The management of a febrile infant is complex and requires obtaining a detailed history of all possible exposures. Published guidelines alone are not always completely accurate for diagnosing or excluding serious illness, and are not a substitute for a thorough examination and history.

Case

The parents of a 45-day-old girl were referred to our regional pediatric hospital by a local community hospital for emergent evaluation of their infant. The day prior, they had taken the infant to the referring ED because of persistent fussiness and subjective fever. They were neither sure of the tests that were obtained during that visit nor why they were instructed to take their daughter to our pediatric facility. They did, however, recall that during the visit to the community ED, the patient had a rectal temperature of 102.7°F, was given an antibiotic injection, and was well appearing and acting normally. Also, at discharge, the infant’s parents were instructed to follow up with the patient’s pediatrician within 24 hours.

Since their daughter’s discharge from the community ED, both parents noted that she seemed more irritable, felt warm, and had not been feeding well. They confirmed that she was an otherwise healthy infant who had been born full term via normal vaginal delivery and without complications.

On initial assessment at our ED, the patient was fussy and had mottled extremities and dusky nail beds. Her vital signs at presentation were: heart rate, 223 beats/minute; respiratory rate, 36 breaths/minute; and rectal temperature, 103.6°F. Oxygen saturation was 96% on room air. The infant was resuscitated with 20 mL/kg of intravenous (IV) normal saline and given oral acetaminophen. Laboratory studies were obtained, and a lumbar puncture (LP) was performed.

She was treated with IV acyclovir, ceftriaxone, and vancomycin. Her complete blood count (CBC) was notable for a white blood cell count (WBC) of 22.60 x 10⁹/L; cerebrospinal fluid (CSF) analysis revealed a WBC of 4.52 x 10⁹/L with 75% neutrophils, and serum glucose of 63 mg/dL.

Since the patient’s parents did not have any paperwork or information from the prior ED visit, our ED contacted the community ED by phone, and a representative provided the following information: the patient had appeared well but was febrile at presentation; laboratory evaluation was obtained, but no LP was performed; she was treated with intramuscular (IM) ceftriaxone and acetaminophen; and she was discharged home in the care of her parents. Regarding laboratory studies performed at the community ED, the only test result made available by phone was the preliminary blood culture report that revealed growth of gram-negative rods with speciation pending, which prompted the referral to our facility.

Based on the information provided by the community ED and our evaluation and work-up, the patient was admitted to the pediatric intensive care unit. Magnetic resonance imaging (MRI) of the brain was performed, which showed debris in the lateral ventricles consistent with ventriculitis—likely secondary to meningitis. The blood, urine, and cerebrospinal fluid (CSF) cultures collected during our evaluation produced no growth; however, blood cultures from the rural ED eventually grew Salmonella.

A further detailed history revealed that the infant and her parents had been living with a family friend who owned an iguana. According to reports, the iguana had free run of the home and often crawled around and across the infant while she was lying on a blanket on the floor. The patient’s parents were not aware of the diseases associated with reptile contact. Due to concerns over the social situation, the patient was kept in the hospital for the entire recommended 21-day course of antibiotic therapy, during which time the parents received assistance finding alternate living arrangements.

Discussion

Current Practice Guidelines for Managing Febrile Infants

Current guidelines from the American Academy of Pediatrics (AAP) and the American College of Emergency Physicians (ACEP) recommend a full sepsis work-up for all neonates (ie, ages 0 to 28 days) who present with a fever (defined as a rectal temperature ≥100.4°F).^1,2 The probability of a serious bacterial infection (SBI) in patients in this age group who present with fever is approximately 12%.³ A full sepsis work-up generally includes a CBC, blood cultures, urinalysis with culture, CSF analysis with culture, and stool cultures if diarrhea is present.

Current guidelines for infants 29 to 90 days of age who present with fever differ between professional associations. The AAP and the American Academy of Family Physicians recommend the following for children in this age range: laboratory evaluation with CBC, blood cultures, CSF analysis, urinalysis, and culture. If laboratory evaluation reveals a WBC of less than 15 x 10⁹/L with an absolute neutrophil count of less than 10 x 10⁹/L, along with a normal CSF and urinalysis, the patient can be given IM ceftriaxone and follow-up arranged in 24 hours. This approach is recommended for patients who are otherwise healthy, nontoxic at presentation, and under the care of a responsible adult.^4,5 By comparison, the Philadelphia protocol, though suggesting an identical work-up, recommends against the use of antibiotics in infants deemed at low risk for SBI.⁶

The ACEP does not specifically endorse a management strategy for febrile infants in the 29- to 90-day age group, but instead acknowledges that no age cut-off within this group can be considered absolute when determining management strategy, and suggests that children up to 60 days old should be managed in a manner similar to neonates.² The published guidelines do not include consideration of specific history exposure in the management recommendations.

Typhoidal Serotypes

Salmonella can be divided into typhoidal (including S typhi and S paratyphi) and nontyphoidal serotypes (NTS), with the two groups manifesting as very different diseases.⁷ Typhoidal serotypes lead to the disease process known as typhoid, which typically presents with fever, chills, abdominal pain, nonbloody diarrhea or constipation, nausea, anorexia, headache, hepatosplenomegaly, and rose spots.⁸ These symptoms typically present after a 14-day incubation period and persist for 21 days.⁹ Humans are the only known infected source of these species, which are spread via the fecal-oral route.¹⁰

In contrast, disease from NTS manifests within 12 hours of exposure with watery diarrhea, nausea, vomiting, and fever, with symptoms lasting up to 10 days.¹¹ Both groups cause disease by invading the intestinal epithelium¹²; however, typhoidal species induce less intestinal inflammation, facilitating bacterial invasion and making systemic disease more likely.¹³

Transmission

Many animals are known to carry NTS, including reptiles, where Salmonella occurs naturally in their gastrointestinal tract.¹⁴ Twenty-five percent of Salmonella infections in children younger than age 5 years have been attributed to contact with a pet,¹⁵ with small turtles (shell diameter <4 inches) accounting for 42% of all pet-related Salmonella infections.

Though gastroenteritis is the most common clinical manifestation of infection with NTS, approximately 5% of patients will develop invasive disease, including bacteremia, meningitis, septic arthritis, or osteomyelitis.¹⁶ Children with invasive disease are more likely to have been exposed to an iguana, snake, or bearded dragon than to a turtle. If the pet is kept indoors, the risk of invasive disease is more likely. The average age of patients with invasive disease is 62 days, versus 2 years for noninvasive disease.¹⁷

Diagnosis

Growth of Salmonella on cultures of stool, blood, urine, or CSF dishes is the mainstay of diagnosis of typhoid and nontyphoidal disease, but bacterial concentrations are higher in bone marrow aspirate, making it superior to blood cultures.¹⁸ Biopsy of the rose spots of typhoid may also provide the diagnosis.

Management

Since Salmonella gastroenteritis is usually a self-limited disease, current recommendations reserve treatment with antibiotics for patients with severe disease or who are immunocompromised. When necessary, treatment consists of 7 to 10 days of a fluoroquinolone or third-generation cephalosporin, which is the same regimen suggested for typhoid. Treatment of central nervous system (CNS) salmonellosis consists of at least 3 weeks of a third-generation cephalosporin; the AAP recommends at least 4 weeks of treatment.¹⁹

Case Conclusion

Prior to the patient’s transfer to our facility, she was treated empirically with ceftriaxone without prior CSF analysis—an approach that does not follow any current guidelines for the treatment of a febrile infant. Though an LP was not performed until approximately 24 hours after the initial antibiotic was given, the patient demonstrated CSF pleocytosis with no organisms on gram stain and no growth on culture. Given this pleocytosis and Salmonella bacteremia in the context of prior antibiotic treatment, and MRI consistent with CNS involvement, the patient was treated for 21 days for presumed Salmonella meningitis. A CSF analysis performed on her initial visit could have more accurately directed the type and duration of treatment if the findings on subsequent imaging studies and CSF analysis were ambiguous.

Summary

Emergency physicians may underestimate the likelihood of SBI in otherwise well-appearing febrile infants. While certain aspects of the history and physical examination in a febrile, well-appearing infant have been shown to correlate with an increased risk of SBI, no single finding can definitively rule in or rule out the disease.²⁰ Opinions differ as to optimal management strategies for febrile, well-appearing infants outside the neonatal period. However, an appropriate level of clinical suspicion, within the context of a thorough investigation into the infant’s health history and social situation, can aid the clinician and guide treatment and disposition.

The management of a febrile infant is complex and requires obtaining a detailed history of all possible exposures. Published guidelines alone are not always completely accurate for diagnosing or excluding serious illness, and are not a substitute for a thorough examination and history.

Case

The parents of a 45-day-old girl were referred to our regional pediatric hospital by a local community hospital for emergent evaluation of their infant. The day prior, they had taken the infant to the referring ED because of persistent fussiness and subjective fever. They were neither sure of the tests that were obtained during that visit nor why they were instructed to take their daughter to our pediatric facility. They did, however, recall that during the visit to the community ED, the patient had a rectal temperature of 102.7°F, was given an antibiotic injection, and was well appearing and acting normally. Also, at discharge, the infant’s parents were instructed to follow up with the patient’s pediatrician within 24 hours.

Since their daughter’s discharge from the community ED, both parents noted that she seemed more irritable, felt warm, and had not been feeding well. They confirmed that she was an otherwise healthy infant who had been born full term via normal vaginal delivery and without complications.

On initial assessment at our ED, the patient was fussy and had mottled extremities and dusky nail beds. Her vital signs at presentation were: heart rate, 223 beats/minute; respiratory rate, 36 breaths/minute; and rectal temperature, 103.6°F. Oxygen saturation was 96% on room air. The infant was resuscitated with 20 mL/kg of intravenous (IV) normal saline and given oral acetaminophen. Laboratory studies were obtained, and a lumbar puncture (LP) was performed.

She was treated with IV acyclovir, ceftriaxone, and vancomycin. Her complete blood count (CBC) was notable for a white blood cell count (WBC) of 22.60 x 10⁹/L; cerebrospinal fluid (CSF) analysis revealed a WBC of 4.52 x 10⁹/L with 75% neutrophils, and serum glucose of 63 mg/dL.

Since the patient’s parents did not have any paperwork or information from the prior ED visit, our ED contacted the community ED by phone, and a representative provided the following information: the patient had appeared well but was febrile at presentation; laboratory evaluation was obtained, but no LP was performed; she was treated with intramuscular (IM) ceftriaxone and acetaminophen; and she was discharged home in the care of her parents. Regarding laboratory studies performed at the community ED, the only test result made available by phone was the preliminary blood culture report that revealed growth of gram-negative rods with speciation pending, which prompted the referral to our facility.

Based on the information provided by the community ED and our evaluation and work-up, the patient was admitted to the pediatric intensive care unit. Magnetic resonance imaging (MRI) of the brain was performed, which showed debris in the lateral ventricles consistent with ventriculitis—likely secondary to meningitis. The blood, urine, and cerebrospinal fluid (CSF) cultures collected during our evaluation produced no growth; however, blood cultures from the rural ED eventually grew Salmonella.

A further detailed history revealed that the infant and her parents had been living with a family friend who owned an iguana. According to reports, the iguana had free run of the home and often crawled around and across the infant while she was lying on a blanket on the floor. The patient’s parents were not aware of the diseases associated with reptile contact. Due to concerns over the social situation, the patient was kept in the hospital for the entire recommended 21-day course of antibiotic therapy, during which time the parents received assistance finding alternate living arrangements.

Discussion

Current Practice Guidelines for Managing Febrile Infants

Current guidelines from the American Academy of Pediatrics (AAP) and the American College of Emergency Physicians (ACEP) recommend a full sepsis work-up for all neonates (ie, ages 0 to 28 days) who present with a fever (defined as a rectal temperature ≥100.4°F).^1,2 The probability of a serious bacterial infection (SBI) in patients in this age group who present with fever is approximately 12%.³ A full sepsis work-up generally includes a CBC, blood cultures, urinalysis with culture, CSF analysis with culture, and stool cultures if diarrhea is present.

Current guidelines for infants 29 to 90 days of age who present with fever differ between professional associations. The AAP and the American Academy of Family Physicians recommend the following for children in this age range: laboratory evaluation with CBC, blood cultures, CSF analysis, urinalysis, and culture. If laboratory evaluation reveals a WBC of less than 15 x 10⁹/L with an absolute neutrophil count of less than 10 x 10⁹/L, along with a normal CSF and urinalysis, the patient can be given IM ceftriaxone and follow-up arranged in 24 hours. This approach is recommended for patients who are otherwise healthy, nontoxic at presentation, and under the care of a responsible adult.^4,5 By comparison, the Philadelphia protocol, though suggesting an identical work-up, recommends against the use of antibiotics in infants deemed at low risk for SBI.⁶

The ACEP does not specifically endorse a management strategy for febrile infants in the 29- to 90-day age group, but instead acknowledges that no age cut-off within this group can be considered absolute when determining management strategy, and suggests that children up to 60 days old should be managed in a manner similar to neonates.² The published guidelines do not include consideration of specific history exposure in the management recommendations.

Typhoidal Serotypes

Salmonella can be divided into typhoidal (including S typhi and S paratyphi) and nontyphoidal serotypes (NTS), with the two groups manifesting as very different diseases.⁷ Typhoidal serotypes lead to the disease process known as typhoid, which typically presents with fever, chills, abdominal pain, nonbloody diarrhea or constipation, nausea, anorexia, headache, hepatosplenomegaly, and rose spots.⁸ These symptoms typically present after a 14-day incubation period and persist for 21 days.⁹ Humans are the only known infected source of these species, which are spread via the fecal-oral route.¹⁰

In contrast, disease from NTS manifests within 12 hours of exposure with watery diarrhea, nausea, vomiting, and fever, with symptoms lasting up to 10 days.¹¹ Both groups cause disease by invading the intestinal epithelium¹²; however, typhoidal species induce less intestinal inflammation, facilitating bacterial invasion and making systemic disease more likely.¹³

Transmission

Many animals are known to carry NTS, including reptiles, where Salmonella occurs naturally in their gastrointestinal tract.¹⁴ Twenty-five percent of Salmonella infections in children younger than age 5 years have been attributed to contact with a pet,¹⁵ with small turtles (shell diameter <4 inches) accounting for 42% of all pet-related Salmonella infections.

Though gastroenteritis is the most common clinical manifestation of infection with NTS, approximately 5% of patients will develop invasive disease, including bacteremia, meningitis, septic arthritis, or osteomyelitis.¹⁶ Children with invasive disease are more likely to have been exposed to an iguana, snake, or bearded dragon than to a turtle. If the pet is kept indoors, the risk of invasive disease is more likely. The average age of patients with invasive disease is 62 days, versus 2 years for noninvasive disease.¹⁷

Diagnosis

Growth of Salmonella on cultures of stool, blood, urine, or CSF dishes is the mainstay of diagnosis of typhoid and nontyphoidal disease, but bacterial concentrations are higher in bone marrow aspirate, making it superior to blood cultures.¹⁸ Biopsy of the rose spots of typhoid may also provide the diagnosis.

Management

Since Salmonella gastroenteritis is usually a self-limited disease, current recommendations reserve treatment with antibiotics for patients with severe disease or who are immunocompromised. When necessary, treatment consists of 7 to 10 days of a fluoroquinolone or third-generation cephalosporin, which is the same regimen suggested for typhoid. Treatment of central nervous system (CNS) salmonellosis consists of at least 3 weeks of a third-generation cephalosporin; the AAP recommends at least 4 weeks of treatment.¹⁹

Case Conclusion

Prior to the patient’s transfer to our facility, she was treated empirically with ceftriaxone without prior CSF analysis—an approach that does not follow any current guidelines for the treatment of a febrile infant. Though an LP was not performed until approximately 24 hours after the initial antibiotic was given, the patient demonstrated CSF pleocytosis with no organisms on gram stain and no growth on culture. Given this pleocytosis and Salmonella bacteremia in the context of prior antibiotic treatment, and MRI consistent with CNS involvement, the patient was treated for 21 days for presumed Salmonella meningitis. A CSF analysis performed on her initial visit could have more accurately directed the type and duration of treatment if the findings on subsequent imaging studies and CSF analysis were ambiguous.

Summary

Emergency physicians may underestimate the likelihood of SBI in otherwise well-appearing febrile infants. While certain aspects of the history and physical examination in a febrile, well-appearing infant have been shown to correlate with an increased risk of SBI, no single finding can definitively rule in or rule out the disease.²⁰ Opinions differ as to optimal management strategies for febrile, well-appearing infants outside the neonatal period. However, an appropriate level of clinical suspicion, within the context of a thorough investigation into the infant’s health history and social situation, can aid the clinician and guide treatment and disposition.

The management of a febrile infant is complex and requires obtaining a detailed history of all possible exposures. Published guidelines alone are not always completely accurate for diagnosing or excluding serious illness, and are not a substitute for a thorough examination and history.

Case

The parents of a 45-day-old girl were referred to our regional pediatric hospital by a local community hospital for emergent evaluation of their infant. The day prior, they had taken the infant to the referring ED because of persistent fussiness and subjective fever. They were neither sure of the tests that were obtained during that visit nor why they were instructed to take their daughter to our pediatric facility. They did, however, recall that during the visit to the community ED, the patient had a rectal temperature of 102.7°F, was given an antibiotic injection, and was well appearing and acting normally. Also, at discharge, the infant’s parents were instructed to follow up with the patient’s pediatrician within 24 hours.

Since their daughter’s discharge from the community ED, both parents noted that she seemed more irritable, felt warm, and had not been feeding well. They confirmed that she was an otherwise healthy infant who had been born full term via normal vaginal delivery and without complications.

On initial assessment at our ED, the patient was fussy and had mottled extremities and dusky nail beds. Her vital signs at presentation were: heart rate, 223 beats/minute; respiratory rate, 36 breaths/minute; and rectal temperature, 103.6°F. Oxygen saturation was 96% on room air. The infant was resuscitated with 20 mL/kg of intravenous (IV) normal saline and given oral acetaminophen. Laboratory studies were obtained, and a lumbar puncture (LP) was performed.

She was treated with IV acyclovir, ceftriaxone, and vancomycin. Her complete blood count (CBC) was notable for a white blood cell count (WBC) of 22.60 x 10⁹/L; cerebrospinal fluid (CSF) analysis revealed a WBC of 4.52 x 10⁹/L with 75% neutrophils, and serum glucose of 63 mg/dL.

Since the patient’s parents did not have any paperwork or information from the prior ED visit, our ED contacted the community ED by phone, and a representative provided the following information: the patient had appeared well but was febrile at presentation; laboratory evaluation was obtained, but no LP was performed; she was treated with intramuscular (IM) ceftriaxone and acetaminophen; and she was discharged home in the care of her parents. Regarding laboratory studies performed at the community ED, the only test result made available by phone was the preliminary blood culture report that revealed growth of gram-negative rods with speciation pending, which prompted the referral to our facility.

Based on the information provided by the community ED and our evaluation and work-up, the patient was admitted to the pediatric intensive care unit. Magnetic resonance imaging (MRI) of the brain was performed, which showed debris in the lateral ventricles consistent with ventriculitis—likely secondary to meningitis. The blood, urine, and cerebrospinal fluid (CSF) cultures collected during our evaluation produced no growth; however, blood cultures from the rural ED eventually grew Salmonella.

A further detailed history revealed that the infant and her parents had been living with a family friend who owned an iguana. According to reports, the iguana had free run of the home and often crawled around and across the infant while she was lying on a blanket on the floor. The patient’s parents were not aware of the diseases associated with reptile contact. Due to concerns over the social situation, the patient was kept in the hospital for the entire recommended 21-day course of antibiotic therapy, during which time the parents received assistance finding alternate living arrangements.

Discussion

Current Practice Guidelines for Managing Febrile Infants

Current guidelines from the American Academy of Pediatrics (AAP) and the American College of Emergency Physicians (ACEP) recommend a full sepsis work-up for all neonates (ie, ages 0 to 28 days) who present with a fever (defined as a rectal temperature ≥100.4°F).^1,2 The probability of a serious bacterial infection (SBI) in patients in this age group who present with fever is approximately 12%.³ A full sepsis work-up generally includes a CBC, blood cultures, urinalysis with culture, CSF analysis with culture, and stool cultures if diarrhea is present.

Current guidelines for infants 29 to 90 days of age who present with fever differ between professional associations. The AAP and the American Academy of Family Physicians recommend the following for children in this age range: laboratory evaluation with CBC, blood cultures, CSF analysis, urinalysis, and culture. If laboratory evaluation reveals a WBC of less than 15 x 10⁹/L with an absolute neutrophil count of less than 10 x 10⁹/L, along with a normal CSF and urinalysis, the patient can be given IM ceftriaxone and follow-up arranged in 24 hours. This approach is recommended for patients who are otherwise healthy, nontoxic at presentation, and under the care of a responsible adult.^4,5 By comparison, the Philadelphia protocol, though suggesting an identical work-up, recommends against the use of antibiotics in infants deemed at low risk for SBI.⁶

The ACEP does not specifically endorse a management strategy for febrile infants in the 29- to 90-day age group, but instead acknowledges that no age cut-off within this group can be considered absolute when determining management strategy, and suggests that children up to 60 days old should be managed in a manner similar to neonates.² The published guidelines do not include consideration of specific history exposure in the management recommendations.

Typhoidal Serotypes

Salmonella can be divided into typhoidal (including S typhi and S paratyphi) and nontyphoidal serotypes (NTS), with the two groups manifesting as very different diseases.⁷ Typhoidal serotypes lead to the disease process known as typhoid, which typically presents with fever, chills, abdominal pain, nonbloody diarrhea or constipation, nausea, anorexia, headache, hepatosplenomegaly, and rose spots.⁸ These symptoms typically present after a 14-day incubation period and persist for 21 days.⁹ Humans are the only known infected source of these species, which are spread via the fecal-oral route.¹⁰

In contrast, disease from NTS manifests within 12 hours of exposure with watery diarrhea, nausea, vomiting, and fever, with symptoms lasting up to 10 days.¹¹ Both groups cause disease by invading the intestinal epithelium¹²; however, typhoidal species induce less intestinal inflammation, facilitating bacterial invasion and making systemic disease more likely.¹³

Transmission

Many animals are known to carry NTS, including reptiles, where Salmonella occurs naturally in their gastrointestinal tract.¹⁴ Twenty-five percent of Salmonella infections in children younger than age 5 years have been attributed to contact with a pet,¹⁵ with small turtles (shell diameter <4 inches) accounting for 42% of all pet-related Salmonella infections.

Though gastroenteritis is the most common clinical manifestation of infection with NTS, approximately 5% of patients will develop invasive disease, including bacteremia, meningitis, septic arthritis, or osteomyelitis.¹⁶ Children with invasive disease are more likely to have been exposed to an iguana, snake, or bearded dragon than to a turtle. If the pet is kept indoors, the risk of invasive disease is more likely. The average age of patients with invasive disease is 62 days, versus 2 years for noninvasive disease.¹⁷

Diagnosis

Growth of Salmonella on cultures of stool, blood, urine, or CSF dishes is the mainstay of diagnosis of typhoid and nontyphoidal disease, but bacterial concentrations are higher in bone marrow aspirate, making it superior to blood cultures.¹⁸ Biopsy of the rose spots of typhoid may also provide the diagnosis.

Management

Since Salmonella gastroenteritis is usually a self-limited disease, current recommendations reserve treatment with antibiotics for patients with severe disease or who are immunocompromised. When necessary, treatment consists of 7 to 10 days of a fluoroquinolone or third-generation cephalosporin, which is the same regimen suggested for typhoid. Treatment of central nervous system (CNS) salmonellosis consists of at least 3 weeks of a third-generation cephalosporin; the AAP recommends at least 4 weeks of treatment.¹⁹

Case Conclusion

Prior to the patient’s transfer to our facility, she was treated empirically with ceftriaxone without prior CSF analysis—an approach that does not follow any current guidelines for the treatment of a febrile infant. Though an LP was not performed until approximately 24 hours after the initial antibiotic was given, the patient demonstrated CSF pleocytosis with no organisms on gram stain and no growth on culture. Given this pleocytosis and Salmonella bacteremia in the context of prior antibiotic treatment, and MRI consistent with CNS involvement, the patient was treated for 21 days for presumed Salmonella meningitis. A CSF analysis performed on her initial visit could have more accurately directed the type and duration of treatment if the findings on subsequent imaging studies and CSF analysis were ambiguous.

Summary

Emergency physicians may underestimate the likelihood of SBI in otherwise well-appearing febrile infants. While certain aspects of the history and physical examination in a febrile, well-appearing infant have been shown to correlate with an increased risk of SBI, no single finding can definitively rule in or rule out the disease.²⁰ Opinions differ as to optimal management strategies for febrile, well-appearing infants outside the neonatal period. However, an appropriate level of clinical suspicion, within the context of a thorough investigation into the infant’s health history and social situation, can aid the clinician and guide treatment and disposition.

Most emergency physicians (EPs) encounter several patients a year with hemorrhages due to factor Xa (FXa) inhibitors. Such bleeding may occur in patterns not previously recognized with traditional anticoagulant therapy. Retrobulbar hemorrhage is typically associated with significant facial or orbital trauma, and spontaneous hemorrhage is a very rare cause of orbital compartment syndrome.¹ Retrobulbar hemorrhage can lead to orbital compartment syndrome due to increased orbital pressure within a closed space. Because orbital compartment syndrome can compromise blood flow to the optic nerve or central retinal artery, it is extremely important to decrease orbital pressure as quickly as possible in affected patients. Therefore, canthotomy/cantholysis should be performed sooner rather than later, as 90 minutes of elevated intraocular pressure (IOP) can lead to permanent vision loss.²

Rivaroxaban, one of the relatively new oral anticoagulant agents that inhibit FXa, is used as an alternative therapy to vitamin K antagonists. The FXa agents have been approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (AF).³ According to a meta-analysis of rivaroxaban and bleeding risk, rivaroxaban was shown to have no increased risk of major or clinically relevant nonmajor bleeding compared to vitamin K antagonists. Rivaroxaban was also associated with a significant decrease in fatal bleeding (relative risk, 0.48, 95%; confidence interval, 0.31 to 0.74).⁴

Case Report

A 79-year-old man with a medical history of hypertension, transient ischemic attacks (TIAs), and AF, for which he was taking rivaroxaban, was referred to our ED by a local rural ED for further evaluation and treatment of a retrobulbar hemorrhage. (The patient’s family refused emergency medical services transport from the rural ED.) The patient stated that upon awakening earlier that morning, he felt “pressure” in his right eye and experienced periorbital swelling that continued to worsen throughout the day. He denied any trauma, falls, or strikes to the face or head. The patient’s account and history were confirmed by the family members with whom he resided.

During the patient’s evaluation at the rural ED, a computed tomography (CT) scan of the head was performed, which demonstrated a retrobulbar hematoma on the right side (See the Figure for an example of a CT scan illustrating a retrobulbar hematoma with proptosis). Since the patient’s initial right IOP was 32 mm Hg (normal range, 12-22 mm Hg), ophthalmology services at this institution performed a lateral canthotomy. The patient’s right IOP postsurgery decreased but remained elevated at 27 mm Hg. In addition to surgical intervention, he was given oral acetazolamide and timolol. Then, because the patient was hemodynamically stable, he was referred to our institution for further evaluation.

Upon arrival at our ED, the patient reported slow bleeding from the canthotomy site. He denied any chest pain, shortness of breath, light-headedness, dizziness, or visual changes. Additional history revealed that in addition to taking rivaroxaban, the patient was also on a daily 81-mg aspirin regimen. His vital signs at presentation were: blood pressure (BP), 130/68 mm Hg; heart rate, 75 beats/minute; and respiratory rate, 16 breaths/minute; and temperature, afebrile. Oxygen saturation was 99% on room air.

Physical examination revealed blood oozing from the right eye at the canthotomy site. There was no other evidence of trauma to the eye or head, and IOP of the right eye was normal at 14 mm Hg. Laboratory studies revealed a hemoglobin value of 16.8 g/dL, a hematocrit of 48%, and a white blood cell (WBC) count of 8.8 x 10⁹/L. The basic metabolic profile, including creatinine, was unremarkable. A type and screen blood pretransfusion compatibility test was also ordered.

Since the patient’s ocular hemorrhaging persisted, ophthalmology services were consulted. The ophthalmology examination measured a right IOP of 14 mm Hg and a visual acuity of 20/200. The patient’s pupils were equal, round, and reactive to light, and a subconjunctival hematoma was noted. The ophthalmologist recommended no further surgical interventions at that time.

Due to the continued ocular bleeding, hematology services were also consulted. The hematologist recommended 50 U/kg of intravenous (IV) prothrombin complex concentrate (PCC) to reverse the anticoagulatory effects of rivaroxaban. The patient was given one dose of PCC in the ED. Throughout his ED course, the patient did not experience any deterioration of visual acuity. However, during repeated IOP checks, he experienced one episode of vasovagal syncope with a systolic BP in the 70s. The syncope resolved promptly after the patient was placed in a supine position and was given an IV bolus of normal saline fluid. The patient still had oozing at the incision site, and was admitted to the general medicine floor. 

During his inpatient stay, the patient remained hemodynamically stable and did not require transfusion of blood or platelet products. All home anticoagulant medications were discontinued. The patient continued to have some oozing the following morning, and was given an additional dose of IV PCC (50 U/kg), which resolved the bleeding. He remained hemostatic and, based on his history of AF, he was discharged home on warfarin without bridge therapy. Both rivaroxaban and daily aspirin therapy were discontinued. The lateral canthotomy and cantholysis healed without need for surgical intervention. An ophthalmology follow-up clinic visit 1 week after discharge from the hospital revealed an already self-healed incision without ectropion or retraction and with only mild laxity. Given the patient’s history of AF with TIAs while off anticoagulants, the ophthalmologist did not recommend any other surgical intervention that would have required discontinuing the warfarin.

Discussion

With any retrobulbar hematoma, one must be concerned for orbital compartment syndrome. Orbital hemorrhage is the most common cause of orbital compartment syndrome, usually occurring secondary to trauma, surgery, or retrobulbar injection. In this case, spontaneous hemorrhage due to anticoagulation was believed to be the cause—albeit a rare one—of orbital compartment syndrome. Because the orbital space is enclosed and cannot expand, it is vulnerable to compartment syndrome, and subsequent ischemia can lead to permanent vision impairment or complete loss of vision.⁵ Early recognition and treatment is imperative to preserve vision as an elevated intraorbital pressure for 60 to 100 minutes can lead to permanent visual sequelae.

Management

Treatment of retrobulbar hemorrhage includes lateral canthotomy and cantholysis, which have been shown to reduce IOP an average of 14.2 mm Hg.⁶ In our patient, IOP in the affected eye was reduced by 18 mm Hg.  In addition to the patient’s high IOP at presentation, another concern was the continued hemorrhaging from both the incision site and its potential to exacerbate the underlying retrobulbar hematoma. Management of this condition posed a challenge because this patient was taking a newer anticoagulant, for which there is currently no specific reversal agent. After consultation with hematology services, the patient was given PCC because small studies have suggested that PCC may reverse rivaroxaban-induced anticoagulation.⁷ While more expensive than fresh frozen plasma, PCC has a high safety profile and should be considered in cases of life-threatening bleeding—especially in patients who have renal failure, as rivaroxaban is renally excreted. The half-life of rivaroxaban is 5 to 9 hours and its effects may last up to 12 hours. An IV dose of 50 U/kg PCC can be effective in reversing rivaroxaban; this dose can be repeated every 12 hours until hemorrhaging abates or until rivaroxaban is cleared. 

Potential Factor Xa Reversal Agent

Phase IV trials are underway in the ANNEX-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa inhibitors – Apixaban) and ANNEX-R (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa inhibitors – Rivaroxaban) studies assessing andexanet alpha, an FXa inhibitor reversal agent and potential FXa inhibitor antidote. Andexanet alpha is a decoy protein that binds to FXa inhibitors in the active site, restoring endogenous FXa and reducing anticoagulant activity.⁸ This serves as another promising reversal agent for apixaban, edoxaban, and rivaroxaban. With the development of these new FXa reversal agents, EPs will have more options for reversal of anticoagulation in patients with unique hemorrhagic presentations.

Conclusion

Rivaroxaban has the potential to replace warfarin as a “novel” oral anticoagulant of choice for multiple indications, especially as more insurance companies cover the use of the FXa inhibitors. As a result of their increased use, the EP is likely to see an increasing number of patients who present with hemorrhagic consequences of the FXa inhibitors, and in turn must be familiar with the properties of this class of anticoagulants—including potential reversal strategies.

Our case of spontaneous retrobulbar hemorrhage may be one of these new patterns of bleeding to be expected from a novel FXa inhibitor. Therefore, it is imperative that EPs consider retrobulbar hemorrhage and other possible bleeding locations in patients on an FXa inhibitor.

Most emergency physicians (EPs) encounter several patients a year with hemorrhages due to factor Xa (FXa) inhibitors. Such bleeding may occur in patterns not previously recognized with traditional anticoagulant therapy. Retrobulbar hemorrhage is typically associated with significant facial or orbital trauma, and spontaneous hemorrhage is a very rare cause of orbital compartment syndrome.¹ Retrobulbar hemorrhage can lead to orbital compartment syndrome due to increased orbital pressure within a closed space. Because orbital compartment syndrome can compromise blood flow to the optic nerve or central retinal artery, it is extremely important to decrease orbital pressure as quickly as possible in affected patients. Therefore, canthotomy/cantholysis should be performed sooner rather than later, as 90 minutes of elevated intraocular pressure (IOP) can lead to permanent vision loss.²

Rivaroxaban, one of the relatively new oral anticoagulant agents that inhibit FXa, is used as an alternative therapy to vitamin K antagonists. The FXa agents have been approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (AF).³ According to a meta-analysis of rivaroxaban and bleeding risk, rivaroxaban was shown to have no increased risk of major or clinically relevant nonmajor bleeding compared to vitamin K antagonists. Rivaroxaban was also associated with a significant decrease in fatal bleeding (relative risk, 0.48, 95%; confidence interval, 0.31 to 0.74).⁴

Case Report

A 79-year-old man with a medical history of hypertension, transient ischemic attacks (TIAs), and AF, for which he was taking rivaroxaban, was referred to our ED by a local rural ED for further evaluation and treatment of a retrobulbar hemorrhage. (The patient’s family refused emergency medical services transport from the rural ED.) The patient stated that upon awakening earlier that morning, he felt “pressure” in his right eye and experienced periorbital swelling that continued to worsen throughout the day. He denied any trauma, falls, or strikes to the face or head. The patient’s account and history were confirmed by the family members with whom he resided.

During the patient’s evaluation at the rural ED, a computed tomography (CT) scan of the head was performed, which demonstrated a retrobulbar hematoma on the right side (See the Figure for an example of a CT scan illustrating a retrobulbar hematoma with proptosis). Since the patient’s initial right IOP was 32 mm Hg (normal range, 12-22 mm Hg), ophthalmology services at this institution performed a lateral canthotomy. The patient’s right IOP postsurgery decreased but remained elevated at 27 mm Hg. In addition to surgical intervention, he was given oral acetazolamide and timolol. Then, because the patient was hemodynamically stable, he was referred to our institution for further evaluation.

Upon arrival at our ED, the patient reported slow bleeding from the canthotomy site. He denied any chest pain, shortness of breath, light-headedness, dizziness, or visual changes. Additional history revealed that in addition to taking rivaroxaban, the patient was also on a daily 81-mg aspirin regimen. His vital signs at presentation were: blood pressure (BP), 130/68 mm Hg; heart rate, 75 beats/minute; and respiratory rate, 16 breaths/minute; and temperature, afebrile. Oxygen saturation was 99% on room air.

Physical examination revealed blood oozing from the right eye at the canthotomy site. There was no other evidence of trauma to the eye or head, and IOP of the right eye was normal at 14 mm Hg. Laboratory studies revealed a hemoglobin value of 16.8 g/dL, a hematocrit of 48%, and a white blood cell (WBC) count of 8.8 x 10⁹/L. The basic metabolic profile, including creatinine, was unremarkable. A type and screen blood pretransfusion compatibility test was also ordered.

Since the patient’s ocular hemorrhaging persisted, ophthalmology services were consulted. The ophthalmology examination measured a right IOP of 14 mm Hg and a visual acuity of 20/200. The patient’s pupils were equal, round, and reactive to light, and a subconjunctival hematoma was noted. The ophthalmologist recommended no further surgical interventions at that time.

Due to the continued ocular bleeding, hematology services were also consulted. The hematologist recommended 50 U/kg of intravenous (IV) prothrombin complex concentrate (PCC) to reverse the anticoagulatory effects of rivaroxaban. The patient was given one dose of PCC in the ED. Throughout his ED course, the patient did not experience any deterioration of visual acuity. However, during repeated IOP checks, he experienced one episode of vasovagal syncope with a systolic BP in the 70s. The syncope resolved promptly after the patient was placed in a supine position and was given an IV bolus of normal saline fluid. The patient still had oozing at the incision site, and was admitted to the general medicine floor. 

During his inpatient stay, the patient remained hemodynamically stable and did not require transfusion of blood or platelet products. All home anticoagulant medications were discontinued. The patient continued to have some oozing the following morning, and was given an additional dose of IV PCC (50 U/kg), which resolved the bleeding. He remained hemostatic and, based on his history of AF, he was discharged home on warfarin without bridge therapy. Both rivaroxaban and daily aspirin therapy were discontinued. The lateral canthotomy and cantholysis healed without need for surgical intervention. An ophthalmology follow-up clinic visit 1 week after discharge from the hospital revealed an already self-healed incision without ectropion or retraction and with only mild laxity. Given the patient’s history of AF with TIAs while off anticoagulants, the ophthalmologist did not recommend any other surgical intervention that would have required discontinuing the warfarin.

Discussion

With any retrobulbar hematoma, one must be concerned for orbital compartment syndrome. Orbital hemorrhage is the most common cause of orbital compartment syndrome, usually occurring secondary to trauma, surgery, or retrobulbar injection. In this case, spontaneous hemorrhage due to anticoagulation was believed to be the cause—albeit a rare one—of orbital compartment syndrome. Because the orbital space is enclosed and cannot expand, it is vulnerable to compartment syndrome, and subsequent ischemia can lead to permanent vision impairment or complete loss of vision.⁵ Early recognition and treatment is imperative to preserve vision as an elevated intraorbital pressure for 60 to 100 minutes can lead to permanent visual sequelae.

Management

Treatment of retrobulbar hemorrhage includes lateral canthotomy and cantholysis, which have been shown to reduce IOP an average of 14.2 mm Hg.⁶ In our patient, IOP in the affected eye was reduced by 18 mm Hg.  In addition to the patient’s high IOP at presentation, another concern was the continued hemorrhaging from both the incision site and its potential to exacerbate the underlying retrobulbar hematoma. Management of this condition posed a challenge because this patient was taking a newer anticoagulant, for which there is currently no specific reversal agent. After consultation with hematology services, the patient was given PCC because small studies have suggested that PCC may reverse rivaroxaban-induced anticoagulation.⁷ While more expensive than fresh frozen plasma, PCC has a high safety profile and should be considered in cases of life-threatening bleeding—especially in patients who have renal failure, as rivaroxaban is renally excreted. The half-life of rivaroxaban is 5 to 9 hours and its effects may last up to 12 hours. An IV dose of 50 U/kg PCC can be effective in reversing rivaroxaban; this dose can be repeated every 12 hours until hemorrhaging abates or until rivaroxaban is cleared. 

Potential Factor Xa Reversal Agent

Phase IV trials are underway in the ANNEX-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa inhibitors – Apixaban) and ANNEX-R (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa inhibitors – Rivaroxaban) studies assessing andexanet alpha, an FXa inhibitor reversal agent and potential FXa inhibitor antidote. Andexanet alpha is a decoy protein that binds to FXa inhibitors in the active site, restoring endogenous FXa and reducing anticoagulant activity.⁸ This serves as another promising reversal agent for apixaban, edoxaban, and rivaroxaban. With the development of these new FXa reversal agents, EPs will have more options for reversal of anticoagulation in patients with unique hemorrhagic presentations.

Conclusion

Rivaroxaban has the potential to replace warfarin as a “novel” oral anticoagulant of choice for multiple indications, especially as more insurance companies cover the use of the FXa inhibitors. As a result of their increased use, the EP is likely to see an increasing number of patients who present with hemorrhagic consequences of the FXa inhibitors, and in turn must be familiar with the properties of this class of anticoagulants—including potential reversal strategies.

Our case of spontaneous retrobulbar hemorrhage may be one of these new patterns of bleeding to be expected from a novel FXa inhibitor. Therefore, it is imperative that EPs consider retrobulbar hemorrhage and other possible bleeding locations in patients on an FXa inhibitor.

Most emergency physicians (EPs) encounter several patients a year with hemorrhages due to factor Xa (FXa) inhibitors. Such bleeding may occur in patterns not previously recognized with traditional anticoagulant therapy. Retrobulbar hemorrhage is typically associated with significant facial or orbital trauma, and spontaneous hemorrhage is a very rare cause of orbital compartment syndrome.¹ Retrobulbar hemorrhage can lead to orbital compartment syndrome due to increased orbital pressure within a closed space. Because orbital compartment syndrome can compromise blood flow to the optic nerve or central retinal artery, it is extremely important to decrease orbital pressure as quickly as possible in affected patients. Therefore, canthotomy/cantholysis should be performed sooner rather than later, as 90 minutes of elevated intraocular pressure (IOP) can lead to permanent vision loss.²

Rivaroxaban, one of the relatively new oral anticoagulant agents that inhibit FXa, is used as an alternative therapy to vitamin K antagonists. The FXa agents have been approved to reduce the risk of stroke in patients with nonvalvular atrial fibrillation (AF).³ According to a meta-analysis of rivaroxaban and bleeding risk, rivaroxaban was shown to have no increased risk of major or clinically relevant nonmajor bleeding compared to vitamin K antagonists. Rivaroxaban was also associated with a significant decrease in fatal bleeding (relative risk, 0.48, 95%; confidence interval, 0.31 to 0.74).⁴

Case Report

A 79-year-old man with a medical history of hypertension, transient ischemic attacks (TIAs), and AF, for which he was taking rivaroxaban, was referred to our ED by a local rural ED for further evaluation and treatment of a retrobulbar hemorrhage. (The patient’s family refused emergency medical services transport from the rural ED.) The patient stated that upon awakening earlier that morning, he felt “pressure” in his right eye and experienced periorbital swelling that continued to worsen throughout the day. He denied any trauma, falls, or strikes to the face or head. The patient’s account and history were confirmed by the family members with whom he resided.

During the patient’s evaluation at the rural ED, a computed tomography (CT) scan of the head was performed, which demonstrated a retrobulbar hematoma on the right side (See the Figure for an example of a CT scan illustrating a retrobulbar hematoma with proptosis). Since the patient’s initial right IOP was 32 mm Hg (normal range, 12-22 mm Hg), ophthalmology services at this institution performed a lateral canthotomy. The patient’s right IOP postsurgery decreased but remained elevated at 27 mm Hg. In addition to surgical intervention, he was given oral acetazolamide and timolol. Then, because the patient was hemodynamically stable, he was referred to our institution for further evaluation.

Upon arrival at our ED, the patient reported slow bleeding from the canthotomy site. He denied any chest pain, shortness of breath, light-headedness, dizziness, or visual changes. Additional history revealed that in addition to taking rivaroxaban, the patient was also on a daily 81-mg aspirin regimen. His vital signs at presentation were: blood pressure (BP), 130/68 mm Hg; heart rate, 75 beats/minute; and respiratory rate, 16 breaths/minute; and temperature, afebrile. Oxygen saturation was 99% on room air.

Physical examination revealed blood oozing from the right eye at the canthotomy site. There was no other evidence of trauma to the eye or head, and IOP of the right eye was normal at 14 mm Hg. Laboratory studies revealed a hemoglobin value of 16.8 g/dL, a hematocrit of 48%, and a white blood cell (WBC) count of 8.8 x 10⁹/L. The basic metabolic profile, including creatinine, was unremarkable. A type and screen blood pretransfusion compatibility test was also ordered.

Since the patient’s ocular hemorrhaging persisted, ophthalmology services were consulted. The ophthalmology examination measured a right IOP of 14 mm Hg and a visual acuity of 20/200. The patient’s pupils were equal, round, and reactive to light, and a subconjunctival hematoma was noted. The ophthalmologist recommended no further surgical interventions at that time.

Due to the continued ocular bleeding, hematology services were also consulted. The hematologist recommended 50 U/kg of intravenous (IV) prothrombin complex concentrate (PCC) to reverse the anticoagulatory effects of rivaroxaban. The patient was given one dose of PCC in the ED. Throughout his ED course, the patient did not experience any deterioration of visual acuity. However, during repeated IOP checks, he experienced one episode of vasovagal syncope with a systolic BP in the 70s. The syncope resolved promptly after the patient was placed in a supine position and was given an IV bolus of normal saline fluid. The patient still had oozing at the incision site, and was admitted to the general medicine floor. 

During his inpatient stay, the patient remained hemodynamically stable and did not require transfusion of blood or platelet products. All home anticoagulant medications were discontinued. The patient continued to have some oozing the following morning, and was given an additional dose of IV PCC (50 U/kg), which resolved the bleeding. He remained hemostatic and, based on his history of AF, he was discharged home on warfarin without bridge therapy. Both rivaroxaban and daily aspirin therapy were discontinued. The lateral canthotomy and cantholysis healed without need for surgical intervention. An ophthalmology follow-up clinic visit 1 week after discharge from the hospital revealed an already self-healed incision without ectropion or retraction and with only mild laxity. Given the patient’s history of AF with TIAs while off anticoagulants, the ophthalmologist did not recommend any other surgical intervention that would have required discontinuing the warfarin.

Discussion

With any retrobulbar hematoma, one must be concerned for orbital compartment syndrome. Orbital hemorrhage is the most common cause of orbital compartment syndrome, usually occurring secondary to trauma, surgery, or retrobulbar injection. In this case, spontaneous hemorrhage due to anticoagulation was believed to be the cause—albeit a rare one—of orbital compartment syndrome. Because the orbital space is enclosed and cannot expand, it is vulnerable to compartment syndrome, and subsequent ischemia can lead to permanent vision impairment or complete loss of vision.⁵ Early recognition and treatment is imperative to preserve vision as an elevated intraorbital pressure for 60 to 100 minutes can lead to permanent visual sequelae.

Management

Treatment of retrobulbar hemorrhage includes lateral canthotomy and cantholysis, which have been shown to reduce IOP an average of 14.2 mm Hg.⁶ In our patient, IOP in the affected eye was reduced by 18 mm Hg.  In addition to the patient’s high IOP at presentation, another concern was the continued hemorrhaging from both the incision site and its potential to exacerbate the underlying retrobulbar hematoma. Management of this condition posed a challenge because this patient was taking a newer anticoagulant, for which there is currently no specific reversal agent. After consultation with hematology services, the patient was given PCC because small studies have suggested that PCC may reverse rivaroxaban-induced anticoagulation.⁷ While more expensive than fresh frozen plasma, PCC has a high safety profile and should be considered in cases of life-threatening bleeding—especially in patients who have renal failure, as rivaroxaban is renally excreted. The half-life of rivaroxaban is 5 to 9 hours and its effects may last up to 12 hours. An IV dose of 50 U/kg PCC can be effective in reversing rivaroxaban; this dose can be repeated every 12 hours until hemorrhaging abates or until rivaroxaban is cleared. 

Potential Factor Xa Reversal Agent

Phase IV trials are underway in the ANNEX-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa inhibitors – Apixaban) and ANNEX-R (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of FXa inhibitors – Rivaroxaban) studies assessing andexanet alpha, an FXa inhibitor reversal agent and potential FXa inhibitor antidote. Andexanet alpha is a decoy protein that binds to FXa inhibitors in the active site, restoring endogenous FXa and reducing anticoagulant activity.⁸ This serves as another promising reversal agent for apixaban, edoxaban, and rivaroxaban. With the development of these new FXa reversal agents, EPs will have more options for reversal of anticoagulation in patients with unique hemorrhagic presentations.

Conclusion

Rivaroxaban has the potential to replace warfarin as a “novel” oral anticoagulant of choice for multiple indications, especially as more insurance companies cover the use of the FXa inhibitors. As a result of their increased use, the EP is likely to see an increasing number of patients who present with hemorrhagic consequences of the FXa inhibitors, and in turn must be familiar with the properties of this class of anticoagulants—including potential reversal strategies.

Our case of spontaneous retrobulbar hemorrhage may be one of these new patterns of bleeding to be expected from a novel FXa inhibitor. Therefore, it is imperative that EPs consider retrobulbar hemorrhage and other possible bleeding locations in patients on an FXa inhibitor.

A 23-year-old woman presents to dermatology with an itchy rash she has had for several months. Although it manifested on her wrists and finger, the rash moves around and causes itching on her legs, trunk, and arms at various times. It has not affected her breasts or axillae.

The patient has been seen in primary care several times and received the usual topical steroids, antihistamines, and at least three courses of prednisone—none affording much relief.

She denies that anyone else in her household is itching. During her last visit to primary care, they treated her with topical permethrin cream, which was to be left on overnight then washed off. No relief was forthcoming.

EXAMINATION
Scattered areas of faint eczematoid rashes can be seen across her thighs and arms. There are two or three tiny excoriated papules on both volar wrists, but no intact vesicles are observed.

A closer inspection of her palms reveals one tiny linear vesicle on the mid right palm. Vigorous scraping with a #10 blade produces material, which is placed on a slide, covered, filled with potassium hydroxide 10%, and examined under a microscope.

What is the diagnosis?

DISCUSSION
Microscopic evaluation revealed a scabies adult, still moving among the dead cells. The paucity of organisms was probably a result of the prior treatment with permethrin, which confused the issue. When scabies is suspected, there’s only one way to confirm it: Perform a KOH prep. Otherwise, it’s just guesswork.

This particular patient was under the (faulty) impression that because her permethrin treatment failed, she didn’t have scabies. But a single treatment with topical antiscabetic cream is rarely curative. It must be done twice, seven to 10 days apart, to kill organisms newly hatched from eggs lain in the skin. In many cases, oral ivermectin is needed as well.

The itching experienced with scabies is due to an allergic response to scabetic material (droppings, tissue juice). The resultant eczematous rash can be very challenging to deal with.

Three other people live in the patient’s house, and it’s likely that these family members have been infested over several months’ time. They need treatment as well and will require two applications of cream.

Thought should also be given to how the patient acquired the infestation, lest she get it again. This may result in the need to avoid contact with certain people or confront them about their possible role as the source.

TAKE-HOME LEARNING POINTS
• The itching and rash of scabies result from an allergic reaction to the scabetic elements deposited in the skin. This reaction can closely resemble eczema.
• A single treatment of permethrin cream is unlikely to clear scabies. In order to have an effect on the eggs lain in the skin (which hatch in seven to 10 days), two treatments are necessary.
• Many cases of scabies will survive permethrin treatment, so consider adding ivermectin (oral antiscabetic medication) to the regimen.
• All family members living in the same house must be treated at the same time, lest they re-infest one another.
• KOH prep is the gold standard for diagnosing scabies.

A 23-year-old woman presents to dermatology with an itchy rash she has had for several months. Although it manifested on her wrists and finger, the rash moves around and causes itching on her legs, trunk, and arms at various times. It has not affected her breasts or axillae.

The patient has been seen in primary care several times and received the usual topical steroids, antihistamines, and at least three courses of prednisone—none affording much relief.

She denies that anyone else in her household is itching. During her last visit to primary care, they treated her with topical permethrin cream, which was to be left on overnight then washed off. No relief was forthcoming.

EXAMINATION
Scattered areas of faint eczematoid rashes can be seen across her thighs and arms. There are two or three tiny excoriated papules on both volar wrists, but no intact vesicles are observed.

A closer inspection of her palms reveals one tiny linear vesicle on the mid right palm. Vigorous scraping with a #10 blade produces material, which is placed on a slide, covered, filled with potassium hydroxide 10%, and examined under a microscope.

What is the diagnosis?

DISCUSSION
Microscopic evaluation revealed a scabies adult, still moving among the dead cells. The paucity of organisms was probably a result of the prior treatment with permethrin, which confused the issue. When scabies is suspected, there’s only one way to confirm it: Perform a KOH prep. Otherwise, it’s just guesswork.

This particular patient was under the (faulty) impression that because her permethrin treatment failed, she didn’t have scabies. But a single treatment with topical antiscabetic cream is rarely curative. It must be done twice, seven to 10 days apart, to kill organisms newly hatched from eggs lain in the skin. In many cases, oral ivermectin is needed as well.

The itching experienced with scabies is due to an allergic response to scabetic material (droppings, tissue juice). The resultant eczematous rash can be very challenging to deal with.

Three other people live in the patient’s house, and it’s likely that these family members have been infested over several months’ time. They need treatment as well and will require two applications of cream.

Thought should also be given to how the patient acquired the infestation, lest she get it again. This may result in the need to avoid contact with certain people or confront them about their possible role as the source.

TAKE-HOME LEARNING POINTS
• The itching and rash of scabies result from an allergic reaction to the scabetic elements deposited in the skin. This reaction can closely resemble eczema.
• A single treatment of permethrin cream is unlikely to clear scabies. In order to have an effect on the eggs lain in the skin (which hatch in seven to 10 days), two treatments are necessary.
• Many cases of scabies will survive permethrin treatment, so consider adding ivermectin (oral antiscabetic medication) to the regimen.
• All family members living in the same house must be treated at the same time, lest they re-infest one another.
• KOH prep is the gold standard for diagnosing scabies.

A 23-year-old woman presents to dermatology with an itchy rash she has had for several months. Although it manifested on her wrists and finger, the rash moves around and causes itching on her legs, trunk, and arms at various times. It has not affected her breasts or axillae.

The patient has been seen in primary care several times and received the usual topical steroids, antihistamines, and at least three courses of prednisone—none affording much relief.

She denies that anyone else in her household is itching. During her last visit to primary care, they treated her with topical permethrin cream, which was to be left on overnight then washed off. No relief was forthcoming.

EXAMINATION
Scattered areas of faint eczematoid rashes can be seen across her thighs and arms. There are two or three tiny excoriated papules on both volar wrists, but no intact vesicles are observed.

A closer inspection of her palms reveals one tiny linear vesicle on the mid right palm. Vigorous scraping with a #10 blade produces material, which is placed on a slide, covered, filled with potassium hydroxide 10%, and examined under a microscope.

What is the diagnosis?

DISCUSSION
Microscopic evaluation revealed a scabies adult, still moving among the dead cells. The paucity of organisms was probably a result of the prior treatment with permethrin, which confused the issue. When scabies is suspected, there’s only one way to confirm it: Perform a KOH prep. Otherwise, it’s just guesswork.

This particular patient was under the (faulty) impression that because her permethrin treatment failed, she didn’t have scabies. But a single treatment with topical antiscabetic cream is rarely curative. It must be done twice, seven to 10 days apart, to kill organisms newly hatched from eggs lain in the skin. In many cases, oral ivermectin is needed as well.

The itching experienced with scabies is due to an allergic response to scabetic material (droppings, tissue juice). The resultant eczematous rash can be very challenging to deal with.

Three other people live in the patient’s house, and it’s likely that these family members have been infested over several months’ time. They need treatment as well and will require two applications of cream.

Thought should also be given to how the patient acquired the infestation, lest she get it again. This may result in the need to avoid contact with certain people or confront them about their possible role as the source.

TAKE-HOME LEARNING POINTS
• The itching and rash of scabies result from an allergic reaction to the scabetic elements deposited in the skin. This reaction can closely resemble eczema.
• A single treatment of permethrin cream is unlikely to clear scabies. In order to have an effect on the eggs lain in the skin (which hatch in seven to 10 days), two treatments are necessary.
• Many cases of scabies will survive permethrin treatment, so consider adding ivermectin (oral antiscabetic medication) to the regimen.
• All family members living in the same house must be treated at the same time, lest they re-infest one another.
• KOH prep is the gold standard for diagnosing scabies.

A 61-year-old woman without any known medical history presented with a chief complaint of right arm numbness and right-sided scalp numbness that had started 2 days earlier. She described a “pins and needles” sensation in her right upper extremity and right scalp, and said the numbness in her scalp was especially noticeable when she combed her hair. The patient denied any chest pain, shortness of breath, weakness in her arms or legs, headache, or blurred vision.

She said that 1 day prior to the onset of the paresthesias, she woke up fatigued and vomited once. Throughout that day, she had symptoms of nausea and fatigue, and sought treatment at an urgent care center that afternoon. At the urgent care center, she was diagnosed with a “stomach virus” and was given an antiemetic. The next day, her nausea improved, but the paresthesias began in her right hand and scalp. On the third day, the patient went to work, but the persistent paresthesias caused her to visit her primary care physician, who sent her to our ED for further work-up.

The patient said she had been in good health until 3 days ago. She reported no medical problems and was taking no medications. The patient denied smoking or using alcohol; her family history was significant only in that her father had a myocardial infarction (MI) while in his 50s.

On physical examination, the patient was alert, oriented, and in no apparent distress. Her body mass index was 28.3 kg/m². Vital signs were: temperature, 99.2°F; blood pressure, 113/73 mm Hg; heart rate, 93 beats/minute; and respiratory rate, 18 breaths/minute. Oxygen saturation was 95% on room air.

Her head was normocephalic and atraumatic, and her eyes, ears, nose, and throat were normal. Her neck was supple and without jugular vein distension. The cardiac examination revealed normal heart sounds without murmurs, rubs, or gallops. Her lungs were clear without rales, wheezes, or rhonchi. Her abdomen was soft, without tenderness, guarding, or rebound, and she had normal bowel sounds.

Her musculoskeletal examination was normal, with +5/5 strength bilaterally in her upper and lower extremities. The patient’s skin examination also was normal. On neurological examination, her right upper extremity and right side of her face were noted to have decreased sensation via pinprick compared to the left side, but the examination was otherwise normal. The National Institutes of Health Stroke Scale score was 1.

The patient’s electrocardiogram (ECG) showed a normal sinus rhythm (rate, 90 beats/min), a lateral infarct of undetermined age, and a left atrial abnormality. Laboratory evaluation was significant only for a brain natriuretic peptide level of 334 pg/mL, a creatine phosphokinase (CPK) level of 782 IU/L, and a troponin I level of >50 ng/mL (Table). Serial cardiac enzyme levels were obtained and showed a decline of CPK from 782 IU/L to 331 IU/L over the following 36 hours. However, the troponin I levels remained >50 ng/mL for 5 days and then declined to 31.6 ng/mL.

A computed  tomography (CT) scan of the brain without contrast revealed an acute to subacute infarct in the left occipital and left thalamic regions (Figure). A stat transthoracic echocardiogram (ECHO) performed in the ED revealed a dilated left ventricle with an ejection fraction of 20% to 25%, along with a hypokinetic anterolateral wall and an akinetic inferolateral wall. No atrial thrombus was visible on the ECHO. Doppler studies of the patient’s lower extremities were negative for deep vein thrombosis. Magnetic resonance imaging of her brain showed an infarct in the posterior circulation distribution involving the left occipital lobes and small areas in the left thalamic and right parietal-occipital regions. Hemorrhagic conversion of the left occipital infarct without mass effect was also noted. The patient was admitted to the neurological intensive care unit for frequent neurological examinations and close monitoring for worsening cerebral hemorrhage.

When the patient had still been in the ED, cardiology services were consulted; the cardiologist initiated a heparin drip with close monitoring of the coagulation studies. Cardiac catheterization was not done immediately because the ECG did not show acute ST elevations. The day after her presentation to the ED, the patient underwent a primary percutaneous coronary catheterization and was found to have a small rudimentary left anterior descending artery, with only small branches supplying the septal region. The right circumflex artery was very large and was supplying the lateral wall. No stents were placed during this procedure. A transesophageal ECHO (TEE) showed no evidence of a left atrial appendage thrombus.

The patient experienced an episode of coffee ground emesis while undergoing the TEE. Her hemoglobin declined from 11.9 g/dL to 7.9 g/dL, which led to a transfusion of 2 U  of packed red blood cells and platelets. Heparin was discontinued and a proton pump inhibitor was started; however, no endoscopy was done at that time.

Throughout her stay, the patient was continuously monitored, but no evidence of arrhythmia or atrial fibrillation was found. Upon discharge, the neurologist recommended the patient receive clopidogrel and aspirin therapy for 3 months with subsequent aspirin monotherapy afterward. The patient was discharged after 10 days in the hospital.

Discussion

Although she had an MI, the patient presented here did not experience any chest pain. Her chief complaint in the ED was paresthesias related to her concomitant stroke, and only on further probing did she describe the additional symptoms of fatigability and vomiting.

Since heart disease and stroke share common risk factors and pathophysiology, acute cerebral ischemic events may happen concurrently with MIs. In a review of studies that included approximately 2,900 patients who had an acute stroke, Kerr et al¹ found that 20% had elevated troponin levels within 7 days of the stroke. In 2013, the American Heart Association and American Stroke Association published guidelines advising that all patients who present with acute cerebral ischemia have an emergent ECG and baseline troponin level.² This was in response to evidence that even low positive troponin levels have been associated with an increased risk of mortality.³ Positive troponin levels are especially important because fatal and nonfatal stroke post-MI events have been found to be increasing in frequency for women, even though there has been a significant overall reduction in post-MI mortality.⁴ Patients who have an ischemic stroke concurrently with an acute MI or soon after have an overall poorer clinical prognosis.⁵

For emergency physicians (EPs),  this is a “chicken or the egg” scenario. It is difficult to determine which came first: the MI or the cerebral ischemia. Similar risk factors can result in an acute embolic event from revascularization, atrial fibrillation without proper anticoagulation, or a poorly functioning left ventricle.⁶ It is important to remember that regardless of the order of occurrence, the incidence of ischemic stroke is markedly increased in conjunction with an acute MI.⁷ Several theories have been advanced regarding the relationship between ischemic stroke and acute MI. One theory proposes that elevated troponin levels could be related to a large catecholamine release after a cerebral ischemic stroke, resulting in subsequent myocardial injury or cardiomyopathy.⁷ However, this theory remains controversial.

Management

The major consideration for the EP is whether or not to give thrombolytics to a patient who presents with concomitant acute MI and ischemic stroke. An acute MI within the 3 months preceding an acute stroke is considered a relative contraindication for intravenous tissue plasminogen activator (tPA).⁸ It has also been found, albeit rarely, that there is an increased risk of cardiac rupture or tamponade due to the breakdown of the fibrin clot within the necrotic cardiac tissue.⁸

How should patients with stroke complicated by acute cardiac compromise be managed in the ED? One acute vascular event cannot be ignored while addressing the other. There are no evidence-based guidelines for the management of patients who present with this picture.⁸ In addition, no published clinical studies have focused on the decision-making process for these patients.⁸

Immediate percutaneous coronary intervention for the MI performed on such patients would prevent the use of tPA for the acute stroke. Though any anticoagulation increases the risk for postischemic cerebral hemorrhage, heparin is necessary to prevent the formation of a left ventricle thrombus.⁷ Alternately, mechanical thrombectomy and cardiac catheterization may be combined as emergent treatments for these patients, but performing these two procedures simultaneously is not widely available.

For a patient who presents to the ED within both the cardiac and stroke treatment windows, tPA might be a viable option, and the only one readily valuable.⁸ However, the EP must be mindful of the varying dosages of tPA and means of administration for different thrombosis sites. Also, care must be taken when treating a patient with dual or triple antiplatelet therapy because of the increased risk of hemorrhage.⁹ Currently, no safe standardized regimens have been established, and further trials need to be performed.¹⁰

If the patient in this case report had presented at our ED with only signs and symptoms of an MI, typically she would have been treated with heparin, aspirin, and an urgent cardiac catheterization. If she had presented with only signs and symptoms of a stroke, she would have been treated with full-dose aspirin and worked up from a neurological perspective. Because she had signs and symptoms of both, she presented a dilemma. She was initially treated with heparin to prevent a thrombus formation, but then later changed to only clopidogrel and aspirin to prevent further episodes of coffee ground emesis or worsening hemorrhagic conversion.

Conclusion

Common risk factors for cardiac and cerebral ischemic events may result in a patient presenting with both acute MI and an acute cerebral ischemic event. There have not been sufficient clinical studies to determine the best decision-making process for these patients. Therefore, patients with this complicated presentation must be assessed on an individual basis. Current treatment options are varied and are based according to history of the present illness, time of presentation to the ED, and the available resources within the hospital.

A 61-year-old woman without any known medical history presented with a chief complaint of right arm numbness and right-sided scalp numbness that had started 2 days earlier. She described a “pins and needles” sensation in her right upper extremity and right scalp, and said the numbness in her scalp was especially noticeable when she combed her hair. The patient denied any chest pain, shortness of breath, weakness in her arms or legs, headache, or blurred vision.

She said that 1 day prior to the onset of the paresthesias, she woke up fatigued and vomited once. Throughout that day, she had symptoms of nausea and fatigue, and sought treatment at an urgent care center that afternoon. At the urgent care center, she was diagnosed with a “stomach virus” and was given an antiemetic. The next day, her nausea improved, but the paresthesias began in her right hand and scalp. On the third day, the patient went to work, but the persistent paresthesias caused her to visit her primary care physician, who sent her to our ED for further work-up.

The patient said she had been in good health until 3 days ago. She reported no medical problems and was taking no medications. The patient denied smoking or using alcohol; her family history was significant only in that her father had a myocardial infarction (MI) while in his 50s.

On physical examination, the patient was alert, oriented, and in no apparent distress. Her body mass index was 28.3 kg/m². Vital signs were: temperature, 99.2°F; blood pressure, 113/73 mm Hg; heart rate, 93 beats/minute; and respiratory rate, 18 breaths/minute. Oxygen saturation was 95% on room air.

Her head was normocephalic and atraumatic, and her eyes, ears, nose, and throat were normal. Her neck was supple and without jugular vein distension. The cardiac examination revealed normal heart sounds without murmurs, rubs, or gallops. Her lungs were clear without rales, wheezes, or rhonchi. Her abdomen was soft, without tenderness, guarding, or rebound, and she had normal bowel sounds.

Her musculoskeletal examination was normal, with +5/5 strength bilaterally in her upper and lower extremities. The patient’s skin examination also was normal. On neurological examination, her right upper extremity and right side of her face were noted to have decreased sensation via pinprick compared to the left side, but the examination was otherwise normal. The National Institutes of Health Stroke Scale score was 1.

The patient’s electrocardiogram (ECG) showed a normal sinus rhythm (rate, 90 beats/min), a lateral infarct of undetermined age, and a left atrial abnormality. Laboratory evaluation was significant only for a brain natriuretic peptide level of 334 pg/mL, a creatine phosphokinase (CPK) level of 782 IU/L, and a troponin I level of >50 ng/mL (Table). Serial cardiac enzyme levels were obtained and showed a decline of CPK from 782 IU/L to 331 IU/L over the following 36 hours. However, the troponin I levels remained >50 ng/mL for 5 days and then declined to 31.6 ng/mL.

A computed  tomography (CT) scan of the brain without contrast revealed an acute to subacute infarct in the left occipital and left thalamic regions (Figure). A stat transthoracic echocardiogram (ECHO) performed in the ED revealed a dilated left ventricle with an ejection fraction of 20% to 25%, along with a hypokinetic anterolateral wall and an akinetic inferolateral wall. No atrial thrombus was visible on the ECHO. Doppler studies of the patient’s lower extremities were negative for deep vein thrombosis. Magnetic resonance imaging of her brain showed an infarct in the posterior circulation distribution involving the left occipital lobes and small areas in the left thalamic and right parietal-occipital regions. Hemorrhagic conversion of the left occipital infarct without mass effect was also noted. The patient was admitted to the neurological intensive care unit for frequent neurological examinations and close monitoring for worsening cerebral hemorrhage.

When the patient had still been in the ED, cardiology services were consulted; the cardiologist initiated a heparin drip with close monitoring of the coagulation studies. Cardiac catheterization was not done immediately because the ECG did not show acute ST elevations. The day after her presentation to the ED, the patient underwent a primary percutaneous coronary catheterization and was found to have a small rudimentary left anterior descending artery, with only small branches supplying the septal region. The right circumflex artery was very large and was supplying the lateral wall. No stents were placed during this procedure. A transesophageal ECHO (TEE) showed no evidence of a left atrial appendage thrombus.

The patient experienced an episode of coffee ground emesis while undergoing the TEE. Her hemoglobin declined from 11.9 g/dL to 7.9 g/dL, which led to a transfusion of 2 U  of packed red blood cells and platelets. Heparin was discontinued and a proton pump inhibitor was started; however, no endoscopy was done at that time.

Throughout her stay, the patient was continuously monitored, but no evidence of arrhythmia or atrial fibrillation was found. Upon discharge, the neurologist recommended the patient receive clopidogrel and aspirin therapy for 3 months with subsequent aspirin monotherapy afterward. The patient was discharged after 10 days in the hospital.

Discussion

Although she had an MI, the patient presented here did not experience any chest pain. Her chief complaint in the ED was paresthesias related to her concomitant stroke, and only on further probing did she describe the additional symptoms of fatigability and vomiting.

Since heart disease and stroke share common risk factors and pathophysiology, acute cerebral ischemic events may happen concurrently with MIs. In a review of studies that included approximately 2,900 patients who had an acute stroke, Kerr et al¹ found that 20% had elevated troponin levels within 7 days of the stroke. In 2013, the American Heart Association and American Stroke Association published guidelines advising that all patients who present with acute cerebral ischemia have an emergent ECG and baseline troponin level.² This was in response to evidence that even low positive troponin levels have been associated with an increased risk of mortality.³ Positive troponin levels are especially important because fatal and nonfatal stroke post-MI events have been found to be increasing in frequency for women, even though there has been a significant overall reduction in post-MI mortality.⁴ Patients who have an ischemic stroke concurrently with an acute MI or soon after have an overall poorer clinical prognosis.⁵

For emergency physicians (EPs),  this is a “chicken or the egg” scenario. It is difficult to determine which came first: the MI or the cerebral ischemia. Similar risk factors can result in an acute embolic event from revascularization, atrial fibrillation without proper anticoagulation, or a poorly functioning left ventricle.⁶ It is important to remember that regardless of the order of occurrence, the incidence of ischemic stroke is markedly increased in conjunction with an acute MI.⁷ Several theories have been advanced regarding the relationship between ischemic stroke and acute MI. One theory proposes that elevated troponin levels could be related to a large catecholamine release after a cerebral ischemic stroke, resulting in subsequent myocardial injury or cardiomyopathy.⁷ However, this theory remains controversial.

Management

The major consideration for the EP is whether or not to give thrombolytics to a patient who presents with concomitant acute MI and ischemic stroke. An acute MI within the 3 months preceding an acute stroke is considered a relative contraindication for intravenous tissue plasminogen activator (tPA).⁸ It has also been found, albeit rarely, that there is an increased risk of cardiac rupture or tamponade due to the breakdown of the fibrin clot within the necrotic cardiac tissue.⁸

How should patients with stroke complicated by acute cardiac compromise be managed in the ED? One acute vascular event cannot be ignored while addressing the other. There are no evidence-based guidelines for the management of patients who present with this picture.⁸ In addition, no published clinical studies have focused on the decision-making process for these patients.⁸

Immediate percutaneous coronary intervention for the MI performed on such patients would prevent the use of tPA for the acute stroke. Though any anticoagulation increases the risk for postischemic cerebral hemorrhage, heparin is necessary to prevent the formation of a left ventricle thrombus.⁷ Alternately, mechanical thrombectomy and cardiac catheterization may be combined as emergent treatments for these patients, but performing these two procedures simultaneously is not widely available.

For a patient who presents to the ED within both the cardiac and stroke treatment windows, tPA might be a viable option, and the only one readily valuable.⁸ However, the EP must be mindful of the varying dosages of tPA and means of administration for different thrombosis sites. Also, care must be taken when treating a patient with dual or triple antiplatelet therapy because of the increased risk of hemorrhage.⁹ Currently, no safe standardized regimens have been established, and further trials need to be performed.¹⁰

If the patient in this case report had presented at our ED with only signs and symptoms of an MI, typically she would have been treated with heparin, aspirin, and an urgent cardiac catheterization. If she had presented with only signs and symptoms of a stroke, she would have been treated with full-dose aspirin and worked up from a neurological perspective. Because she had signs and symptoms of both, she presented a dilemma. She was initially treated with heparin to prevent a thrombus formation, but then later changed to only clopidogrel and aspirin to prevent further episodes of coffee ground emesis or worsening hemorrhagic conversion.

Conclusion

Common risk factors for cardiac and cerebral ischemic events may result in a patient presenting with both acute MI and an acute cerebral ischemic event. There have not been sufficient clinical studies to determine the best decision-making process for these patients. Therefore, patients with this complicated presentation must be assessed on an individual basis. Current treatment options are varied and are based according to history of the present illness, time of presentation to the ED, and the available resources within the hospital.

A 61-year-old woman without any known medical history presented with a chief complaint of right arm numbness and right-sided scalp numbness that had started 2 days earlier. She described a “pins and needles” sensation in her right upper extremity and right scalp, and said the numbness in her scalp was especially noticeable when she combed her hair. The patient denied any chest pain, shortness of breath, weakness in her arms or legs, headache, or blurred vision.

She said that 1 day prior to the onset of the paresthesias, she woke up fatigued and vomited once. Throughout that day, she had symptoms of nausea and fatigue, and sought treatment at an urgent care center that afternoon. At the urgent care center, she was diagnosed with a “stomach virus” and was given an antiemetic. The next day, her nausea improved, but the paresthesias began in her right hand and scalp. On the third day, the patient went to work, but the persistent paresthesias caused her to visit her primary care physician, who sent her to our ED for further work-up.

The patient said she had been in good health until 3 days ago. She reported no medical problems and was taking no medications. The patient denied smoking or using alcohol; her family history was significant only in that her father had a myocardial infarction (MI) while in his 50s.

On physical examination, the patient was alert, oriented, and in no apparent distress. Her body mass index was 28.3 kg/m². Vital signs were: temperature, 99.2°F; blood pressure, 113/73 mm Hg; heart rate, 93 beats/minute; and respiratory rate, 18 breaths/minute. Oxygen saturation was 95% on room air.

Her head was normocephalic and atraumatic, and her eyes, ears, nose, and throat were normal. Her neck was supple and without jugular vein distension. The cardiac examination revealed normal heart sounds without murmurs, rubs, or gallops. Her lungs were clear without rales, wheezes, or rhonchi. Her abdomen was soft, without tenderness, guarding, or rebound, and she had normal bowel sounds.

Her musculoskeletal examination was normal, with +5/5 strength bilaterally in her upper and lower extremities. The patient’s skin examination also was normal. On neurological examination, her right upper extremity and right side of her face were noted to have decreased sensation via pinprick compared to the left side, but the examination was otherwise normal. The National Institutes of Health Stroke Scale score was 1.

The patient’s electrocardiogram (ECG) showed a normal sinus rhythm (rate, 90 beats/min), a lateral infarct of undetermined age, and a left atrial abnormality. Laboratory evaluation was significant only for a brain natriuretic peptide level of 334 pg/mL, a creatine phosphokinase (CPK) level of 782 IU/L, and a troponin I level of >50 ng/mL (Table). Serial cardiac enzyme levels were obtained and showed a decline of CPK from 782 IU/L to 331 IU/L over the following 36 hours. However, the troponin I levels remained >50 ng/mL for 5 days and then declined to 31.6 ng/mL.

A computed  tomography (CT) scan of the brain without contrast revealed an acute to subacute infarct in the left occipital and left thalamic regions (Figure). A stat transthoracic echocardiogram (ECHO) performed in the ED revealed a dilated left ventricle with an ejection fraction of 20% to 25%, along with a hypokinetic anterolateral wall and an akinetic inferolateral wall. No atrial thrombus was visible on the ECHO. Doppler studies of the patient’s lower extremities were negative for deep vein thrombosis. Magnetic resonance imaging of her brain showed an infarct in the posterior circulation distribution involving the left occipital lobes and small areas in the left thalamic and right parietal-occipital regions. Hemorrhagic conversion of the left occipital infarct without mass effect was also noted. The patient was admitted to the neurological intensive care unit for frequent neurological examinations and close monitoring for worsening cerebral hemorrhage.

When the patient had still been in the ED, cardiology services were consulted; the cardiologist initiated a heparin drip with close monitoring of the coagulation studies. Cardiac catheterization was not done immediately because the ECG did not show acute ST elevations. The day after her presentation to the ED, the patient underwent a primary percutaneous coronary catheterization and was found to have a small rudimentary left anterior descending artery, with only small branches supplying the septal region. The right circumflex artery was very large and was supplying the lateral wall. No stents were placed during this procedure. A transesophageal ECHO (TEE) showed no evidence of a left atrial appendage thrombus.

The patient experienced an episode of coffee ground emesis while undergoing the TEE. Her hemoglobin declined from 11.9 g/dL to 7.9 g/dL, which led to a transfusion of 2 U  of packed red blood cells and platelets. Heparin was discontinued and a proton pump inhibitor was started; however, no endoscopy was done at that time.

Throughout her stay, the patient was continuously monitored, but no evidence of arrhythmia or atrial fibrillation was found. Upon discharge, the neurologist recommended the patient receive clopidogrel and aspirin therapy for 3 months with subsequent aspirin monotherapy afterward. The patient was discharged after 10 days in the hospital.

Discussion

Although she had an MI, the patient presented here did not experience any chest pain. Her chief complaint in the ED was paresthesias related to her concomitant stroke, and only on further probing did she describe the additional symptoms of fatigability and vomiting.

Since heart disease and stroke share common risk factors and pathophysiology, acute cerebral ischemic events may happen concurrently with MIs. In a review of studies that included approximately 2,900 patients who had an acute stroke, Kerr et al¹ found that 20% had elevated troponin levels within 7 days of the stroke. In 2013, the American Heart Association and American Stroke Association published guidelines advising that all patients who present with acute cerebral ischemia have an emergent ECG and baseline troponin level.² This was in response to evidence that even low positive troponin levels have been associated with an increased risk of mortality.³ Positive troponin levels are especially important because fatal and nonfatal stroke post-MI events have been found to be increasing in frequency for women, even though there has been a significant overall reduction in post-MI mortality.⁴ Patients who have an ischemic stroke concurrently with an acute MI or soon after have an overall poorer clinical prognosis.⁵

For emergency physicians (EPs),  this is a “chicken or the egg” scenario. It is difficult to determine which came first: the MI or the cerebral ischemia. Similar risk factors can result in an acute embolic event from revascularization, atrial fibrillation without proper anticoagulation, or a poorly functioning left ventricle.⁶ It is important to remember that regardless of the order of occurrence, the incidence of ischemic stroke is markedly increased in conjunction with an acute MI.⁷ Several theories have been advanced regarding the relationship between ischemic stroke and acute MI. One theory proposes that elevated troponin levels could be related to a large catecholamine release after a cerebral ischemic stroke, resulting in subsequent myocardial injury or cardiomyopathy.⁷ However, this theory remains controversial.

Management

The major consideration for the EP is whether or not to give thrombolytics to a patient who presents with concomitant acute MI and ischemic stroke. An acute MI within the 3 months preceding an acute stroke is considered a relative contraindication for intravenous tissue plasminogen activator (tPA).⁸ It has also been found, albeit rarely, that there is an increased risk of cardiac rupture or tamponade due to the breakdown of the fibrin clot within the necrotic cardiac tissue.⁸

How should patients with stroke complicated by acute cardiac compromise be managed in the ED? One acute vascular event cannot be ignored while addressing the other. There are no evidence-based guidelines for the management of patients who present with this picture.⁸ In addition, no published clinical studies have focused on the decision-making process for these patients.⁸

Immediate percutaneous coronary intervention for the MI performed on such patients would prevent the use of tPA for the acute stroke. Though any anticoagulation increases the risk for postischemic cerebral hemorrhage, heparin is necessary to prevent the formation of a left ventricle thrombus.⁷ Alternately, mechanical thrombectomy and cardiac catheterization may be combined as emergent treatments for these patients, but performing these two procedures simultaneously is not widely available.

For a patient who presents to the ED within both the cardiac and stroke treatment windows, tPA might be a viable option, and the only one readily valuable.⁸ However, the EP must be mindful of the varying dosages of tPA and means of administration for different thrombosis sites. Also, care must be taken when treating a patient with dual or triple antiplatelet therapy because of the increased risk of hemorrhage.⁹ Currently, no safe standardized regimens have been established, and further trials need to be performed.¹⁰

If the patient in this case report had presented at our ED with only signs and symptoms of an MI, typically she would have been treated with heparin, aspirin, and an urgent cardiac catheterization. If she had presented with only signs and symptoms of a stroke, she would have been treated with full-dose aspirin and worked up from a neurological perspective. Because she had signs and symptoms of both, she presented a dilemma. She was initially treated with heparin to prevent a thrombus formation, but then later changed to only clopidogrel and aspirin to prevent further episodes of coffee ground emesis or worsening hemorrhagic conversion.

Conclusion

Common risk factors for cardiac and cerebral ischemic events may result in a patient presenting with both acute MI and an acute cerebral ischemic event. There have not been sufficient clinical studies to determine the best decision-making process for these patients. Therefore, patients with this complicated presentation must be assessed on an individual basis. Current treatment options are varied and are based according to history of the present illness, time of presentation to the ED, and the available resources within the hospital.

Internal carotid artery dissection (ICAD) is an uncommon cause of stroke that typically occurs in the setting of (often minor) trauma but can also occur spontaneously. Patients with ICAD typically present with ipsilateral head, face, or neck pain. In approximately half of ICAD cases, an acute partial, painful Horner syndrome is present on examination. Although computed tomography angiography (CTA) is currently the imaging study of choice, magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) and Doppler ultrasound can also be used. Management options include thrombolysis, antiplatelet or anticoagulation therapy, and endovascular or surgical intervention.

Case

A 56-year-old man with a history of migraines presented to the ED with a chief complaint of a 4-day history of right-sided headache. He stated that the pain felt different from his usual migraines and was located behind his right eye. Prior to presentation at the ED, the patient had initially visited an urgent care facility for evaluation. The physician who evaluated the patient at the urgent care facility noted the patient’s left eye appeared dilated and referred him to the ED for evaluation.

The patient further stated that the day prior to presentation, one of his friends had also remarked that the patient’s left eye appeared to be enlarged. The patient denied any visual disturbances, focal weakness, nausea, vomiting, neck pain, or stiffness. His medical history was significant for paroxysmal atrial flutter and hypertension. Regarding medications, the patient was taking dronedarone, clonazepam, omeprazole, and metoprolol.

On physical examination, the patient’s vital signs were: blood pressure, 162/109 mm Hg; heart rate, 85 beats/minute and regular; respiratory rate, 18 breaths/minute; and temperature, 98.6°F. Oxygen saturation was 98% on room air. The patient appeared to be in no acute distress. Ocular examination revealed a dilated left pupil of approximately 5 to 6 mm, and a right pupil measuring approximately 3 mm. Both pupils reacted to light, and the extraocular muscles were intact. The patient’s face appeared symmetrical and had intact sensation. He had normal speech, midline tongue, and good bilateral shoulder shrug. The neck examination revealed normal range of motion with full flexion, without jugular vein distention, lymphadenopathy, or palpable thyroid. The cardiovascular, lung, and abdominal examinations were all normal. The neurological examination showed the patient to be awake, alert, and oriented to person, place, and time. He exhibited 5/5 motor strength in all four extremities, normal gait, and normal finger-to-nose performance; his reflexes were 2+ and symmetrical.

The emergency physician (EP) ordered a stat noncontrast CT scan of the head, complete blood count (CBC), and basic metabolic panel (BMP). The CT scan of the head was interpreted by the radiologist as “no acute intracranial abnormality,” and the CBC and the BMP were normal. Since the EP was concerned about a carotid artery aneurysm or dissection, he ordered a CTA of the head and neck (Figures 1 and 2). The CTA was read as:

Long segment dissection of postbulbar cervical segment of right internal carotid artery, very likely extending into the intracranial segment with critical stenosis at the junction of the high cervical segment and proximal petrous segment. Preserved runoff circulation to the anterior and middle cerebral arteries with robust capacity for collateral support in the context of patent anterior and posterior communicating arteries.

Based on the radiology report, the EP consulted with vascular surgery services, and ordered a Doppler study of the ICAs. The Doppler study demonstrated “arterial thrombus in the right distal extracranial internal carotid artery with hemodynamics suggestive of a distal occlusion/significant obstruction.” The patient was started on an intravenous (IV) heparin drip and admitted to the hospital. Three days later he experienced sudden onset of left arm weakness. An emergent CTA of the head and neck revealed an embolic occlusion of mid-to-distal M1 segment of the right middle cerebral artery. The patient was immediately evaluated by interventional radiology for possible clot removal; however, based on his rapid neurological improvement, he was instead treated medically with aspirin and clopidogrel and continued to show significant neurological improvement. He was discharged home on hospital day 8 on both antiplatelet agents with minimal neurological deficit.

Discussion

Even though ICAD accounts for only 1% to 2% of all strokes, it is responsible for 10% to 25% of strokes in young and middle-aged adults.^1-3 The peak incidence for ICAD is in the fifth decade, and it affects men and women equally.⁴ The extracranial portion of the ICA is the most commonly affected vessel (>90%); dissections of the intracranial portion are associated with greater neurological deficits and have a poorer prognosis.^2,5 Cerebral ischemia resulting from a dissection of the extracranial ICA may occur days to weeks after the onset of local symptoms such as head or neck pain, Horner syndrome, or tinnitus.⁵

In ICAD, a tear in the artery wall causes blood to enter the tunica media of the vessel, forming an intramural hematoma.^2,6 This may result in either stenosis of the lumen of the vessel from the enlarging hematoma or an outward aneurysmal dilatation of the vessel that compresses surrounding structures.^2,6 Subsequent cerebral ischemia is the result of either arterial embolism or hemodynamic compromise from vessel stenosis.^2,3

Causes

Dissections often occur secondary to trauma, though the severity of the trauma may be quite minor.^2,6 Seemingly trivial mechanisms that have been associated with dissections include nose blowing, coughing, sudden neck turning, and prolonged telephone conversations. Other known causes are motor vehicle accidents and chiropractic maneuvers. Inherited connective tissue disorders, including Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, and osteogenesis imperfecta, are associated with spontaneous ICAD.^2,6

Symptoms

The most common presenting symptom of carotid dissection in approximately two-thirds of patients is ipsilateral head, face, or neck pain,^2,6 typically described as sharp, constant, and nonthrobbing. Patients report a subjective bruit in 21% to 39% of cases.⁷ An acute partial painful Horner syndrome is strongly associated with ICAD, but is present in fewer than half of such patients.⁶ It is characterized by miosis and ptosis and is the result of compression of the ascending sympathetic fibers that travel alongside the ICA within the carotid sheath. Anhidrosis is not present because the fibers for sweat function in the face travel along the external carotid artery.²

Differential Diagnosis

While there is overlap between strokes caused by ICAD versus plaque, some features can help guide the clinician. Symptomatic carotid disease will frequently present with a history of one or more transient ischemic attacks characterized by focal neurological dysfunction or transient monocular blindness—typically within the previous 6 months.⁸ This history is not usually present in patients with ICAD. Secondly, pain is a much more prominent symptom in ICAD compared to patients with severe carotid atherosclerosis. The history of trauma, even minor, should make dissection higher on the differential diagnosis. Fortunately, the imaging studies to evaluate for these two diseases are the same.

Assessing Pupillary Asymmetry and Ptosis

Careful attention must be paid to assessing a patient for pupillary asymmetry. In a patient with anisocoria, determining the abnormal pupil may require examination of the patient in both bright and dark lighting conditions. The first step is to examine the patient’s pupils under normal lighting conditions. The next step is to assess each pupil’s response to shining a bright light in each eye. The abnormal pupil is the pupil that does not respond well or at all to bright light shone directly in the eye. If the anisocoria is greatest in bright light, the larger pupil is the abnormal pupil. When the anisocoria is greater in dark conditions, the smaller pupil is the abnormal pupil. In this case, the patient’s abnormal pupil was incorrectly diagnosed as the contralateral larger pupil (ie, left)—highlighting the importance of performing a complete pupillary examination in all patients presenting with neurological symptoms.⁹

Furthermore, as demonstrated in this case, ptosis in a patient with Horner syndrome caused by an ICAD can be subtle. The ptosis is the result of paralysis of Müeller’s muscle, which is innervated by the sympathetic pathway. The levator palpebrae superioris, which causes the more profound ptosis seen in third nerve palsies, is unaffected.¹⁰

Imaging Studies

Once the diagnosis of ICAD is suspected, appropriate vascular imaging must be obtained. Digital subtraction angiography has historically been the gold standard for vascular imaging of the neck vessels, but it has largely been replaced by less invasive and more readily available imaging modalities such as CTA and MRI/MRA.¹¹

Computed Tomography Angiography. This is a widely available, rapid imaging choice and has a sensitivity of 80% to 95% in the detection of ICAD.⁷ It has a greater ability than MRI to identify dissection features such as intimal flaps, pseudoaneurysms, and high-grade stenosis versus occlusion. One of its disadvantages is the need for iodinated contrast, which can limit the ability to obtain the test in those with renal disease or patients with true allergies to IV contrast material. In addition, a mural hematoma can be mistaken for a noncalcified atherosclerotic plaque in the vessel lumen.⁶

Magnetic Resonance Imaging and Magnetic Resonance Angiography. Both MRI and MRA are also frequently used to diagnose ICAD. The intramural hematoma displays a hyperdense signal on T1-weighted images and has a characteristic crescent shape adjacent to the lumen.¹¹ Magnetic resonance imaging studies are also sensitive in detecting cerebral ischemia resulting from the dissection. However, the sensitivity of MRI/MRA is highest 2 days after the dissection has occurred.²

Doppler Ultrasound. This is another imaging modality used to detect ICAD—one that is noninvasive, less expensive, requires no contrast material, and is widely available. Limitations of Doppler ultrasound include the inability to scan the distal ICA and a lower sensitivity in detecting dissections that cause low-grade stenosis.² It is more commonly used for follow-up monitoring of dissections.

Management

There are several options for managing ICAD. In patients with unstable lesions, progressing neurological deficit, or further strokes, endovascular stenting has been shown to have a technical success rate of 99% and a procedural complication rate of 1.3%.¹² Similarly, if the patient exhibits symptoms of cerebral ischemia, severe narrowing of the arterial lumen, or an unstable plaque, IV heparin is frequently used, followed by warfarin.¹³ However, since the majority of carotid and vertebral artery dissections heal spontaneously,¹⁴ antithrombotic therapies, including aspirin, clopidogrel or warfarin, are often prescribed to prevent thromboembolic complications.

Conclusion

Diagnosing ICAD requires knowledge of the typical history and presenting features of the disease. Careful attention to the ocular examination must be undertaken in any patient presenting with headache or face or neck pain, because the findings can be subtle. In a patient in whom ICAD is suspected, imaging with CTA or MRI/MRA should be performed. Early consultation with vascular surgery services  can help determine the most appropriate treatment strategy.

Internal carotid artery dissection (ICAD) is an uncommon cause of stroke that typically occurs in the setting of (often minor) trauma but can also occur spontaneously. Patients with ICAD typically present with ipsilateral head, face, or neck pain. In approximately half of ICAD cases, an acute partial, painful Horner syndrome is present on examination. Although computed tomography angiography (CTA) is currently the imaging study of choice, magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) and Doppler ultrasound can also be used. Management options include thrombolysis, antiplatelet or anticoagulation therapy, and endovascular or surgical intervention.

Case

A 56-year-old man with a history of migraines presented to the ED with a chief complaint of a 4-day history of right-sided headache. He stated that the pain felt different from his usual migraines and was located behind his right eye. Prior to presentation at the ED, the patient had initially visited an urgent care facility for evaluation. The physician who evaluated the patient at the urgent care facility noted the patient’s left eye appeared dilated and referred him to the ED for evaluation.

The patient further stated that the day prior to presentation, one of his friends had also remarked that the patient’s left eye appeared to be enlarged. The patient denied any visual disturbances, focal weakness, nausea, vomiting, neck pain, or stiffness. His medical history was significant for paroxysmal atrial flutter and hypertension. Regarding medications, the patient was taking dronedarone, clonazepam, omeprazole, and metoprolol.

On physical examination, the patient’s vital signs were: blood pressure, 162/109 mm Hg; heart rate, 85 beats/minute and regular; respiratory rate, 18 breaths/minute; and temperature, 98.6°F. Oxygen saturation was 98% on room air. The patient appeared to be in no acute distress. Ocular examination revealed a dilated left pupil of approximately 5 to 6 mm, and a right pupil measuring approximately 3 mm. Both pupils reacted to light, and the extraocular muscles were intact. The patient’s face appeared symmetrical and had intact sensation. He had normal speech, midline tongue, and good bilateral shoulder shrug. The neck examination revealed normal range of motion with full flexion, without jugular vein distention, lymphadenopathy, or palpable thyroid. The cardiovascular, lung, and abdominal examinations were all normal. The neurological examination showed the patient to be awake, alert, and oriented to person, place, and time. He exhibited 5/5 motor strength in all four extremities, normal gait, and normal finger-to-nose performance; his reflexes were 2+ and symmetrical.

The emergency physician (EP) ordered a stat noncontrast CT scan of the head, complete blood count (CBC), and basic metabolic panel (BMP). The CT scan of the head was interpreted by the radiologist as “no acute intracranial abnormality,” and the CBC and the BMP were normal. Since the EP was concerned about a carotid artery aneurysm or dissection, he ordered a CTA of the head and neck (Figures 1 and 2). The CTA was read as:

Long segment dissection of postbulbar cervical segment of right internal carotid artery, very likely extending into the intracranial segment with critical stenosis at the junction of the high cervical segment and proximal petrous segment. Preserved runoff circulation to the anterior and middle cerebral arteries with robust capacity for collateral support in the context of patent anterior and posterior communicating arteries.

Based on the radiology report, the EP consulted with vascular surgery services, and ordered a Doppler study of the ICAs. The Doppler study demonstrated “arterial thrombus in the right distal extracranial internal carotid artery with hemodynamics suggestive of a distal occlusion/significant obstruction.” The patient was started on an intravenous (IV) heparin drip and admitted to the hospital. Three days later he experienced sudden onset of left arm weakness. An emergent CTA of the head and neck revealed an embolic occlusion of mid-to-distal M1 segment of the right middle cerebral artery. The patient was immediately evaluated by interventional radiology for possible clot removal; however, based on his rapid neurological improvement, he was instead treated medically with aspirin and clopidogrel and continued to show significant neurological improvement. He was discharged home on hospital day 8 on both antiplatelet agents with minimal neurological deficit.

Discussion

Even though ICAD accounts for only 1% to 2% of all strokes, it is responsible for 10% to 25% of strokes in young and middle-aged adults.^1-3 The peak incidence for ICAD is in the fifth decade, and it affects men and women equally.⁴ The extracranial portion of the ICA is the most commonly affected vessel (>90%); dissections of the intracranial portion are associated with greater neurological deficits and have a poorer prognosis.^2,5 Cerebral ischemia resulting from a dissection of the extracranial ICA may occur days to weeks after the onset of local symptoms such as head or neck pain, Horner syndrome, or tinnitus.⁵

In ICAD, a tear in the artery wall causes blood to enter the tunica media of the vessel, forming an intramural hematoma.^2,6 This may result in either stenosis of the lumen of the vessel from the enlarging hematoma or an outward aneurysmal dilatation of the vessel that compresses surrounding structures.^2,6 Subsequent cerebral ischemia is the result of either arterial embolism or hemodynamic compromise from vessel stenosis.^2,3

Causes

Dissections often occur secondary to trauma, though the severity of the trauma may be quite minor.^2,6 Seemingly trivial mechanisms that have been associated with dissections include nose blowing, coughing, sudden neck turning, and prolonged telephone conversations. Other known causes are motor vehicle accidents and chiropractic maneuvers. Inherited connective tissue disorders, including Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, and osteogenesis imperfecta, are associated with spontaneous ICAD.^2,6

Symptoms

The most common presenting symptom of carotid dissection in approximately two-thirds of patients is ipsilateral head, face, or neck pain,^2,6 typically described as sharp, constant, and nonthrobbing. Patients report a subjective bruit in 21% to 39% of cases.⁷ An acute partial painful Horner syndrome is strongly associated with ICAD, but is present in fewer than half of such patients.⁶ It is characterized by miosis and ptosis and is the result of compression of the ascending sympathetic fibers that travel alongside the ICA within the carotid sheath. Anhidrosis is not present because the fibers for sweat function in the face travel along the external carotid artery.²

Differential Diagnosis

While there is overlap between strokes caused by ICAD versus plaque, some features can help guide the clinician. Symptomatic carotid disease will frequently present with a history of one or more transient ischemic attacks characterized by focal neurological dysfunction or transient monocular blindness—typically within the previous 6 months.⁸ This history is not usually present in patients with ICAD. Secondly, pain is a much more prominent symptom in ICAD compared to patients with severe carotid atherosclerosis. The history of trauma, even minor, should make dissection higher on the differential diagnosis. Fortunately, the imaging studies to evaluate for these two diseases are the same.

Assessing Pupillary Asymmetry and Ptosis

Careful attention must be paid to assessing a patient for pupillary asymmetry. In a patient with anisocoria, determining the abnormal pupil may require examination of the patient in both bright and dark lighting conditions. The first step is to examine the patient’s pupils under normal lighting conditions. The next step is to assess each pupil’s response to shining a bright light in each eye. The abnormal pupil is the pupil that does not respond well or at all to bright light shone directly in the eye. If the anisocoria is greatest in bright light, the larger pupil is the abnormal pupil. When the anisocoria is greater in dark conditions, the smaller pupil is the abnormal pupil. In this case, the patient’s abnormal pupil was incorrectly diagnosed as the contralateral larger pupil (ie, left)—highlighting the importance of performing a complete pupillary examination in all patients presenting with neurological symptoms.⁹

Furthermore, as demonstrated in this case, ptosis in a patient with Horner syndrome caused by an ICAD can be subtle. The ptosis is the result of paralysis of Müeller’s muscle, which is innervated by the sympathetic pathway. The levator palpebrae superioris, which causes the more profound ptosis seen in third nerve palsies, is unaffected.¹⁰

Imaging Studies

Once the diagnosis of ICAD is suspected, appropriate vascular imaging must be obtained. Digital subtraction angiography has historically been the gold standard for vascular imaging of the neck vessels, but it has largely been replaced by less invasive and more readily available imaging modalities such as CTA and MRI/MRA.¹¹

Computed Tomography Angiography. This is a widely available, rapid imaging choice and has a sensitivity of 80% to 95% in the detection of ICAD.⁷ It has a greater ability than MRI to identify dissection features such as intimal flaps, pseudoaneurysms, and high-grade stenosis versus occlusion. One of its disadvantages is the need for iodinated contrast, which can limit the ability to obtain the test in those with renal disease or patients with true allergies to IV contrast material. In addition, a mural hematoma can be mistaken for a noncalcified atherosclerotic plaque in the vessel lumen.⁶

Magnetic Resonance Imaging and Magnetic Resonance Angiography. Both MRI and MRA are also frequently used to diagnose ICAD. The intramural hematoma displays a hyperdense signal on T1-weighted images and has a characteristic crescent shape adjacent to the lumen.¹¹ Magnetic resonance imaging studies are also sensitive in detecting cerebral ischemia resulting from the dissection. However, the sensitivity of MRI/MRA is highest 2 days after the dissection has occurred.²

Doppler Ultrasound. This is another imaging modality used to detect ICAD—one that is noninvasive, less expensive, requires no contrast material, and is widely available. Limitations of Doppler ultrasound include the inability to scan the distal ICA and a lower sensitivity in detecting dissections that cause low-grade stenosis.² It is more commonly used for follow-up monitoring of dissections.

Management

There are several options for managing ICAD. In patients with unstable lesions, progressing neurological deficit, or further strokes, endovascular stenting has been shown to have a technical success rate of 99% and a procedural complication rate of 1.3%.¹² Similarly, if the patient exhibits symptoms of cerebral ischemia, severe narrowing of the arterial lumen, or an unstable plaque, IV heparin is frequently used, followed by warfarin.¹³ However, since the majority of carotid and vertebral artery dissections heal spontaneously,¹⁴ antithrombotic therapies, including aspirin, clopidogrel or warfarin, are often prescribed to prevent thromboembolic complications.

Conclusion

Diagnosing ICAD requires knowledge of the typical history and presenting features of the disease. Careful attention to the ocular examination must be undertaken in any patient presenting with headache or face or neck pain, because the findings can be subtle. In a patient in whom ICAD is suspected, imaging with CTA or MRI/MRA should be performed. Early consultation with vascular surgery services  can help determine the most appropriate treatment strategy.

Internal carotid artery dissection (ICAD) is an uncommon cause of stroke that typically occurs in the setting of (often minor) trauma but can also occur spontaneously. Patients with ICAD typically present with ipsilateral head, face, or neck pain. In approximately half of ICAD cases, an acute partial, painful Horner syndrome is present on examination. Although computed tomography angiography (CTA) is currently the imaging study of choice, magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) and Doppler ultrasound can also be used. Management options include thrombolysis, antiplatelet or anticoagulation therapy, and endovascular or surgical intervention.

Case

A 56-year-old man with a history of migraines presented to the ED with a chief complaint of a 4-day history of right-sided headache. He stated that the pain felt different from his usual migraines and was located behind his right eye. Prior to presentation at the ED, the patient had initially visited an urgent care facility for evaluation. The physician who evaluated the patient at the urgent care facility noted the patient’s left eye appeared dilated and referred him to the ED for evaluation.

The patient further stated that the day prior to presentation, one of his friends had also remarked that the patient’s left eye appeared to be enlarged. The patient denied any visual disturbances, focal weakness, nausea, vomiting, neck pain, or stiffness. His medical history was significant for paroxysmal atrial flutter and hypertension. Regarding medications, the patient was taking dronedarone, clonazepam, omeprazole, and metoprolol.

On physical examination, the patient’s vital signs were: blood pressure, 162/109 mm Hg; heart rate, 85 beats/minute and regular; respiratory rate, 18 breaths/minute; and temperature, 98.6°F. Oxygen saturation was 98% on room air. The patient appeared to be in no acute distress. Ocular examination revealed a dilated left pupil of approximately 5 to 6 mm, and a right pupil measuring approximately 3 mm. Both pupils reacted to light, and the extraocular muscles were intact. The patient’s face appeared symmetrical and had intact sensation. He had normal speech, midline tongue, and good bilateral shoulder shrug. The neck examination revealed normal range of motion with full flexion, without jugular vein distention, lymphadenopathy, or palpable thyroid. The cardiovascular, lung, and abdominal examinations were all normal. The neurological examination showed the patient to be awake, alert, and oriented to person, place, and time. He exhibited 5/5 motor strength in all four extremities, normal gait, and normal finger-to-nose performance; his reflexes were 2+ and symmetrical.

The emergency physician (EP) ordered a stat noncontrast CT scan of the head, complete blood count (CBC), and basic metabolic panel (BMP). The CT scan of the head was interpreted by the radiologist as “no acute intracranial abnormality,” and the CBC and the BMP were normal. Since the EP was concerned about a carotid artery aneurysm or dissection, he ordered a CTA of the head and neck (Figures 1 and 2). The CTA was read as:

Long segment dissection of postbulbar cervical segment of right internal carotid artery, very likely extending into the intracranial segment with critical stenosis at the junction of the high cervical segment and proximal petrous segment. Preserved runoff circulation to the anterior and middle cerebral arteries with robust capacity for collateral support in the context of patent anterior and posterior communicating arteries.

Based on the radiology report, the EP consulted with vascular surgery services, and ordered a Doppler study of the ICAs. The Doppler study demonstrated “arterial thrombus in the right distal extracranial internal carotid artery with hemodynamics suggestive of a distal occlusion/significant obstruction.” The patient was started on an intravenous (IV) heparin drip and admitted to the hospital. Three days later he experienced sudden onset of left arm weakness. An emergent CTA of the head and neck revealed an embolic occlusion of mid-to-distal M1 segment of the right middle cerebral artery. The patient was immediately evaluated by interventional radiology for possible clot removal; however, based on his rapid neurological improvement, he was instead treated medically with aspirin and clopidogrel and continued to show significant neurological improvement. He was discharged home on hospital day 8 on both antiplatelet agents with minimal neurological deficit.

Discussion

Even though ICAD accounts for only 1% to 2% of all strokes, it is responsible for 10% to 25% of strokes in young and middle-aged adults.^1-3 The peak incidence for ICAD is in the fifth decade, and it affects men and women equally.⁴ The extracranial portion of the ICA is the most commonly affected vessel (>90%); dissections of the intracranial portion are associated with greater neurological deficits and have a poorer prognosis.^2,5 Cerebral ischemia resulting from a dissection of the extracranial ICA may occur days to weeks after the onset of local symptoms such as head or neck pain, Horner syndrome, or tinnitus.⁵

In ICAD, a tear in the artery wall causes blood to enter the tunica media of the vessel, forming an intramural hematoma.^2,6 This may result in either stenosis of the lumen of the vessel from the enlarging hematoma or an outward aneurysmal dilatation of the vessel that compresses surrounding structures.^2,6 Subsequent cerebral ischemia is the result of either arterial embolism or hemodynamic compromise from vessel stenosis.^2,3

Causes

Dissections often occur secondary to trauma, though the severity of the trauma may be quite minor.^2,6 Seemingly trivial mechanisms that have been associated with dissections include nose blowing, coughing, sudden neck turning, and prolonged telephone conversations. Other known causes are motor vehicle accidents and chiropractic maneuvers. Inherited connective tissue disorders, including Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, and osteogenesis imperfecta, are associated with spontaneous ICAD.^2,6

Symptoms

The most common presenting symptom of carotid dissection in approximately two-thirds of patients is ipsilateral head, face, or neck pain,^2,6 typically described as sharp, constant, and nonthrobbing. Patients report a subjective bruit in 21% to 39% of cases.⁷ An acute partial painful Horner syndrome is strongly associated with ICAD, but is present in fewer than half of such patients.⁶ It is characterized by miosis and ptosis and is the result of compression of the ascending sympathetic fibers that travel alongside the ICA within the carotid sheath. Anhidrosis is not present because the fibers for sweat function in the face travel along the external carotid artery.²

Differential Diagnosis

While there is overlap between strokes caused by ICAD versus plaque, some features can help guide the clinician. Symptomatic carotid disease will frequently present with a history of one or more transient ischemic attacks characterized by focal neurological dysfunction or transient monocular blindness—typically within the previous 6 months.⁸ This history is not usually present in patients with ICAD. Secondly, pain is a much more prominent symptom in ICAD compared to patients with severe carotid atherosclerosis. The history of trauma, even minor, should make dissection higher on the differential diagnosis. Fortunately, the imaging studies to evaluate for these two diseases are the same.

Assessing Pupillary Asymmetry and Ptosis

Careful attention must be paid to assessing a patient for pupillary asymmetry. In a patient with anisocoria, determining the abnormal pupil may require examination of the patient in both bright and dark lighting conditions. The first step is to examine the patient’s pupils under normal lighting conditions. The next step is to assess each pupil’s response to shining a bright light in each eye. The abnormal pupil is the pupil that does not respond well or at all to bright light shone directly in the eye. If the anisocoria is greatest in bright light, the larger pupil is the abnormal pupil. When the anisocoria is greater in dark conditions, the smaller pupil is the abnormal pupil. In this case, the patient’s abnormal pupil was incorrectly diagnosed as the contralateral larger pupil (ie, left)—highlighting the importance of performing a complete pupillary examination in all patients presenting with neurological symptoms.⁹

Furthermore, as demonstrated in this case, ptosis in a patient with Horner syndrome caused by an ICAD can be subtle. The ptosis is the result of paralysis of Müeller’s muscle, which is innervated by the sympathetic pathway. The levator palpebrae superioris, which causes the more profound ptosis seen in third nerve palsies, is unaffected.¹⁰

Imaging Studies

Once the diagnosis of ICAD is suspected, appropriate vascular imaging must be obtained. Digital subtraction angiography has historically been the gold standard for vascular imaging of the neck vessels, but it has largely been replaced by less invasive and more readily available imaging modalities such as CTA and MRI/MRA.¹¹

Computed Tomography Angiography. This is a widely available, rapid imaging choice and has a sensitivity of 80% to 95% in the detection of ICAD.⁷ It has a greater ability than MRI to identify dissection features such as intimal flaps, pseudoaneurysms, and high-grade stenosis versus occlusion. One of its disadvantages is the need for iodinated contrast, which can limit the ability to obtain the test in those with renal disease or patients with true allergies to IV contrast material. In addition, a mural hematoma can be mistaken for a noncalcified atherosclerotic plaque in the vessel lumen.⁶

Magnetic Resonance Imaging and Magnetic Resonance Angiography. Both MRI and MRA are also frequently used to diagnose ICAD. The intramural hematoma displays a hyperdense signal on T1-weighted images and has a characteristic crescent shape adjacent to the lumen.¹¹ Magnetic resonance imaging studies are also sensitive in detecting cerebral ischemia resulting from the dissection. However, the sensitivity of MRI/MRA is highest 2 days after the dissection has occurred.²

Doppler Ultrasound. This is another imaging modality used to detect ICAD—one that is noninvasive, less expensive, requires no contrast material, and is widely available. Limitations of Doppler ultrasound include the inability to scan the distal ICA and a lower sensitivity in detecting dissections that cause low-grade stenosis.² It is more commonly used for follow-up monitoring of dissections.

Management

There are several options for managing ICAD. In patients with unstable lesions, progressing neurological deficit, or further strokes, endovascular stenting has been shown to have a technical success rate of 99% and a procedural complication rate of 1.3%.¹² Similarly, if the patient exhibits symptoms of cerebral ischemia, severe narrowing of the arterial lumen, or an unstable plaque, IV heparin is frequently used, followed by warfarin.¹³ However, since the majority of carotid and vertebral artery dissections heal spontaneously,¹⁴ antithrombotic therapies, including aspirin, clopidogrel or warfarin, are often prescribed to prevent thromboembolic complications.

Conclusion

Diagnosing ICAD requires knowledge of the typical history and presenting features of the disease. Careful attention to the ocular examination must be undertaken in any patient presenting with headache or face or neck pain, because the findings can be subtle. In a patient in whom ICAD is suspected, imaging with CTA or MRI/MRA should be performed. Early consultation with vascular surgery services  can help determine the most appropriate treatment strategy.

In The Case Report Issue, we feature four separate case reports presenting different conditions, much like patients may present in succession to a busy ED. Though considered of lesser importance than other types of peer-reviewed literature in this era of evidence-based medicine, case reports nevertheless fulfill an important role in clinical practice, medical education, and even medical research by identifying and tracking an important cause of a developing disease--especially one with a toxicologic or infectious etiology. In some instances, case reports also identify effective or ineffective treatments (though the latter is more rarely reported) and adverse effects of approved treatments, especially those of a newly introduced “Phase IV” medication.

Often, the ED is the initial setting for many reportable occurrences, and in recent years, patients first presenting to EDs have alerted the entire medical community to serious emerging illnesses such as Legionnaires’ disease, HIV and AIDS, anthrax, and Ebola. Most recently, firsthand reports by a pair of mother/daughter physicians in Brazil linked an alarming appearance of several new cases of microcephaly to a rash that followed a mosquito bite during pregnancy, and ultimately to identification of the mosquito-borne Zika virus.

Similarly, toxicologists at urban poison centers have been able to rapidly link cases of new and puzzling adverse effects and deaths reported by area emergency physicians to a dangerous new street drug or combination of drugs in that area, such as synthetic cannabinoid agonists, or heroin mixed with scopolamine, and then immediately alert other physicians and the public to these dangers.

As recently described by Florek and Dellavalle in Journal of Medical Case Reports (http://bit.ly/28PLi7w), case reports make meaningful contributions to the knowledge and education of medical students, residents, fellows, and (we would add) attendings. Written with the goal of sharing information for medical or scientific purposes, they often serve as a young physician’s first experience with medical writing and provide a solid foundation for manuscript preparation and publication.

Finally, a good ED case report that includes accurate descriptions of all relevant features along with any unique departures from classical presentations, followed by an up-to-date review of current treatments, presents most of us with a vivid means of identifying and remembering the salient features of a clinical problem or disease.

In The Case Report Issue, we feature four separate case reports presenting different conditions, much like patients may present in succession to a busy ED. Though considered of lesser importance than other types of peer-reviewed literature in this era of evidence-based medicine, case reports nevertheless fulfill an important role in clinical practice, medical education, and even medical research by identifying and tracking an important cause of a developing disease--especially one with a toxicologic or infectious etiology. In some instances, case reports also identify effective or ineffective treatments (though the latter is more rarely reported) and adverse effects of approved treatments, especially those of a newly introduced “Phase IV” medication.

Often, the ED is the initial setting for many reportable occurrences, and in recent years, patients first presenting to EDs have alerted the entire medical community to serious emerging illnesses such as Legionnaires’ disease, HIV and AIDS, anthrax, and Ebola. Most recently, firsthand reports by a pair of mother/daughter physicians in Brazil linked an alarming appearance of several new cases of microcephaly to a rash that followed a mosquito bite during pregnancy, and ultimately to identification of the mosquito-borne Zika virus.

Similarly, toxicologists at urban poison centers have been able to rapidly link cases of new and puzzling adverse effects and deaths reported by area emergency physicians to a dangerous new street drug or combination of drugs in that area, such as synthetic cannabinoid agonists, or heroin mixed with scopolamine, and then immediately alert other physicians and the public to these dangers.

As recently described by Florek and Dellavalle in Journal of Medical Case Reports (http://bit.ly/28PLi7w), case reports make meaningful contributions to the knowledge and education of medical students, residents, fellows, and (we would add) attendings. Written with the goal of sharing information for medical or scientific purposes, they often serve as a young physician’s first experience with medical writing and provide a solid foundation for manuscript preparation and publication.

Finally, a good ED case report that includes accurate descriptions of all relevant features along with any unique departures from classical presentations, followed by an up-to-date review of current treatments, presents most of us with a vivid means of identifying and remembering the salient features of a clinical problem or disease.

In The Case Report Issue, we feature four separate case reports presenting different conditions, much like patients may present in succession to a busy ED. Though considered of lesser importance than other types of peer-reviewed literature in this era of evidence-based medicine, case reports nevertheless fulfill an important role in clinical practice, medical education, and even medical research by identifying and tracking an important cause of a developing disease--especially one with a toxicologic or infectious etiology. In some instances, case reports also identify effective or ineffective treatments (though the latter is more rarely reported) and adverse effects of approved treatments, especially those of a newly introduced “Phase IV” medication.

Often, the ED is the initial setting for many reportable occurrences, and in recent years, patients first presenting to EDs have alerted the entire medical community to serious emerging illnesses such as Legionnaires’ disease, HIV and AIDS, anthrax, and Ebola. Most recently, firsthand reports by a pair of mother/daughter physicians in Brazil linked an alarming appearance of several new cases of microcephaly to a rash that followed a mosquito bite during pregnancy, and ultimately to identification of the mosquito-borne Zika virus.

Similarly, toxicologists at urban poison centers have been able to rapidly link cases of new and puzzling adverse effects and deaths reported by area emergency physicians to a dangerous new street drug or combination of drugs in that area, such as synthetic cannabinoid agonists, or heroin mixed with scopolamine, and then immediately alert other physicians and the public to these dangers.

As recently described by Florek and Dellavalle in Journal of Medical Case Reports (http://bit.ly/28PLi7w), case reports make meaningful contributions to the knowledge and education of medical students, residents, fellows, and (we would add) attendings. Written with the goal of sharing information for medical or scientific purposes, they often serve as a young physician’s first experience with medical writing and provide a solid foundation for manuscript preparation and publication.

Finally, a good ED case report that includes accurate descriptions of all relevant features along with any unique departures from classical presentations, followed by an up-to-date review of current treatments, presents most of us with a vivid means of identifying and remembering the salient features of a clinical problem or disease.

CDC Issues Advisory About First Mcr-1 Gene in E Coli Found in a Human in the United States

BY JEFF BAUER

The Centers for Disease Control and Prevention (CDC) issued a health advisory to emphasize the importance of taking measures to prevent the transmission of antibiotic-resistant bacteria after a Pennsylvania woman with no recent travel outside of the United States was found to have Escherichia coli (E coli) bacteria carrying the mcr-1 gene. The mcr-1 gene makes bacteria resistant to colistin, which is used as a last-resort antibiotic to treat patients who have multidrug-resistant infections, including carbapenem-resistant Enterobacteriaceae (CRE).  The mcr-1 gene exists on a small piece of DNA that is capable of moving from one bacterium to another, which would allow it to spread antibiotic resistance among species.  The CDC has been on alert for this gene in the United States ever since its emergence in China in 2015. 

The patient in Pennsylvania, who was being treated for a urinary tract infection (UTI), is believed to be the first human case of mcr-1 E coli in the United States. Although the E coli isolate from the patient was also resistant to antibiotics in five additional antibiotic classes (cephalosporins, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines), the woman did not have CRE and the bacteria identified were not resistant to all antibiotics. However, the presence of the mcr-1 gene and its ability to share its colistin resistance with other bacteria increases the risk that pan-resistant bacteria could develop. The CDC’s laboratories have developed protocols for testing microorganisms for the mcr-1 gene and the CDC was performing screening tests to see if people in contact with the patient with mcr-1 might be colonized with this organism.

The CDC recommends that clinicians follow Standard and Contact Precautions for any patients colonized or infected with antibiotic-resistant bacteria, including patients found to have mcr-1-mediated resistant organisms. If a patient is found to have Enterobacteriaceae with mcr-1, healthcare facilities and laboratories should immediately notify local or state public health authorities, and inform all clinicians who are caring for the patient. Any room in which a patient with an antibiotic-resistant infection has been placed should receive thorough daily and terminal cleaning.

1.    Centers for Disease Control and Prevention. Alert to U.S. healthcare facilities: first mcr-1 gene in E. coli bacteria found in a human in the United States. https://emergency.cdc.gov/han/han00390.asp. Accessed June 23, 2016.

Emergency Medicine Associate Editor Named as Chair of EM at Rutgers

Lewis S. Nelson, MD, has been appointed as the Chair of the Department of Emergency Medicine at Rutgers New Jersey Medical School and Chief of Service of the Emergency Department at University Hospital in Newark. For many years, Dr Nelson has been serving as associate editor, toxicology, for Emergency Medicine, overseeing the journal’s Case Studies in Toxicology department. 

HIV Rapid Tests Miss 1 in 7 Infections

BY RICHARD PIZZI

FROM AIDS

apid human immunodeficiency virus (HIV) tests in high-income countries miss about one in seven infections and should be used in combination with fourth-generation enzyme immunoassays (EIA) or nucleic acid amplification tests (NAAT) in clinical settings whenever possible, according to a study in the journal AIDS.

“These infections are likely to be particularly transmissible due to the high HIV viral load in early infection...in high-income countries, rapid tests should be used in combination with fourth-generation EIA or NAAT, except in special circumstances,” the Australian researchers said.

Researchers performed a systematic review and meta-analysis of 18 studies involving 110,122 HIV rapid test results. The primary outcome was the test’s sensitivity for detecting acute or established HIV infections. Sensitivity was calculated by dividing the number of confirmed positive rapid tests by the number of confirmed positive comparator tests. Specificity was calculated by dividing the number of confirmed negative rapid tests by the number of negative comparator tests.

Compared with EIA, the estimated sensitivity of rapid tests was 94.5% (95% confidence interval [CI], 87.4-97.7). Compared with NAAT, the sensitivity of rapid tests was 93.7% (95% CI, 88.7-96.5). The sensitivity of rapid tests in high-income countries was 85.7% (95% CI, 81.9-88.9), and in low-income countries it was 97.7% (95% CI, 95.2-98.9), compared with either EIA or NAAT (P < .01 for difference between settings). Proportions of antibody-negative acute infections were 13.6% (95% CI, 10.1-18.0) and 4.7% (95% CI, 2.8-7.7) in studies from high- and low-income countries, respectively (P < .01).

Rapid tests were less sensitive when used in clinical settings in high-income countries, regardless of whether they were compared with a NAAT or fourth-generation EIA. However, the researchers noted that the discrepancy between high- and low-income countries could be attributed to the higher proportion of acute HIV infections (antibody-negative NAAT positive) in populations tested in high-income countries, which might reflect higher background testing rates or a higher incidence of HIV in men who have sex with men.

1.    Tan WS, Chow EP, Fairley CK, Chen MY, Bradshaw CS, Read TR. Sensitivity of HIV rapid tests compared to fourth generation enzyme immunoassays or HIV RNA tests - a systematic review and meta-analysis. AIDS. 2016 Apr 27. [Epub ahead of print]

Two-Step ED Urinary Tract Infection Screening Cuts Catheterization Rate in Half

BY TARA HAELLE

FROM PEDIATRICS

fter implementation of a quality improvement initiative to more effectively screen febrile children for UTIs in the ED, catheterization rates dropped from 63% to 30% over a 6-month period, a study found.

The sustained drop prevented more than 350 young children from catheterization without increasing revisit rates or missing UTIs in the 39% of children who were followed in the care network. This was in a study that compared catheterization rates in 1,520 children aged 6 to 24 months in the year before the intervention and 828 children in the 6 months during the intervention.

“Although urine catheterization remains the gold standard in diagnosing UTIs, it is an invasive procedure that may be avoided in most patients who are being screened,” wrote Dr Jane M. Lavelle of Children’s Hospital of Philadelphia (CHOP) and her associates. Screening for UTIs by this method can be “painful, time consuming, and costly,” they added.

An alternative method to automatic catheterization is a two-step process already included as an option in the American Academy of Pediatrics guidelines: instead of collecting urine through catheterization just once for screening and culture, an ED first noninvasively collects urine with a urine bag for screening in those indicated with evidence-based risk factors, and then catheterizes only those who screen positive.

“Due to the predictive models’ higher sensitivity than specificity for screening, most urine samples will have a negative screen for pyuria or bacteriuria by urine dipstick or microscopy,” the authors wrote.

At baseline, CHOP’s ED was screening 63% of febrile children under age 24 months using catheterization, but screens were most commonly negative and only 4.3% had positive cultures. The authors therefore initiated a switch to the two-step method as a pilot run in one ED area before educating all ED personnel and expanding to the full department in the second month.

Children aged 6 to 24 months comprised approximately 20% of the ED’s more than 90,000 annual patients, and about 22% of these children presented with fever as the primary concern. Children with a history of genitourinary problems or immune deficiency were excluded.

The pilot ran in an “urgent care section of ED where there are typically more children with less complex medical histories and where ‘fever’ is a common complaint,” the investigators said. The staff completed a learning module with assessment and then received in-person and visual reminders of the procedure.

While 69% of 828 febrile young children still underwent screening during the 6-month intervention period, only 16% still underwent urethral catheterization as the initial screening step, typically because of strong clinical indications for a UTI. Another 14% underwent catheterization only after a positive urine screen from an initial noninvasive urine collection or because of an inability to get an adequate urine specimen with the bag. The reduction in catheterization dropped to 55% within 2 weeks of the intervention’s start and spread to other hospital departments. The drop to a 30% catheterization rate remained throughout 18 additional months of monitoring.

The research did not use external funding, and the researchers reported they had no financial disclosures.

1.    Lavelle JM, Blackstone MM, Funari MK, et al. Two-step process for ED UTI screening in febrile young children: reducing catheterization rates. Pediatrics. 2016 Jun 2. pii: e20153023. [Epub ahead of print].

CDC Issues Advisory About First Mcr-1 Gene in E Coli Found in a Human in the United States

BY JEFF BAUER

The Centers for Disease Control and Prevention (CDC) issued a health advisory to emphasize the importance of taking measures to prevent the transmission of antibiotic-resistant bacteria after a Pennsylvania woman with no recent travel outside of the United States was found to have Escherichia coli (E coli) bacteria carrying the mcr-1 gene. The mcr-1 gene makes bacteria resistant to colistin, which is used as a last-resort antibiotic to treat patients who have multidrug-resistant infections, including carbapenem-resistant Enterobacteriaceae (CRE).  The mcr-1 gene exists on a small piece of DNA that is capable of moving from one bacterium to another, which would allow it to spread antibiotic resistance among species.  The CDC has been on alert for this gene in the United States ever since its emergence in China in 2015. 

The patient in Pennsylvania, who was being treated for a urinary tract infection (UTI), is believed to be the first human case of mcr-1 E coli in the United States. Although the E coli isolate from the patient was also resistant to antibiotics in five additional antibiotic classes (cephalosporins, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines), the woman did not have CRE and the bacteria identified were not resistant to all antibiotics. However, the presence of the mcr-1 gene and its ability to share its colistin resistance with other bacteria increases the risk that pan-resistant bacteria could develop. The CDC’s laboratories have developed protocols for testing microorganisms for the mcr-1 gene and the CDC was performing screening tests to see if people in contact with the patient with mcr-1 might be colonized with this organism.

The CDC recommends that clinicians follow Standard and Contact Precautions for any patients colonized or infected with antibiotic-resistant bacteria, including patients found to have mcr-1-mediated resistant organisms. If a patient is found to have Enterobacteriaceae with mcr-1, healthcare facilities and laboratories should immediately notify local or state public health authorities, and inform all clinicians who are caring for the patient. Any room in which a patient with an antibiotic-resistant infection has been placed should receive thorough daily and terminal cleaning.

1.    Centers for Disease Control and Prevention. Alert to U.S. healthcare facilities: first mcr-1 gene in E. coli bacteria found in a human in the United States. https://emergency.cdc.gov/han/han00390.asp. Accessed June 23, 2016.

Emergency Medicine Associate Editor Named as Chair of EM at Rutgers

Lewis S. Nelson, MD, has been appointed as the Chair of the Department of Emergency Medicine at Rutgers New Jersey Medical School and Chief of Service of the Emergency Department at University Hospital in Newark. For many years, Dr Nelson has been serving as associate editor, toxicology, for Emergency Medicine, overseeing the journal’s Case Studies in Toxicology department. 

HIV Rapid Tests Miss 1 in 7 Infections

BY RICHARD PIZZI

FROM AIDS

apid human immunodeficiency virus (HIV) tests in high-income countries miss about one in seven infections and should be used in combination with fourth-generation enzyme immunoassays (EIA) or nucleic acid amplification tests (NAAT) in clinical settings whenever possible, according to a study in the journal AIDS.

“These infections are likely to be particularly transmissible due to the high HIV viral load in early infection...in high-income countries, rapid tests should be used in combination with fourth-generation EIA or NAAT, except in special circumstances,” the Australian researchers said.

Researchers performed a systematic review and meta-analysis of 18 studies involving 110,122 HIV rapid test results. The primary outcome was the test’s sensitivity for detecting acute or established HIV infections. Sensitivity was calculated by dividing the number of confirmed positive rapid tests by the number of confirmed positive comparator tests. Specificity was calculated by dividing the number of confirmed negative rapid tests by the number of negative comparator tests.

Compared with EIA, the estimated sensitivity of rapid tests was 94.5% (95% confidence interval [CI], 87.4-97.7). Compared with NAAT, the sensitivity of rapid tests was 93.7% (95% CI, 88.7-96.5). The sensitivity of rapid tests in high-income countries was 85.7% (95% CI, 81.9-88.9), and in low-income countries it was 97.7% (95% CI, 95.2-98.9), compared with either EIA or NAAT (P < .01 for difference between settings). Proportions of antibody-negative acute infections were 13.6% (95% CI, 10.1-18.0) and 4.7% (95% CI, 2.8-7.7) in studies from high- and low-income countries, respectively (P < .01).

Rapid tests were less sensitive when used in clinical settings in high-income countries, regardless of whether they were compared with a NAAT or fourth-generation EIA. However, the researchers noted that the discrepancy between high- and low-income countries could be attributed to the higher proportion of acute HIV infections (antibody-negative NAAT positive) in populations tested in high-income countries, which might reflect higher background testing rates or a higher incidence of HIV in men who have sex with men.

1.    Tan WS, Chow EP, Fairley CK, Chen MY, Bradshaw CS, Read TR. Sensitivity of HIV rapid tests compared to fourth generation enzyme immunoassays or HIV RNA tests - a systematic review and meta-analysis. AIDS. 2016 Apr 27. [Epub ahead of print]

Two-Step ED Urinary Tract Infection Screening Cuts Catheterization Rate in Half

BY TARA HAELLE

FROM PEDIATRICS

fter implementation of a quality improvement initiative to more effectively screen febrile children for UTIs in the ED, catheterization rates dropped from 63% to 30% over a 6-month period, a study found.

The sustained drop prevented more than 350 young children from catheterization without increasing revisit rates or missing UTIs in the 39% of children who were followed in the care network. This was in a study that compared catheterization rates in 1,520 children aged 6 to 24 months in the year before the intervention and 828 children in the 6 months during the intervention.

“Although urine catheterization remains the gold standard in diagnosing UTIs, it is an invasive procedure that may be avoided in most patients who are being screened,” wrote Dr Jane M. Lavelle of Children’s Hospital of Philadelphia (CHOP) and her associates. Screening for UTIs by this method can be “painful, time consuming, and costly,” they added.

An alternative method to automatic catheterization is a two-step process already included as an option in the American Academy of Pediatrics guidelines: instead of collecting urine through catheterization just once for screening and culture, an ED first noninvasively collects urine with a urine bag for screening in those indicated with evidence-based risk factors, and then catheterizes only those who screen positive.

“Due to the predictive models’ higher sensitivity than specificity for screening, most urine samples will have a negative screen for pyuria or bacteriuria by urine dipstick or microscopy,” the authors wrote.

At baseline, CHOP’s ED was screening 63% of febrile children under age 24 months using catheterization, but screens were most commonly negative and only 4.3% had positive cultures. The authors therefore initiated a switch to the two-step method as a pilot run in one ED area before educating all ED personnel and expanding to the full department in the second month.

Children aged 6 to 24 months comprised approximately 20% of the ED’s more than 90,000 annual patients, and about 22% of these children presented with fever as the primary concern. Children with a history of genitourinary problems or immune deficiency were excluded.

The pilot ran in an “urgent care section of ED where there are typically more children with less complex medical histories and where ‘fever’ is a common complaint,” the investigators said. The staff completed a learning module with assessment and then received in-person and visual reminders of the procedure.

While 69% of 828 febrile young children still underwent screening during the 6-month intervention period, only 16% still underwent urethral catheterization as the initial screening step, typically because of strong clinical indications for a UTI. Another 14% underwent catheterization only after a positive urine screen from an initial noninvasive urine collection or because of an inability to get an adequate urine specimen with the bag. The reduction in catheterization dropped to 55% within 2 weeks of the intervention’s start and spread to other hospital departments. The drop to a 30% catheterization rate remained throughout 18 additional months of monitoring.

The research did not use external funding, and the researchers reported they had no financial disclosures.

1.    Lavelle JM, Blackstone MM, Funari MK, et al. Two-step process for ED UTI screening in febrile young children: reducing catheterization rates. Pediatrics. 2016 Jun 2. pii: e20153023. [Epub ahead of print].

CDC Issues Advisory About First Mcr-1 Gene in E Coli Found in a Human in the United States

BY JEFF BAUER

The Centers for Disease Control and Prevention (CDC) issued a health advisory to emphasize the importance of taking measures to prevent the transmission of antibiotic-resistant bacteria after a Pennsylvania woman with no recent travel outside of the United States was found to have Escherichia coli (E coli) bacteria carrying the mcr-1 gene. The mcr-1 gene makes bacteria resistant to colistin, which is used as a last-resort antibiotic to treat patients who have multidrug-resistant infections, including carbapenem-resistant Enterobacteriaceae (CRE).  The mcr-1 gene exists on a small piece of DNA that is capable of moving from one bacterium to another, which would allow it to spread antibiotic resistance among species.  The CDC has been on alert for this gene in the United States ever since its emergence in China in 2015. 

The patient in Pennsylvania, who was being treated for a urinary tract infection (UTI), is believed to be the first human case of mcr-1 E coli in the United States. Although the E coli isolate from the patient was also resistant to antibiotics in five additional antibiotic classes (cephalosporins, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines), the woman did not have CRE and the bacteria identified were not resistant to all antibiotics. However, the presence of the mcr-1 gene and its ability to share its colistin resistance with other bacteria increases the risk that pan-resistant bacteria could develop. The CDC’s laboratories have developed protocols for testing microorganisms for the mcr-1 gene and the CDC was performing screening tests to see if people in contact with the patient with mcr-1 might be colonized with this organism.

The CDC recommends that clinicians follow Standard and Contact Precautions for any patients colonized or infected with antibiotic-resistant bacteria, including patients found to have mcr-1-mediated resistant organisms. If a patient is found to have Enterobacteriaceae with mcr-1, healthcare facilities and laboratories should immediately notify local or state public health authorities, and inform all clinicians who are caring for the patient. Any room in which a patient with an antibiotic-resistant infection has been placed should receive thorough daily and terminal cleaning.

1.    Centers for Disease Control and Prevention. Alert to U.S. healthcare facilities: first mcr-1 gene in E. coli bacteria found in a human in the United States. https://emergency.cdc.gov/han/han00390.asp. Accessed June 23, 2016.

Emergency Medicine Associate Editor Named as Chair of EM at Rutgers

Lewis S. Nelson, MD, has been appointed as the Chair of the Department of Emergency Medicine at Rutgers New Jersey Medical School and Chief of Service of the Emergency Department at University Hospital in Newark. For many years, Dr Nelson has been serving as associate editor, toxicology, for Emergency Medicine, overseeing the journal’s Case Studies in Toxicology department. 

HIV Rapid Tests Miss 1 in 7 Infections

BY RICHARD PIZZI

FROM AIDS

apid human immunodeficiency virus (HIV) tests in high-income countries miss about one in seven infections and should be used in combination with fourth-generation enzyme immunoassays (EIA) or nucleic acid amplification tests (NAAT) in clinical settings whenever possible, according to a study in the journal AIDS.

“These infections are likely to be particularly transmissible due to the high HIV viral load in early infection...in high-income countries, rapid tests should be used in combination with fourth-generation EIA or NAAT, except in special circumstances,” the Australian researchers said.

Researchers performed a systematic review and meta-analysis of 18 studies involving 110,122 HIV rapid test results. The primary outcome was the test’s sensitivity for detecting acute or established HIV infections. Sensitivity was calculated by dividing the number of confirmed positive rapid tests by the number of confirmed positive comparator tests. Specificity was calculated by dividing the number of confirmed negative rapid tests by the number of negative comparator tests.

Compared with EIA, the estimated sensitivity of rapid tests was 94.5% (95% confidence interval [CI], 87.4-97.7). Compared with NAAT, the sensitivity of rapid tests was 93.7% (95% CI, 88.7-96.5). The sensitivity of rapid tests in high-income countries was 85.7% (95% CI, 81.9-88.9), and in low-income countries it was 97.7% (95% CI, 95.2-98.9), compared with either EIA or NAAT (P < .01 for difference between settings). Proportions of antibody-negative acute infections were 13.6% (95% CI, 10.1-18.0) and 4.7% (95% CI, 2.8-7.7) in studies from high- and low-income countries, respectively (P < .01).

Rapid tests were less sensitive when used in clinical settings in high-income countries, regardless of whether they were compared with a NAAT or fourth-generation EIA. However, the researchers noted that the discrepancy between high- and low-income countries could be attributed to the higher proportion of acute HIV infections (antibody-negative NAAT positive) in populations tested in high-income countries, which might reflect higher background testing rates or a higher incidence of HIV in men who have sex with men.

1.    Tan WS, Chow EP, Fairley CK, Chen MY, Bradshaw CS, Read TR. Sensitivity of HIV rapid tests compared to fourth generation enzyme immunoassays or HIV RNA tests - a systematic review and meta-analysis. AIDS. 2016 Apr 27. [Epub ahead of print]

Two-Step ED Urinary Tract Infection Screening Cuts Catheterization Rate in Half

BY TARA HAELLE

FROM PEDIATRICS

fter implementation of a quality improvement initiative to more effectively screen febrile children for UTIs in the ED, catheterization rates dropped from 63% to 30% over a 6-month period, a study found.

The sustained drop prevented more than 350 young children from catheterization without increasing revisit rates or missing UTIs in the 39% of children who were followed in the care network. This was in a study that compared catheterization rates in 1,520 children aged 6 to 24 months in the year before the intervention and 828 children in the 6 months during the intervention.

“Although urine catheterization remains the gold standard in diagnosing UTIs, it is an invasive procedure that may be avoided in most patients who are being screened,” wrote Dr Jane M. Lavelle of Children’s Hospital of Philadelphia (CHOP) and her associates. Screening for UTIs by this method can be “painful, time consuming, and costly,” they added.

An alternative method to automatic catheterization is a two-step process already included as an option in the American Academy of Pediatrics guidelines: instead of collecting urine through catheterization just once for screening and culture, an ED first noninvasively collects urine with a urine bag for screening in those indicated with evidence-based risk factors, and then catheterizes only those who screen positive.

“Due to the predictive models’ higher sensitivity than specificity for screening, most urine samples will have a negative screen for pyuria or bacteriuria by urine dipstick or microscopy,” the authors wrote.

At baseline, CHOP’s ED was screening 63% of febrile children under age 24 months using catheterization, but screens were most commonly negative and only 4.3% had positive cultures. The authors therefore initiated a switch to the two-step method as a pilot run in one ED area before educating all ED personnel and expanding to the full department in the second month.

Children aged 6 to 24 months comprised approximately 20% of the ED’s more than 90,000 annual patients, and about 22% of these children presented with fever as the primary concern. Children with a history of genitourinary problems or immune deficiency were excluded.

The pilot ran in an “urgent care section of ED where there are typically more children with less complex medical histories and where ‘fever’ is a common complaint,” the investigators said. The staff completed a learning module with assessment and then received in-person and visual reminders of the procedure.

While 69% of 828 febrile young children still underwent screening during the 6-month intervention period, only 16% still underwent urethral catheterization as the initial screening step, typically because of strong clinical indications for a UTI. Another 14% underwent catheterization only after a positive urine screen from an initial noninvasive urine collection or because of an inability to get an adequate urine specimen with the bag. The reduction in catheterization dropped to 55% within 2 weeks of the intervention’s start and spread to other hospital departments. The drop to a 30% catheterization rate remained throughout 18 additional months of monitoring.

The research did not use external funding, and the researchers reported they had no financial disclosures.

1.    Lavelle JM, Blackstone MM, Funari MK, et al. Two-step process for ED UTI screening in febrile young children: reducing catheterization rates. Pediatrics. 2016 Jun 2. pii: e20153023. [Epub ahead of print].

The 2015 American Heart Association CPR/ACLS update categorizes amiodarone and lidocaine as IIb drugs that “may be considered” for ventricular fibrillation or pulseless ventricular tachycardia unresponsive to CPR, defibrillation, or vasopressors. Out-of-hospital use of these drugs has previously been shown to increase survival rate to hospital admission, but not necessarily to hospital discharge.

The effects of amiodarone and lidocaine on the rate of survival to hospital discharge are addressed in a recent randomized, double-blind, out-of-hospital trial comparing amiodarone, lidocaine, and placebo in the treatment of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (N Engl J Med. 2016;374[18]:1711-1722). This study was conducted by the Resuscitation Outcomes Consortium (ROC) in 3,026 patients at 10 US and Canadian sites. The ROC authors concluded that “overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo.” But the article raises concerns about its methodology, appropriateness of its primary and secondary outcomes to out-of-hospital (or prehospital) care, and the manner in which its findings were reported.

Because of the condition (unconscious) and circumstances (out of hospital) of the patients at the time medication or placebo must be administered, this NIH-supported trial was conducted under exception from informed consent in emergency research, with FDA and Health Canada oversight, and with approval by trial-site Institutional Review Boards. Notwithstanding the list of regulatory bodies that approved the exception, is the trial appropriate for drugs previously demonstrated to be efficacious in improving survival rates to hospital admission—long considered the goal of prehospital care—when subsequent care from admission to hospital discharge is not standardized or controlled across multiple sites in two countries?

Another concern is the way the results were reported. Will the authors’ conclusion that overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival  suggest to hurried readers that there is no benefit to any patient to hospital discharge from either antiarrhythmic agent? In the results section, the authors report “active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest.” Also noted in the accompanying editorial entitled “Out-of-Hospital Cardiac Arrest—Are Drugs Ever the Answer?” (N Engl J Med. 2016;374[18]:1781-1782), both drugs were associated with nonsignificant increases in survival rate, fewer subsequent shocks, and less administration of rhythm-control medications or need for CPR during hospitalization, compared with patients’ courses after placebo. 

The ROC trial is not the first or only out-of-hospital trial to use survival to hospital discharge as its primary outcome measure. A 1990-1991 study using death or discharge home to determine survival from out-of-hospital cardiac arrests in New York City found that of the 2,329 patients who met entry criteria for that study, overall survival was only 1.4%—which the authors attributed partly to lengthy elapsed time intervals at every step in the chain of survival, lack of adequate bystander CPR, and possibly sociodemographic features common to victims of cardiac arrest in large cities (JAMA. 1994;271[9]:678-683). The poor results  led to increases in first responders and AED availability but not the abandonment of properly performed CPR and ACLS. In the ROC trial, length of time from cardiac arrest to administration of medications clearly was shown to be a significant outcome determinant and was emphasized in the accompanying editorial. Here too shouldn’t we concentrate on optimizing the setting and timing of CPR and ACLS measures?  

The 2015 American Heart Association CPR/ACLS update categorizes amiodarone and lidocaine as IIb drugs that “may be considered” for ventricular fibrillation or pulseless ventricular tachycardia unresponsive to CPR, defibrillation, or vasopressors. Out-of-hospital use of these drugs has previously been shown to increase survival rate to hospital admission, but not necessarily to hospital discharge.

The effects of amiodarone and lidocaine on the rate of survival to hospital discharge are addressed in a recent randomized, double-blind, out-of-hospital trial comparing amiodarone, lidocaine, and placebo in the treatment of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (N Engl J Med. 2016;374[18]:1711-1722). This study was conducted by the Resuscitation Outcomes Consortium (ROC) in 3,026 patients at 10 US and Canadian sites. The ROC authors concluded that “overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo.” But the article raises concerns about its methodology, appropriateness of its primary and secondary outcomes to out-of-hospital (or prehospital) care, and the manner in which its findings were reported.

Because of the condition (unconscious) and circumstances (out of hospital) of the patients at the time medication or placebo must be administered, this NIH-supported trial was conducted under exception from informed consent in emergency research, with FDA and Health Canada oversight, and with approval by trial-site Institutional Review Boards. Notwithstanding the list of regulatory bodies that approved the exception, is the trial appropriate for drugs previously demonstrated to be efficacious in improving survival rates to hospital admission—long considered the goal of prehospital care—when subsequent care from admission to hospital discharge is not standardized or controlled across multiple sites in two countries?

Another concern is the way the results were reported. Will the authors’ conclusion that overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival  suggest to hurried readers that there is no benefit to any patient to hospital discharge from either antiarrhythmic agent? In the results section, the authors report “active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest.” Also noted in the accompanying editorial entitled “Out-of-Hospital Cardiac Arrest—Are Drugs Ever the Answer?” (N Engl J Med. 2016;374[18]:1781-1782), both drugs were associated with nonsignificant increases in survival rate, fewer subsequent shocks, and less administration of rhythm-control medications or need for CPR during hospitalization, compared with patients’ courses after placebo. 

The ROC trial is not the first or only out-of-hospital trial to use survival to hospital discharge as its primary outcome measure. A 1990-1991 study using death or discharge home to determine survival from out-of-hospital cardiac arrests in New York City found that of the 2,329 patients who met entry criteria for that study, overall survival was only 1.4%—which the authors attributed partly to lengthy elapsed time intervals at every step in the chain of survival, lack of adequate bystander CPR, and possibly sociodemographic features common to victims of cardiac arrest in large cities (JAMA. 1994;271[9]:678-683). The poor results  led to increases in first responders and AED availability but not the abandonment of properly performed CPR and ACLS. In the ROC trial, length of time from cardiac arrest to administration of medications clearly was shown to be a significant outcome determinant and was emphasized in the accompanying editorial. Here too shouldn’t we concentrate on optimizing the setting and timing of CPR and ACLS measures?  

The 2015 American Heart Association CPR/ACLS update categorizes amiodarone and lidocaine as IIb drugs that “may be considered” for ventricular fibrillation or pulseless ventricular tachycardia unresponsive to CPR, defibrillation, or vasopressors. Out-of-hospital use of these drugs has previously been shown to increase survival rate to hospital admission, but not necessarily to hospital discharge.

The effects of amiodarone and lidocaine on the rate of survival to hospital discharge are addressed in a recent randomized, double-blind, out-of-hospital trial comparing amiodarone, lidocaine, and placebo in the treatment of shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (N Engl J Med. 2016;374[18]:1711-1722). This study was conducted by the Resuscitation Outcomes Consortium (ROC) in 3,026 patients at 10 US and Canadian sites. The ROC authors concluded that “overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo.” But the article raises concerns about its methodology, appropriateness of its primary and secondary outcomes to out-of-hospital (or prehospital) care, and the manner in which its findings were reported.

Because of the condition (unconscious) and circumstances (out of hospital) of the patients at the time medication or placebo must be administered, this NIH-supported trial was conducted under exception from informed consent in emergency research, with FDA and Health Canada oversight, and with approval by trial-site Institutional Review Boards. Notwithstanding the list of regulatory bodies that approved the exception, is the trial appropriate for drugs previously demonstrated to be efficacious in improving survival rates to hospital admission—long considered the goal of prehospital care—when subsequent care from admission to hospital discharge is not standardized or controlled across multiple sites in two countries?

Another concern is the way the results were reported. Will the authors’ conclusion that overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival  suggest to hurried readers that there is no benefit to any patient to hospital discharge from either antiarrhythmic agent? In the results section, the authors report “active drugs were associated with a survival rate that was significantly higher than the rate with placebo among patients with bystander-witnessed arrest but not among those with unwitnessed arrest.” Also noted in the accompanying editorial entitled “Out-of-Hospital Cardiac Arrest—Are Drugs Ever the Answer?” (N Engl J Med. 2016;374[18]:1781-1782), both drugs were associated with nonsignificant increases in survival rate, fewer subsequent shocks, and less administration of rhythm-control medications or need for CPR during hospitalization, compared with patients’ courses after placebo. 

The ROC trial is not the first or only out-of-hospital trial to use survival to hospital discharge as its primary outcome measure. A 1990-1991 study using death or discharge home to determine survival from out-of-hospital cardiac arrests in New York City found that of the 2,329 patients who met entry criteria for that study, overall survival was only 1.4%—which the authors attributed partly to lengthy elapsed time intervals at every step in the chain of survival, lack of adequate bystander CPR, and possibly sociodemographic features common to victims of cardiac arrest in large cities (JAMA. 1994;271[9]:678-683). The poor results  led to increases in first responders and AED availability but not the abandonment of properly performed CPR and ACLS. In the ROC trial, length of time from cardiac arrest to administration of medications clearly was shown to be a significant outcome determinant and was emphasized in the accompanying editorial. Here too shouldn’t we concentrate on optimizing the setting and timing of CPR and ACLS measures?  

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

PD-1 checkpoint blockade via pembrolizumab is a potential option for classical Hodgkin’s lymphoma that progressed despite brentuximab vedotin therapy, based on a phase Ib, single-arm, open-label, industry-sponsored study of 31 patients.

After a median follow-up of 17 months, five (16%) patients achieved complete remission (90% confidence interval, 7%-31%), and 15 (48%) patients achieved partial remission (90% CI, 33%-64%), for an overall response rate of 65% (48%-79%). Furthermore, 70% of responses lasted at least 24 weeks, reported Philippe Armand, MD, of Dana-Farber Cancer Institute, Boston, and his associates.

“Since the time of study design, it has become apparent that complete responses are not commonly achieved with checkpoint blockade in solid tumors or hematologic malignancies,” they added. “Yet partial responses can be durable, suggesting that the achievement of complete response with checkpoint blockade is not necessary to derive significant clinical benefit.”

Pembrolizumab (Keytruda) is a humanized, highly selective IgG4 anti-PD-1 (programmed death-1) monoclonal antibody approved in the United States for patients with unresectable or metastatic melanoma or metastatic PDL-1 expressing non–small cell lung cancer. Tumor cells in classical Hodgkin lymphoma (HL) often overexpress PD-1 ligands, which “strongly suggests” that HL is PD-1 dependent, the researchers noted (J Clin Oncol. 2016 Jun 27. doi: 10.1200/JCO.2016.67.3467).

The researchers analyzed data for one group of patients within a phase Ib study of pembrolizumab in hematologic malignancies (KEYNOTE-013; NCT01953692). These 31 adults (median age, 32 years; 58% male) all had heavily pretreated classical HL – more than half had received at least five prior lines of therapy, and all had progressed on or after brentuximab vedotin therapy. Most patients (71%) also had received autologous stem cell transplantation. All 31 patients in the study received intravenous pembrolizumab (10 mg/kg) every other week.

Rates of progression-free survival were 69% at 24 weeks and 46% at 52 weeks, the researchers said. “Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-gamma, T-cell receptor, and expanded immune-related signaling pathways,” they reported. Those findings indicate that PD-1 blockade activates T-cell and IFN-gamma signaling pathways, which provides “a compelling rationale for the further development of PD-1 blockade in HL,” they concluded.

The most common treatment-related adverse effects were hypothyroidism (16%), diarrhea (16%), nausea (13%), and pneumonitis (10%). Five patients (16%) developed grade 3 treatment-related adverse events, including elevated hepatic transaminases, axillary pain, back pain, joint swelling, colitis, and nephrotic syndrome. Two patients stopped treatment because of adverse effects, but there were no grade 4 events or deaths related to treatment, and no treatment-induced cases of hepatitis, hypophysitis, or uveitis, the researchers noted.

Merck, maker of pembrolizumab, funded the study. Dr. Armand reported financial ties to Merck, Bristol-Myers Squibb, Infinity Pharmaceuticals, Sequenta, Tensha Therapeutics, and Sigma-Tau. Senior author Craig Moskowitz, MD, and five coinvestigators disclosed consulting or advisory relationships or employment with Merck.

NEW YORK - CT scans identify all clinically significant cervical spine injuries in intoxicated patients with blunt trauma, according to a new study.

"I don't think any of the results were particularly surprising to any of us who regularly do trauma care, but what I do think is remarkable about them is that they dispel several long-held myths about the c-spine, intoxicated patients, and the clearance process," Dr. Matthew J. Martin from Legacy Emanuel Medical Center, Portland, Oregon told Reuters Health.

"I think it again confirms that modern CT scan is highly reliable for identifying significant c-spine injuries, but also that the majority of so called 'intoxicated' patients are examinable enough to determine whether the collar can be removed (when combined with the CT scan)," he said.

Up to half of trauma patients are intoxicated, making clearance of the cervical spine a commonly encountered dilemma with both medical and medicolegal implications. Most guidelines indicate that the cervical spine should not be cleared in such patients, resulting in prolonged immobilization or additional imaging even in the face of a normal CT scan.

Dr. Martin's team examined cervical spine clearance practices for intoxicated trauma patients, examined the reliability of cervical spine CT scans for identifying clinically significant injuries (CSIs), and looked for CSIs that might have been missed by CT scans.

Among 1,429 patients who had an alcohol or drug screen performed, 44.2% were intoxicated, the researchers report in JAMA Surgery, online June 15.

Cervical spine injuries were identified in 11.3% of the sober group, 8.1% of the alcohol-intoxicated group, and 12.0% of the drug-intoxicated group.

CT scans yielded negative predictive values of 99.2% for all injuries and 99.8% for unstable injuries. There were five false-negative CT scans, including four central cord syndromes without associated fractures and one potentially unstable injury in a drug-intoxicated patient who presented with clear quadriplegia on examination.

Half of the intoxicated patients were admitted with continued cervical spine immobilization only on the basis of their intoxication. There were no missed CSIs in this group, and all patients were discharged without evidence of an injury or neurologic deficit. They underwent cervical spine immobilization for an average of 15.1 hours, about four times the average time to cervical spine clearance among sober patients (3.7 hours).

"The finding of how long we are keeping these patients in a c-collar based solely on intoxication should raise some eyebrows, and identifies an easy target for process improvement," Dr. Martin said.

"Cervical collars and immobilization are not therapeutic for the vast majority of c-spine injuries; they are really only to prevent inadvertent motion of an unstable c-spine injury," Dr. Martin said. "This is exceedingly rare in a patient who presents with no gross motor deficit, and a high quality CT scan will identify these unstable injuries very reliably. In addition, there are multiple adverse effects of prolonged immobilization, and even of getting an MRI."

"When these are factored in, I think the risk:benefit analysis falls squarely on the side of early clearance based on CT scan," he concluded.

"A key point is that this should be done by experts who are familiar with not only the global concept (the collar can be removed with a negative CT scan), but also the finer points where you could potentially cause harm, or where you should not remove the collar," Dr. Martin added. "This is where a very clear written protocol comes into play and reduces variation or errors that could cause patient harm."

"The results of this study suggest that it is unnecessary to delay cervical spine clearance until intoxicated patients are sober or until magnetic resonance imaging is performed," write Dr. Olubode A. Olufajo and Dr. Ali Salim from Brigham and Women's Hospital, Boston, in a related editorial. "However, caution must be taken in making conclusions based on these data."

"Although the authors conducted the study at an institution with high-quality CT technology and well-trained radiologists, they still recorded a false-negative CT report consistent with a misread," they note. "With the higher potential for this nature of error in lower-resourced settings, it becomes important to compare the costs and benefits of early removal of cervical collars."

They wonder, "With our knowledge that intoxicated patients form up to half of the population of trauma patients, is it really safe to risk irreversible injuries in 1% of the population to save a few hours in cervical clearance times?"

Dr. Stephen Asha from the University of New South Wales in Sydney, Australia, who has reported on various aspects of cervical spine imaging, told Reuters Health by email, "I think this study confirms what clinical experience as well as much of the more recent studies on cervical spine CT scanning tells us, which is that if there is nothing abnormal detected on a new generation, multi-slice CT, then the neck can be cleared."

"Of course there were a few missed injuries, but this needs to be put into context: no one just does a test in isolation, it is always combined with a clinical assessment, and a consideration the mechanism of injury," said Dr. Asha, who was not involved in the new work. "In this case there were five injuries not apparent on the CT scan, but all had obvious spinal cord injury on clinical examination before the CT was done, so these injuries were never going to be missed in a real clinical setting."

"MRI use should be carefully considered because the problem with MRI is that it can be over-sensitive, demonstrating abnormal signal suggesting ligamentous injury in patient who simply have a ligamentous 'strain,'" Dr. Asha explained. "The false-positive results then lead to further periods of inappropriate immobilization and testing, with the accompanying costs, inconvenience, and complications."

"In patients in whom the clinical assessment raises no concerns for injury, then a normal CT should herald the end of investigations," he said. "MRI should be reserved for those where the clinical assessment is abnormal or where the CT is abnormal and further evaluation for ligamentous or spinal injury is required."

Dr. Asha concluded, "If the clinical exam is not concerning and the CT is normal, then clear the neck."

SOURCE: http://bit.ly/28MxHxA and http://bit.ly/28MxHO5

JAMA Surg 2016.

NEW YORK - CT scans identify all clinically significant cervical spine injuries in intoxicated patients with blunt trauma, according to a new study.

"I don't think any of the results were particularly surprising to any of us who regularly do trauma care, but what I do think is remarkable about them is that they dispel several long-held myths about the c-spine, intoxicated patients, and the clearance process," Dr. Matthew J. Martin from Legacy Emanuel Medical Center, Portland, Oregon told Reuters Health.

"I think it again confirms that modern CT scan is highly reliable for identifying significant c-spine injuries, but also that the majority of so called 'intoxicated' patients are examinable enough to determine whether the collar can be removed (when combined with the CT scan)," he said.

Up to half of trauma patients are intoxicated, making clearance of the cervical spine a commonly encountered dilemma with both medical and medicolegal implications. Most guidelines indicate that the cervical spine should not be cleared in such patients, resulting in prolonged immobilization or additional imaging even in the face of a normal CT scan.

Dr. Martin's team examined cervical spine clearance practices for intoxicated trauma patients, examined the reliability of cervical spine CT scans for identifying clinically significant injuries (CSIs), and looked for CSIs that might have been missed by CT scans.

Among 1,429 patients who had an alcohol or drug screen performed, 44.2% were intoxicated, the researchers report in JAMA Surgery, online June 15.

Cervical spine injuries were identified in 11.3% of the sober group, 8.1% of the alcohol-intoxicated group, and 12.0% of the drug-intoxicated group.

CT scans yielded negative predictive values of 99.2% for all injuries and 99.8% for unstable injuries. There were five false-negative CT scans, including four central cord syndromes without associated fractures and one potentially unstable injury in a drug-intoxicated patient who presented with clear quadriplegia on examination.

Half of the intoxicated patients were admitted with continued cervical spine immobilization only on the basis of their intoxication. There were no missed CSIs in this group, and all patients were discharged without evidence of an injury or neurologic deficit. They underwent cervical spine immobilization for an average of 15.1 hours, about four times the average time to cervical spine clearance among sober patients (3.7 hours).

"The finding of how long we are keeping these patients in a c-collar based solely on intoxication should raise some eyebrows, and identifies an easy target for process improvement," Dr. Martin said.

"Cervical collars and immobilization are not therapeutic for the vast majority of c-spine injuries; they are really only to prevent inadvertent motion of an unstable c-spine injury," Dr. Martin said. "This is exceedingly rare in a patient who presents with no gross motor deficit, and a high quality CT scan will identify these unstable injuries very reliably. In addition, there are multiple adverse effects of prolonged immobilization, and even of getting an MRI."

"When these are factored in, I think the risk:benefit analysis falls squarely on the side of early clearance based on CT scan," he concluded.

"A key point is that this should be done by experts who are familiar with not only the global concept (the collar can be removed with a negative CT scan), but also the finer points where you could potentially cause harm, or where you should not remove the collar," Dr. Martin added. "This is where a very clear written protocol comes into play and reduces variation or errors that could cause patient harm."

"The results of this study suggest that it is unnecessary to delay cervical spine clearance until intoxicated patients are sober or until magnetic resonance imaging is performed," write Dr. Olubode A. Olufajo and Dr. Ali Salim from Brigham and Women's Hospital, Boston, in a related editorial. "However, caution must be taken in making conclusions based on these data."

"Although the authors conducted the study at an institution with high-quality CT technology and well-trained radiologists, they still recorded a false-negative CT report consistent with a misread," they note. "With the higher potential for this nature of error in lower-resourced settings, it becomes important to compare the costs and benefits of early removal of cervical collars."

They wonder, "With our knowledge that intoxicated patients form up to half of the population of trauma patients, is it really safe to risk irreversible injuries in 1% of the population to save a few hours in cervical clearance times?"

Dr. Stephen Asha from the University of New South Wales in Sydney, Australia, who has reported on various aspects of cervical spine imaging, told Reuters Health by email, "I think this study confirms what clinical experience as well as much of the more recent studies on cervical spine CT scanning tells us, which is that if there is nothing abnormal detected on a new generation, multi-slice CT, then the neck can be cleared."

"Of course there were a few missed injuries, but this needs to be put into context: no one just does a test in isolation, it is always combined with a clinical assessment, and a consideration the mechanism of injury," said Dr. Asha, who was not involved in the new work. "In this case there were five injuries not apparent on the CT scan, but all had obvious spinal cord injury on clinical examination before the CT was done, so these injuries were never going to be missed in a real clinical setting."

"MRI use should be carefully considered because the problem with MRI is that it can be over-sensitive, demonstrating abnormal signal suggesting ligamentous injury in patient who simply have a ligamentous 'strain,'" Dr. Asha explained. "The false-positive results then lead to further periods of inappropriate immobilization and testing, with the accompanying costs, inconvenience, and complications."

"In patients in whom the clinical assessment raises no concerns for injury, then a normal CT should herald the end of investigations," he said. "MRI should be reserved for those where the clinical assessment is abnormal or where the CT is abnormal and further evaluation for ligamentous or spinal injury is required."

Dr. Asha concluded, "If the clinical exam is not concerning and the CT is normal, then clear the neck."

SOURCE: http://bit.ly/28MxHxA and http://bit.ly/28MxHO5

JAMA Surg 2016.

NEW YORK - CT scans identify all clinically significant cervical spine injuries in intoxicated patients with blunt trauma, according to a new study.

"I don't think any of the results were particularly surprising to any of us who regularly do trauma care, but what I do think is remarkable about them is that they dispel several long-held myths about the c-spine, intoxicated patients, and the clearance process," Dr. Matthew J. Martin from Legacy Emanuel Medical Center, Portland, Oregon told Reuters Health.

"I think it again confirms that modern CT scan is highly reliable for identifying significant c-spine injuries, but also that the majority of so called 'intoxicated' patients are examinable enough to determine whether the collar can be removed (when combined with the CT scan)," he said.

Up to half of trauma patients are intoxicated, making clearance of the cervical spine a commonly encountered dilemma with both medical and medicolegal implications. Most guidelines indicate that the cervical spine should not be cleared in such patients, resulting in prolonged immobilization or additional imaging even in the face of a normal CT scan.

Dr. Martin's team examined cervical spine clearance practices for intoxicated trauma patients, examined the reliability of cervical spine CT scans for identifying clinically significant injuries (CSIs), and looked for CSIs that might have been missed by CT scans.

Among 1,429 patients who had an alcohol or drug screen performed, 44.2% were intoxicated, the researchers report in JAMA Surgery, online June 15.

Cervical spine injuries were identified in 11.3% of the sober group, 8.1% of the alcohol-intoxicated group, and 12.0% of the drug-intoxicated group.

CT scans yielded negative predictive values of 99.2% for all injuries and 99.8% for unstable injuries. There were five false-negative CT scans, including four central cord syndromes without associated fractures and one potentially unstable injury in a drug-intoxicated patient who presented with clear quadriplegia on examination.

Half of the intoxicated patients were admitted with continued cervical spine immobilization only on the basis of their intoxication. There were no missed CSIs in this group, and all patients were discharged without evidence of an injury or neurologic deficit. They underwent cervical spine immobilization for an average of 15.1 hours, about four times the average time to cervical spine clearance among sober patients (3.7 hours).

"The finding of how long we are keeping these patients in a c-collar based solely on intoxication should raise some eyebrows, and identifies an easy target for process improvement," Dr. Martin said.

"Cervical collars and immobilization are not therapeutic for the vast majority of c-spine injuries; they are really only to prevent inadvertent motion of an unstable c-spine injury," Dr. Martin said. "This is exceedingly rare in a patient who presents with no gross motor deficit, and a high quality CT scan will identify these unstable injuries very reliably. In addition, there are multiple adverse effects of prolonged immobilization, and even of getting an MRI."

"When these are factored in, I think the risk:benefit analysis falls squarely on the side of early clearance based on CT scan," he concluded.

"A key point is that this should be done by experts who are familiar with not only the global concept (the collar can be removed with a negative CT scan), but also the finer points where you could potentially cause harm, or where you should not remove the collar," Dr. Martin added. "This is where a very clear written protocol comes into play and reduces variation or errors that could cause patient harm."

"The results of this study suggest that it is unnecessary to delay cervical spine clearance until intoxicated patients are sober or until magnetic resonance imaging is performed," write Dr. Olubode A. Olufajo and Dr. Ali Salim from Brigham and Women's Hospital, Boston, in a related editorial. "However, caution must be taken in making conclusions based on these data."

"Although the authors conducted the study at an institution with high-quality CT technology and well-trained radiologists, they still recorded a false-negative CT report consistent with a misread," they note. "With the higher potential for this nature of error in lower-resourced settings, it becomes important to compare the costs and benefits of early removal of cervical collars."

They wonder, "With our knowledge that intoxicated patients form up to half of the population of trauma patients, is it really safe to risk irreversible injuries in 1% of the population to save a few hours in cervical clearance times?"

Dr. Stephen Asha from the University of New South Wales in Sydney, Australia, who has reported on various aspects of cervical spine imaging, told Reuters Health by email, "I think this study confirms what clinical experience as well as much of the more recent studies on cervical spine CT scanning tells us, which is that if there is nothing abnormal detected on a new generation, multi-slice CT, then the neck can be cleared."

"Of course there were a few missed injuries, but this needs to be put into context: no one just does a test in isolation, it is always combined with a clinical assessment, and a consideration the mechanism of injury," said Dr. Asha, who was not involved in the new work. "In this case there were five injuries not apparent on the CT scan, but all had obvious spinal cord injury on clinical examination before the CT was done, so these injuries were never going to be missed in a real clinical setting."

"MRI use should be carefully considered because the problem with MRI is that it can be over-sensitive, demonstrating abnormal signal suggesting ligamentous injury in patient who simply have a ligamentous 'strain,'" Dr. Asha explained. "The false-positive results then lead to further periods of inappropriate immobilization and testing, with the accompanying costs, inconvenience, and complications."

"In patients in whom the clinical assessment raises no concerns for injury, then a normal CT should herald the end of investigations," he said. "MRI should be reserved for those where the clinical assessment is abnormal or where the CT is abnormal and further evaluation for ligamentous or spinal injury is required."

Dr. Asha concluded, "If the clinical exam is not concerning and the CT is normal, then clear the neck."

SOURCE: http://bit.ly/28MxHxA and http://bit.ly/28MxHO5

JAMA Surg 2016.