endotracheal intubation in the OSA group (79.9% vs 73.9% in the control group, P = .017).

The OSA group was less likely to have a laryngeal mask airway used during surgery for their airway management (5.1% vs 10.7% in the control group, P = .017). The only significantly different complication between the 2 groups was unplanned admissions to an ICU in the postoperative period (although numbers/percentages were not listed in the article). However, there was no difference in the overall unplanned hospital admission rate between the 2 groups. One limitation to this study was that the control group had not been tested for OSA, and therefore, it was possible that some in the control group might have had undiagnosed OSA.¹⁹

It is recommended that the surgeon and anesthesiologist ask about a diagnosis of OSA or sleep apnea symptoms during the preanesthesia assessment for any surgery. The provider performing the preoperative physical examination should pay attention to the circumference of the neck, chin-throat length, Mallampati classification, mandible position, and BMI. Any findings that suggest undiagnosed OSA should prompt further evaluation before any elective surgery.

Those who are at risk of OSA anesthesia-related complications should be offered regional anesthesia if possible. It is undesirable to premedicate with sedatives or opioids for this population. The sniffing position during surgery has been found to reduce the collapsibility of the airway and improve its dimensions. All patients who use CPAP therapy at home should have this therapy available for use in the recovery room with the lateral position preferred.¹⁷

Outpatient surgery using sedation and local anesthetics can also be a higher risk for patients with OSA. The unprotected, potentially problematic airway is still a serious concern. Patients requiring short procedures may do well with titrated sedation if well positioned and appropriately selected for this before the procedure. Clinicians must be prepared to handle any complications that occur. One complication that occurs commonly in obese patients related to a smaller functional residual capacity is rapid oxygen desaturation.¹⁷

A Chinese study evaluated complications in patients who had received tongue base reduction through RFA. Complications, both intraoperative and postoperative, included hematoma of the tongue base, bleeding, altered taste, an abscess at the base of the tongue, speech dysfunction, numbness, and deviation of the tongue extension movement. One cardiac death occurred 37 hours following surgery related to swelling of the tongue base and pain, which aggravated sleep apnea and nocturnal hypoxemia and induced a fatal arrhythmia.¹⁵

The Future of OSA Treatments

Research is underway to evaluate the effectiveness of an implanted system to stimulate the hypoglossal nerve with the intent of activating the upper airway musculature. A small study of 8 patients found improvement in the degree of upper airway collapsibility and the severity of OSA. Continued research on the device is focusing on the parameters for the nerve stimulation. The criteria for patient selection are also being established.²⁰

Another study of hypoglossal nerve stimulation (HNS) evaluated 21 patients who were unable to tolerate CPAP therapy. The researchers found significant improvement in AHI (43.1 + 17.5 to 19.5 + 16.7); Functional Outcomes of Sleep Questionnaire (14.4 + 2.0 to 16.7 + 2.2); ESS (12.1 + 4.7 to 8.1 + 4.4); Beck Depression Inventory (15.8 + 9.0 to 9.7 + 7.6); and the Calgary Sleep Apnea Quality of Life Index (3.2 + 1.0 to 4.9 to 4.9 + 1.3). The researchers concluded HNS decreased OSA-related symptoms and the severity of OSA.²¹ At least one of these devices, the Inspire device, has been approved for use in Europe (Figure 2).²² In addition, the FDA has approve the Inspire Upper Airway Stimulation therapy for use in a subset of patients with moderate to severe OSA who are unable to use CPAP.²³

A recent study investigated the effect of HNS on the severity of OSA among patients who had moderate to severe OSA and had not had a response to CPAP therapy. The HNS was associated with significant improvement in reducing the frequency of respiratory events. The median AHI at 12 months decreased from 29.3 events per hour to 9.0 events per hour (P < .001), and the number of times per hour of sleep that the blood oxygen level dropped by ≥ 4% from the baseline (oxygen desaturation index score) decreased from 25.4 to 7.4 events per hour (P < .001).²⁴

Another area being studied is the development of a device to advance the tongue. Forty-two patients had mandibular bone anchors inserted with a flexible tether connected to a surgically inserted anchor in the posterior tongue. Unfortunately, 31% of the participants developed tissue anchor barb fractures that were asymptomatic and detected through radiography. At this time, the failure rate does not warrant clinical use. However, some patients showed significant improvement in multiple measures for sleep apnea, and more research is ongoing with the device.²⁵

Similarly, a surgically inserted tongue pin that connects to an oral device during sleep has been studied. This pin prevents the tongue from moving back and obstructing the upper airway. Polysomnographies were performed both before and after and showed an increased rate of apnea in the 10 subjects. Visualization with magnetic resonance imaging showed that the upper airway was not kept open by this fixation device. Additional research with a modified design for the device is recommended.²⁶     

Reshaping of the epiglottis using a CO₂ laser has been studied with cadaver specimens. The researchers believe scar formation following the reshaping would aid in retraction of the epiglottis anteriorly. Studies with animals are being conducted with different laser types. Future studies involving selected patients with OSA who have epiglottis malformations would be the next step.²⁷

More studies about both minimally invasive and invasive surgeries for OSA are needed. There are many unanswered questions, including the timing of follow-up assessments, how long to observe a patient after surgery, whether the use of multilevel surgery affects the rate of relapse, and what are the best follow-up tools to use. Research needs to be performed in diverse populations, including gender, race/ethnicity, and age groups. Complications of surgical procedures need to be studied and clarified over both short- and long-term periods.⁹

Conclusions

Although there have been some successes in using surgical procedures to treat OSA, CPAP therapy remains the first-line treatment. Invasive surgeries have higher rates of complications and risks than do those of minimally invasive procedures. There are also additional risks related to the use of anesthesia both during and after surgery. Referrals for surgery should include information about a diagnosis of OSA, and patients should be instructed to discuss this with the anesthesiologist or certified nurse anesthetist.

With careful selection by the surgeon and sleep providers, patients who do not tolerate CPAP therapy or respond to other noninvasive interventions can benefit from a surgical procedure. Minimally invasive surgeries are less risky for the patient and should be considered. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

WEB EXCLUSIVE CASE STUDY

A Physical Examination of the Upper Airway by an Ear, Nose, and Throat Physician

Obstructive sleep apnea (OSA) is recognized primarily as a problem of the upper airway. Although narrowing or actual obstruction of the airway during the night can be found in only 1 or 2 areas of the upper airway, most often sleep apnea involves the entire pharyngeal upper airway passages. Three regions are considered to be of major concern: the nasal cavity region, the retropalatal region, and the retrolingual region. As the level of these 3 regions descends, the volume of tissue from the nose to the base of the tongue increases significantly. This leads to increased difficulty treating OSA with each descending region as well as to a lower success rate overall. Sometimes, the problem causing OSA is limited to only 1 region but may involve 2 or even all 3 regions.¹

Continuous positive airway pressure (CPAP) therapy and other positive airway pressure (PAP) therapies have been considered a safe and effective treatment for OSA. Unfortunately, compliance rates, even among patients who use it to successfully eliminate their symptoms, can vary from 50% to 70%. Complaints about using CPAP and other PAP therapies range from skin irritation, discomfort to the nose or nasal passages, and eye problems to claustrophobia from wearing a mask. Patients who are unable or unwilling to use CPAP therapy can be candidates for surgical treatment of OSA.²

This article discusses surgical options for adult patients who have OSA who choose not to use CPAP therapy, the reasons to perform surgery for adults who have OSA, and the desired outcomes of surgery for OSA with a focus on minimally invasive procedures. Interventions for pediatric patients are not addressed.

Treatment Options          

Treatments other than CPAP can help lessen the severity of OSA. Noninvasive treatments include weight loss, positional treatment (avoiding sleeping on one’s back), and oral appliances. Practice parameters from the American Academy of Sleep Medicine (AASM) for the treatment of OSA include dietary weight loss in addition to the primary therapy. An improvement in the apnea-hypopnea index (AHI) may occur with dietary weight loss.³

Major weight loss through the use of bariatric surgery has been shown to be effective in treating OSA and obesity hypoventilation syndrome (OHS), which is defined as daytime hypercapnia and hypoxemia (PaCO₂ > 45 mm Hg and PaO₂ < 70 mm Hg at sea level) in an obese patient (body mass index [BMI] > 30 kg/m²) with sleep-disordered breathing in the absence of any other cause of hypoventilation.⁴ Some individuals may have both conditions. However, CPAP therapy should not be discontinued even when major weight loss occurs until repeat polysomnography has been performed. Major weight loss may cure OHS and help improve the severity of OSA but will not totally resolve the condition.⁴ According to Woodson, sleep apnea in patients who are morbidly obese may be different from traditional OSA as rapid eye movement (REM), REM-related apneas, and hypoventilation occur more often in this population. Although weight loss is strongly recommended for patients with OSA, bariatric surgery is not recommended as the sole treatment for traditional OSA.⁵

Positional therapy, wherein the patient avoids the supine position, can be effective as a secondary or supplemental therapy in addition to treatment with CPAP. Guidelines recommend this primarily for individuals who have a lower AHI when in the nonsupine position than when lying on their backs. Patients who benefit from positional therapy tend to be younger, less obese, and with a less severe condition. The AASM practice parameter was based on 3 level II studies—randomized trials with high alpha and beta levels.⁶ One of the level II studies compared supine with an upright position, stating: “Because not all patients normalize AHI when non-supine, the committee’s opinion is that correction of OSA by position should be documented with an appropriate test.” Special pillows have been described in 2 papers reviewed by AASM, which seemed to improve OSA.⁶

The AASM guidelines state that oral appliances are indicated for some patients, although they are not as efficacious in treating OSA as CPAP therapy. Oral appliances are recommended for patients with mild to moderate OSA who have not responded to CPAP therapy, cannot tolerate CPAP therapy, are not appropriate for treatment with CPAP for some reason, or fail treatment with CPAP along with other behavioral measures, such as weight loss or positional therapy.⁶  

In addition, the AASM guidelines recommend that patients with severe OSA, “should have an initial trial of nasal CPAP because greater effectiveness has been shown with this intervention than with the use of oral appliances. Upper airway surgery (including tonsillectomy and adenoidectomy, craniofacial operations, and tracheostomy) may also supersede use of oral appliances in patients for whom these operations are predicted to be highly effective in treating sleep apnea.”⁶

Nasal expiratory positive end pressure (EPAP) devices may be helpful in treating OSA in some patients. These devices contain a mechanical valve with very low inspiratory resistance but high expiratory resistance. The device has an adhesive and is applied by the patient to create a seal. Exhalation causes a high expiratory resistance that splints the upper airway open. This increases the resistance of the airway to close on inspiration.⁷ An EPAP device is recommended for potential use in mild to moderate OSA for patients who either have an intolerance to CPAP therapy or have failed to respond to it.⁸            

Finally, there are major surgeries performed by oral surgeons that can benefit some patients with OSA. One of these is maxillomandibular advancement (MMA). According to the AASM practice parameter: MMA “involves simultaneous advancement of the maxilla and mandible through sagittal split osteotomies. It provides enlargement of the retrolingual airway and some advancement of the retropalatal airway.”⁹ It is indicated as a surgical treatment for patients with severe OSA who are either unwilling or do not tolerate CPAP treatment. These individuals would not benefit from an oral appliance (recommended for mild to moderate OSA) or would find it undesirable.⁹

There is also stepwise or multilevel surgery (MLS) that can be performed. These include a number of combined procedures, which address multiple sites with narrowing in the upper airway. Frequently, MLS will consist of
2 phases: the first involves use of the uvulopalatopharyngoplasty (UPPP) procedure “and or genioglossus advancement and hyoid myotomy (GAHM). The second phase surgeries consist of utilizing maxillary and mandibular advancement osteotomy (MMO), offered to those failing Phase I surgeries.”⁹

OSA Surgical Procedures

Tracheostomies are first estimated to have been performed in 2000 BC.¹⁰ Performing a tracheostomy to bypass the upper airway was used in the 1960s and 1970s for the treatment of OSA and for many years was the only treatment available for people with Pickwickian syndrome (OHS) and nocturnal upper airway obstruction. The procedure was generally not tolerated or accepted by patients, even though it improved their quality of life and added to their life expectancy. Once CPAP treatment proved successful for OSA, tracheostomy has rarely been necessary.¹¹

Uvulopalatopharyngoplasty surgery was introduced in 1981. The aim of this surgery is to decrease snoring and treat OSA by removing obstructive tissues, enlarging the cross-sectional portion of the upper airway, and bypassing the upper airway. Tissue that is removed includes the tonsils, uvula, and the distal portion of the soft palate.¹²

Woodson considers surgery for OSA to be the third-line of treatment. The first-line treatment would be CPAP therapy, and second-line therapy would include oral appliances to enlarge the airway or retain the tongue (if the individual has no dentition). The intent of surgery falls into 3 categories: curative, salvage, and ancillary.

In a chronic disease such as OSA, “many may question whether a cure exists.” Instead of eliminating OSA, the curative intent is definitively to reduce symptoms and disease morbidity for long periods. The criteria for defining a responder or cure to surgery for OSA are found in Table 1.⁵

Surgery for salvage aims at treating patients who have failed CPAP therapy. Successful treatment with the intent of salvage can occur with a lessening of disease severity, including morbidity and mortality, but not necessarily totally eliminating the symptoms. Finally, ancillary surgery for OSA aims to combine a surgical procedure with the first-line therapy (positive pressure) to add an additional therapeutic benefit. The combination of CPAP and ancillary procedures may be of the most benefit to patients with OSA.⁵

As mentioned previously, the AASM has developed practice parameters for the treatment of OSA, including surgery. Desired outcomes of treatment for OSA include the resolution of symptoms and clinical signs, normalization of the quality of sleep, AHI, and levels of oxyhemoglobin saturation. It is recognized that normalization of the AHI may not reverse all the components of OSA, and up to 22% of patients continue to have residual hypersomnia with CPAP therapy.⁹

Despite this, most studies that show significant benefits in lowering cardiovascular risk, mortality rates, symptoms, and neurocognitive effects have also shown significant reductions in the AHI.⁹ Therefore, the AASM puts a high value on treating OSA with the goal of normalization of the AHI. There exists a lack of quality studies and good evidence regarding the effectiveness of surgical procedures of the upper airway as treatment for OSA. Despite this, the AASM recommendation is that “all reasonable treatment alternatives for OSA be discussed in a manner that allows the patient to make an informed decision.”⁹

Types of OSA Surgeries

Surgery for OSA can be divided into 2 categories, invasive surgery and minimally invasive surgery (Table 2). Invasive surgeries for OSA have a higher risk of complications and postoperative pain.⁹

Invasive Surgery
The UPPP surgery is perhaps the best-known invasive procedure for treating OSA. A meta-analysis of 15 studies on UPPP outcomes found overall improvement in AHI of 33% but with postoperative AHI remaining elevated at an average of 29.8 events per hour.¹³

Adverse effects for the procedure include changes in taste, dysphagia, nasal regurgitation, and voice alterations. Seven of the 15 studies reported at least 1 death following the UPPP procedure. The effects of UPPP surgery on systemic and cardiovascular sequelae of OSA are not fully known and need to be further researched. ¹³

Another invasive procedure that is similar to the UPPP is the laser-assisted uvulopalatoplasty (LAUP) procedure. First reported in 1990, LAUP was developed as a procedure to eliminate snoring and was found to be effective. Other studies have been conducted since then, but there are inconsistencies in the specific types of procedures performed and a lack of detailed data analysis.

Adverse effects of the LAUP procedure include minor bleeding, globus sensation, local infection, minor dysphagia and dysphonia, and transient velopharyngeal insufficiency.¹⁴ However, studies have also shown that about one-quarter of the participants developed persistent dysphagia or mild to moderate scar fibrosis. Postoperative swelling can reduce an already narrow airway, and the use of sedatives or narcotics can make this problem worse. Some studies have noted structural changes following this procedure that lower airway resistance, resulting in the collapse of the upper airway and the narrowing of the airway during inhalation with worsening OSA.^13,14

Practice parameters for the LAUP procedure were developed by the AASM in 1994. The AASM recommended against using LAUP to treat OSA (and other sleep-related breathing disorders) and against substituting LAUP for UPPP surgery. The AASM also suggested criteria for choosing candidates for LAUP and urged that patients be given full information about the procedure and a preoperative evaluation from their provider.^5,14

Minimally Invasive Surgery
Radiofrequency surgery and soft palate implants are considered minimally invasive procedures, according to the criteria established in a study by Maurer.¹¹ Various nasal surgeries (eg, septoplasty, adenoidectomy, and polyp removal) could also be considered minimally invasive and are often performed in patients with OSA to improve tolerance of CPAP by improving the ability to breathe nasally. However, nasal surgery with improvement of nasal breathing has not been found to have a significant impact on adults who have OSA. An advantage of nasal surgery is that some studies have shown longer use of CPAP therapy, up to 2 hours longer per night.⁵

With radiofrequency of the tongue base, high-frequency radio waves, either monopolar or bipolar, are used to coagulate the interstitial tissue at the base of the tongue. This, in turn, leads to necrosis and scarring, which then leads to stiffening of the tissue and in some cases, volume reduction. The surgeon controls the temperature to avoid overdosing and tissue carbonization. A number of lesions are produced during a session and the number of sessions necessary for full treatment varies per surgeon and the technical system used in procedures.

Although radiofrequency ablation (RFA) has been used on the tonsils and soft palate, RFA is currently available only to patients with OSA on the tongue base. A reduction in AHI of 33% on average was achieved in a review of 6 studies, and the reduction was stable over a 2-year period.¹¹ The average presurgery AHI was 39.5, and the average postsurgery AHI was 28.7. In this same review, the average Epworth Sleepiness Scale (ESS) (a commonly used subjective tool to measure levels of daytime sleepiness) score was 10.4 presurgery and 4.5 postsurgery.¹¹

A Chinese study looked at complications from RFA of the tongue base. According to the abstract (the article was written in Chinese), 1 patient (n = 193) developed a fatal arrhythmia. The authors’ recommendation was for close monitoring after surgery until the swelling subsided.¹⁵

With soft palate implants, small cylinders of woven polyester (“polyethylene terephthalate, commonly marketed as Dacron polyester”) yarn, 18 mm long by 2 mm diameter, are inserted at the junction of the hard palate and soft palate. Placed into the proximal soft palate tissue, these implants are designed to stiffen the soft palate “through fibrotic tissue encapsulation and tissue ingrowth over time.” Many patients with only snoring or mild to moderate OSA have found improvement with this procedure. Improved reduction of snoring was found in 1 study (n = 79), which looked at the use of Pillar implants to reduce snoring (Figure 1). This reduction of snoring occurred in patients with lower AHI levels before the procedure.¹⁶ Mauer reviewed 3 studies of the palatal implants and found a pooled reduction of 26% in AHI after placement.¹¹

Criteria for Surgery

The mechanism that causes collapse of a patient’s airway will vary from one person to the next. Variables include age, body weight, anatomy, and body position. Thus, different findings will require different surgical techniques, and there is no one-size-fits-all surgery for OSA.¹¹

A thorough physical examination of the upper airway is important. Maurer recommends considering the use of videoendoscopy under sedation, which allows a view of the mechanism and site of obstruction, with pressure catheters inserted to collect data. This procedure was developed in the 1990s to improve the analysis of obstruction within the upper airway. Unfortunately, the data are unclear about whether this aids in the surgical outcome.¹¹ Powell stated that sleep endoscopy is currently considered investigational because medication-induced sleep may differ from natural sleep without medication.¹

Nasopharyngoscopy, using fiberoptics, and lateral cephalometric analysis have been used for several years as primary diagnostic tools for patients being considered for a surgical procedure for OSA. Some new imaging procedures (eg, 3-D imaging coupled with advanced software programs) have been developed that may be helpful to assess regions that are constricted as well as provide a more exact measurement of the airway from the nose to the larynx.¹

Risks and Complications of Surgery
The higher risk of anesthesia-related complications during or after surgery related to OSA is one reason that surgery is usually considered to be the third-line of treatment. Patients with OSA commonly have hypertension and other cardiovascular disease, which adds to the risk of anesthesia-related complications. Patients who have anatomical abnormalities of the jaw or portions of the upper airway will also be at a higher risk. Initial intubation and providing anesthesia during procedures may be more difficult for patients with these jaw or airway abnormalities. Postsurgical pain management with opioids contributes to the higher rate of apnea. After extubation, the incidence of apnea has been found to be higher in the population with OSA as well.¹⁷

A study published in 2001 used a case-control matched population methodology to examine patients who were undergoing elective surgeries for either hip or knee joint replacements. Significant differences in overall complication rates were found among the patients with OSA (n = 101) compared with those of the control group (n = 101). These differences were not related to the type of anesthesia, narcotic use after surgery, or the type of operation performed. The OSA group had a significantly higher number of patients who required higher flow rates of oxygen postoperatively and for a longer period. Serious complications, including the reintubation of 2  patients and unplanned intensive care unit (ICU) transfers, were noted in the patients with OSA (24%) compared with the control group (P = .004). The mean length of hospital stay was significantly longer for patients with OSA (6.8 + 2.8 days) compared with those in the control group (5.1 + 4.1 days, P = .007).¹⁸

The OSA group in the aforementioned study was divided into 2 types during this investigation: one group (n = 36) included patients undiagnosed with OSA until after their surgery (mean 1.8 years); the other group (n = 65) had a confirmed diagnosis at the time of surgery. All 36 in the first group and 32 from the second group with diagnosed OSA did not use CPAP therapy at home; a total of 68 patients (67.3%) who had not received therapy before the surgery. The 33 patients with diagnosed OSA (32.7%) who did use CPAP therapy before surgery had lower complication rates, including shorter hospital stays (6.0 + 2.1 days) compared with their counterparts with untreated OSA (7.2 + 3.1 days). The authors surmised that there might be a carryover protective effect at least for the first postoperative day.¹⁸

A retrospective study examined patients with OSA who had outpatient surgical procedures performed under either major regional anesthesia (central neuraxial) or general anesthesia. The study looked at the first outpatient surgical procedure for the patient with OSA following the diagnosis except for otorhinolaryngologic surgeries, which were excluded from the study. The 234 patients with OSA were then matched to the same number of control patients who had also had outpatient surgical procedures (excluding the otorhinolaryngologic procedures). The researchers noted a higher incidence of endotracheal intubation in the OSA group (79.9% vs 73.9% in the control group, P = .017).

The OSA group was less likely to have a laryngeal mask airway used during surgery for their airway management (5.1% vs 10.7% in the control group, P = .017). The only significantly different complication between the 2 groups was unplanned admissions to an ICU in the postoperative period (although numbers/percentages were not listed in the article). However, there was no difference in the overall unplanned hospital admission rate between the 2 groups. One limitation to this study was that the control group had not been tested for OSA, and therefore, it was possible that some in the control group might have had undiagnosed OSA.¹⁹

It is recommended that the surgeon and anesthesiologist ask about a diagnosis of OSA or sleep apnea symptoms during the preanesthesia assessment for any surgery. The provider performing the preoperative physical examination should pay attention to the circumference of the neck, chin-throat length, Mallampati classification, mandible position, and BMI. Any findings that suggest undiagnosed OSA should prompt further evaluation before any elective surgery.

Those who are at risk of OSA anesthesia-related complications should be offered regional anesthesia if possible. It is undesirable to premedicate with sedatives or opioids for this population. The sniffing position during surgery has been found to reduce the collapsibility of the airway and improve its dimensions. All patients who use CPAP therapy at home should have this therapy available for use in the recovery room with the lateral position preferred.¹⁷

Outpatient surgery using sedation and local anesthetics can also be a higher risk for patients with OSA. The unprotected, potentially problematic airway is still a serious concern. Patients requiring short procedures may do well with titrated sedation if well positioned and appropriately selected for this before the procedure. Clinicians must be prepared to handle any complications that occur. One complication that occurs commonly in obese patients related to a smaller functional residual capacity is rapid oxygen desaturation.¹⁷

A Chinese study evaluated complications in patients who had received tongue base reduction through RFA. Complications, both intraoperative and postoperative, included hematoma of the tongue base, bleeding, altered taste, an abscess at the base of the tongue, speech dysfunction, numbness, and deviation of the tongue extension movement. One cardiac death occurred 37 hours following surgery related to swelling of the tongue base and pain, which aggravated sleep apnea and nocturnal hypoxemia and induced a fatal arrhythmia.¹⁵

The Future of OSA Treatments

Research is underway to evaluate the effectiveness of an implanted system to stimulate the hypoglossal nerve with the intent of activating the upper airway musculature. A small study of 8 patients found improvement in the degree of upper airway collapsibility and the severity of OSA. Continued research on the device is focusing on the parameters for the nerve stimulation. The criteria for patient selection are also being established.²⁰

Another study of hypoglossal nerve stimulation (HNS) evaluated 21 patients who were unable to tolerate CPAP therapy. The researchers found significant improvement in AHI (43.1 + 17.5 to 19.5 + 16.7); Functional Outcomes of Sleep Questionnaire (14.4 + 2.0 to 16.7 + 2.2); ESS (12.1 + 4.7 to 8.1 + 4.4); Beck Depression Inventory (15.8 + 9.0 to 9.7 + 7.6); and the Calgary Sleep Apnea Quality of Life Index (3.2 + 1.0 to 4.9 to 4.9 + 1.3). The researchers concluded HNS decreased OSA-related symptoms and the severity of OSA.²¹ At least one of these devices, the Inspire device, has been approved for use in Europe (Figure 2).²² In addition, the FDA has approve the Inspire Upper Airway Stimulation therapy for use in a subset of patients with moderate to severe OSA who are unable to use CPAP.²³

A recent study investigated the effect of HNS on the severity of OSA among patients who had moderate to severe OSA and had not had a response to CPAP therapy. The HNS was associated with significant improvement in reducing the frequency of respiratory events. The median AHI at 12 months decreased from 29.3 events per hour to 9.0 events per hour (P < .001), and the number of times per hour of sleep that the blood oxygen level dropped by ≥ 4% from the baseline (oxygen desaturation index score) decreased from 25.4 to 7.4 events per hour (P < .001).²⁴

Another area being studied is the development of a device to advance the tongue. Forty-two patients had mandibular bone anchors inserted with a flexible tether connected to a surgically inserted anchor in the posterior tongue. Unfortunately, 31% of the participants developed tissue anchor barb fractures that were asymptomatic and detected through radiography. At this time, the failure rate does not warrant clinical use. However, some patients showed significant improvement in multiple measures for sleep apnea, and more research is ongoing with the device.²⁵

Similarly, a surgically inserted tongue pin that connects to an oral device during sleep has been studied. This pin prevents the tongue from moving back and obstructing the upper airway. Polysomnographies were performed both before and after and showed an increased rate of apnea in the 10 subjects. Visualization with magnetic resonance imaging showed that the upper airway was not kept open by this fixation device. Additional research with a modified design for the device is recommended.²⁶     

Reshaping of the epiglottis using a CO₂ laser has been studied with cadaver specimens. The researchers believe scar formation following the reshaping would aid in retraction of the epiglottis anteriorly. Studies with animals are being conducted with different laser types. Future studies involving selected patients with OSA who have epiglottis malformations would be the next step.²⁷

More studies about both minimally invasive and invasive surgeries for OSA are needed. There are many unanswered questions, including the timing of follow-up assessments, how long to observe a patient after surgery, whether the use of multilevel surgery affects the rate of relapse, and what are the best follow-up tools to use. Research needs to be performed in diverse populations, including gender, race/ethnicity, and age groups. Complications of surgical procedures need to be studied and clarified over both short- and long-term periods.⁹

Conclusions

Although there have been some successes in using surgical procedures to treat OSA, CPAP therapy remains the first-line treatment. Invasive surgeries have higher rates of complications and risks than do those of minimally invasive procedures. There are also additional risks related to the use of anesthesia both during and after surgery. Referrals for surgery should include information about a diagnosis of OSA, and patients should be instructed to discuss this with the anesthesiologist or certified nurse anesthetist.

With careful selection by the surgeon and sleep providers, patients who do not tolerate CPAP therapy or respond to other noninvasive interventions can benefit from a surgical procedure. Minimally invasive surgeries are less risky for the patient and should be considered. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

WEB EXCLUSIVE CASE STUDY

A Physical Examination of the Upper Airway by an Ear, Nose, and Throat Physician

Antimicrobial stewardship activities have been in place at the Edward Hines, Jr. VA Hospital in Hines, Illinois, since 1988. Initial activities, including antimicrobial restriction and the start of an outpatient-infusion program justified and led to dedicated funding for hiring the first infectious diseases (ID) clinical pharmacist. This position was initiated in 1992 and has been maintained since then. The committed multidisciplinary team, including ID physicians, ID clinical pharmacists, venous access nurses (VAN), microbiologists, infection control practitioners, and an outpatient-infusion coordinator have led stewardship activities at this VA.

One of the first efforts of the team was the development of the outpatient parenteral antibiotic therapy (OPAT) program.¹ The program began in 1989 and has served more than 1,200 veterans. Outpatient parenteral antibiotic therapy is only one component of the stewardship program, which provides safe, effective, and cost-minimizing care for veterans, and is the focus of this article.

Background

Complex medical care and escalating costs have pushed all but the most seriously ill patients out of the hospital setting for care delivery. The reality is that patients who might have received care for non–life-threatening problems in a hospital bed are now relegated to an outpatient status. Beginning in the 1970s, OPAT has been used to facilitate the cost-effective, safe administration of antibiotics as an  alternative to an extensive, expensive hospital stay.² Initially developed for use in a nonhospital health care setting, the administration of antibiotics under the guidance of a health care provider (HCP) has now been extended to a self-administered infusion program.^3,4 Under the latter, patients and caregivers are educated to safely administer IV antibiotics for extended periods at home.

This program uses elements of both health care–associated OPAT and self-administered OPAT (S-OPAT) to accomplish its goals: (1) safe, effective administration of antibiotic therapy to a variety of patients; (2) reduction in bed days of care (BDOC); (3) reduction of the economic burden to the hospitals’ global budgets; and (4) reduction in the incidence of common nosocomially-acquired infections, including those caused by Clostridium difficile (C difficile), methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococcus.³

The advantages of S-OPAT have been fully realized in a variety of countries, enabling patients to receive necessary therapy in the comfort of their homes and providing them with the ability to lead normal lives without the confinement of a protracted hospital stay.^5-7

Description of OPAT

The outpatient-infusion team provides specialized care for patients in accordance with the OPAT national guidelines from patient screening to program discharge.⁸ The dedicated staff include the OPAT nurse coordinator, VAN, pharmacists, and ID consultants. The VAN places the venous access device (VAD), educates the patient and caregiver in the care and safety of the catheter, aseptic technique, and infusion of the selected antimicrobial agent, and monitors the laboratory work. The VA may contract an outside nursing agency to provide support and reinforcement of IV administration for the patient and caregiver.

The pharmacists oversee the pharmacokinetics and pharmacodynamics of the antimicrobials as well as monitor for any toxicities that could potentially arise during and after therapy. The ID consultants identify the infection, collaborate with the pharmacists to select the most appropriate antimicrobial regimen, and determine the duration of required therapy. The team then regularly monitors the patient in the ID clinic until there is evidence of infection resolution.

Primary care providers who want to enroll patients in the OPAT program place a formal electronic consult to the ID team for antibiotic recommendation, to the outpatient infusion team for assessment of potential outpatient therapy, and to the venous access team for insertion of the VAD. The consults are completed after receiving consent from the patient, developing a patient-centered treatment plan, and determining the patient’s ability to comprehend and adhere to the program requirements. The patient or caregiver must be able to competently demonstrate aseptic technique for IV administration prior to discharge. The pharmacist educates the patient or caregiver about the stability, storage requirements, and potential adverse drug reactions of the antimicrobial.

Eligible patients must have resolved their acute medical problems and require > 1 week of therapy to treat their infection. Patients chosen for OPAT or S-OPAT must have a suitable living environment with access to a refrigerator, a telephone, and transportation to return to the hospital for follow-up. Most patients and caregivers are eager to learn and recognize the advantages of home-based care.

The VANs are a central component of the program. They maintain open communication with the patient during the entire treatment course and help triage issues to the appropriate HCP. In addition, they are responsible for submitting catheter-related bloodstream infection (CRBSI) information to the hospital administration, which then gets reported to the National Healthcare Safety Network (NHSN).

Not all patients qualify for S-OPAT. Other options include returning to the hospital daily for infusions, being discharged to a skilled care facility, or arranging for a VA-contracted agency to provide nursing care while the VA provides all required medications and supplies.

On completion of OPAT, patients are asked to evaluate the program. The anonymous survey includes open-ended questions for patients to better express their experience with the program and staff. Patients are given the opportunity to suggest improvements and provide overall feedback. The team for quality assurance and patient satisfaction reviews every survey, which is used as a tool to improve team functions.

Data are also collected in the OPAT program to measure efficacy and monitor for safety. Data obtained from the start of the program in February 1989 through fiscal year (FY) 2011 include the number of patients who were candidates for outpatient-infusion therapy, type of infection, antibiotic selection, CRBSIs, hospital readmission rates, cost savings, and patient satisfaction.

Results

The Edward Hines, Jr. VA Hospital has a proven, successful OPAT program. Most of the patients in the program during the study period were men, which reflects a typical VA population. Patients with spinal cord injury comprised a large portion of those treated. Table 1 provides the number of patients treated and lists the frequency of infections. The data are divided into 3 periods. From 1989 to September 30, 1995, OPAT used other VADs before using peripherally inserted central catheters. During the second period (October 1, 1995-September 30, 2003), patients remained with a VAD for an average of 48.6 days; whereas in Period 3 (October 1, 2003-September 30, 2011), the patients had a VAD average of 34.7 days. Consequently, with fewer VAD days, there was a decreased incidence of complications (Table 2).

Osteomyelitis accounted for the majority of the infections (40.6%), which required ≥ 6 weeks of therapy. Complicated urinary tract infection (UTI), including pyelonephritis, perinephric abscess, and complicated cystitis, was the next most common (14.9%). Bacteremia was the third most common infection (7.9%), whereas abscesses of a diverse variety affected 6.2%, including brain, liver, intra-abdominal, soft tissue, and epidural abscesses. Endocarditis and septic arthritis accounted for 4.4% and 4.7%, respectively, of infected patients.

Three periods of the OPAT program were selected at random (1996, 2003, and 2011) to examine trends in antimicrobial selection. Overall, ceftriaxone was the most commonly used antibiotic (35%). Vancomycin was the next most commonly prescribed (27%). Since its 2001 FDA approval, ertapenem has become the third most commonly prescribed antibiotic for the OPAT program (11%).  As expected, antimicrobial agents that have to be dosed more frequently than twice a day were rarely used for OPAT. In addition, there was low usage of aminoglycosides due to the need for the close monitoring of levels and potential toxicity.

Outcomes

Catheter Complications
The majority of catheter complications occurring in the first period were multifactorial, relating to nursing education, product selection, program development, insertion techniques, and a less comprehensive infection control program.

Hospital Readmissions
A snapshot of FY 2011 data was used to evaluate hospital readmissions. One hundred one patients were reviewed. Of these patients, 9 (9%) were readmitted to the hospital at some point after being discharged from OPAT. Readmission due to complications of OPAT was found in 2 of the 9 patients. One was due to an adverse drug reaction from the antibiotic; the other was due to a possible relapse of a hip osteomyelitis.

Cost Analysis
The OPAT program has resulted in a total savings to the global hospital budget from the deferred BDOC of more than $65 million (Table 3) since 1989. The OPAT program eliminated > 47,000 days of inpatient care. In FY 2009 the program cost the hospital $691.35 for each of the 106 patients enrolled (total cost: $73,283.10). This included all IV supplies, antimicrobials, visiting nurse costs when applicable, as well as nursing and pharmacy time dedicated to training the patient and making therapeutic decisions. Expenses for 3,109 BDOC would have cost about $6,218,000. The outpatient-infusion program saved the hospital nearly $6 million in 2009 alone.

Patient Satisfaction
About 60% of the patients discharged from the OPAT program responded to an evaluation survey. The feedback was overwhelmingly positive with about 99% of respondents reporting satisfaction relating to an improved quality of life. Most of the positive comments were directed toward the outpatient-infusion coordinator for resolving issues, being easily accessible, and acting as a patient advocate.

Discussion

The number and types of reasons for OPAT have grown with the knowledge that it is a safe, cost-effective method for the delivery of parenteral antimicrobials. In the early years of the program, before effective antiretroviral therapy was available, cytomegalovirus retinitis was the second most commonly treated infection of the OPAT program. In recent years, the rise of multidrug-resistant organisms has led to limited oral treatment options for UTIs, which are now the second most commonly treated infection of OPAT. Osteomyelitis clearly remains the top indication for OPAT because it requires long-term therapy. Ceftriaxone remains the drug of choice due to once-daily dosing, spectrum of activity, overall safety, and cost-effectiveness.

Catheter complication rates in the OPAT program were lower than those reported in the literature. According to the 2009 NHSN report, the catheter complication rate in the inpatient long-term care units was 1.0 CRBSI/1,000 catheter days.⁹ Moreover, this program has been instrumental in providing care that otherwise would be administered through the use of home health agencies.

In the private sector, OPAT is frequently contracted to agencies that provide the same type of service to outpatients who have insurance. These agencies charge for the antimicrobials, IV supplies, nursing visits, and laboratory costs for patient-safety monitoring. Use of an agency could raise expenses by a factor of 8-fold or more above the cost of a hospital-based OPAT program, an estimate based on a comparison with a local federally contracted home-infusion agency that provides specialized home-infusion services at a cost.

Although costs related to hospital readmissions were not factored in to the cost savings calculations, the rate of readmission was low in the snapshot analysis that was conducted at the Edward Hines, Jr. VA Hospital. It is believed that this is the result of the close follow-up and continuity of care that the patients in this OPAT program received.

In addition to cost containment, the data reflect the safe, effective care that resulted from treatment outside the hospital setting. One of the key attributes that has made the Edward Hines, Jr. VA Hospital OPAT program unique is that it is recognized in the community as the only VA facility in the area to provide OPAT as an option for the veteran patient. Other VA facilities in the area contract with home-infusion agencies, which are responsible for supplying the antibiotics and nursing care. The Edward Hines, Jr. VA Hospital is the only VA hospital in VISN 12 that has a facility-supported  program that provides all supplies and antimicrobials from the VA—a major contributing factor to the cost savings. Continuity of care is provided to the patient who transitions from inpatient to outpatient status with the same team of providers contributing to the significant patient satisfaction that the program has engendered.

Conclusions

One of the main benefits realized with this transition of antibiotic therapy to the home setting is the avoidance of newly acquired nosocomial infections, including C difficile infection, fungal, and multidrug-resistant bacterial infections. Other benefits include early IV to oral switch in therapy when the patient is deemed a candidate, the ability to go back to work sooner, and the ability to receive treatment in the comfort of the patient’s home. Plans for data collection may include a more in-depth review of repeat admissions due to unresolved infections and the number of patients who are unable to complete OPAT at home.

The Edward Hines, Jr. VA Hospital OPAT program has shown that in a large, federally-funded hospital, OPAT is safe, cost-effective, convenient and leads to increased patient satisfaction in a diverse group of veterans.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Antimicrobial stewardship activities have been in place at the Edward Hines, Jr. VA Hospital in Hines, Illinois, since 1988. Initial activities, including antimicrobial restriction and the start of an outpatient-infusion program justified and led to dedicated funding for hiring the first infectious diseases (ID) clinical pharmacist. This position was initiated in 1992 and has been maintained since then. The committed multidisciplinary team, including ID physicians, ID clinical pharmacists, venous access nurses (VAN), microbiologists, infection control practitioners, and an outpatient-infusion coordinator have led stewardship activities at this VA.

One of the first efforts of the team was the development of the outpatient parenteral antibiotic therapy (OPAT) program.¹ The program began in 1989 and has served more than 1,200 veterans. Outpatient parenteral antibiotic therapy is only one component of the stewardship program, which provides safe, effective, and cost-minimizing care for veterans, and is the focus of this article.

Background

Complex medical care and escalating costs have pushed all but the most seriously ill patients out of the hospital setting for care delivery. The reality is that patients who might have received care for non–life-threatening problems in a hospital bed are now relegated to an outpatient status. Beginning in the 1970s, OPAT has been used to facilitate the cost-effective, safe administration of antibiotics as an  alternative to an extensive, expensive hospital stay.² Initially developed for use in a nonhospital health care setting, the administration of antibiotics under the guidance of a health care provider (HCP) has now been extended to a self-administered infusion program.^3,4 Under the latter, patients and caregivers are educated to safely administer IV antibiotics for extended periods at home.

This program uses elements of both health care–associated OPAT and self-administered OPAT (S-OPAT) to accomplish its goals: (1) safe, effective administration of antibiotic therapy to a variety of patients; (2) reduction in bed days of care (BDOC); (3) reduction of the economic burden to the hospitals’ global budgets; and (4) reduction in the incidence of common nosocomially-acquired infections, including those caused by Clostridium difficile (C difficile), methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococcus.³

The advantages of S-OPAT have been fully realized in a variety of countries, enabling patients to receive necessary therapy in the comfort of their homes and providing them with the ability to lead normal lives without the confinement of a protracted hospital stay.^5-7

Description of OPAT

The outpatient-infusion team provides specialized care for patients in accordance with the OPAT national guidelines from patient screening to program discharge.⁸ The dedicated staff include the OPAT nurse coordinator, VAN, pharmacists, and ID consultants. The VAN places the venous access device (VAD), educates the patient and caregiver in the care and safety of the catheter, aseptic technique, and infusion of the selected antimicrobial agent, and monitors the laboratory work. The VA may contract an outside nursing agency to provide support and reinforcement of IV administration for the patient and caregiver.

The pharmacists oversee the pharmacokinetics and pharmacodynamics of the antimicrobials as well as monitor for any toxicities that could potentially arise during and after therapy. The ID consultants identify the infection, collaborate with the pharmacists to select the most appropriate antimicrobial regimen, and determine the duration of required therapy. The team then regularly monitors the patient in the ID clinic until there is evidence of infection resolution.

Primary care providers who want to enroll patients in the OPAT program place a formal electronic consult to the ID team for antibiotic recommendation, to the outpatient infusion team for assessment of potential outpatient therapy, and to the venous access team for insertion of the VAD. The consults are completed after receiving consent from the patient, developing a patient-centered treatment plan, and determining the patient’s ability to comprehend and adhere to the program requirements. The patient or caregiver must be able to competently demonstrate aseptic technique for IV administration prior to discharge. The pharmacist educates the patient or caregiver about the stability, storage requirements, and potential adverse drug reactions of the antimicrobial.

Eligible patients must have resolved their acute medical problems and require > 1 week of therapy to treat their infection. Patients chosen for OPAT or S-OPAT must have a suitable living environment with access to a refrigerator, a telephone, and transportation to return to the hospital for follow-up. Most patients and caregivers are eager to learn and recognize the advantages of home-based care.

The VANs are a central component of the program. They maintain open communication with the patient during the entire treatment course and help triage issues to the appropriate HCP. In addition, they are responsible for submitting catheter-related bloodstream infection (CRBSI) information to the hospital administration, which then gets reported to the National Healthcare Safety Network (NHSN).

Not all patients qualify for S-OPAT. Other options include returning to the hospital daily for infusions, being discharged to a skilled care facility, or arranging for a VA-contracted agency to provide nursing care while the VA provides all required medications and supplies.

On completion of OPAT, patients are asked to evaluate the program. The anonymous survey includes open-ended questions for patients to better express their experience with the program and staff. Patients are given the opportunity to suggest improvements and provide overall feedback. The team for quality assurance and patient satisfaction reviews every survey, which is used as a tool to improve team functions.

Data are also collected in the OPAT program to measure efficacy and monitor for safety. Data obtained from the start of the program in February 1989 through fiscal year (FY) 2011 include the number of patients who were candidates for outpatient-infusion therapy, type of infection, antibiotic selection, CRBSIs, hospital readmission rates, cost savings, and patient satisfaction.

Results

The Edward Hines, Jr. VA Hospital has a proven, successful OPAT program. Most of the patients in the program during the study period were men, which reflects a typical VA population. Patients with spinal cord injury comprised a large portion of those treated. Table 1 provides the number of patients treated and lists the frequency of infections. The data are divided into 3 periods. From 1989 to September 30, 1995, OPAT used other VADs before using peripherally inserted central catheters. During the second period (October 1, 1995-September 30, 2003), patients remained with a VAD for an average of 48.6 days; whereas in Period 3 (October 1, 2003-September 30, 2011), the patients had a VAD average of 34.7 days. Consequently, with fewer VAD days, there was a decreased incidence of complications (Table 2).

Osteomyelitis accounted for the majority of the infections (40.6%), which required ≥ 6 weeks of therapy. Complicated urinary tract infection (UTI), including pyelonephritis, perinephric abscess, and complicated cystitis, was the next most common (14.9%). Bacteremia was the third most common infection (7.9%), whereas abscesses of a diverse variety affected 6.2%, including brain, liver, intra-abdominal, soft tissue, and epidural abscesses. Endocarditis and septic arthritis accounted for 4.4% and 4.7%, respectively, of infected patients.

Three periods of the OPAT program were selected at random (1996, 2003, and 2011) to examine trends in antimicrobial selection. Overall, ceftriaxone was the most commonly used antibiotic (35%). Vancomycin was the next most commonly prescribed (27%). Since its 2001 FDA approval, ertapenem has become the third most commonly prescribed antibiotic for the OPAT program (11%).  As expected, antimicrobial agents that have to be dosed more frequently than twice a day were rarely used for OPAT. In addition, there was low usage of aminoglycosides due to the need for the close monitoring of levels and potential toxicity.

Outcomes

Catheter Complications
The majority of catheter complications occurring in the first period were multifactorial, relating to nursing education, product selection, program development, insertion techniques, and a less comprehensive infection control program.

Hospital Readmissions
A snapshot of FY 2011 data was used to evaluate hospital readmissions. One hundred one patients were reviewed. Of these patients, 9 (9%) were readmitted to the hospital at some point after being discharged from OPAT. Readmission due to complications of OPAT was found in 2 of the 9 patients. One was due to an adverse drug reaction from the antibiotic; the other was due to a possible relapse of a hip osteomyelitis.

Cost Analysis
The OPAT program has resulted in a total savings to the global hospital budget from the deferred BDOC of more than $65 million (Table 3) since 1989. The OPAT program eliminated > 47,000 days of inpatient care. In FY 2009 the program cost the hospital $691.35 for each of the 106 patients enrolled (total cost: $73,283.10). This included all IV supplies, antimicrobials, visiting nurse costs when applicable, as well as nursing and pharmacy time dedicated to training the patient and making therapeutic decisions. Expenses for 3,109 BDOC would have cost about $6,218,000. The outpatient-infusion program saved the hospital nearly $6 million in 2009 alone.

Patient Satisfaction
About 60% of the patients discharged from the OPAT program responded to an evaluation survey. The feedback was overwhelmingly positive with about 99% of respondents reporting satisfaction relating to an improved quality of life. Most of the positive comments were directed toward the outpatient-infusion coordinator for resolving issues, being easily accessible, and acting as a patient advocate.

Discussion

The number and types of reasons for OPAT have grown with the knowledge that it is a safe, cost-effective method for the delivery of parenteral antimicrobials. In the early years of the program, before effective antiretroviral therapy was available, cytomegalovirus retinitis was the second most commonly treated infection of the OPAT program. In recent years, the rise of multidrug-resistant organisms has led to limited oral treatment options for UTIs, which are now the second most commonly treated infection of OPAT. Osteomyelitis clearly remains the top indication for OPAT because it requires long-term therapy. Ceftriaxone remains the drug of choice due to once-daily dosing, spectrum of activity, overall safety, and cost-effectiveness.

Catheter complication rates in the OPAT program were lower than those reported in the literature. According to the 2009 NHSN report, the catheter complication rate in the inpatient long-term care units was 1.0 CRBSI/1,000 catheter days.⁹ Moreover, this program has been instrumental in providing care that otherwise would be administered through the use of home health agencies.

In the private sector, OPAT is frequently contracted to agencies that provide the same type of service to outpatients who have insurance. These agencies charge for the antimicrobials, IV supplies, nursing visits, and laboratory costs for patient-safety monitoring. Use of an agency could raise expenses by a factor of 8-fold or more above the cost of a hospital-based OPAT program, an estimate based on a comparison with a local federally contracted home-infusion agency that provides specialized home-infusion services at a cost.

Although costs related to hospital readmissions were not factored in to the cost savings calculations, the rate of readmission was low in the snapshot analysis that was conducted at the Edward Hines, Jr. VA Hospital. It is believed that this is the result of the close follow-up and continuity of care that the patients in this OPAT program received.

In addition to cost containment, the data reflect the safe, effective care that resulted from treatment outside the hospital setting. One of the key attributes that has made the Edward Hines, Jr. VA Hospital OPAT program unique is that it is recognized in the community as the only VA facility in the area to provide OPAT as an option for the veteran patient. Other VA facilities in the area contract with home-infusion agencies, which are responsible for supplying the antibiotics and nursing care. The Edward Hines, Jr. VA Hospital is the only VA hospital in VISN 12 that has a facility-supported  program that provides all supplies and antimicrobials from the VA—a major contributing factor to the cost savings. Continuity of care is provided to the patient who transitions from inpatient to outpatient status with the same team of providers contributing to the significant patient satisfaction that the program has engendered.

Conclusions

One of the main benefits realized with this transition of antibiotic therapy to the home setting is the avoidance of newly acquired nosocomial infections, including C difficile infection, fungal, and multidrug-resistant bacterial infections. Other benefits include early IV to oral switch in therapy when the patient is deemed a candidate, the ability to go back to work sooner, and the ability to receive treatment in the comfort of the patient’s home. Plans for data collection may include a more in-depth review of repeat admissions due to unresolved infections and the number of patients who are unable to complete OPAT at home.

The Edward Hines, Jr. VA Hospital OPAT program has shown that in a large, federally-funded hospital, OPAT is safe, cost-effective, convenient and leads to increased patient satisfaction in a diverse group of veterans.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Antimicrobial stewardship activities have been in place at the Edward Hines, Jr. VA Hospital in Hines, Illinois, since 1988. Initial activities, including antimicrobial restriction and the start of an outpatient-infusion program justified and led to dedicated funding for hiring the first infectious diseases (ID) clinical pharmacist. This position was initiated in 1992 and has been maintained since then. The committed multidisciplinary team, including ID physicians, ID clinical pharmacists, venous access nurses (VAN), microbiologists, infection control practitioners, and an outpatient-infusion coordinator have led stewardship activities at this VA.

One of the first efforts of the team was the development of the outpatient parenteral antibiotic therapy (OPAT) program.¹ The program began in 1989 and has served more than 1,200 veterans. Outpatient parenteral antibiotic therapy is only one component of the stewardship program, which provides safe, effective, and cost-minimizing care for veterans, and is the focus of this article.

Background

Complex medical care and escalating costs have pushed all but the most seriously ill patients out of the hospital setting for care delivery. The reality is that patients who might have received care for non–life-threatening problems in a hospital bed are now relegated to an outpatient status. Beginning in the 1970s, OPAT has been used to facilitate the cost-effective, safe administration of antibiotics as an  alternative to an extensive, expensive hospital stay.² Initially developed for use in a nonhospital health care setting, the administration of antibiotics under the guidance of a health care provider (HCP) has now been extended to a self-administered infusion program.^3,4 Under the latter, patients and caregivers are educated to safely administer IV antibiotics for extended periods at home.

This program uses elements of both health care–associated OPAT and self-administered OPAT (S-OPAT) to accomplish its goals: (1) safe, effective administration of antibiotic therapy to a variety of patients; (2) reduction in bed days of care (BDOC); (3) reduction of the economic burden to the hospitals’ global budgets; and (4) reduction in the incidence of common nosocomially-acquired infections, including those caused by Clostridium difficile (C difficile), methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococcus.³

The advantages of S-OPAT have been fully realized in a variety of countries, enabling patients to receive necessary therapy in the comfort of their homes and providing them with the ability to lead normal lives without the confinement of a protracted hospital stay.^5-7

Description of OPAT

The outpatient-infusion team provides specialized care for patients in accordance with the OPAT national guidelines from patient screening to program discharge.⁸ The dedicated staff include the OPAT nurse coordinator, VAN, pharmacists, and ID consultants. The VAN places the venous access device (VAD), educates the patient and caregiver in the care and safety of the catheter, aseptic technique, and infusion of the selected antimicrobial agent, and monitors the laboratory work. The VA may contract an outside nursing agency to provide support and reinforcement of IV administration for the patient and caregiver.

The pharmacists oversee the pharmacokinetics and pharmacodynamics of the antimicrobials as well as monitor for any toxicities that could potentially arise during and after therapy. The ID consultants identify the infection, collaborate with the pharmacists to select the most appropriate antimicrobial regimen, and determine the duration of required therapy. The team then regularly monitors the patient in the ID clinic until there is evidence of infection resolution.

Primary care providers who want to enroll patients in the OPAT program place a formal electronic consult to the ID team for antibiotic recommendation, to the outpatient infusion team for assessment of potential outpatient therapy, and to the venous access team for insertion of the VAD. The consults are completed after receiving consent from the patient, developing a patient-centered treatment plan, and determining the patient’s ability to comprehend and adhere to the program requirements. The patient or caregiver must be able to competently demonstrate aseptic technique for IV administration prior to discharge. The pharmacist educates the patient or caregiver about the stability, storage requirements, and potential adverse drug reactions of the antimicrobial.

Eligible patients must have resolved their acute medical problems and require > 1 week of therapy to treat their infection. Patients chosen for OPAT or S-OPAT must have a suitable living environment with access to a refrigerator, a telephone, and transportation to return to the hospital for follow-up. Most patients and caregivers are eager to learn and recognize the advantages of home-based care.

The VANs are a central component of the program. They maintain open communication with the patient during the entire treatment course and help triage issues to the appropriate HCP. In addition, they are responsible for submitting catheter-related bloodstream infection (CRBSI) information to the hospital administration, which then gets reported to the National Healthcare Safety Network (NHSN).

Not all patients qualify for S-OPAT. Other options include returning to the hospital daily for infusions, being discharged to a skilled care facility, or arranging for a VA-contracted agency to provide nursing care while the VA provides all required medications and supplies.

On completion of OPAT, patients are asked to evaluate the program. The anonymous survey includes open-ended questions for patients to better express their experience with the program and staff. Patients are given the opportunity to suggest improvements and provide overall feedback. The team for quality assurance and patient satisfaction reviews every survey, which is used as a tool to improve team functions.

Data are also collected in the OPAT program to measure efficacy and monitor for safety. Data obtained from the start of the program in February 1989 through fiscal year (FY) 2011 include the number of patients who were candidates for outpatient-infusion therapy, type of infection, antibiotic selection, CRBSIs, hospital readmission rates, cost savings, and patient satisfaction.

Results

The Edward Hines, Jr. VA Hospital has a proven, successful OPAT program. Most of the patients in the program during the study period were men, which reflects a typical VA population. Patients with spinal cord injury comprised a large portion of those treated. Table 1 provides the number of patients treated and lists the frequency of infections. The data are divided into 3 periods. From 1989 to September 30, 1995, OPAT used other VADs before using peripherally inserted central catheters. During the second period (October 1, 1995-September 30, 2003), patients remained with a VAD for an average of 48.6 days; whereas in Period 3 (October 1, 2003-September 30, 2011), the patients had a VAD average of 34.7 days. Consequently, with fewer VAD days, there was a decreased incidence of complications (Table 2).

Osteomyelitis accounted for the majority of the infections (40.6%), which required ≥ 6 weeks of therapy. Complicated urinary tract infection (UTI), including pyelonephritis, perinephric abscess, and complicated cystitis, was the next most common (14.9%). Bacteremia was the third most common infection (7.9%), whereas abscesses of a diverse variety affected 6.2%, including brain, liver, intra-abdominal, soft tissue, and epidural abscesses. Endocarditis and septic arthritis accounted for 4.4% and 4.7%, respectively, of infected patients.

Three periods of the OPAT program were selected at random (1996, 2003, and 2011) to examine trends in antimicrobial selection. Overall, ceftriaxone was the most commonly used antibiotic (35%). Vancomycin was the next most commonly prescribed (27%). Since its 2001 FDA approval, ertapenem has become the third most commonly prescribed antibiotic for the OPAT program (11%).  As expected, antimicrobial agents that have to be dosed more frequently than twice a day were rarely used for OPAT. In addition, there was low usage of aminoglycosides due to the need for the close monitoring of levels and potential toxicity.

Outcomes

Catheter Complications
The majority of catheter complications occurring in the first period were multifactorial, relating to nursing education, product selection, program development, insertion techniques, and a less comprehensive infection control program.

Hospital Readmissions
A snapshot of FY 2011 data was used to evaluate hospital readmissions. One hundred one patients were reviewed. Of these patients, 9 (9%) were readmitted to the hospital at some point after being discharged from OPAT. Readmission due to complications of OPAT was found in 2 of the 9 patients. One was due to an adverse drug reaction from the antibiotic; the other was due to a possible relapse of a hip osteomyelitis.

Cost Analysis
The OPAT program has resulted in a total savings to the global hospital budget from the deferred BDOC of more than $65 million (Table 3) since 1989. The OPAT program eliminated > 47,000 days of inpatient care. In FY 2009 the program cost the hospital $691.35 for each of the 106 patients enrolled (total cost: $73,283.10). This included all IV supplies, antimicrobials, visiting nurse costs when applicable, as well as nursing and pharmacy time dedicated to training the patient and making therapeutic decisions. Expenses for 3,109 BDOC would have cost about $6,218,000. The outpatient-infusion program saved the hospital nearly $6 million in 2009 alone.

Patient Satisfaction
About 60% of the patients discharged from the OPAT program responded to an evaluation survey. The feedback was overwhelmingly positive with about 99% of respondents reporting satisfaction relating to an improved quality of life. Most of the positive comments were directed toward the outpatient-infusion coordinator for resolving issues, being easily accessible, and acting as a patient advocate.

Discussion

The number and types of reasons for OPAT have grown with the knowledge that it is a safe, cost-effective method for the delivery of parenteral antimicrobials. In the early years of the program, before effective antiretroviral therapy was available, cytomegalovirus retinitis was the second most commonly treated infection of the OPAT program. In recent years, the rise of multidrug-resistant organisms has led to limited oral treatment options for UTIs, which are now the second most commonly treated infection of OPAT. Osteomyelitis clearly remains the top indication for OPAT because it requires long-term therapy. Ceftriaxone remains the drug of choice due to once-daily dosing, spectrum of activity, overall safety, and cost-effectiveness.

Catheter complication rates in the OPAT program were lower than those reported in the literature. According to the 2009 NHSN report, the catheter complication rate in the inpatient long-term care units was 1.0 CRBSI/1,000 catheter days.⁹ Moreover, this program has been instrumental in providing care that otherwise would be administered through the use of home health agencies.

In the private sector, OPAT is frequently contracted to agencies that provide the same type of service to outpatients who have insurance. These agencies charge for the antimicrobials, IV supplies, nursing visits, and laboratory costs for patient-safety monitoring. Use of an agency could raise expenses by a factor of 8-fold or more above the cost of a hospital-based OPAT program, an estimate based on a comparison with a local federally contracted home-infusion agency that provides specialized home-infusion services at a cost.

Although costs related to hospital readmissions were not factored in to the cost savings calculations, the rate of readmission was low in the snapshot analysis that was conducted at the Edward Hines, Jr. VA Hospital. It is believed that this is the result of the close follow-up and continuity of care that the patients in this OPAT program received.

In addition to cost containment, the data reflect the safe, effective care that resulted from treatment outside the hospital setting. One of the key attributes that has made the Edward Hines, Jr. VA Hospital OPAT program unique is that it is recognized in the community as the only VA facility in the area to provide OPAT as an option for the veteran patient. Other VA facilities in the area contract with home-infusion agencies, which are responsible for supplying the antibiotics and nursing care. The Edward Hines, Jr. VA Hospital is the only VA hospital in VISN 12 that has a facility-supported  program that provides all supplies and antimicrobials from the VA—a major contributing factor to the cost savings. Continuity of care is provided to the patient who transitions from inpatient to outpatient status with the same team of providers contributing to the significant patient satisfaction that the program has engendered.

Conclusions

One of the main benefits realized with this transition of antibiotic therapy to the home setting is the avoidance of newly acquired nosocomial infections, including C difficile infection, fungal, and multidrug-resistant bacterial infections. Other benefits include early IV to oral switch in therapy when the patient is deemed a candidate, the ability to go back to work sooner, and the ability to receive treatment in the comfort of the patient’s home. Plans for data collection may include a more in-depth review of repeat admissions due to unresolved infections and the number of patients who are unable to complete OPAT at home.

The Edward Hines, Jr. VA Hospital OPAT program has shown that in a large, federally-funded hospital, OPAT is safe, cost-effective, convenient and leads to increased patient satisfaction in a diverse group of veterans.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

A history of surgery with anesthesia may raise the risk of dementia for some patients, particularly those who have been repeatedly exposed to general anesthesia (GA), say researchers from China Medical University in Taichung, Taiwan.

Their study of 26,725 patients, including 5,345 newly diagnosed with dementia and a 21,380 person control group of patients without dementia, evaluated the effects of 3 types of GA: endotracheal tube intubation (ETGA); intravenous injection (IVGA) or intramuscular injection (IMGA); and heavy sedation. The patients were also divided into subgroups: a group of high-risk patients who underwent cardiac, orthopedic, or emergency surgery; moderate-risk patients who underwent general surgery, neurosurgery, gynecologic surgery, cosmetic, rectal, thoracic, or digestive surgery; and patients who underwent other surgeries, such as dental. Patients who did not receive anesthesia were grouped as with or without surgery.

Of the patients with dementia, 32% were exposed to ETGA and 9.3% were exposed to IVGA or IMGA. Exposure to both types of anesthesia was higher in the patients with dementia. Nearly 0.5% of the total sample was exposed to heavy sedation.

The patients who were exposed to ETGA, IVGA, or IMGA had a higher risk of dementia after the researchers adjusted for age, sex, depression, diabetes, hypertension, stroke, and atherosclerosis, all of which were also independent, significant risk factors for dementia. Patients who had been exposed 2 or more times to GA had the highest risk of developing dementia. Heavy sedation was not associated with increased risk.

The relationship between surgery with GA and dementia is complex, the researchers say, because patients who receive anesthesia all undergo surgery. Hospitalization has been associated with the development of dementia, with multiple potential mechanisms. Surgery and GA may play individual or synergistic roles in the development of dementia, with the risk heightened by a patient’s comorbidities.

Further, the researchers say, the inhalation of general anesthetics may have neurotoxic effects that correlate with dementia. The major pathologic hallmark of Alzheimer dementia (AD) is excessive accumulation of amyloid beta (Aβ) protein in the brain. Exposure to inhalational general anesthetics may promote AD processes by inducing apoptosis and Aβ generation.

If surgery with general anesthesia is unavoidable, the researchers advise using less-toxic anesthetics, particularly in elderly patients with systemic vascular comorbidities.

Source
Chen C-W, Lin C-C, Chen K-B, Kuo Y-C, Li C-Y, Chung C-J. Alzheimers Dement. 2014;10(2):196-204.
doi: 10.1016/j.jalz.2013.05.1766.

A history of surgery with anesthesia may raise the risk of dementia for some patients, particularly those who have been repeatedly exposed to general anesthesia (GA), say researchers from China Medical University in Taichung, Taiwan.

Their study of 26,725 patients, including 5,345 newly diagnosed with dementia and a 21,380 person control group of patients without dementia, evaluated the effects of 3 types of GA: endotracheal tube intubation (ETGA); intravenous injection (IVGA) or intramuscular injection (IMGA); and heavy sedation. The patients were also divided into subgroups: a group of high-risk patients who underwent cardiac, orthopedic, or emergency surgery; moderate-risk patients who underwent general surgery, neurosurgery, gynecologic surgery, cosmetic, rectal, thoracic, or digestive surgery; and patients who underwent other surgeries, such as dental. Patients who did not receive anesthesia were grouped as with or without surgery.

Of the patients with dementia, 32% were exposed to ETGA and 9.3% were exposed to IVGA or IMGA. Exposure to both types of anesthesia was higher in the patients with dementia. Nearly 0.5% of the total sample was exposed to heavy sedation.

The patients who were exposed to ETGA, IVGA, or IMGA had a higher risk of dementia after the researchers adjusted for age, sex, depression, diabetes, hypertension, stroke, and atherosclerosis, all of which were also independent, significant risk factors for dementia. Patients who had been exposed 2 or more times to GA had the highest risk of developing dementia. Heavy sedation was not associated with increased risk.

The relationship between surgery with GA and dementia is complex, the researchers say, because patients who receive anesthesia all undergo surgery. Hospitalization has been associated with the development of dementia, with multiple potential mechanisms. Surgery and GA may play individual or synergistic roles in the development of dementia, with the risk heightened by a patient’s comorbidities.

Further, the researchers say, the inhalation of general anesthetics may have neurotoxic effects that correlate with dementia. The major pathologic hallmark of Alzheimer dementia (AD) is excessive accumulation of amyloid beta (Aβ) protein in the brain. Exposure to inhalational general anesthetics may promote AD processes by inducing apoptosis and Aβ generation.

If surgery with general anesthesia is unavoidable, the researchers advise using less-toxic anesthetics, particularly in elderly patients with systemic vascular comorbidities.

Source
Chen C-W, Lin C-C, Chen K-B, Kuo Y-C, Li C-Y, Chung C-J. Alzheimers Dement. 2014;10(2):196-204.
doi: 10.1016/j.jalz.2013.05.1766.

A history of surgery with anesthesia may raise the risk of dementia for some patients, particularly those who have been repeatedly exposed to general anesthesia (GA), say researchers from China Medical University in Taichung, Taiwan.

Their study of 26,725 patients, including 5,345 newly diagnosed with dementia and a 21,380 person control group of patients without dementia, evaluated the effects of 3 types of GA: endotracheal tube intubation (ETGA); intravenous injection (IVGA) or intramuscular injection (IMGA); and heavy sedation. The patients were also divided into subgroups: a group of high-risk patients who underwent cardiac, orthopedic, or emergency surgery; moderate-risk patients who underwent general surgery, neurosurgery, gynecologic surgery, cosmetic, rectal, thoracic, or digestive surgery; and patients who underwent other surgeries, such as dental. Patients who did not receive anesthesia were grouped as with or without surgery.

Of the patients with dementia, 32% were exposed to ETGA and 9.3% were exposed to IVGA or IMGA. Exposure to both types of anesthesia was higher in the patients with dementia. Nearly 0.5% of the total sample was exposed to heavy sedation.

The patients who were exposed to ETGA, IVGA, or IMGA had a higher risk of dementia after the researchers adjusted for age, sex, depression, diabetes, hypertension, stroke, and atherosclerosis, all of which were also independent, significant risk factors for dementia. Patients who had been exposed 2 or more times to GA had the highest risk of developing dementia. Heavy sedation was not associated with increased risk.

The relationship between surgery with GA and dementia is complex, the researchers say, because patients who receive anesthesia all undergo surgery. Hospitalization has been associated with the development of dementia, with multiple potential mechanisms. Surgery and GA may play individual or synergistic roles in the development of dementia, with the risk heightened by a patient’s comorbidities.

Further, the researchers say, the inhalation of general anesthetics may have neurotoxic effects that correlate with dementia. The major pathologic hallmark of Alzheimer dementia (AD) is excessive accumulation of amyloid beta (Aβ) protein in the brain. Exposure to inhalational general anesthetics may promote AD processes by inducing apoptosis and Aβ generation.

If surgery with general anesthesia is unavoidable, the researchers advise using less-toxic anesthetics, particularly in elderly patients with systemic vascular comorbidities.

Source
Chen C-W, Lin C-C, Chen K-B, Kuo Y-C, Li C-Y, Chung C-J. Alzheimers Dement. 2014;10(2):196-204.
doi: 10.1016/j.jalz.2013.05.1766.

For many years, articles about autism cited prevalence rates of approximately 7 in 10,000.¹ Over the past few years, however, there appears to have been an explosion in the rate at which autism is diagnosed: More recent estimates range from about 30 in 10,000² to one in 68.³ References to an autism epidemic appear to have originated in a 2002 California legislative report suggesting a 273% increase in autism from 1987 to 1998.⁴

Concerns about rising rates of autism, however, are not new. In 1943, Leo Kanner, MD, a psychiatrist and pioneer in the study of autism, published a paper titled, “Autistic disturbances of affective contact.”⁵ The result? “Almost overnight, the country seemed to be populated by a multitude of autistic children,” he later observed.⁶

To what should we attribute the current rise in reported autism rates? Even a casual review of the autism literature suggests a number of potential causes that may account for at least a portion of the recent increase.

We know more about the disorder

In his paper, Kanner described the “peculiarities” of 11 children whom he had cared for.⁵ While several had been diagnosed with mental retardation, childhood schizophrenia, or both, what stood out to Kanner was an “autistic aloneness” evident from the beginning of life. This was in contrast to childhood schizophrenia, in which a child experienced a departure from previously normal interrelations. His insight contributed to our understanding of what is now recognized as autism spectrum disorder (ASD).

Also in 1943, Hans Asperger, MD, was studying families with children exhibiting behaviors similar to those described by Kanner. The following year, Asperger published an article (in German) describing these children. Unfortunately, this paper—titled “Autistic psychopathy in childhood”⁷—was not translated into English until the early 1990s.⁸

Since Kanner and Asperger first called attention to the disorder, there have been numerous changes in societal and medical understanding of autism. Bruno Bettelheim, PhD, an Austrian-born child psychologist with a particular interest in emotionally disturbed children, theorized that poor maternal bonding and lack of maternal affection were responsible for autistic characteristics.⁹ Bernard Rimland, PhD, a psychologist and the father of an autistic child, argued for a biological basis of the disorder.¹⁰ Rimland’s theory of autism as a neurodevelopmental disorder with an unidentified organic etiology is most consistent with current medical opinion.

Definitions and diagnostic criteria have evolved

The first edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in 1952.¹¹ Although it was nearly a decade after Dr. Kanner clearly described autism as an entity separate from childhood schizophrenia, the word autism was used in this edition only once—to describe psychotic reactions associated with schizophrenia. Similarly, autism was referred to only in relation to childhood schizophrenia in the DSMII,¹² published in 1968.

DSM-III adds diagnostic criteria. In DSM-III (1980),13 specific diagnostic criteria for infantile autism and pervasive developmental disorder (PDD) appeared for the first time. Both diagnoses were clearly contrasted with a diagnosis of schizophrenia, and were used to identify children who exhibited a pervasive lack of responsiveness to others.

The DSM-III-Revised (R) (1987)14 added a classification scheme more consistent with the current standard. It included: 1) qualitative impairment in reciprocal social interaction; 2) qualitative impairment in communication and imaginative activity; and 3) restricted activity/interests.

PDD Not Otherwise Specified was also included, and served to identify those who had qualitative impairments in social interaction and communication skills but did not meet the full criteria for autism disorder or PDD.

The publication of DSM-IV (1994)¹⁵ brought another change: Specific criteria were outlined for the diagnoses of Asperger syndrome, Rett syndrome, and childhood disintegrative disorders; in the DSM-IV-Text Revision (TR) (2000),16 this structure remained relatively stable.

DSM-5 (2013) took another step, consolidating these various disorders into a single, unifying diagnosis of ASD.¹⁷ Significant controversy surrounded this change, with some viewing it as an oversimplification that does not accurately reflect important distinctions among divergent disorders18 and others arguing that it will result in unrecognized cases and exclusion of affected individuals.¹⁹ Notably, a recent study using concurrent DSM-IV and DSM-5 criteria to diagnose autism and PDD in more than 4000 children documented a high level of agreement between them.²⁰

Diagnostic tools have improved

As the number of children diagnosed with autism has increased, so have efforts to more accurately diagnose autism as a distinct disorder.

A blood test to identify differences in gene expression between children with and without ASD has shown initial promise—particularly in males. In the 1960s, guidelines for diagnosing autism focused primarily on Kanner’s original descriptive criteria. Even in the 1980s, after DSM-III criteria identified autism as a distinct disorder, children were being evaluated with generalized developmental screening tools focused on behaviors characteristic of a severe mental handicap, without differentiating between autistic and nonautistic children.

Early autism-specific observational and structured interview tools (eg, Childhood Autism Rating Scale,²¹ Autism Diagnostic Interview [ADI],²² and Autistic Diagnostic Observation Schedule)²³ emerged from a need for standardized diagnostic instruments that were comparable and reproducible.²⁴ But because these tools were highly specific and initially studied in research settings with high-risk populations, they lacked the sensitivity to identify children at risk in the general population, particularly those with milder symptoms.

As the diagnosis of autism became more standardized following publication of the DSM III-R in 1987, developmental specialists were able to construct increasingly sensitive evaluation tools. The ADI was revised²⁵ to facilitate earlier and more efficient diagnosis, allowing for assessment of children as young as 19 months of age. The Checklist for Autism in Toddlers (CHAT)²⁶ and subsequent modification (M-CHAT)²⁷ were among the earliest and most effective screening tools, appropriate for use in children as young as 16 months old.

Tools that followed the original CHAT (eg, the Autism Spectrum Screening Questionnaire [ASSQ]²⁸) were adapted to better identify high-functioning children with Asperger syndrome, as well as those with autism.

Another revision of the M-CHAT—the M-CHAT-R/F (Revised with Follow-up) was validated earlier this year. In a study involving 16,000 children, 95% of those who had positive tests were found to have some form of developmental delay and almost half (47%) received an ASD diagnosis.²⁹

Other diagnostic aids are being explored as a means of promoting earlier identification of ASD. For example, a blood test to identify differences in gene expression between children with and without ASD³⁰ has shown initial promise, particularly in males. This test is licensed by SynapDx (Lexington, Mass) and a clinical trial to evaluate it has begun.

Recent studies suggest that advanced paternal age can increase the risk of autism.Results of another study demonstrating normalization of brain activity in autistic children after they’ve undergone intensive treatment³¹ raise the possibility of using cortical activation as measured by electroencephalography as an early biomarker for autism.

Treatment options, advocacy affect rate of diagnosis

Improvements in diagnosis and targeted identification of potentially treatable symptoms³² led to the development of new treatment options. And greater use of day care and preschool programs prompted networking among parents, who touted the benefits of early evaluation, diagnosis, and treatment. Earlier screening, not surprisingly, led to an increase in the target population.

Local as well as national advocacy groups, led primarily by parents, have become powerful voices for improvements in services offered to children with autism. And research studies with varying degrees of sophistication continue to be published, further fueling the demand for school systems to provide supportive learning environments as required by the Individuals with Disabilities Education Act, initially enacted in 1975 and amended in 2004.³³

Federal and state funds in the form of Medicaid waivers are available to provide long-term care services in home and community settings, while private insurers typically pay for associated treatment modalities for those with an autism diagnosis, including physical, occupational, and speech therapy, among other services.

Finally, politicians and celebrities with personal connections to autism have joined the effort to increase awareness and improve the quality and availability of services—further assuring that autism is recognized as a legitimate, definable, and treatable disorder.

As an autism diagnosis has become more socially acceptable, it has at times replaced diagnoses of learning disability and mental retardation, a trend known as “diagnostic substitution.”³⁴ Indeed, having a child with an ASD diagnosis often makes it possible for parents to secure services that might otherwise be unavailable to them.

Is the incidence of autism linked to the environment?

Numerous environmental, nutritional, and pharmaceutical changes have been cited as reasons for what is perceived as an increasing incidence of autism in recent years. For example, some contend that greater use of food preservatives and greater exposure of young children to environmental toxins are contributing factors.³⁵

Thimerosal. Perhaps most notable is the assertion—since disproven—that thimerosal, a substance previously used in the manufacture of several childhood vaccines, was a leading cause of autism.^36,37 In fact, one study documented an increase in autism after thimerosal had been discontinued.³⁸ (For more on the thimerosal controversy, see “Autism: 5 misconceptions that can complicate care”.)

Autism comorbidity. As autism is frequently comorbid with other developmental disabilities, advances in medical technology that have led to a decline in neonatal death and overall mortality among the disabled may mean more survivors are subsequently diagnosed with an autism comorbidity.

Biological factors. Recent studies suggest that advanced paternal age can increase the risk of autism.³⁹ Twin studies suggest moderate genetic heritability, along with a substantial environmental contribution to the development of autism.⁴⁰ And new research suggests that maternal stressors during pregnancy—eg, trauma, illness, or substance abuse—may increase a child’s risk of developing autism, among other psychiatric disorders.⁴¹

The important role you play in the diagnosis of autism

It is clear that autism is more common than previously thought³ and that various factors are at work. Ensuring that children are promptly and properly evaluated begins when primary care physicians take parents’ concerns seriously and keep an eye out for common symptoms and characteristic developmental delays that may be evident even in the first year of life.

If symptoms are not severe enough to be detected in the child’s first several years, the next likely presentation will be when a parent gets a call from school suggesting that their child be tested for autism. While this delayed presentation suggests a higher level of functioning, a full evaluation, including the use of questionnaires such as the Social Responsiveness Scale⁴² and ASSQ,²⁸ and appropriate referrals are still vital.

Puberty is another time when characteristics suggestive of autism that escaped earlier detection may be noted, and vague behavioral issues or concerns about intellectual impairment may become sufficiently troublesome to prompt a thorough evaluation. While behavioral therapy can be very helpful in such cases, medical therapy directed at co-occurring conditions (ie, a mood or anxiety disorder, including obsessive-compulsive disorder) may also provide significant benefit.

Puberty is another time when characteristics suggestive of autism that escaped earlier detection may be noted. Whatever the age of the child, his or her parents should be counseled as to the general nature of autism, reassured of the availability of treatment options and given the appropriate referrals, and encouraged to learn more by availing themselves of resources (TABLE) and support groups. A consumer update from the US Food and Drug Administration titled “Beware of false or misleading claims for treating autism” (http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm394757.htm) will be helpful for many parents, as well.

CORRESPONDENCE
Robert G. Zylstra, EdD, LCSW, Department of Family Medicine, The University of Tennessee College of Medicine, 110 East Third Street, Chattanooga, TN 37403; [email protected]

For many years, articles about autism cited prevalence rates of approximately 7 in 10,000.¹ Over the past few years, however, there appears to have been an explosion in the rate at which autism is diagnosed: More recent estimates range from about 30 in 10,000² to one in 68.³ References to an autism epidemic appear to have originated in a 2002 California legislative report suggesting a 273% increase in autism from 1987 to 1998.⁴

Concerns about rising rates of autism, however, are not new. In 1943, Leo Kanner, MD, a psychiatrist and pioneer in the study of autism, published a paper titled, “Autistic disturbances of affective contact.”⁵ The result? “Almost overnight, the country seemed to be populated by a multitude of autistic children,” he later observed.⁶

To what should we attribute the current rise in reported autism rates? Even a casual review of the autism literature suggests a number of potential causes that may account for at least a portion of the recent increase.

We know more about the disorder

In his paper, Kanner described the “peculiarities” of 11 children whom he had cared for.⁵ While several had been diagnosed with mental retardation, childhood schizophrenia, or both, what stood out to Kanner was an “autistic aloneness” evident from the beginning of life. This was in contrast to childhood schizophrenia, in which a child experienced a departure from previously normal interrelations. His insight contributed to our understanding of what is now recognized as autism spectrum disorder (ASD).

Also in 1943, Hans Asperger, MD, was studying families with children exhibiting behaviors similar to those described by Kanner. The following year, Asperger published an article (in German) describing these children. Unfortunately, this paper—titled “Autistic psychopathy in childhood”⁷—was not translated into English until the early 1990s.⁸

Since Kanner and Asperger first called attention to the disorder, there have been numerous changes in societal and medical understanding of autism. Bruno Bettelheim, PhD, an Austrian-born child psychologist with a particular interest in emotionally disturbed children, theorized that poor maternal bonding and lack of maternal affection were responsible for autistic characteristics.⁹ Bernard Rimland, PhD, a psychologist and the father of an autistic child, argued for a biological basis of the disorder.¹⁰ Rimland’s theory of autism as a neurodevelopmental disorder with an unidentified organic etiology is most consistent with current medical opinion.

Definitions and diagnostic criteria have evolved

The first edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in 1952.¹¹ Although it was nearly a decade after Dr. Kanner clearly described autism as an entity separate from childhood schizophrenia, the word autism was used in this edition only once—to describe psychotic reactions associated with schizophrenia. Similarly, autism was referred to only in relation to childhood schizophrenia in the DSMII,¹² published in 1968.

DSM-III adds diagnostic criteria. In DSM-III (1980),13 specific diagnostic criteria for infantile autism and pervasive developmental disorder (PDD) appeared for the first time. Both diagnoses were clearly contrasted with a diagnosis of schizophrenia, and were used to identify children who exhibited a pervasive lack of responsiveness to others.

The DSM-III-Revised (R) (1987)14 added a classification scheme more consistent with the current standard. It included: 1) qualitative impairment in reciprocal social interaction; 2) qualitative impairment in communication and imaginative activity; and 3) restricted activity/interests.

PDD Not Otherwise Specified was also included, and served to identify those who had qualitative impairments in social interaction and communication skills but did not meet the full criteria for autism disorder or PDD.

The publication of DSM-IV (1994)¹⁵ brought another change: Specific criteria were outlined for the diagnoses of Asperger syndrome, Rett syndrome, and childhood disintegrative disorders; in the DSM-IV-Text Revision (TR) (2000),16 this structure remained relatively stable.

DSM-5 (2013) took another step, consolidating these various disorders into a single, unifying diagnosis of ASD.¹⁷ Significant controversy surrounded this change, with some viewing it as an oversimplification that does not accurately reflect important distinctions among divergent disorders18 and others arguing that it will result in unrecognized cases and exclusion of affected individuals.¹⁹ Notably, a recent study using concurrent DSM-IV and DSM-5 criteria to diagnose autism and PDD in more than 4000 children documented a high level of agreement between them.²⁰

Diagnostic tools have improved

As the number of children diagnosed with autism has increased, so have efforts to more accurately diagnose autism as a distinct disorder.

A blood test to identify differences in gene expression between children with and without ASD has shown initial promise—particularly in males. In the 1960s, guidelines for diagnosing autism focused primarily on Kanner’s original descriptive criteria. Even in the 1980s, after DSM-III criteria identified autism as a distinct disorder, children were being evaluated with generalized developmental screening tools focused on behaviors characteristic of a severe mental handicap, without differentiating between autistic and nonautistic children.

Early autism-specific observational and structured interview tools (eg, Childhood Autism Rating Scale,²¹ Autism Diagnostic Interview [ADI],²² and Autistic Diagnostic Observation Schedule)²³ emerged from a need for standardized diagnostic instruments that were comparable and reproducible.²⁴ But because these tools were highly specific and initially studied in research settings with high-risk populations, they lacked the sensitivity to identify children at risk in the general population, particularly those with milder symptoms.

As the diagnosis of autism became more standardized following publication of the DSM III-R in 1987, developmental specialists were able to construct increasingly sensitive evaluation tools. The ADI was revised²⁵ to facilitate earlier and more efficient diagnosis, allowing for assessment of children as young as 19 months of age. The Checklist for Autism in Toddlers (CHAT)²⁶ and subsequent modification (M-CHAT)²⁷ were among the earliest and most effective screening tools, appropriate for use in children as young as 16 months old.

Tools that followed the original CHAT (eg, the Autism Spectrum Screening Questionnaire [ASSQ]²⁸) were adapted to better identify high-functioning children with Asperger syndrome, as well as those with autism.

Another revision of the M-CHAT—the M-CHAT-R/F (Revised with Follow-up) was validated earlier this year. In a study involving 16,000 children, 95% of those who had positive tests were found to have some form of developmental delay and almost half (47%) received an ASD diagnosis.²⁹

Other diagnostic aids are being explored as a means of promoting earlier identification of ASD. For example, a blood test to identify differences in gene expression between children with and without ASD³⁰ has shown initial promise, particularly in males. This test is licensed by SynapDx (Lexington, Mass) and a clinical trial to evaluate it has begun.

Recent studies suggest that advanced paternal age can increase the risk of autism.Results of another study demonstrating normalization of brain activity in autistic children after they’ve undergone intensive treatment³¹ raise the possibility of using cortical activation as measured by electroencephalography as an early biomarker for autism.

Treatment options, advocacy affect rate of diagnosis

Improvements in diagnosis and targeted identification of potentially treatable symptoms³² led to the development of new treatment options. And greater use of day care and preschool programs prompted networking among parents, who touted the benefits of early evaluation, diagnosis, and treatment. Earlier screening, not surprisingly, led to an increase in the target population.

Local as well as national advocacy groups, led primarily by parents, have become powerful voices for improvements in services offered to children with autism. And research studies with varying degrees of sophistication continue to be published, further fueling the demand for school systems to provide supportive learning environments as required by the Individuals with Disabilities Education Act, initially enacted in 1975 and amended in 2004.³³

Federal and state funds in the form of Medicaid waivers are available to provide long-term care services in home and community settings, while private insurers typically pay for associated treatment modalities for those with an autism diagnosis, including physical, occupational, and speech therapy, among other services.

Finally, politicians and celebrities with personal connections to autism have joined the effort to increase awareness and improve the quality and availability of services—further assuring that autism is recognized as a legitimate, definable, and treatable disorder.

As an autism diagnosis has become more socially acceptable, it has at times replaced diagnoses of learning disability and mental retardation, a trend known as “diagnostic substitution.”³⁴ Indeed, having a child with an ASD diagnosis often makes it possible for parents to secure services that might otherwise be unavailable to them.

Is the incidence of autism linked to the environment?

Numerous environmental, nutritional, and pharmaceutical changes have been cited as reasons for what is perceived as an increasing incidence of autism in recent years. For example, some contend that greater use of food preservatives and greater exposure of young children to environmental toxins are contributing factors.³⁵

Thimerosal. Perhaps most notable is the assertion—since disproven—that thimerosal, a substance previously used in the manufacture of several childhood vaccines, was a leading cause of autism.^36,37 In fact, one study documented an increase in autism after thimerosal had been discontinued.³⁸ (For more on the thimerosal controversy, see “Autism: 5 misconceptions that can complicate care”.)

Autism comorbidity. As autism is frequently comorbid with other developmental disabilities, advances in medical technology that have led to a decline in neonatal death and overall mortality among the disabled may mean more survivors are subsequently diagnosed with an autism comorbidity.

Biological factors. Recent studies suggest that advanced paternal age can increase the risk of autism.³⁹ Twin studies suggest moderate genetic heritability, along with a substantial environmental contribution to the development of autism.⁴⁰ And new research suggests that maternal stressors during pregnancy—eg, trauma, illness, or substance abuse—may increase a child’s risk of developing autism, among other psychiatric disorders.⁴¹

The important role you play in the diagnosis of autism

It is clear that autism is more common than previously thought³ and that various factors are at work. Ensuring that children are promptly and properly evaluated begins when primary care physicians take parents’ concerns seriously and keep an eye out for common symptoms and characteristic developmental delays that may be evident even in the first year of life.

If symptoms are not severe enough to be detected in the child’s first several years, the next likely presentation will be when a parent gets a call from school suggesting that their child be tested for autism. While this delayed presentation suggests a higher level of functioning, a full evaluation, including the use of questionnaires such as the Social Responsiveness Scale⁴² and ASSQ,²⁸ and appropriate referrals are still vital.

Puberty is another time when characteristics suggestive of autism that escaped earlier detection may be noted, and vague behavioral issues or concerns about intellectual impairment may become sufficiently troublesome to prompt a thorough evaluation. While behavioral therapy can be very helpful in such cases, medical therapy directed at co-occurring conditions (ie, a mood or anxiety disorder, including obsessive-compulsive disorder) may also provide significant benefit.

Puberty is another time when characteristics suggestive of autism that escaped earlier detection may be noted. Whatever the age of the child, his or her parents should be counseled as to the general nature of autism, reassured of the availability of treatment options and given the appropriate referrals, and encouraged to learn more by availing themselves of resources (TABLE) and support groups. A consumer update from the US Food and Drug Administration titled “Beware of false or misleading claims for treating autism” (http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm394757.htm) will be helpful for many parents, as well.

CORRESPONDENCE
Robert G. Zylstra, EdD, LCSW, Department of Family Medicine, The University of Tennessee College of Medicine, 110 East Third Street, Chattanooga, TN 37403; [email protected]

For many years, articles about autism cited prevalence rates of approximately 7 in 10,000.¹ Over the past few years, however, there appears to have been an explosion in the rate at which autism is diagnosed: More recent estimates range from about 30 in 10,000² to one in 68.³ References to an autism epidemic appear to have originated in a 2002 California legislative report suggesting a 273% increase in autism from 1987 to 1998.⁴

Concerns about rising rates of autism, however, are not new. In 1943, Leo Kanner, MD, a psychiatrist and pioneer in the study of autism, published a paper titled, “Autistic disturbances of affective contact.”⁵ The result? “Almost overnight, the country seemed to be populated by a multitude of autistic children,” he later observed.⁶

To what should we attribute the current rise in reported autism rates? Even a casual review of the autism literature suggests a number of potential causes that may account for at least a portion of the recent increase.

We know more about the disorder

In his paper, Kanner described the “peculiarities” of 11 children whom he had cared for.⁵ While several had been diagnosed with mental retardation, childhood schizophrenia, or both, what stood out to Kanner was an “autistic aloneness” evident from the beginning of life. This was in contrast to childhood schizophrenia, in which a child experienced a departure from previously normal interrelations. His insight contributed to our understanding of what is now recognized as autism spectrum disorder (ASD).

Also in 1943, Hans Asperger, MD, was studying families with children exhibiting behaviors similar to those described by Kanner. The following year, Asperger published an article (in German) describing these children. Unfortunately, this paper—titled “Autistic psychopathy in childhood”⁷—was not translated into English until the early 1990s.⁸

Since Kanner and Asperger first called attention to the disorder, there have been numerous changes in societal and medical understanding of autism. Bruno Bettelheim, PhD, an Austrian-born child psychologist with a particular interest in emotionally disturbed children, theorized that poor maternal bonding and lack of maternal affection were responsible for autistic characteristics.⁹ Bernard Rimland, PhD, a psychologist and the father of an autistic child, argued for a biological basis of the disorder.¹⁰ Rimland’s theory of autism as a neurodevelopmental disorder with an unidentified organic etiology is most consistent with current medical opinion.

Definitions and diagnostic criteria have evolved

The first edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in 1952.¹¹ Although it was nearly a decade after Dr. Kanner clearly described autism as an entity separate from childhood schizophrenia, the word autism was used in this edition only once—to describe psychotic reactions associated with schizophrenia. Similarly, autism was referred to only in relation to childhood schizophrenia in the DSMII,¹² published in 1968.

DSM-III adds diagnostic criteria. In DSM-III (1980),13 specific diagnostic criteria for infantile autism and pervasive developmental disorder (PDD) appeared for the first time. Both diagnoses were clearly contrasted with a diagnosis of schizophrenia, and were used to identify children who exhibited a pervasive lack of responsiveness to others.

The DSM-III-Revised (R) (1987)14 added a classification scheme more consistent with the current standard. It included: 1) qualitative impairment in reciprocal social interaction; 2) qualitative impairment in communication and imaginative activity; and 3) restricted activity/interests.

PDD Not Otherwise Specified was also included, and served to identify those who had qualitative impairments in social interaction and communication skills but did not meet the full criteria for autism disorder or PDD.

The publication of DSM-IV (1994)¹⁵ brought another change: Specific criteria were outlined for the diagnoses of Asperger syndrome, Rett syndrome, and childhood disintegrative disorders; in the DSM-IV-Text Revision (TR) (2000),16 this structure remained relatively stable.

DSM-5 (2013) took another step, consolidating these various disorders into a single, unifying diagnosis of ASD.¹⁷ Significant controversy surrounded this change, with some viewing it as an oversimplification that does not accurately reflect important distinctions among divergent disorders18 and others arguing that it will result in unrecognized cases and exclusion of affected individuals.¹⁹ Notably, a recent study using concurrent DSM-IV and DSM-5 criteria to diagnose autism and PDD in more than 4000 children documented a high level of agreement between them.²⁰

Diagnostic tools have improved

As the number of children diagnosed with autism has increased, so have efforts to more accurately diagnose autism as a distinct disorder.

A blood test to identify differences in gene expression between children with and without ASD has shown initial promise—particularly in males. In the 1960s, guidelines for diagnosing autism focused primarily on Kanner’s original descriptive criteria. Even in the 1980s, after DSM-III criteria identified autism as a distinct disorder, children were being evaluated with generalized developmental screening tools focused on behaviors characteristic of a severe mental handicap, without differentiating between autistic and nonautistic children.

Early autism-specific observational and structured interview tools (eg, Childhood Autism Rating Scale,²¹ Autism Diagnostic Interview [ADI],²² and Autistic Diagnostic Observation Schedule)²³ emerged from a need for standardized diagnostic instruments that were comparable and reproducible.²⁴ But because these tools were highly specific and initially studied in research settings with high-risk populations, they lacked the sensitivity to identify children at risk in the general population, particularly those with milder symptoms.

As the diagnosis of autism became more standardized following publication of the DSM III-R in 1987, developmental specialists were able to construct increasingly sensitive evaluation tools. The ADI was revised²⁵ to facilitate earlier and more efficient diagnosis, allowing for assessment of children as young as 19 months of age. The Checklist for Autism in Toddlers (CHAT)²⁶ and subsequent modification (M-CHAT)²⁷ were among the earliest and most effective screening tools, appropriate for use in children as young as 16 months old.

Tools that followed the original CHAT (eg, the Autism Spectrum Screening Questionnaire [ASSQ]²⁸) were adapted to better identify high-functioning children with Asperger syndrome, as well as those with autism.

Another revision of the M-CHAT—the M-CHAT-R/F (Revised with Follow-up) was validated earlier this year. In a study involving 16,000 children, 95% of those who had positive tests were found to have some form of developmental delay and almost half (47%) received an ASD diagnosis.²⁹

Other diagnostic aids are being explored as a means of promoting earlier identification of ASD. For example, a blood test to identify differences in gene expression between children with and without ASD³⁰ has shown initial promise, particularly in males. This test is licensed by SynapDx (Lexington, Mass) and a clinical trial to evaluate it has begun.

Recent studies suggest that advanced paternal age can increase the risk of autism.Results of another study demonstrating normalization of brain activity in autistic children after they’ve undergone intensive treatment³¹ raise the possibility of using cortical activation as measured by electroencephalography as an early biomarker for autism.

Treatment options, advocacy affect rate of diagnosis

Improvements in diagnosis and targeted identification of potentially treatable symptoms³² led to the development of new treatment options. And greater use of day care and preschool programs prompted networking among parents, who touted the benefits of early evaluation, diagnosis, and treatment. Earlier screening, not surprisingly, led to an increase in the target population.

Local as well as national advocacy groups, led primarily by parents, have become powerful voices for improvements in services offered to children with autism. And research studies with varying degrees of sophistication continue to be published, further fueling the demand for school systems to provide supportive learning environments as required by the Individuals with Disabilities Education Act, initially enacted in 1975 and amended in 2004.³³

Federal and state funds in the form of Medicaid waivers are available to provide long-term care services in home and community settings, while private insurers typically pay for associated treatment modalities for those with an autism diagnosis, including physical, occupational, and speech therapy, among other services.

Finally, politicians and celebrities with personal connections to autism have joined the effort to increase awareness and improve the quality and availability of services—further assuring that autism is recognized as a legitimate, definable, and treatable disorder.

As an autism diagnosis has become more socially acceptable, it has at times replaced diagnoses of learning disability and mental retardation, a trend known as “diagnostic substitution.”³⁴ Indeed, having a child with an ASD diagnosis often makes it possible for parents to secure services that might otherwise be unavailable to them.

Is the incidence of autism linked to the environment?

Numerous environmental, nutritional, and pharmaceutical changes have been cited as reasons for what is perceived as an increasing incidence of autism in recent years. For example, some contend that greater use of food preservatives and greater exposure of young children to environmental toxins are contributing factors.³⁵

Thimerosal. Perhaps most notable is the assertion—since disproven—that thimerosal, a substance previously used in the manufacture of several childhood vaccines, was a leading cause of autism.^36,37 In fact, one study documented an increase in autism after thimerosal had been discontinued.³⁸ (For more on the thimerosal controversy, see “Autism: 5 misconceptions that can complicate care”.)

Autism comorbidity. As autism is frequently comorbid with other developmental disabilities, advances in medical technology that have led to a decline in neonatal death and overall mortality among the disabled may mean more survivors are subsequently diagnosed with an autism comorbidity.

Biological factors. Recent studies suggest that advanced paternal age can increase the risk of autism.³⁹ Twin studies suggest moderate genetic heritability, along with a substantial environmental contribution to the development of autism.⁴⁰ And new research suggests that maternal stressors during pregnancy—eg, trauma, illness, or substance abuse—may increase a child’s risk of developing autism, among other psychiatric disorders.⁴¹

The important role you play in the diagnosis of autism

It is clear that autism is more common than previously thought³ and that various factors are at work. Ensuring that children are promptly and properly evaluated begins when primary care physicians take parents’ concerns seriously and keep an eye out for common symptoms and characteristic developmental delays that may be evident even in the first year of life.

If symptoms are not severe enough to be detected in the child’s first several years, the next likely presentation will be when a parent gets a call from school suggesting that their child be tested for autism. While this delayed presentation suggests a higher level of functioning, a full evaluation, including the use of questionnaires such as the Social Responsiveness Scale⁴² and ASSQ,²⁸ and appropriate referrals are still vital.

Puberty is another time when characteristics suggestive of autism that escaped earlier detection may be noted, and vague behavioral issues or concerns about intellectual impairment may become sufficiently troublesome to prompt a thorough evaluation. While behavioral therapy can be very helpful in such cases, medical therapy directed at co-occurring conditions (ie, a mood or anxiety disorder, including obsessive-compulsive disorder) may also provide significant benefit.

Puberty is another time when characteristics suggestive of autism that escaped earlier detection may be noted. Whatever the age of the child, his or her parents should be counseled as to the general nature of autism, reassured of the availability of treatment options and given the appropriate referrals, and encouraged to learn more by availing themselves of resources (TABLE) and support groups. A consumer update from the US Food and Drug Administration titled “Beware of false or misleading claims for treating autism” (http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm394757.htm) will be helpful for many parents, as well.

CORRESPONDENCE
Robert G. Zylstra, EdD, LCSW, Department of Family Medicine, The University of Tennessee College of Medicine, 110 East Third Street, Chattanooga, TN 37403; [email protected]

Pain, one of the most common reasons patients present to the ED, may be a primary complaint or a warning sign encouraging further evaluation. The decision to treat pain is one of the most frequent therapeutic decisions made by emergency physicians (EPs) and involves a variety of options and considerations. Moreover, the decision of how to treat pain similarly encompasses a wide selection of variables, including etiology and severity of the pain; intravenous (IV) access; medication allergies; renal function; alcohol use; rapidity of onset; patients’ vital signs; patient preference; and mode of transport upon discharge. Given all of these considerations, there is no perfect analgesic to suit every circumstance. Rather, EPs must tailor their analgesic selection to the individual clinical situation and patient.

The literature over the past 20 years is replete with studies demonstrating the undertreatment or inadequate treatment of pain in the ED.^1-5 Often referred to as oligoanalgesia,⁶ contributing factors include physician concerns regarding adverse side effects, secondary gain, and drug addiction. In addition, the increasing pressure placed on EPs to diagnose and dispose patients quickly likely relegates pain control to a secondary concern.

Further complicating the issue, physicians’ own prejudices and perceptions appear to influence their analgesic prescription practice. For example, several studies have demonstrated that black patients do not receive prescriptions for analgesics similar to those written for white patients in general, and particularly not for opioid analgesics. In a meta-analysis of pain treatment disparity studies, blacks were 22% less likely than whites to receive any analgesics, and 29% less likely than whites to receive opioid treatment for the same type of painful conditions.⁷ Likewise, Hispanic/Latino patients were also 22% less likely than their white counterparts to receive opioid treatment for similar pain.⁷ Physicians must keep these common biases in mind when treating patients for pain.

The administration of analgesics and the prescription habits of physicians has never been under greater scrutiny. The Centers for Medicare and Medicaid Services has benchmarked “median time to pain management for long bone fractures” as a core measure, possibly affecting hospital reimbursement rates. Similarly, every patient satisfaction survey specifically inquires about the timeliness and adequacy of pain control. At the same time, though, the increasing problem of prescription opioid abuse has become the nation’s fastest growing drug problem. In 2013, prescription drug abuse was second only to marijuana as the most abused drug category.⁸ Contributing to this problem are the frequency and ease with which many physicians prescribe opioids. From 1997 to 2007, the milligram-per-person use of prescription opioids in the United States increased from 74 mg per year to 369 mg per year—an increase of 402%.⁹ As a result, some legislators are now calling for mandatory educational sessions for any physician prescribing medications containing opioids.

Though there are many classes of medications used to treat pain, and numerous individual drugs within each class, this article focuses on several of the more commonly prescribed medications in the ED, including their mechanisms of action, advantages, and disadvantages. The management of pediatric pain and procedural sedation and analgesia are not discussed in this review, as each of these topics deserves a separate detailed discussion.

Recognizing and Quantifying Pain

The first step in treating pain appropriately is recognition. Physicians must specifically inquire about pain and not rely solely on a patient’s unprompted complaint. Several pain scales exist, including the Faces Pain Scale (ie, pictorial representation of a smiling face on one end indicating “no pain” to a frowning face on the opposite end); the verbal quantitative scale or numerical rating scale (ie, “how would you rate your pain on a scale of 0 to 10, with 10 the worst pain ever?”); and the visual analog scale (ie, a 10-cm linear scale marked at one end with “no pain” and “worst pain imaginable” at the opposite end).^10,11 Probably the most commonly used scale in the ED is some variation of the numerical rating scale (NRS).¹

Each of these scales has its own advantages and disadvantages, but the important point is that patients are given the opportunity to express the type and degree of pain to the healthcare provider. In addition, a pain scale provides a starting point against which the practitioner (or later practitioners) can determine the success (or failure) of a pain treatment strategy.

Three-Step Ladder

In 1996, the World Health Organization developed a three-step analgesic ladder to guide the management of cancer pain.¹² Its use has been expanded over time to include treating pain of noncancer etiology. Mild pain (NRS of 1 to 3) is considered Step 1; moderate pain (NRS 4 to 6) is considered Step 2; and severe pain (NRS 7 to 10) is Step 3. For Step 1 (mild pain), acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) is recommended. For Step 2 (moderate pain), a weak opioid (ie, codeine or hydrocodone) with or without acetaminophen or an NSAID is recommended. Finally, for Step 3 (severe pain), a strong opioid such as morphine or hydromorphone is recommended.

Again, the purpose of the ladder is not to provide a strict protocol for adherence, but rather to provide a reasonable starting point as a guide to the clinician. The key to its successful use is reassessment of the patient to determine if adequate pain relief is achieved. 

Routes of Administration

Acetaminophen

Acetaminophen, the active ingredient in Tylenol, was first marketed in the United States in 1955 as an antipyretic and pain reliever.¹³ It is a synthetic centrally acting analgesic that is metabolized in the liver. Acetaminophen has been used alone or in combination in hundreds of formulations to treat a wide variety of pain and fever-related conditions. In the ED setting, acetaminophen is frequently used as an antipyretic and—either alone or in combination with opioids—for oral pain control.

Acetaminophen is very well tolerated by most patients, with minimal gastrointestinal (GI) distress. It is inexpensive, and the wide variety of formulations (eg, liquid, tablet, suppository) make it useful in a number of clinical scenarios. Acetaminophen is generally considered to be the only nonopioid analgesic that is safe in pregnancy,¹⁴ and it has no sedative or addictive effects.

There are, however, some disadvantages to using acetaminophen. Concerns about its safety and accidental overdose have recently led to the introduction of a 4,000-mg maximum daily dose recommendation¹⁵ and heightened concern over using multiple medications containing acetaminophen. In January 2014, the US Food and Drug Administration recommended that no combination medication contain more than 325 mg of acetaminophen because of the risk of toxicity when multiple drugs containing acetaminophen are consumed.

In addition to concerns of inadvertent overdose, another disadvantage of acetaminophen is that while it may be an effective antipyretic and analgesic, it has little or no anti-inflammatory properties. Therefore, in cases requiring an anti-inflammatory agent, an NSAID, when appropriate, would be the more effective option.

NSAIDs

Nonsteroidal anti-inflammatory drugs function by inhibiting prostaglandin production in the cyclooxygenase 1 and 2 (COX-1 and COX-2) pathways. Ibuprofen, indomethacin, ketorolac, naproxen, and other NSAIDs are chiefly utilized to control pain, inflammation, and fever via the oral route. As production of various prostaglandins via the COX-2 pathway is thought to contribute to fever, inflammation, and pain, inhibition of this pathway by NSAIDs can help alleviate these symptoms. The COX-1 pathway contributes many factors important to the protection and health of the GI tract, and inhibition of this pathway can lead to GI distress and damage. Unfortunately, the most commonly used and available NSAIDs inhibit both COX pathways simultaneously, and in doing so, prompt the GI symptoms which are the most common adverse side effects of therapy. In addition to GI effects of the COX-1 and COX-2 inhibitors, there are also concerns over the associated antiplatelet effects in patients undergoing surgery or potentially suffering from occult or intracranial bleeding.¹³

Ibuprofen
This is the most commonly used NSAID in the United States and is available without a prescription. Ibuprofen is typically used to treat mild-to-moderate pain from a musculoskeletal or inflammatory source. As an oral nonprescription medication, it can be used advantageously to treat acute pain in the ED and continued in the outpatient setting. Ibuprofen is neither sedating nor addicting, with a rapid onset of action and a plasma half-life of approximately 2 hours.¹³ However, there is a dose-dependent feature which allows large doses (eg, 800 mg) to be spaced-out every 8 hours while maintaining effective analgesia. Typical doses range from 200 mg to 800 mg orally every 6 to 8 hours, with a maximum dose of 3.2 g/d. Patients should be instructed to take each dose with a meal or snack to help alleviate GI side effects.

The greatest advantage of ibuprofen and other NSAIDs is their effect on inflammation and the ability to treat the inflammatory cause of pain—not just the symptom. Nonsteroidal anti-inflammatory drugs are well tolerated by most patients and can be obtained without prescription at low cost. Additionally, doses of ibuprofen and acetaminophen can be alternated.

Ketorolac
Often marketed as Toradol, ketorolac is a powerful NSAID available in IV, IM, and oral formulations. Typical doses are 30 mg IV, 60 mg IM, or 10 mg orally every 4 to 6 hours (maximum of 40 mg/d). The basic pharmacology and mechanism of action of ketorolac are similar to ibuprofen. Though ketorolac is useful to treat more severe pain, it should only be used for short-term management of pain (ie, 5 days or less). Ketorolac is often used for postoperative pain, but also is helpful for pain control in patients using opioids. It has been shown to be effective for acute renal colic and can also provide relief for migraine headaches.^16,17 In a direct comparison between ketorolac and meperidine (Demerol) for patients suffering from renal stones, ketorolac was found to be more effective and provide longer lasting pain relief.¹⁸

The major concern regarding ketorolac relates to potential renal toxicity, and thus caution should be undertaken in prescribing it to patients with known or suspected renal disease. Although this risk is associated with even a single dose, multiple doses increase the danger and therefore should be avoided.

Ketorolac should also be used with caution in patients with asthma. As a subset of asthma patients will experience severe bronchospasm after NSAID administration, clinicians should always determine whether a patient can tolerate NSAIDs.

Renal Toxicity and GI Effects
Concerns over renal toxicity and potential GI distress are the chief disadvantages of NSAID use. While renal toxicity has been reported in patients without pre-existing kidney dysfunction, it is of much greater concern in patients with pre-existing renal disease or decreased glomerular filtration rate. For this reason, care must be exercised when prescribing NSAIDS to elderly patients, patients with diabetes mellitus, or patients with hypertension (or even worse, a combination of these). Prolonged use of NSAIDs can also cause upper GI bleeding. Nonsteroidal anti-inflammatory drugs are contraindicated in pregnant patients.

Opioid analgesics

Morphine
Morphine is the prototypical compound in the opioid class, and has been utilized for more than two centuries since its isolation in 1804.¹⁹ Other opioid compounds include codeine, hydrocodone, oxycodone, morphine, and hydromorphone, which represent different functional groups substituted onto the base morphine molecule. All share similar pharmacology, differing primarily only in potency. The onset of action for codeine, hydrocodone, and oxycodone is 30 to 60 minutes when taken orally, with a peak time of 60 to 90 minutes. Codeine and hydrocodone are at the weak-end of the spectrum (Step 2 medications), while morphine and hydromorphone are more potent (Step 3 medications). The majority of opioids and their metabolites are primarily excreted renally (90%-95%).²⁰ Therefore, care must be exercised regarding dosing and frequency when used in patients with renal insufficiency or disease.

Morphine has several features that make it an attractive analgesic for use in the ED. The ability to administer morphine via IV, IM, subcutaneous, or oral route; its quick onset of action; and safety profile are all advantageous. The onset of action is 5 to 10 minutes when given IV. For oral administration, it is 30 to 60 minutes (similar to the other opioids discussed) and can be given as a tablet or syrup.

Morphine decreases the severity of pain, with an apparent increase in tolerance for any remaining discomfort. The potency and central action of morphine make it ideal for managing moderate and severe pain.

As with other analgesics, morphine and its related compounds have associated drawbacks, of which respiratory depression is the most feared, though this is uncommon at therapeutic doses. The respiratory depressant effect is more pronounced in patients with underlying lung disease, depressed mental status, or concurrent use of sedating medication (eg, benzodiazepines).

Another disadvantage to morphine is that it can cause hypotension, limiting its use in certain clinical situations. Repeated or prolonged use may cause slowing or complete arrest of peristaltic waves in the GI tract, which can lead to significant constipation. Pruritus and nausea are two other frequently reported side effects and may necessitate, respectively, coadministration of diphenhydramine (eg, Benadryl) or an antiemetic (eg, Phenergan or Zofran). As an opioid, morphine is potentially addictive, though it is generally thought to require significant intake over several weeks before such problems arise.

The sedation caused by morphine is also of concern, as patients who are under its influence immediately following discharge cannot safely drive, and may actually not be safe to walk or even utilize public transportation. This concern can be lessened by verifying the patient’s mode of transport prior to administration of the medication, ensuring that patients are not overly sedated at the time of discharge and, as much as possible, accompanied home by an adult relative or friend. In comparison to other frequently used opioids, several features can be considered. The duration of action for codeine, hydromorphone, and morphine is similar at 3 to 5 hours.

Hydromorphone
Hydromorphone (Dilaudid) is approximately seven times more potent than morphine, but otherwise very similar. It is frequently the IV opioid of choice for severe pain and also appears to cause pruritus less frequently than morphine. Hydromorphone has a rapid onset of action (1-5 minutes IV; 15-30 minutes orally) and can be titrated to effect when given via the IV route, making it an ideal agent for the pain associated with long bone or pelvic fractures, vasoocclusive crises in patients with sickle cell disease, and renal colic. The oral formulation of hydromorphone can be utilized for severe pain in the appropriate patient population, usually at a dose of 2 to 4 mg every 4 hours.

Codeine
Codeine is frequently prescribed in combination with acetaminophen in a product marketed as Tylenol #3 for mild-to-moderate pain. Because codeine is metabolized in the liver to morphine, it is contraindicated in patients with morphine allergy. Also, the clinician must be aware that codeine is ineffective in 7% to 10% of the population due to an enzyme deficiency.

Tramadol
Tramadol (Ultram), another oral analgesic with opioid properties, affects several neurotransmitters and is less reliant on the opioid receptors compared to the opioid compounds described above. It is used to treat moderate-to-severe pain and can be considered another option along with codeine, hydrocodone, and oxycodone for oral pain control. Although the complete mechanism of action for tramadol is poorly understood, it appears to be effective in patients who do not respond well to pure opioids, and in patients with neuropathic pain or persistent pain of unclear etiology (eg, fibromyalgia).¹⁹ Because of its limited interaction with opioid receptors, tramadol has less potential for abuse and addiction than the opioids. It is also available in several combinations with acetaminophen or ibuprofen.

Conclusion

The ideal medication for treating pain in the ED is one that is effective, easy to administer, and has minimal adverse or residual effects. Generally, the least potent medication that will control pain should be chosen initially. When treating minor traumatic or musculoskeletal pain, initiating pain control with oral medication in the ED may provide patients with relief during imaging or splinting, and help control pain until they can fill outpatient prescriptions. All of the medications discussed in this article can be given in the oral form. However, IV usage may be appropriate when there is need for rapid onset of action, to titrate the medication, or for ease of administration in patients who are vomiting or unable to take anything orally.

When prescribing analgesics for pain control after discharge, the clinician must consider potential relative and absolute contraindications. For acetamino­­phen, liver toxicity is the major concern, and care must be taken not to exceed recommended daily dosing limits with the multitude of available products containing acetaminophen. Physicians should avoid recommending or prescribing acetaminophen to patients with liver disease (ie, cirrhosis) or habitual alcohol abuse.

Nonsteroidal anti-inflammatory drugs such as ibuprofen and naproxen carry the risk of renal damage, as well as concerns about antiplatelet activity. Because of the tendency for renal function to decline with age, caution must be exercised in using these compounds in older patients and those with preexisting renal dysfunction.

Opioid-containing medications are known for their potency in pain control, but also for their side effects. The most common side effect involves the GI tract, with nausea, vomiting, and constipation. The most dangerous side effect of opioids is respiratory depression; fortunately, this is rarely seen with therapeutic doses. However, somnolence and decreased coordination are significant concerns when prescribing opioids to elderly patients or those already at risk for falls.

There is no ideal single medication to treat all types of pain or situations. However, the choice of medication begins with a decision by the EP to treat pain. Utilizing a stepwise approach, oral medication will usually be effective for mild pain, but IV narcotics will probably be required for severe pain. Frequent reassessment of the patient is critically important for successful pain management in the ED.

Dr Byers is an emergency physician at the Presbyterian Medical Group, department of emergency medicine, Presbyterian Healthcare Services, Albuquerque, New Mexico. Dr Counselman is a distinguished professor of emergency medicine and chairman, department of emergency medicine, Eastern Virginia Medical School and Emergency Physicians of Tidewater, Norfolk, Virginia. He is also associate editor-in-chief of the Emergency Medicine editorial board.

Pain, one of the most common reasons patients present to the ED, may be a primary complaint or a warning sign encouraging further evaluation. The decision to treat pain is one of the most frequent therapeutic decisions made by emergency physicians (EPs) and involves a variety of options and considerations. Moreover, the decision of how to treat pain similarly encompasses a wide selection of variables, including etiology and severity of the pain; intravenous (IV) access; medication allergies; renal function; alcohol use; rapidity of onset; patients’ vital signs; patient preference; and mode of transport upon discharge. Given all of these considerations, there is no perfect analgesic to suit every circumstance. Rather, EPs must tailor their analgesic selection to the individual clinical situation and patient.

The literature over the past 20 years is replete with studies demonstrating the undertreatment or inadequate treatment of pain in the ED.^1-5 Often referred to as oligoanalgesia,⁶ contributing factors include physician concerns regarding adverse side effects, secondary gain, and drug addiction. In addition, the increasing pressure placed on EPs to diagnose and dispose patients quickly likely relegates pain control to a secondary concern.

Further complicating the issue, physicians’ own prejudices and perceptions appear to influence their analgesic prescription practice. For example, several studies have demonstrated that black patients do not receive prescriptions for analgesics similar to those written for white patients in general, and particularly not for opioid analgesics. In a meta-analysis of pain treatment disparity studies, blacks were 22% less likely than whites to receive any analgesics, and 29% less likely than whites to receive opioid treatment for the same type of painful conditions.⁷ Likewise, Hispanic/Latino patients were also 22% less likely than their white counterparts to receive opioid treatment for similar pain.⁷ Physicians must keep these common biases in mind when treating patients for pain.

The administration of analgesics and the prescription habits of physicians has never been under greater scrutiny. The Centers for Medicare and Medicaid Services has benchmarked “median time to pain management for long bone fractures” as a core measure, possibly affecting hospital reimbursement rates. Similarly, every patient satisfaction survey specifically inquires about the timeliness and adequacy of pain control. At the same time, though, the increasing problem of prescription opioid abuse has become the nation’s fastest growing drug problem. In 2013, prescription drug abuse was second only to marijuana as the most abused drug category.⁸ Contributing to this problem are the frequency and ease with which many physicians prescribe opioids. From 1997 to 2007, the milligram-per-person use of prescription opioids in the United States increased from 74 mg per year to 369 mg per year—an increase of 402%.⁹ As a result, some legislators are now calling for mandatory educational sessions for any physician prescribing medications containing opioids.

Though there are many classes of medications used to treat pain, and numerous individual drugs within each class, this article focuses on several of the more commonly prescribed medications in the ED, including their mechanisms of action, advantages, and disadvantages. The management of pediatric pain and procedural sedation and analgesia are not discussed in this review, as each of these topics deserves a separate detailed discussion.

Recognizing and Quantifying Pain

The first step in treating pain appropriately is recognition. Physicians must specifically inquire about pain and not rely solely on a patient’s unprompted complaint. Several pain scales exist, including the Faces Pain Scale (ie, pictorial representation of a smiling face on one end indicating “no pain” to a frowning face on the opposite end); the verbal quantitative scale or numerical rating scale (ie, “how would you rate your pain on a scale of 0 to 10, with 10 the worst pain ever?”); and the visual analog scale (ie, a 10-cm linear scale marked at one end with “no pain” and “worst pain imaginable” at the opposite end).^10,11 Probably the most commonly used scale in the ED is some variation of the numerical rating scale (NRS).¹

Each of these scales has its own advantages and disadvantages, but the important point is that patients are given the opportunity to express the type and degree of pain to the healthcare provider. In addition, a pain scale provides a starting point against which the practitioner (or later practitioners) can determine the success (or failure) of a pain treatment strategy.

Three-Step Ladder

In 1996, the World Health Organization developed a three-step analgesic ladder to guide the management of cancer pain.¹² Its use has been expanded over time to include treating pain of noncancer etiology. Mild pain (NRS of 1 to 3) is considered Step 1; moderate pain (NRS 4 to 6) is considered Step 2; and severe pain (NRS 7 to 10) is Step 3. For Step 1 (mild pain), acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) is recommended. For Step 2 (moderate pain), a weak opioid (ie, codeine or hydrocodone) with or without acetaminophen or an NSAID is recommended. Finally, for Step 3 (severe pain), a strong opioid such as morphine or hydromorphone is recommended.

Again, the purpose of the ladder is not to provide a strict protocol for adherence, but rather to provide a reasonable starting point as a guide to the clinician. The key to its successful use is reassessment of the patient to determine if adequate pain relief is achieved. 

Routes of Administration

Acetaminophen

Acetaminophen, the active ingredient in Tylenol, was first marketed in the United States in 1955 as an antipyretic and pain reliever.¹³ It is a synthetic centrally acting analgesic that is metabolized in the liver. Acetaminophen has been used alone or in combination in hundreds of formulations to treat a wide variety of pain and fever-related conditions. In the ED setting, acetaminophen is frequently used as an antipyretic and—either alone or in combination with opioids—for oral pain control.

Acetaminophen is very well tolerated by most patients, with minimal gastrointestinal (GI) distress. It is inexpensive, and the wide variety of formulations (eg, liquid, tablet, suppository) make it useful in a number of clinical scenarios. Acetaminophen is generally considered to be the only nonopioid analgesic that is safe in pregnancy,¹⁴ and it has no sedative or addictive effects.

There are, however, some disadvantages to using acetaminophen. Concerns about its safety and accidental overdose have recently led to the introduction of a 4,000-mg maximum daily dose recommendation¹⁵ and heightened concern over using multiple medications containing acetaminophen. In January 2014, the US Food and Drug Administration recommended that no combination medication contain more than 325 mg of acetaminophen because of the risk of toxicity when multiple drugs containing acetaminophen are consumed.

In addition to concerns of inadvertent overdose, another disadvantage of acetaminophen is that while it may be an effective antipyretic and analgesic, it has little or no anti-inflammatory properties. Therefore, in cases requiring an anti-inflammatory agent, an NSAID, when appropriate, would be the more effective option.

NSAIDs

Nonsteroidal anti-inflammatory drugs function by inhibiting prostaglandin production in the cyclooxygenase 1 and 2 (COX-1 and COX-2) pathways. Ibuprofen, indomethacin, ketorolac, naproxen, and other NSAIDs are chiefly utilized to control pain, inflammation, and fever via the oral route. As production of various prostaglandins via the COX-2 pathway is thought to contribute to fever, inflammation, and pain, inhibition of this pathway by NSAIDs can help alleviate these symptoms. The COX-1 pathway contributes many factors important to the protection and health of the GI tract, and inhibition of this pathway can lead to GI distress and damage. Unfortunately, the most commonly used and available NSAIDs inhibit both COX pathways simultaneously, and in doing so, prompt the GI symptoms which are the most common adverse side effects of therapy. In addition to GI effects of the COX-1 and COX-2 inhibitors, there are also concerns over the associated antiplatelet effects in patients undergoing surgery or potentially suffering from occult or intracranial bleeding.¹³

Ibuprofen
This is the most commonly used NSAID in the United States and is available without a prescription. Ibuprofen is typically used to treat mild-to-moderate pain from a musculoskeletal or inflammatory source. As an oral nonprescription medication, it can be used advantageously to treat acute pain in the ED and continued in the outpatient setting. Ibuprofen is neither sedating nor addicting, with a rapid onset of action and a plasma half-life of approximately 2 hours.¹³ However, there is a dose-dependent feature which allows large doses (eg, 800 mg) to be spaced-out every 8 hours while maintaining effective analgesia. Typical doses range from 200 mg to 800 mg orally every 6 to 8 hours, with a maximum dose of 3.2 g/d. Patients should be instructed to take each dose with a meal or snack to help alleviate GI side effects.

The greatest advantage of ibuprofen and other NSAIDs is their effect on inflammation and the ability to treat the inflammatory cause of pain—not just the symptom. Nonsteroidal anti-inflammatory drugs are well tolerated by most patients and can be obtained without prescription at low cost. Additionally, doses of ibuprofen and acetaminophen can be alternated.

Ketorolac
Often marketed as Toradol, ketorolac is a powerful NSAID available in IV, IM, and oral formulations. Typical doses are 30 mg IV, 60 mg IM, or 10 mg orally every 4 to 6 hours (maximum of 40 mg/d). The basic pharmacology and mechanism of action of ketorolac are similar to ibuprofen. Though ketorolac is useful to treat more severe pain, it should only be used for short-term management of pain (ie, 5 days or less). Ketorolac is often used for postoperative pain, but also is helpful for pain control in patients using opioids. It has been shown to be effective for acute renal colic and can also provide relief for migraine headaches.^16,17 In a direct comparison between ketorolac and meperidine (Demerol) for patients suffering from renal stones, ketorolac was found to be more effective and provide longer lasting pain relief.¹⁸

The major concern regarding ketorolac relates to potential renal toxicity, and thus caution should be undertaken in prescribing it to patients with known or suspected renal disease. Although this risk is associated with even a single dose, multiple doses increase the danger and therefore should be avoided.

Ketorolac should also be used with caution in patients with asthma. As a subset of asthma patients will experience severe bronchospasm after NSAID administration, clinicians should always determine whether a patient can tolerate NSAIDs.

Renal Toxicity and GI Effects
Concerns over renal toxicity and potential GI distress are the chief disadvantages of NSAID use. While renal toxicity has been reported in patients without pre-existing kidney dysfunction, it is of much greater concern in patients with pre-existing renal disease or decreased glomerular filtration rate. For this reason, care must be exercised when prescribing NSAIDS to elderly patients, patients with diabetes mellitus, or patients with hypertension (or even worse, a combination of these). Prolonged use of NSAIDs can also cause upper GI bleeding. Nonsteroidal anti-inflammatory drugs are contraindicated in pregnant patients.

Opioid analgesics

Morphine
Morphine is the prototypical compound in the opioid class, and has been utilized for more than two centuries since its isolation in 1804.¹⁹ Other opioid compounds include codeine, hydrocodone, oxycodone, morphine, and hydromorphone, which represent different functional groups substituted onto the base morphine molecule. All share similar pharmacology, differing primarily only in potency. The onset of action for codeine, hydrocodone, and oxycodone is 30 to 60 minutes when taken orally, with a peak time of 60 to 90 minutes. Codeine and hydrocodone are at the weak-end of the spectrum (Step 2 medications), while morphine and hydromorphone are more potent (Step 3 medications). The majority of opioids and their metabolites are primarily excreted renally (90%-95%).²⁰ Therefore, care must be exercised regarding dosing and frequency when used in patients with renal insufficiency or disease.

Morphine has several features that make it an attractive analgesic for use in the ED. The ability to administer morphine via IV, IM, subcutaneous, or oral route; its quick onset of action; and safety profile are all advantageous. The onset of action is 5 to 10 minutes when given IV. For oral administration, it is 30 to 60 minutes (similar to the other opioids discussed) and can be given as a tablet or syrup.

Morphine decreases the severity of pain, with an apparent increase in tolerance for any remaining discomfort. The potency and central action of morphine make it ideal for managing moderate and severe pain.

As with other analgesics, morphine and its related compounds have associated drawbacks, of which respiratory depression is the most feared, though this is uncommon at therapeutic doses. The respiratory depressant effect is more pronounced in patients with underlying lung disease, depressed mental status, or concurrent use of sedating medication (eg, benzodiazepines).

Another disadvantage to morphine is that it can cause hypotension, limiting its use in certain clinical situations. Repeated or prolonged use may cause slowing or complete arrest of peristaltic waves in the GI tract, which can lead to significant constipation. Pruritus and nausea are two other frequently reported side effects and may necessitate, respectively, coadministration of diphenhydramine (eg, Benadryl) or an antiemetic (eg, Phenergan or Zofran). As an opioid, morphine is potentially addictive, though it is generally thought to require significant intake over several weeks before such problems arise.

The sedation caused by morphine is also of concern, as patients who are under its influence immediately following discharge cannot safely drive, and may actually not be safe to walk or even utilize public transportation. This concern can be lessened by verifying the patient’s mode of transport prior to administration of the medication, ensuring that patients are not overly sedated at the time of discharge and, as much as possible, accompanied home by an adult relative or friend. In comparison to other frequently used opioids, several features can be considered. The duration of action for codeine, hydromorphone, and morphine is similar at 3 to 5 hours.

Hydromorphone
Hydromorphone (Dilaudid) is approximately seven times more potent than morphine, but otherwise very similar. It is frequently the IV opioid of choice for severe pain and also appears to cause pruritus less frequently than morphine. Hydromorphone has a rapid onset of action (1-5 minutes IV; 15-30 minutes orally) and can be titrated to effect when given via the IV route, making it an ideal agent for the pain associated with long bone or pelvic fractures, vasoocclusive crises in patients with sickle cell disease, and renal colic. The oral formulation of hydromorphone can be utilized for severe pain in the appropriate patient population, usually at a dose of 2 to 4 mg every 4 hours.

Codeine
Codeine is frequently prescribed in combination with acetaminophen in a product marketed as Tylenol #3 for mild-to-moderate pain. Because codeine is metabolized in the liver to morphine, it is contraindicated in patients with morphine allergy. Also, the clinician must be aware that codeine is ineffective in 7% to 10% of the population due to an enzyme deficiency.

Tramadol
Tramadol (Ultram), another oral analgesic with opioid properties, affects several neurotransmitters and is less reliant on the opioid receptors compared to the opioid compounds described above. It is used to treat moderate-to-severe pain and can be considered another option along with codeine, hydrocodone, and oxycodone for oral pain control. Although the complete mechanism of action for tramadol is poorly understood, it appears to be effective in patients who do not respond well to pure opioids, and in patients with neuropathic pain or persistent pain of unclear etiology (eg, fibromyalgia).¹⁹ Because of its limited interaction with opioid receptors, tramadol has less potential for abuse and addiction than the opioids. It is also available in several combinations with acetaminophen or ibuprofen.

Conclusion

The ideal medication for treating pain in the ED is one that is effective, easy to administer, and has minimal adverse or residual effects. Generally, the least potent medication that will control pain should be chosen initially. When treating minor traumatic or musculoskeletal pain, initiating pain control with oral medication in the ED may provide patients with relief during imaging or splinting, and help control pain until they can fill outpatient prescriptions. All of the medications discussed in this article can be given in the oral form. However, IV usage may be appropriate when there is need for rapid onset of action, to titrate the medication, or for ease of administration in patients who are vomiting or unable to take anything orally.

When prescribing analgesics for pain control after discharge, the clinician must consider potential relative and absolute contraindications. For acetamino­­phen, liver toxicity is the major concern, and care must be taken not to exceed recommended daily dosing limits with the multitude of available products containing acetaminophen. Physicians should avoid recommending or prescribing acetaminophen to patients with liver disease (ie, cirrhosis) or habitual alcohol abuse.

Nonsteroidal anti-inflammatory drugs such as ibuprofen and naproxen carry the risk of renal damage, as well as concerns about antiplatelet activity. Because of the tendency for renal function to decline with age, caution must be exercised in using these compounds in older patients and those with preexisting renal dysfunction.

Opioid-containing medications are known for their potency in pain control, but also for their side effects. The most common side effect involves the GI tract, with nausea, vomiting, and constipation. The most dangerous side effect of opioids is respiratory depression; fortunately, this is rarely seen with therapeutic doses. However, somnolence and decreased coordination are significant concerns when prescribing opioids to elderly patients or those already at risk for falls.

There is no ideal single medication to treat all types of pain or situations. However, the choice of medication begins with a decision by the EP to treat pain. Utilizing a stepwise approach, oral medication will usually be effective for mild pain, but IV narcotics will probably be required for severe pain. Frequent reassessment of the patient is critically important for successful pain management in the ED.

Dr Byers is an emergency physician at the Presbyterian Medical Group, department of emergency medicine, Presbyterian Healthcare Services, Albuquerque, New Mexico. Dr Counselman is a distinguished professor of emergency medicine and chairman, department of emergency medicine, Eastern Virginia Medical School and Emergency Physicians of Tidewater, Norfolk, Virginia. He is also associate editor-in-chief of the Emergency Medicine editorial board.

Pain, one of the most common reasons patients present to the ED, may be a primary complaint or a warning sign encouraging further evaluation. The decision to treat pain is one of the most frequent therapeutic decisions made by emergency physicians (EPs) and involves a variety of options and considerations. Moreover, the decision of how to treat pain similarly encompasses a wide selection of variables, including etiology and severity of the pain; intravenous (IV) access; medication allergies; renal function; alcohol use; rapidity of onset; patients’ vital signs; patient preference; and mode of transport upon discharge. Given all of these considerations, there is no perfect analgesic to suit every circumstance. Rather, EPs must tailor their analgesic selection to the individual clinical situation and patient.

The literature over the past 20 years is replete with studies demonstrating the undertreatment or inadequate treatment of pain in the ED.^1-5 Often referred to as oligoanalgesia,⁶ contributing factors include physician concerns regarding adverse side effects, secondary gain, and drug addiction. In addition, the increasing pressure placed on EPs to diagnose and dispose patients quickly likely relegates pain control to a secondary concern.

Further complicating the issue, physicians’ own prejudices and perceptions appear to influence their analgesic prescription practice. For example, several studies have demonstrated that black patients do not receive prescriptions for analgesics similar to those written for white patients in general, and particularly not for opioid analgesics. In a meta-analysis of pain treatment disparity studies, blacks were 22% less likely than whites to receive any analgesics, and 29% less likely than whites to receive opioid treatment for the same type of painful conditions.⁷ Likewise, Hispanic/Latino patients were also 22% less likely than their white counterparts to receive opioid treatment for similar pain.⁷ Physicians must keep these common biases in mind when treating patients for pain.

The administration of analgesics and the prescription habits of physicians has never been under greater scrutiny. The Centers for Medicare and Medicaid Services has benchmarked “median time to pain management for long bone fractures” as a core measure, possibly affecting hospital reimbursement rates. Similarly, every patient satisfaction survey specifically inquires about the timeliness and adequacy of pain control. At the same time, though, the increasing problem of prescription opioid abuse has become the nation’s fastest growing drug problem. In 2013, prescription drug abuse was second only to marijuana as the most abused drug category.⁸ Contributing to this problem are the frequency and ease with which many physicians prescribe opioids. From 1997 to 2007, the milligram-per-person use of prescription opioids in the United States increased from 74 mg per year to 369 mg per year—an increase of 402%.⁹ As a result, some legislators are now calling for mandatory educational sessions for any physician prescribing medications containing opioids.

Though there are many classes of medications used to treat pain, and numerous individual drugs within each class, this article focuses on several of the more commonly prescribed medications in the ED, including their mechanisms of action, advantages, and disadvantages. The management of pediatric pain and procedural sedation and analgesia are not discussed in this review, as each of these topics deserves a separate detailed discussion.

Recognizing and Quantifying Pain

The first step in treating pain appropriately is recognition. Physicians must specifically inquire about pain and not rely solely on a patient’s unprompted complaint. Several pain scales exist, including the Faces Pain Scale (ie, pictorial representation of a smiling face on one end indicating “no pain” to a frowning face on the opposite end); the verbal quantitative scale or numerical rating scale (ie, “how would you rate your pain on a scale of 0 to 10, with 10 the worst pain ever?”); and the visual analog scale (ie, a 10-cm linear scale marked at one end with “no pain” and “worst pain imaginable” at the opposite end).^10,11 Probably the most commonly used scale in the ED is some variation of the numerical rating scale (NRS).¹

Each of these scales has its own advantages and disadvantages, but the important point is that patients are given the opportunity to express the type and degree of pain to the healthcare provider. In addition, a pain scale provides a starting point against which the practitioner (or later practitioners) can determine the success (or failure) of a pain treatment strategy.

Three-Step Ladder

In 1996, the World Health Organization developed a three-step analgesic ladder to guide the management of cancer pain.¹² Its use has been expanded over time to include treating pain of noncancer etiology. Mild pain (NRS of 1 to 3) is considered Step 1; moderate pain (NRS 4 to 6) is considered Step 2; and severe pain (NRS 7 to 10) is Step 3. For Step 1 (mild pain), acetaminophen or a nonsteroidal anti-inflammatory drug (NSAID) is recommended. For Step 2 (moderate pain), a weak opioid (ie, codeine or hydrocodone) with or without acetaminophen or an NSAID is recommended. Finally, for Step 3 (severe pain), a strong opioid such as morphine or hydromorphone is recommended.

Again, the purpose of the ladder is not to provide a strict protocol for adherence, but rather to provide a reasonable starting point as a guide to the clinician. The key to its successful use is reassessment of the patient to determine if adequate pain relief is achieved. 

Routes of Administration

Acetaminophen

Acetaminophen, the active ingredient in Tylenol, was first marketed in the United States in 1955 as an antipyretic and pain reliever.¹³ It is a synthetic centrally acting analgesic that is metabolized in the liver. Acetaminophen has been used alone or in combination in hundreds of formulations to treat a wide variety of pain and fever-related conditions. In the ED setting, acetaminophen is frequently used as an antipyretic and—either alone or in combination with opioids—for oral pain control.

Acetaminophen is very well tolerated by most patients, with minimal gastrointestinal (GI) distress. It is inexpensive, and the wide variety of formulations (eg, liquid, tablet, suppository) make it useful in a number of clinical scenarios. Acetaminophen is generally considered to be the only nonopioid analgesic that is safe in pregnancy,¹⁴ and it has no sedative or addictive effects.

There are, however, some disadvantages to using acetaminophen. Concerns about its safety and accidental overdose have recently led to the introduction of a 4,000-mg maximum daily dose recommendation¹⁵ and heightened concern over using multiple medications containing acetaminophen. In January 2014, the US Food and Drug Administration recommended that no combination medication contain more than 325 mg of acetaminophen because of the risk of toxicity when multiple drugs containing acetaminophen are consumed.

In addition to concerns of inadvertent overdose, another disadvantage of acetaminophen is that while it may be an effective antipyretic and analgesic, it has little or no anti-inflammatory properties. Therefore, in cases requiring an anti-inflammatory agent, an NSAID, when appropriate, would be the more effective option.

NSAIDs

Nonsteroidal anti-inflammatory drugs function by inhibiting prostaglandin production in the cyclooxygenase 1 and 2 (COX-1 and COX-2) pathways. Ibuprofen, indomethacin, ketorolac, naproxen, and other NSAIDs are chiefly utilized to control pain, inflammation, and fever via the oral route. As production of various prostaglandins via the COX-2 pathway is thought to contribute to fever, inflammation, and pain, inhibition of this pathway by NSAIDs can help alleviate these symptoms. The COX-1 pathway contributes many factors important to the protection and health of the GI tract, and inhibition of this pathway can lead to GI distress and damage. Unfortunately, the most commonly used and available NSAIDs inhibit both COX pathways simultaneously, and in doing so, prompt the GI symptoms which are the most common adverse side effects of therapy. In addition to GI effects of the COX-1 and COX-2 inhibitors, there are also concerns over the associated antiplatelet effects in patients undergoing surgery or potentially suffering from occult or intracranial bleeding.¹³

Ibuprofen
This is the most commonly used NSAID in the United States and is available without a prescription. Ibuprofen is typically used to treat mild-to-moderate pain from a musculoskeletal or inflammatory source. As an oral nonprescription medication, it can be used advantageously to treat acute pain in the ED and continued in the outpatient setting. Ibuprofen is neither sedating nor addicting, with a rapid onset of action and a plasma half-life of approximately 2 hours.¹³ However, there is a dose-dependent feature which allows large doses (eg, 800 mg) to be spaced-out every 8 hours while maintaining effective analgesia. Typical doses range from 200 mg to 800 mg orally every 6 to 8 hours, with a maximum dose of 3.2 g/d. Patients should be instructed to take each dose with a meal or snack to help alleviate GI side effects.

The greatest advantage of ibuprofen and other NSAIDs is their effect on inflammation and the ability to treat the inflammatory cause of pain—not just the symptom. Nonsteroidal anti-inflammatory drugs are well tolerated by most patients and can be obtained without prescription at low cost. Additionally, doses of ibuprofen and acetaminophen can be alternated.

Ketorolac
Often marketed as Toradol, ketorolac is a powerful NSAID available in IV, IM, and oral formulations. Typical doses are 30 mg IV, 60 mg IM, or 10 mg orally every 4 to 6 hours (maximum of 40 mg/d). The basic pharmacology and mechanism of action of ketorolac are similar to ibuprofen. Though ketorolac is useful to treat more severe pain, it should only be used for short-term management of pain (ie, 5 days or less). Ketorolac is often used for postoperative pain, but also is helpful for pain control in patients using opioids. It has been shown to be effective for acute renal colic and can also provide relief for migraine headaches.^16,17 In a direct comparison between ketorolac and meperidine (Demerol) for patients suffering from renal stones, ketorolac was found to be more effective and provide longer lasting pain relief.¹⁸

The major concern regarding ketorolac relates to potential renal toxicity, and thus caution should be undertaken in prescribing it to patients with known or suspected renal disease. Although this risk is associated with even a single dose, multiple doses increase the danger and therefore should be avoided.

Ketorolac should also be used with caution in patients with asthma. As a subset of asthma patients will experience severe bronchospasm after NSAID administration, clinicians should always determine whether a patient can tolerate NSAIDs.

Renal Toxicity and GI Effects
Concerns over renal toxicity and potential GI distress are the chief disadvantages of NSAID use. While renal toxicity has been reported in patients without pre-existing kidney dysfunction, it is of much greater concern in patients with pre-existing renal disease or decreased glomerular filtration rate. For this reason, care must be exercised when prescribing NSAIDS to elderly patients, patients with diabetes mellitus, or patients with hypertension (or even worse, a combination of these). Prolonged use of NSAIDs can also cause upper GI bleeding. Nonsteroidal anti-inflammatory drugs are contraindicated in pregnant patients.

Opioid analgesics

Morphine
Morphine is the prototypical compound in the opioid class, and has been utilized for more than two centuries since its isolation in 1804.¹⁹ Other opioid compounds include codeine, hydrocodone, oxycodone, morphine, and hydromorphone, which represent different functional groups substituted onto the base morphine molecule. All share similar pharmacology, differing primarily only in potency. The onset of action for codeine, hydrocodone, and oxycodone is 30 to 60 minutes when taken orally, with a peak time of 60 to 90 minutes. Codeine and hydrocodone are at the weak-end of the spectrum (Step 2 medications), while morphine and hydromorphone are more potent (Step 3 medications). The majority of opioids and their metabolites are primarily excreted renally (90%-95%).²⁰ Therefore, care must be exercised regarding dosing and frequency when used in patients with renal insufficiency or disease.

Morphine has several features that make it an attractive analgesic for use in the ED. The ability to administer morphine via IV, IM, subcutaneous, or oral route; its quick onset of action; and safety profile are all advantageous. The onset of action is 5 to 10 minutes when given IV. For oral administration, it is 30 to 60 minutes (similar to the other opioids discussed) and can be given as a tablet or syrup.

Morphine decreases the severity of pain, with an apparent increase in tolerance for any remaining discomfort. The potency and central action of morphine make it ideal for managing moderate and severe pain.

As with other analgesics, morphine and its related compounds have associated drawbacks, of which respiratory depression is the most feared, though this is uncommon at therapeutic doses. The respiratory depressant effect is more pronounced in patients with underlying lung disease, depressed mental status, or concurrent use of sedating medication (eg, benzodiazepines).

Another disadvantage to morphine is that it can cause hypotension, limiting its use in certain clinical situations. Repeated or prolonged use may cause slowing or complete arrest of peristaltic waves in the GI tract, which can lead to significant constipation. Pruritus and nausea are two other frequently reported side effects and may necessitate, respectively, coadministration of diphenhydramine (eg, Benadryl) or an antiemetic (eg, Phenergan or Zofran). As an opioid, morphine is potentially addictive, though it is generally thought to require significant intake over several weeks before such problems arise.

The sedation caused by morphine is also of concern, as patients who are under its influence immediately following discharge cannot safely drive, and may actually not be safe to walk or even utilize public transportation. This concern can be lessened by verifying the patient’s mode of transport prior to administration of the medication, ensuring that patients are not overly sedated at the time of discharge and, as much as possible, accompanied home by an adult relative or friend. In comparison to other frequently used opioids, several features can be considered. The duration of action for codeine, hydromorphone, and morphine is similar at 3 to 5 hours.

Hydromorphone
Hydromorphone (Dilaudid) is approximately seven times more potent than morphine, but otherwise very similar. It is frequently the IV opioid of choice for severe pain and also appears to cause pruritus less frequently than morphine. Hydromorphone has a rapid onset of action (1-5 minutes IV; 15-30 minutes orally) and can be titrated to effect when given via the IV route, making it an ideal agent for the pain associated with long bone or pelvic fractures, vasoocclusive crises in patients with sickle cell disease, and renal colic. The oral formulation of hydromorphone can be utilized for severe pain in the appropriate patient population, usually at a dose of 2 to 4 mg every 4 hours.

Codeine
Codeine is frequently prescribed in combination with acetaminophen in a product marketed as Tylenol #3 for mild-to-moderate pain. Because codeine is metabolized in the liver to morphine, it is contraindicated in patients with morphine allergy. Also, the clinician must be aware that codeine is ineffective in 7% to 10% of the population due to an enzyme deficiency.

Tramadol
Tramadol (Ultram), another oral analgesic with opioid properties, affects several neurotransmitters and is less reliant on the opioid receptors compared to the opioid compounds described above. It is used to treat moderate-to-severe pain and can be considered another option along with codeine, hydrocodone, and oxycodone for oral pain control. Although the complete mechanism of action for tramadol is poorly understood, it appears to be effective in patients who do not respond well to pure opioids, and in patients with neuropathic pain or persistent pain of unclear etiology (eg, fibromyalgia).¹⁹ Because of its limited interaction with opioid receptors, tramadol has less potential for abuse and addiction than the opioids. It is also available in several combinations with acetaminophen or ibuprofen.

Conclusion

The ideal medication for treating pain in the ED is one that is effective, easy to administer, and has minimal adverse or residual effects. Generally, the least potent medication that will control pain should be chosen initially. When treating minor traumatic or musculoskeletal pain, initiating pain control with oral medication in the ED may provide patients with relief during imaging or splinting, and help control pain until they can fill outpatient prescriptions. All of the medications discussed in this article can be given in the oral form. However, IV usage may be appropriate when there is need for rapid onset of action, to titrate the medication, or for ease of administration in patients who are vomiting or unable to take anything orally.

When prescribing analgesics for pain control after discharge, the clinician must consider potential relative and absolute contraindications. For acetamino­­phen, liver toxicity is the major concern, and care must be taken not to exceed recommended daily dosing limits with the multitude of available products containing acetaminophen. Physicians should avoid recommending or prescribing acetaminophen to patients with liver disease (ie, cirrhosis) or habitual alcohol abuse.

Nonsteroidal anti-inflammatory drugs such as ibuprofen and naproxen carry the risk of renal damage, as well as concerns about antiplatelet activity. Because of the tendency for renal function to decline with age, caution must be exercised in using these compounds in older patients and those with preexisting renal dysfunction.

Opioid-containing medications are known for their potency in pain control, but also for their side effects. The most common side effect involves the GI tract, with nausea, vomiting, and constipation. The most dangerous side effect of opioids is respiratory depression; fortunately, this is rarely seen with therapeutic doses. However, somnolence and decreased coordination are significant concerns when prescribing opioids to elderly patients or those already at risk for falls.

There is no ideal single medication to treat all types of pain or situations. However, the choice of medication begins with a decision by the EP to treat pain. Utilizing a stepwise approach, oral medication will usually be effective for mild pain, but IV narcotics will probably be required for severe pain. Frequent reassessment of the patient is critically important for successful pain management in the ED.

Dr Byers is an emergency physician at the Presbyterian Medical Group, department of emergency medicine, Presbyterian Healthcare Services, Albuquerque, New Mexico. Dr Counselman is a distinguished professor of emergency medicine and chairman, department of emergency medicine, Eastern Virginia Medical School and Emergency Physicians of Tidewater, Norfolk, Virginia. He is also associate editor-in-chief of the Emergency Medicine editorial board.

Case 1 

An 82-year-old man presented to the ED accompanied by his son, who stated that his father “had not been acting right” for the past 2 days. The patient was combative, yelling “Go away,” and was intermittently more confused than his baseline; he was also eating and drinking less than usual. He had a history of mild dementia, noninsulin-dependent diabetes, hypertension, and arthritis; there were no recent changes in his medication. The patient lived alone in an apartment across the hall from his son and had home healthcare aide 4 hours a day, 3 days a week. He was independent of activities of daily living (ADL), but needed help with shopping and cooking. 

At presentation, the patient’s vital signs were: temperature, afebrile; heart rate (HR), 94 beats/minute; blood pressure (BP), 146/92 mm hg; respiratory rate (RR), 22 breaths/minute. Oxygen (O₂) saturation was 96% on room air. A finger-stick glucose test was 103 mg/dL. He was hyperalert and agitated, and did not appear oriented to place or time. There were no focal neurological deficits; mucous membranes were mildly dry; and faint crackles were heard at the right base of the lungs. The patient was placed on a monitor in a curtained room in the ED, and was given 2 L O2 via nasal cannula, which improved O2 saturation to 99%. With his son present, an intravenous (IV) line was placed and blood was drawn. An electrocardiogram (ECG) showed a sinus rhythm without ischemic findings.

During evaluation, the patient continued to pull at the monitor lines and attempted to get off the stretcher. To calm his agitation, he was given haloperidol 2.5 mg and lorazepam 1 mg; 10 minutes after administration, he became sedated and difficult to arouse. His vital signs remained stable.

Laboratory analysis revealed a white blood cell count (WBC) of 12.5 K/uL, a negative troponin, a brain natriuretic peptide (BNP) of 80 pg/mL, and normal blood urea nitrogen (BUN) and creatinine levels. Urinalysis was negative for infection, but chest X-ray showed a right lower lobe infiltrate. Blood cultures were drawn, and the patient was continued on maintenance fluids and started on IV antibiotics to cover community-acquired pneumonia. He was admitted to the hospital for pneumonia and altered mental status.

As the patient’s sedative state was followed by periods of agitation, he was treated with additional haloperidol and lorazepam by the inpatient medical team, which resulted in further sedation. On hospital day 3, his urinary output decreased. He was given an IV bolus of 3 L normal saline over 6 hours, after which his mental status began to improve, and he was switched to oral antibiotics. His mental status returned to baseline and O₂ saturation was 99% on room air. He was discharged home on hospital day 5 accompanied by his son.

Case 2

A 75-year-old man was brought to the ED with a 3-day history of worsening dyspnea on exertion, increased orthopnea, and increased bilateral lower extremity edema. He had a history of congestive heart failure (CHF), with an ejection fraction of 40%, and had been on 40 mg of furosemide daily at home; there were no recent changes to his medication. The patient was independent of ADL at baseline, living with his wife in a home with stairs. 

His vital signs at presentation were: temperature, afebrile; HR, 86 beats/minute; BP, 160/90 mm hg; RR 30 breaths/minute; O₂ saturation was 92% on room air. The patient had increased work of breathing and was speaking in four- to five-word sentences. Pulmonary examination revealed crackles half way up bilaterally. He also had 2+ pitting edema bilaterally in his lower extremities. He was otherwise alert and oriented.  

On 4 L O₂ via nasal cannula, the patient’s O₂ saturation was 98%.  Laboratory analysis revealed a BNP of 600 pg/mL, negative troponin, and normal creatinine level. Urinalysis was negative for evidence of infection. An ECG showed no changes, and chest X-ray revealed mild pulmonary congestion without an infiltrate. In the ED, an indwelling urinary catheter (IUC) was placed to monitor urinary output before the patient was given 40 mg of IV furosemide for diuresis. The patient was then admitted for management of exacerbation of CHF. As the medical team was preparing to discharge him on hospital day 2, his wife noticed that he was confused and not acting “like himself.” An investigation for causes of delirium included evaluation for infectious disease, which revealed an elevated WBC of 14.0 K/uL, stable creatinine; and urinalysis positive for bacteria, WBCs, leukocyte esterase, and nitrites. Since chest X-ray showed resolution of the vascular congestion, the patient no longer required supplemental O₂.

The IUC was removed, and the patient was started on IV antibiotics for a urinary tract infection (UTI) secondary to IUC placement. The inpatient stay was prolonged for an additional 3 days until his delirium cleared and he could be continued on oral antibiotics as an outpatient.

Discussion

There is nothing extraordinary about these two cases. Every day elderly adults present to EDs throughout the country with confusion caused by pneumonia and dehydration that is sometimes initially attributed to worsening dementia and then complicated or prolonged by overuse of powerful sedating medications. Also, complications resulting from IUCs inserted in the ED all too often prolong hospitalizations. But by using protocols designed for better, more efficient emergency care of elderly patients, their ED care can be substantially improved and any subsequent inpatient care shortened.

The older adult population (ages 65 years and older) often presents to the ED with similar complaints to their younger counterparts—eg, chest pain, abdominal pain, dyspnea. However, the history, physical examination, and social assessment of elderly patients usually lead to a more comprehensive work-up, as older adults tend to present in an atypical fashion for both illness and trauma, thus necessitating a broader differential. In addition, they are more susceptible to adverse reactions from medications and procedures.

Regardless of the ultimate diagnosis, simply presenting to an ED as a patient (and sometimes spending many hours there) places older adults at elevated risk of morbidity and mortality. The challenge is to develop reliable tools to streamline the management of this population in order to increase diagnostic accuracy, decrease adverse events, and improve patient outcomes.

Clinical Protocols
Clinical protocols are one way in which we can educate and standardize the practice of multiple levels of provider, including nurses, midlevel providers, and physicians. Adopting protocols is natural for EPs—the key is to make sure the clinical protocol to be implemented is designed or modified for the ED setting in which it will be implemented.

In our ED, we have recently implemented the following two protocols for common scenarios in older adults: (1) assessment and management of delirium; and (2) decreased use of IUCs. These protocols employ the following stepwise project plan:

1. Focus groups involving nurses, midlevels, residents, and attendings to assess ED provider knowledge, attitudes, and practice patterns regarding the clinical issue  in older adult patients, and to guide development of the clinical protocol by understanding needs and constraints of the current ED environment;
2. An extensive literature review of the clinical topic;
3. Development of the clinical protocol by the workgroup;
4. Implementation of protocol after multiple educational sessions using a scripted slide presentation to ensure all providers receive the same information; and
5. Subsequent data analysis from the electronic medical record to assess the impact (ie, outcome) of the protocol.

Delirium
Delirium is a common syndrome in older adults, but is often unrecognized despite its clinical importance. Although 7% to 17% of older adults who present to the ED suffer from delirium,^1-6 emergency physicians (EPs) miss 64% to 83% of cases, and 12% to 38% of patients with unrecognized delirium are actually discharged from the ED.^1,6-8 Unfortunately, patients discharged from the ED with undetected delirium are three times more likely to die within 3 months than those whose delirium was recognized.

Life-threatening causes are more apt to be recognized early on in the ED. With this in mind, we developed a new, comprehensive, evidence-based protocol for recognition, diagnosis, management, and disposition of agitated delirium in older adults in the ED, with a focus on identifying and treating the commonly missed contributing causes: analgesia, bladder-urine retention, constipation, dehydration, environment, and medications.⁹

IUC Placement in the ED
The second protocol implemented at our institution is a new, evidence-based protocol for the placement, management, and reassessment of IUCs. As emphasized by the National American College of Emergency Physicians (ACEP) 2013 Choosing Wisely Campaign,¹⁰ inserting an IUC is a procedure that should be undertaken judiciously as it is associated with an elevated risk of infection, delirium, falls, and other adverse events. As of 2008, the Centers for Medicare and Medicaid Services no longer reimburses for hospital-acquired catheter-associated UTIs.¹¹

After conducting focus groups of our ED providers, we learned that IUCs are placed more frequently than needed—often for reasons of convenience—and are rarely reassessed or removed if the patient is admitted to the hospital. Thus, our protocol highlights appropriate, possibly appropriate, and inappropriate indications for IUC placement, with an emphasis on trying alternative modes of urine collection, communicating among healthcare providers regarding the necessity of an IUC, and reassessment of the patient for IUC removal.

Our protocols have yielded early promising results, but further research is underway to determine their specific impact. The goal is to create a protocol that is feasible and effective for the specific institution and department to which it is applied. By ensuring all members of the healthcare team are involved in the development and design of a protocol, there is ownership of its implementation and use, with the overarching goal of improving patient care.

Geriatric ED Guidelines
In the beginning of 2014, new consensus-based Geriatric Emergency Department (GED) guidelines were published in order to “provide a standardized set of guidelines that can effectively improve the care of the geriatric population and are feasible to implement in the ED.”¹² These guidelines are the result of a 2-year effort by representatives from ACEP, the American Geriatrics Society, the Society of Academic Emergency Medicine, and the Emergency Nurses Association, who were committed to optimizing the emergency-care delivery model for geriatrics. The participants encompassed both academic and community providers and included clinicians and researchers. These guidelines were formulated based on an 80% consensus among the representatives and, when possible, validated using existing literature at the time.

The genesis of the GED guidelines was multifactorial. In addition to the formation and rapid growth of geriatric interest groups and sections within EM academic organizations over the last 14 years, as well as the development of geriatric core competencies for EM residents in training, the 2010 Census Data results sharply outlined the details of the rapidly growing population of older adults in the United States. This acted as an alarm highlighting the need for a structured document containing best practice recommendations from geriatric emergency healthcare providers, researchers, and advocates. “The subsequent increased need for healthcare for this burgeoning geriatric population represents an unprecedented and overwhelming challenge to the American healthcare system as a whole and to emergency departments specifically,” the authors of the GED guidelines noted.

In response to a growing national interest in geriatric ED patients and an ever-increasing competition to attract patients from this demographic by EDs across the country, there has been a surge of self-designated GEDs during the last few years. Currently, more than 70 hospitals claim to have GEDs, raising the question of what sort of geriatric patient care is actually being delivered in these EDs. The question is of increased importance because very few of these “GEDs” are in academic centers or are associated with thought leaders in EM. In fact, when 30 self-designated GEDs that were snowball sampled in 2013 by researchers who asked what specific changes they had made toward the goal of improving care for the elderly, several rescinded this self-designation.

Because of heightened concerns for the needs of the increasing geriatric population overall, and the rise in the proportion of ED visits by this demographic, the authors of the GED guidelines state that “the contemporary emergency medicine management model may not be adequate for geriatric adults,” and offer the new GED guidelines as a basis on which EDs can consider ways to improve care for older adults while addressing the unique needs of this population. The GED guidelines propose specific methods and processes by which ED care of the elderly can be optimized. The authors note that “similar programs designed for other age groups (pediatrics) or directed towards specific diseases (STEMI, stroke, and trauma) have improved the care both in individual EDs and system-wide, resulting in better, more cost-effective care and ultimately better patient outcomes.”

The GED guidelines consist of 40 specific recommendations in six general categories: (1) staffing/administration; (2) equipment/supplies; (3) education; (4) policies/procedures/protocols; (5) follow-up/transitions of care; and (6) quality-improvement measures. This template outlines how to construct an effective GED program. The following highlights recommendations for each of these categories:

Staffing/Administration. Set qualifications and responsibilities for the medical director, nurse manager, staff physicians, nurses, and specialists, as well as accessibility to specialist ancillary services, with the goal of establishing hospital site-specific staff and coordination of local resources.

Equipment/Supplies. Develop potential physical and structural enhancements that address issues of mobility, comfort, safety, and behavioral needs (including memory cues and sensorial perception) while decreasing iatrogenic complications, such as the development of pressure ulcers (eg, the use of reclining chairs and pressure-redistributing foam mattresses).

Education. Provide nurse and clinical provider education and specialty-specific training focusing on contemporary, research-based geriatric-specific material, with regular assessment for interdisciplinary core competencies.

Policies/Procedures/Protocols. Implement a directed, comprehensive approach to facilitate screening and assessment of geriatric patients for added needs/post-ED adverse outcomes, as well as validated, ED-feasible screening tools/instruments for delirium and dementia, medication management, falls, use of urinary catheters, and the provision of palliative care.

Follow-up/Transitions of Care. Design discharge processes best suited for older patients (eg, large-font instructions), as well as collaborate with community resources to provide home-health services and home safety assessment in order to facilitate care following discharge.

Quality Improvement. Implement a system to collect and monitor pertinent and prevalent geriatric emergency care indicators (eg, incidence of injurious falls and documentation of fall risk assessment) designed to increase staff education and program success.

The authors clearly state that the GED guidelines represent recommendations. They are not a mandate for every ED, nor are they a list that requires 100% compliance. Instead, the document provides the potential steps to be taken, the rationale for these recommendations, and an outline of the resources available to aid in the transition from theory to implementation in any ED. The goal is to ensure better, safer, and age-appropriate treatment. In summary, these guidelines represent an effort to improve and even transform emergency care for older adults on the brink of one of the most significant challenges facing our healthcare system both in and beyond the ED.

Moving forward, the authors of the GED guidelines have defined a plan that “includes dissemination, implementation, adaptation, and refinement.” In addition to approval by each of the organization’s board of directors and the copyright of the material in 2013, the ED guidelines have now been widely disseminated through publication in numerous news articles (including international publications) and discussions on satellite radio. Tracking of new GEDs is planned. In addition, the prioritization of the guidelines is underway using a modified Delphi method, with the express purpose of assessing the relative potential benefits and harms associated with each recommendation by providing a weighted list from most important to least important.

A “Geriatric Emergency Department Boot Camp” is being developed to bring the recommendations to hospitals interested in “geriatricizing” their EDs. Geriatric EM leaders will act as consultants, providing training and a toolbox of resources. Specific reviews and revisions of the GED guidelines will take place in a 4- to 5-year cycle. Clearly, a next important step is the development of a GED certification system based on outcome studies of the individual components.

Criticisms of the GED guidelines have already been voiced among some EM providers. Specific concerns include a fear of partitioning the ED (as has occurred with pediatrics); an increase in cost and decreased efficiency; the need to maintain general expertise among EM physicians; the lack of evidence-based data upon which the recommendations were made; the fact that some guidelines were extrapolated from other clinical settings; and the belief that these changes will be too logistically difficult and take too much time.

The fact remains that the wave of geriatric patients (the “silver tsunami”) is already beginning to hit the shores of our hospitals. And GEDs are already here to help absorb the impact. The lack of iron-clad evidence for many of the recommendations should not be an absolute obstacle, but rather part of the natural evolution and improvement of similar endeavors. Nor should GEDs contain empty beds while younger adults sit in the waiting room, or conversely, force the elderly to wait for space in the GED when there are empty beds in the main ED. Ideally, the GED should be the location where the ED staff can implement these guidelines, which they can afterwards utilize in any part of the ED. These guidelines are designed to provide the best available expert opinion on how to deliver better geriatric care in the ED. The imperative for this goal is clear and necessitates this educated “leap-of-faith.” Change is never easy and often comes with an upfront cost of time, resources, and money. Moreover, there is nothing in a well-designed GED that may not also benefit, or at least will not adversely affect care of a younger adult as well. Therefore, flexibility and optimal utilization of space in a busy ED need not be sacrificed.

Conclusion

To improve diagnostic evaluation and care of the increasing number of geriatric patients presenting to the ED, reliable tools, protocols, and guidelines must be developed and implemented to ensure diagnostic accuracy, decrease adverse events, and improve patient outcomes. Fortunately, the new GED consensus guidelines are flexible and do not need to be wholly embraced—lending themselves to modifications and institution-specific adoptions. The “protocolization” and implementation of the guidelines may improve patient flow, operational efficiency, and, most importantly, the quality of care delivered. And likely, these guidelines will provide the foundation for future education and research into the improved emergency care of older adults.

The GED guidelines can be accessed at http://www.saem.org/docs/education/geri_ed_guidelines_final.pdf?sfvrsn=2.

Dr Stern is an assistant professor of medicine and codirector, geriatric emergency medicine fellowship, department of emergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York; and an assistant attending physician, department of emergency medicine, New York-Presbyterian Hospital.
Dr Mulcare is an instructor of medicine and an assistant attending physician, department of emergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York. She is a former fellow of geriatric emergency medicine.

Case 1 

An 82-year-old man presented to the ED accompanied by his son, who stated that his father “had not been acting right” for the past 2 days. The patient was combative, yelling “Go away,” and was intermittently more confused than his baseline; he was also eating and drinking less than usual. He had a history of mild dementia, noninsulin-dependent diabetes, hypertension, and arthritis; there were no recent changes in his medication. The patient lived alone in an apartment across the hall from his son and had home healthcare aide 4 hours a day, 3 days a week. He was independent of activities of daily living (ADL), but needed help with shopping and cooking. 

At presentation, the patient’s vital signs were: temperature, afebrile; heart rate (HR), 94 beats/minute; blood pressure (BP), 146/92 mm hg; respiratory rate (RR), 22 breaths/minute. Oxygen (O₂) saturation was 96% on room air. A finger-stick glucose test was 103 mg/dL. He was hyperalert and agitated, and did not appear oriented to place or time. There were no focal neurological deficits; mucous membranes were mildly dry; and faint crackles were heard at the right base of the lungs. The patient was placed on a monitor in a curtained room in the ED, and was given 2 L O2 via nasal cannula, which improved O2 saturation to 99%. With his son present, an intravenous (IV) line was placed and blood was drawn. An electrocardiogram (ECG) showed a sinus rhythm without ischemic findings.

During evaluation, the patient continued to pull at the monitor lines and attempted to get off the stretcher. To calm his agitation, he was given haloperidol 2.5 mg and lorazepam 1 mg; 10 minutes after administration, he became sedated and difficult to arouse. His vital signs remained stable.

Laboratory analysis revealed a white blood cell count (WBC) of 12.5 K/uL, a negative troponin, a brain natriuretic peptide (BNP) of 80 pg/mL, and normal blood urea nitrogen (BUN) and creatinine levels. Urinalysis was negative for infection, but chest X-ray showed a right lower lobe infiltrate. Blood cultures were drawn, and the patient was continued on maintenance fluids and started on IV antibiotics to cover community-acquired pneumonia. He was admitted to the hospital for pneumonia and altered mental status.

As the patient’s sedative state was followed by periods of agitation, he was treated with additional haloperidol and lorazepam by the inpatient medical team, which resulted in further sedation. On hospital day 3, his urinary output decreased. He was given an IV bolus of 3 L normal saline over 6 hours, after which his mental status began to improve, and he was switched to oral antibiotics. His mental status returned to baseline and O₂ saturation was 99% on room air. He was discharged home on hospital day 5 accompanied by his son.

Case 2

A 75-year-old man was brought to the ED with a 3-day history of worsening dyspnea on exertion, increased orthopnea, and increased bilateral lower extremity edema. He had a history of congestive heart failure (CHF), with an ejection fraction of 40%, and had been on 40 mg of furosemide daily at home; there were no recent changes to his medication. The patient was independent of ADL at baseline, living with his wife in a home with stairs. 

His vital signs at presentation were: temperature, afebrile; HR, 86 beats/minute; BP, 160/90 mm hg; RR 30 breaths/minute; O₂ saturation was 92% on room air. The patient had increased work of breathing and was speaking in four- to five-word sentences. Pulmonary examination revealed crackles half way up bilaterally. He also had 2+ pitting edema bilaterally in his lower extremities. He was otherwise alert and oriented.  

On 4 L O₂ via nasal cannula, the patient’s O₂ saturation was 98%.  Laboratory analysis revealed a BNP of 600 pg/mL, negative troponin, and normal creatinine level. Urinalysis was negative for evidence of infection. An ECG showed no changes, and chest X-ray revealed mild pulmonary congestion without an infiltrate. In the ED, an indwelling urinary catheter (IUC) was placed to monitor urinary output before the patient was given 40 mg of IV furosemide for diuresis. The patient was then admitted for management of exacerbation of CHF. As the medical team was preparing to discharge him on hospital day 2, his wife noticed that he was confused and not acting “like himself.” An investigation for causes of delirium included evaluation for infectious disease, which revealed an elevated WBC of 14.0 K/uL, stable creatinine; and urinalysis positive for bacteria, WBCs, leukocyte esterase, and nitrites. Since chest X-ray showed resolution of the vascular congestion, the patient no longer required supplemental O₂.

The IUC was removed, and the patient was started on IV antibiotics for a urinary tract infection (UTI) secondary to IUC placement. The inpatient stay was prolonged for an additional 3 days until his delirium cleared and he could be continued on oral antibiotics as an outpatient.

Discussion

There is nothing extraordinary about these two cases. Every day elderly adults present to EDs throughout the country with confusion caused by pneumonia and dehydration that is sometimes initially attributed to worsening dementia and then complicated or prolonged by overuse of powerful sedating medications. Also, complications resulting from IUCs inserted in the ED all too often prolong hospitalizations. But by using protocols designed for better, more efficient emergency care of elderly patients, their ED care can be substantially improved and any subsequent inpatient care shortened.

The older adult population (ages 65 years and older) often presents to the ED with similar complaints to their younger counterparts—eg, chest pain, abdominal pain, dyspnea. However, the history, physical examination, and social assessment of elderly patients usually lead to a more comprehensive work-up, as older adults tend to present in an atypical fashion for both illness and trauma, thus necessitating a broader differential. In addition, they are more susceptible to adverse reactions from medications and procedures.

Regardless of the ultimate diagnosis, simply presenting to an ED as a patient (and sometimes spending many hours there) places older adults at elevated risk of morbidity and mortality. The challenge is to develop reliable tools to streamline the management of this population in order to increase diagnostic accuracy, decrease adverse events, and improve patient outcomes.

Clinical Protocols
Clinical protocols are one way in which we can educate and standardize the practice of multiple levels of provider, including nurses, midlevel providers, and physicians. Adopting protocols is natural for EPs—the key is to make sure the clinical protocol to be implemented is designed or modified for the ED setting in which it will be implemented.

In our ED, we have recently implemented the following two protocols for common scenarios in older adults: (1) assessment and management of delirium; and (2) decreased use of IUCs. These protocols employ the following stepwise project plan:

1. Focus groups involving nurses, midlevels, residents, and attendings to assess ED provider knowledge, attitudes, and practice patterns regarding the clinical issue  in older adult patients, and to guide development of the clinical protocol by understanding needs and constraints of the current ED environment;
2. An extensive literature review of the clinical topic;
3. Development of the clinical protocol by the workgroup;
4. Implementation of protocol after multiple educational sessions using a scripted slide presentation to ensure all providers receive the same information; and
5. Subsequent data analysis from the electronic medical record to assess the impact (ie, outcome) of the protocol.

Delirium
Delirium is a common syndrome in older adults, but is often unrecognized despite its clinical importance. Although 7% to 17% of older adults who present to the ED suffer from delirium,^1-6 emergency physicians (EPs) miss 64% to 83% of cases, and 12% to 38% of patients with unrecognized delirium are actually discharged from the ED.^1,6-8 Unfortunately, patients discharged from the ED with undetected delirium are three times more likely to die within 3 months than those whose delirium was recognized.

Life-threatening causes are more apt to be recognized early on in the ED. With this in mind, we developed a new, comprehensive, evidence-based protocol for recognition, diagnosis, management, and disposition of agitated delirium in older adults in the ED, with a focus on identifying and treating the commonly missed contributing causes: analgesia, bladder-urine retention, constipation, dehydration, environment, and medications.⁹

IUC Placement in the ED
The second protocol implemented at our institution is a new, evidence-based protocol for the placement, management, and reassessment of IUCs. As emphasized by the National American College of Emergency Physicians (ACEP) 2013 Choosing Wisely Campaign,¹⁰ inserting an IUC is a procedure that should be undertaken judiciously as it is associated with an elevated risk of infection, delirium, falls, and other adverse events. As of 2008, the Centers for Medicare and Medicaid Services no longer reimburses for hospital-acquired catheter-associated UTIs.¹¹

After conducting focus groups of our ED providers, we learned that IUCs are placed more frequently than needed—often for reasons of convenience—and are rarely reassessed or removed if the patient is admitted to the hospital. Thus, our protocol highlights appropriate, possibly appropriate, and inappropriate indications for IUC placement, with an emphasis on trying alternative modes of urine collection, communicating among healthcare providers regarding the necessity of an IUC, and reassessment of the patient for IUC removal.

Our protocols have yielded early promising results, but further research is underway to determine their specific impact. The goal is to create a protocol that is feasible and effective for the specific institution and department to which it is applied. By ensuring all members of the healthcare team are involved in the development and design of a protocol, there is ownership of its implementation and use, with the overarching goal of improving patient care.

Geriatric ED Guidelines
In the beginning of 2014, new consensus-based Geriatric Emergency Department (GED) guidelines were published in order to “provide a standardized set of guidelines that can effectively improve the care of the geriatric population and are feasible to implement in the ED.”¹² These guidelines are the result of a 2-year effort by representatives from ACEP, the American Geriatrics Society, the Society of Academic Emergency Medicine, and the Emergency Nurses Association, who were committed to optimizing the emergency-care delivery model for geriatrics. The participants encompassed both academic and community providers and included clinicians and researchers. These guidelines were formulated based on an 80% consensus among the representatives and, when possible, validated using existing literature at the time.

The genesis of the GED guidelines was multifactorial. In addition to the formation and rapid growth of geriatric interest groups and sections within EM academic organizations over the last 14 years, as well as the development of geriatric core competencies for EM residents in training, the 2010 Census Data results sharply outlined the details of the rapidly growing population of older adults in the United States. This acted as an alarm highlighting the need for a structured document containing best practice recommendations from geriatric emergency healthcare providers, researchers, and advocates. “The subsequent increased need for healthcare for this burgeoning geriatric population represents an unprecedented and overwhelming challenge to the American healthcare system as a whole and to emergency departments specifically,” the authors of the GED guidelines noted.

In response to a growing national interest in geriatric ED patients and an ever-increasing competition to attract patients from this demographic by EDs across the country, there has been a surge of self-designated GEDs during the last few years. Currently, more than 70 hospitals claim to have GEDs, raising the question of what sort of geriatric patient care is actually being delivered in these EDs. The question is of increased importance because very few of these “GEDs” are in academic centers or are associated with thought leaders in EM. In fact, when 30 self-designated GEDs that were snowball sampled in 2013 by researchers who asked what specific changes they had made toward the goal of improving care for the elderly, several rescinded this self-designation.

Because of heightened concerns for the needs of the increasing geriatric population overall, and the rise in the proportion of ED visits by this demographic, the authors of the GED guidelines state that “the contemporary emergency medicine management model may not be adequate for geriatric adults,” and offer the new GED guidelines as a basis on which EDs can consider ways to improve care for older adults while addressing the unique needs of this population. The GED guidelines propose specific methods and processes by which ED care of the elderly can be optimized. The authors note that “similar programs designed for other age groups (pediatrics) or directed towards specific diseases (STEMI, stroke, and trauma) have improved the care both in individual EDs and system-wide, resulting in better, more cost-effective care and ultimately better patient outcomes.”

The GED guidelines consist of 40 specific recommendations in six general categories: (1) staffing/administration; (2) equipment/supplies; (3) education; (4) policies/procedures/protocols; (5) follow-up/transitions of care; and (6) quality-improvement measures. This template outlines how to construct an effective GED program. The following highlights recommendations for each of these categories:

Staffing/Administration. Set qualifications and responsibilities for the medical director, nurse manager, staff physicians, nurses, and specialists, as well as accessibility to specialist ancillary services, with the goal of establishing hospital site-specific staff and coordination of local resources.

Equipment/Supplies. Develop potential physical and structural enhancements that address issues of mobility, comfort, safety, and behavioral needs (including memory cues and sensorial perception) while decreasing iatrogenic complications, such as the development of pressure ulcers (eg, the use of reclining chairs and pressure-redistributing foam mattresses).

Education. Provide nurse and clinical provider education and specialty-specific training focusing on contemporary, research-based geriatric-specific material, with regular assessment for interdisciplinary core competencies.

Policies/Procedures/Protocols. Implement a directed, comprehensive approach to facilitate screening and assessment of geriatric patients for added needs/post-ED adverse outcomes, as well as validated, ED-feasible screening tools/instruments for delirium and dementia, medication management, falls, use of urinary catheters, and the provision of palliative care.

Follow-up/Transitions of Care. Design discharge processes best suited for older patients (eg, large-font instructions), as well as collaborate with community resources to provide home-health services and home safety assessment in order to facilitate care following discharge.

Quality Improvement. Implement a system to collect and monitor pertinent and prevalent geriatric emergency care indicators (eg, incidence of injurious falls and documentation of fall risk assessment) designed to increase staff education and program success.

The authors clearly state that the GED guidelines represent recommendations. They are not a mandate for every ED, nor are they a list that requires 100% compliance. Instead, the document provides the potential steps to be taken, the rationale for these recommendations, and an outline of the resources available to aid in the transition from theory to implementation in any ED. The goal is to ensure better, safer, and age-appropriate treatment. In summary, these guidelines represent an effort to improve and even transform emergency care for older adults on the brink of one of the most significant challenges facing our healthcare system both in and beyond the ED.

Moving forward, the authors of the GED guidelines have defined a plan that “includes dissemination, implementation, adaptation, and refinement.” In addition to approval by each of the organization’s board of directors and the copyright of the material in 2013, the ED guidelines have now been widely disseminated through publication in numerous news articles (including international publications) and discussions on satellite radio. Tracking of new GEDs is planned. In addition, the prioritization of the guidelines is underway using a modified Delphi method, with the express purpose of assessing the relative potential benefits and harms associated with each recommendation by providing a weighted list from most important to least important.

A “Geriatric Emergency Department Boot Camp” is being developed to bring the recommendations to hospitals interested in “geriatricizing” their EDs. Geriatric EM leaders will act as consultants, providing training and a toolbox of resources. Specific reviews and revisions of the GED guidelines will take place in a 4- to 5-year cycle. Clearly, a next important step is the development of a GED certification system based on outcome studies of the individual components.

Criticisms of the GED guidelines have already been voiced among some EM providers. Specific concerns include a fear of partitioning the ED (as has occurred with pediatrics); an increase in cost and decreased efficiency; the need to maintain general expertise among EM physicians; the lack of evidence-based data upon which the recommendations were made; the fact that some guidelines were extrapolated from other clinical settings; and the belief that these changes will be too logistically difficult and take too much time.

The fact remains that the wave of geriatric patients (the “silver tsunami”) is already beginning to hit the shores of our hospitals. And GEDs are already here to help absorb the impact. The lack of iron-clad evidence for many of the recommendations should not be an absolute obstacle, but rather part of the natural evolution and improvement of similar endeavors. Nor should GEDs contain empty beds while younger adults sit in the waiting room, or conversely, force the elderly to wait for space in the GED when there are empty beds in the main ED. Ideally, the GED should be the location where the ED staff can implement these guidelines, which they can afterwards utilize in any part of the ED. These guidelines are designed to provide the best available expert opinion on how to deliver better geriatric care in the ED. The imperative for this goal is clear and necessitates this educated “leap-of-faith.” Change is never easy and often comes with an upfront cost of time, resources, and money. Moreover, there is nothing in a well-designed GED that may not also benefit, or at least will not adversely affect care of a younger adult as well. Therefore, flexibility and optimal utilization of space in a busy ED need not be sacrificed.

Conclusion

To improve diagnostic evaluation and care of the increasing number of geriatric patients presenting to the ED, reliable tools, protocols, and guidelines must be developed and implemented to ensure diagnostic accuracy, decrease adverse events, and improve patient outcomes. Fortunately, the new GED consensus guidelines are flexible and do not need to be wholly embraced—lending themselves to modifications and institution-specific adoptions. The “protocolization” and implementation of the guidelines may improve patient flow, operational efficiency, and, most importantly, the quality of care delivered. And likely, these guidelines will provide the foundation for future education and research into the improved emergency care of older adults.

The GED guidelines can be accessed at http://www.saem.org/docs/education/geri_ed_guidelines_final.pdf?sfvrsn=2.

Dr Stern is an assistant professor of medicine and codirector, geriatric emergency medicine fellowship, department of emergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York; and an assistant attending physician, department of emergency medicine, New York-Presbyterian Hospital.
Dr Mulcare is an instructor of medicine and an assistant attending physician, department of emergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York. She is a former fellow of geriatric emergency medicine.

Case 1 

An 82-year-old man presented to the ED accompanied by his son, who stated that his father “had not been acting right” for the past 2 days. The patient was combative, yelling “Go away,” and was intermittently more confused than his baseline; he was also eating and drinking less than usual. He had a history of mild dementia, noninsulin-dependent diabetes, hypertension, and arthritis; there were no recent changes in his medication. The patient lived alone in an apartment across the hall from his son and had home healthcare aide 4 hours a day, 3 days a week. He was independent of activities of daily living (ADL), but needed help with shopping and cooking. 

At presentation, the patient’s vital signs were: temperature, afebrile; heart rate (HR), 94 beats/minute; blood pressure (BP), 146/92 mm hg; respiratory rate (RR), 22 breaths/minute. Oxygen (O₂) saturation was 96% on room air. A finger-stick glucose test was 103 mg/dL. He was hyperalert and agitated, and did not appear oriented to place or time. There were no focal neurological deficits; mucous membranes were mildly dry; and faint crackles were heard at the right base of the lungs. The patient was placed on a monitor in a curtained room in the ED, and was given 2 L O2 via nasal cannula, which improved O2 saturation to 99%. With his son present, an intravenous (IV) line was placed and blood was drawn. An electrocardiogram (ECG) showed a sinus rhythm without ischemic findings.

During evaluation, the patient continued to pull at the monitor lines and attempted to get off the stretcher. To calm his agitation, he was given haloperidol 2.5 mg and lorazepam 1 mg; 10 minutes after administration, he became sedated and difficult to arouse. His vital signs remained stable.

Laboratory analysis revealed a white blood cell count (WBC) of 12.5 K/uL, a negative troponin, a brain natriuretic peptide (BNP) of 80 pg/mL, and normal blood urea nitrogen (BUN) and creatinine levels. Urinalysis was negative for infection, but chest X-ray showed a right lower lobe infiltrate. Blood cultures were drawn, and the patient was continued on maintenance fluids and started on IV antibiotics to cover community-acquired pneumonia. He was admitted to the hospital for pneumonia and altered mental status.

As the patient’s sedative state was followed by periods of agitation, he was treated with additional haloperidol and lorazepam by the inpatient medical team, which resulted in further sedation. On hospital day 3, his urinary output decreased. He was given an IV bolus of 3 L normal saline over 6 hours, after which his mental status began to improve, and he was switched to oral antibiotics. His mental status returned to baseline and O₂ saturation was 99% on room air. He was discharged home on hospital day 5 accompanied by his son.

Case 2

A 75-year-old man was brought to the ED with a 3-day history of worsening dyspnea on exertion, increased orthopnea, and increased bilateral lower extremity edema. He had a history of congestive heart failure (CHF), with an ejection fraction of 40%, and had been on 40 mg of furosemide daily at home; there were no recent changes to his medication. The patient was independent of ADL at baseline, living with his wife in a home with stairs. 

His vital signs at presentation were: temperature, afebrile; HR, 86 beats/minute; BP, 160/90 mm hg; RR 30 breaths/minute; O₂ saturation was 92% on room air. The patient had increased work of breathing and was speaking in four- to five-word sentences. Pulmonary examination revealed crackles half way up bilaterally. He also had 2+ pitting edema bilaterally in his lower extremities. He was otherwise alert and oriented.  

On 4 L O₂ via nasal cannula, the patient’s O₂ saturation was 98%.  Laboratory analysis revealed a BNP of 600 pg/mL, negative troponin, and normal creatinine level. Urinalysis was negative for evidence of infection. An ECG showed no changes, and chest X-ray revealed mild pulmonary congestion without an infiltrate. In the ED, an indwelling urinary catheter (IUC) was placed to monitor urinary output before the patient was given 40 mg of IV furosemide for diuresis. The patient was then admitted for management of exacerbation of CHF. As the medical team was preparing to discharge him on hospital day 2, his wife noticed that he was confused and not acting “like himself.” An investigation for causes of delirium included evaluation for infectious disease, which revealed an elevated WBC of 14.0 K/uL, stable creatinine; and urinalysis positive for bacteria, WBCs, leukocyte esterase, and nitrites. Since chest X-ray showed resolution of the vascular congestion, the patient no longer required supplemental O₂.

The IUC was removed, and the patient was started on IV antibiotics for a urinary tract infection (UTI) secondary to IUC placement. The inpatient stay was prolonged for an additional 3 days until his delirium cleared and he could be continued on oral antibiotics as an outpatient.

Discussion

There is nothing extraordinary about these two cases. Every day elderly adults present to EDs throughout the country with confusion caused by pneumonia and dehydration that is sometimes initially attributed to worsening dementia and then complicated or prolonged by overuse of powerful sedating medications. Also, complications resulting from IUCs inserted in the ED all too often prolong hospitalizations. But by using protocols designed for better, more efficient emergency care of elderly patients, their ED care can be substantially improved and any subsequent inpatient care shortened.

The older adult population (ages 65 years and older) often presents to the ED with similar complaints to their younger counterparts—eg, chest pain, abdominal pain, dyspnea. However, the history, physical examination, and social assessment of elderly patients usually lead to a more comprehensive work-up, as older adults tend to present in an atypical fashion for both illness and trauma, thus necessitating a broader differential. In addition, they are more susceptible to adverse reactions from medications and procedures.

Regardless of the ultimate diagnosis, simply presenting to an ED as a patient (and sometimes spending many hours there) places older adults at elevated risk of morbidity and mortality. The challenge is to develop reliable tools to streamline the management of this population in order to increase diagnostic accuracy, decrease adverse events, and improve patient outcomes.

Clinical Protocols
Clinical protocols are one way in which we can educate and standardize the practice of multiple levels of provider, including nurses, midlevel providers, and physicians. Adopting protocols is natural for EPs—the key is to make sure the clinical protocol to be implemented is designed or modified for the ED setting in which it will be implemented.

In our ED, we have recently implemented the following two protocols for common scenarios in older adults: (1) assessment and management of delirium; and (2) decreased use of IUCs. These protocols employ the following stepwise project plan:

1. Focus groups involving nurses, midlevels, residents, and attendings to assess ED provider knowledge, attitudes, and practice patterns regarding the clinical issue  in older adult patients, and to guide development of the clinical protocol by understanding needs and constraints of the current ED environment;
2. An extensive literature review of the clinical topic;
3. Development of the clinical protocol by the workgroup;
4. Implementation of protocol after multiple educational sessions using a scripted slide presentation to ensure all providers receive the same information; and
5. Subsequent data analysis from the electronic medical record to assess the impact (ie, outcome) of the protocol.

Delirium
Delirium is a common syndrome in older adults, but is often unrecognized despite its clinical importance. Although 7% to 17% of older adults who present to the ED suffer from delirium,^1-6 emergency physicians (EPs) miss 64% to 83% of cases, and 12% to 38% of patients with unrecognized delirium are actually discharged from the ED.^1,6-8 Unfortunately, patients discharged from the ED with undetected delirium are three times more likely to die within 3 months than those whose delirium was recognized.

Life-threatening causes are more apt to be recognized early on in the ED. With this in mind, we developed a new, comprehensive, evidence-based protocol for recognition, diagnosis, management, and disposition of agitated delirium in older adults in the ED, with a focus on identifying and treating the commonly missed contributing causes: analgesia, bladder-urine retention, constipation, dehydration, environment, and medications.⁹

IUC Placement in the ED
The second protocol implemented at our institution is a new, evidence-based protocol for the placement, management, and reassessment of IUCs. As emphasized by the National American College of Emergency Physicians (ACEP) 2013 Choosing Wisely Campaign,¹⁰ inserting an IUC is a procedure that should be undertaken judiciously as it is associated with an elevated risk of infection, delirium, falls, and other adverse events. As of 2008, the Centers for Medicare and Medicaid Services no longer reimburses for hospital-acquired catheter-associated UTIs.¹¹

After conducting focus groups of our ED providers, we learned that IUCs are placed more frequently than needed—often for reasons of convenience—and are rarely reassessed or removed if the patient is admitted to the hospital. Thus, our protocol highlights appropriate, possibly appropriate, and inappropriate indications for IUC placement, with an emphasis on trying alternative modes of urine collection, communicating among healthcare providers regarding the necessity of an IUC, and reassessment of the patient for IUC removal.

Our protocols have yielded early promising results, but further research is underway to determine their specific impact. The goal is to create a protocol that is feasible and effective for the specific institution and department to which it is applied. By ensuring all members of the healthcare team are involved in the development and design of a protocol, there is ownership of its implementation and use, with the overarching goal of improving patient care.

Geriatric ED Guidelines
In the beginning of 2014, new consensus-based Geriatric Emergency Department (GED) guidelines were published in order to “provide a standardized set of guidelines that can effectively improve the care of the geriatric population and are feasible to implement in the ED.”¹² These guidelines are the result of a 2-year effort by representatives from ACEP, the American Geriatrics Society, the Society of Academic Emergency Medicine, and the Emergency Nurses Association, who were committed to optimizing the emergency-care delivery model for geriatrics. The participants encompassed both academic and community providers and included clinicians and researchers. These guidelines were formulated based on an 80% consensus among the representatives and, when possible, validated using existing literature at the time.

The genesis of the GED guidelines was multifactorial. In addition to the formation and rapid growth of geriatric interest groups and sections within EM academic organizations over the last 14 years, as well as the development of geriatric core competencies for EM residents in training, the 2010 Census Data results sharply outlined the details of the rapidly growing population of older adults in the United States. This acted as an alarm highlighting the need for a structured document containing best practice recommendations from geriatric emergency healthcare providers, researchers, and advocates. “The subsequent increased need for healthcare for this burgeoning geriatric population represents an unprecedented and overwhelming challenge to the American healthcare system as a whole and to emergency departments specifically,” the authors of the GED guidelines noted.

In response to a growing national interest in geriatric ED patients and an ever-increasing competition to attract patients from this demographic by EDs across the country, there has been a surge of self-designated GEDs during the last few years. Currently, more than 70 hospitals claim to have GEDs, raising the question of what sort of geriatric patient care is actually being delivered in these EDs. The question is of increased importance because very few of these “GEDs” are in academic centers or are associated with thought leaders in EM. In fact, when 30 self-designated GEDs that were snowball sampled in 2013 by researchers who asked what specific changes they had made toward the goal of improving care for the elderly, several rescinded this self-designation.

Because of heightened concerns for the needs of the increasing geriatric population overall, and the rise in the proportion of ED visits by this demographic, the authors of the GED guidelines state that “the contemporary emergency medicine management model may not be adequate for geriatric adults,” and offer the new GED guidelines as a basis on which EDs can consider ways to improve care for older adults while addressing the unique needs of this population. The GED guidelines propose specific methods and processes by which ED care of the elderly can be optimized. The authors note that “similar programs designed for other age groups (pediatrics) or directed towards specific diseases (STEMI, stroke, and trauma) have improved the care both in individual EDs and system-wide, resulting in better, more cost-effective care and ultimately better patient outcomes.”

The GED guidelines consist of 40 specific recommendations in six general categories: (1) staffing/administration; (2) equipment/supplies; (3) education; (4) policies/procedures/protocols; (5) follow-up/transitions of care; and (6) quality-improvement measures. This template outlines how to construct an effective GED program. The following highlights recommendations for each of these categories:

Staffing/Administration. Set qualifications and responsibilities for the medical director, nurse manager, staff physicians, nurses, and specialists, as well as accessibility to specialist ancillary services, with the goal of establishing hospital site-specific staff and coordination of local resources.

Equipment/Supplies. Develop potential physical and structural enhancements that address issues of mobility, comfort, safety, and behavioral needs (including memory cues and sensorial perception) while decreasing iatrogenic complications, such as the development of pressure ulcers (eg, the use of reclining chairs and pressure-redistributing foam mattresses).

Education. Provide nurse and clinical provider education and specialty-specific training focusing on contemporary, research-based geriatric-specific material, with regular assessment for interdisciplinary core competencies.

Policies/Procedures/Protocols. Implement a directed, comprehensive approach to facilitate screening and assessment of geriatric patients for added needs/post-ED adverse outcomes, as well as validated, ED-feasible screening tools/instruments for delirium and dementia, medication management, falls, use of urinary catheters, and the provision of palliative care.

Follow-up/Transitions of Care. Design discharge processes best suited for older patients (eg, large-font instructions), as well as collaborate with community resources to provide home-health services and home safety assessment in order to facilitate care following discharge.

Quality Improvement. Implement a system to collect and monitor pertinent and prevalent geriatric emergency care indicators (eg, incidence of injurious falls and documentation of fall risk assessment) designed to increase staff education and program success.

The authors clearly state that the GED guidelines represent recommendations. They are not a mandate for every ED, nor are they a list that requires 100% compliance. Instead, the document provides the potential steps to be taken, the rationale for these recommendations, and an outline of the resources available to aid in the transition from theory to implementation in any ED. The goal is to ensure better, safer, and age-appropriate treatment. In summary, these guidelines represent an effort to improve and even transform emergency care for older adults on the brink of one of the most significant challenges facing our healthcare system both in and beyond the ED.

Moving forward, the authors of the GED guidelines have defined a plan that “includes dissemination, implementation, adaptation, and refinement.” In addition to approval by each of the organization’s board of directors and the copyright of the material in 2013, the ED guidelines have now been widely disseminated through publication in numerous news articles (including international publications) and discussions on satellite radio. Tracking of new GEDs is planned. In addition, the prioritization of the guidelines is underway using a modified Delphi method, with the express purpose of assessing the relative potential benefits and harms associated with each recommendation by providing a weighted list from most important to least important.

A “Geriatric Emergency Department Boot Camp” is being developed to bring the recommendations to hospitals interested in “geriatricizing” their EDs. Geriatric EM leaders will act as consultants, providing training and a toolbox of resources. Specific reviews and revisions of the GED guidelines will take place in a 4- to 5-year cycle. Clearly, a next important step is the development of a GED certification system based on outcome studies of the individual components.

Criticisms of the GED guidelines have already been voiced among some EM providers. Specific concerns include a fear of partitioning the ED (as has occurred with pediatrics); an increase in cost and decreased efficiency; the need to maintain general expertise among EM physicians; the lack of evidence-based data upon which the recommendations were made; the fact that some guidelines were extrapolated from other clinical settings; and the belief that these changes will be too logistically difficult and take too much time.

The fact remains that the wave of geriatric patients (the “silver tsunami”) is already beginning to hit the shores of our hospitals. And GEDs are already here to help absorb the impact. The lack of iron-clad evidence for many of the recommendations should not be an absolute obstacle, but rather part of the natural evolution and improvement of similar endeavors. Nor should GEDs contain empty beds while younger adults sit in the waiting room, or conversely, force the elderly to wait for space in the GED when there are empty beds in the main ED. Ideally, the GED should be the location where the ED staff can implement these guidelines, which they can afterwards utilize in any part of the ED. These guidelines are designed to provide the best available expert opinion on how to deliver better geriatric care in the ED. The imperative for this goal is clear and necessitates this educated “leap-of-faith.” Change is never easy and often comes with an upfront cost of time, resources, and money. Moreover, there is nothing in a well-designed GED that may not also benefit, or at least will not adversely affect care of a younger adult as well. Therefore, flexibility and optimal utilization of space in a busy ED need not be sacrificed.

Conclusion

To improve diagnostic evaluation and care of the increasing number of geriatric patients presenting to the ED, reliable tools, protocols, and guidelines must be developed and implemented to ensure diagnostic accuracy, decrease adverse events, and improve patient outcomes. Fortunately, the new GED consensus guidelines are flexible and do not need to be wholly embraced—lending themselves to modifications and institution-specific adoptions. The “protocolization” and implementation of the guidelines may improve patient flow, operational efficiency, and, most importantly, the quality of care delivered. And likely, these guidelines will provide the foundation for future education and research into the improved emergency care of older adults.

The GED guidelines can be accessed at http://www.saem.org/docs/education/geri_ed_guidelines_final.pdf?sfvrsn=2.

Dr Stern is an assistant professor of medicine and codirector, geriatric emergency medicine fellowship, department of emergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York; and an assistant attending physician, department of emergency medicine, New York-Presbyterian Hospital.
Dr Mulcare is an instructor of medicine and an assistant attending physician, department of emergency medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York. She is a former fellow of geriatric emergency medicine.