CASE REPORT
Fatal Intracranial Bleeding Associated With Prehospital Use of Epinephrine From the Division of Emergency Medicine, University of California, Davis, Medical Center, Sacramento, California.
B Zane Horowitz, MD Sami Jadallah, MD Robert W Derlet, MD
Received for publication March 5, 1996. Revision received June 1O, 1996. Accepted for publication July I, 1996.
Copyright @ by the American College oj Emergency Physicians.
We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution. [Horowitz BZ, Jadallah S, Uerlet RW: Fatal intracranial bleeding associated with prehospital use of epinephrine. Ann EmergMed December 1996;28:725-727.]
INTRODUCTION Epinephrine is one of the essentialdrugs of Advanced Cardiac Life Support. 1,2 It was among the first agents to be used by prehospital providers on standing orders in many emergency medical services systems. It is considered a class 1 agent by the American Heart Association for use in pulseless ventricular arrhythmias, asystole, and pulseless electrical activity (PEA). s It is also used in many EMS systems to treat allergic reactions and anaphylaxis. 3,4 Although there is little doubt that epinephrine is truly one of the lifesaving medications that every EMS system should have available 2,5, its potent sympathomimetic effects mandate caution in use on standing orders in the prehospital arena outside of CPR. Administration in non-cardiac arrest situations requires careful medical supervision. Previous studies have shown that paramedics, given their limited scope of diagnostics in the field, may misdiagnose respiratory distress in one of eight patients. 6-s Although previous reports of prehospital treatment of respiratory emergencies have detailed few adverse effects, we report a case in which epinephrine was used subcutaneously for suspected allergic reaction and was associated with fatal subarachnoid hemorrhage.
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A 39-year-old man called 911 complaining of shortness of breath of several hours' duration. He told paramedics on the scene that he had first begun having difficulty breathing 7 hours before calling 911; by the time the EMS personnel arrived he could speak only four to five words at a time. The paramedic report notes that the patient had been given a new, unknown medication 3 days previously for treatment of hypertension, after which a generalized, itching rash developed. Initial vital signs included a pulse of 104, a respiratory rate of 32, and a blood pressure of 220/160 mm Hg. Lung sounds were described as wheezing; at one point stridor was noted. The patient denied drug allergies or prior cardiac history. He was treated in accordance with prehospital standing orders for allergic reaction/anaphylaxis with subcutaneous epinephrine. 5 rag. During transportation to the hospital, high-flow oxygen was administered by face mask. Two attempts to start an IV line were made. Nine minutes after receiving the epinephrine, the patient became unresponsive, bradycardic, and apneic. CPR was begun, but attempts at oral intubation in the field were unsuccessful. Bag-valve-mask ventilation was performed until the patient arrived at the emergency department. At this point the initial collapse rhythm of PEA, with a rate of 40, had deteriorated to asystole. In the ED the patient was intubated with an oral endotracheal tube. His cardiac rhythm after intubation was PEA. He was given epinephrine 2 mg endotracheally, IV epinephrine 1 mg twice, and IV atropine 1 rag, after which his rhythm converted to ventricular fibrillation. After three defibrillations, three additional 5-mg doses of epinephrine, and fidocaine 100 mg, a narrow-complex sinus rhythm at a rate of 143 was established. CPR time totaled 18 minutes; total epinephrine doses were 17 mg intravenously, 2 mg endotracheally, and .5 mg subcutaneously. Immediately after resuscitation the patient's blood pressure was 220/120 mm Hg. Examination showed fixed, midposition pupils. Lung auscultation revealed bilateral tales. Cardiac examination showed no murmurs or gallops. The abdomen was distended. The extremities were notable for 2+ pitting edema. ECG findings showed sinus tachycardia, met criteria for left atrial enlargement and left ventricular hypertrophy, and revealed ST-segment depression in leads I, aVL, VS, and V6. Chest radiography demonstrated bilateral diffuse infiltrates consistent with pulmonary edema. IV furosemide 80 mg and IV nitroglycerine 10 big/ minute to maintain blood pressure control were administered. IV lidocaine 2 rag/minute was infused to prevent reversion to ventricular fibrillation. Computed tomography of the patient's head was interpreted as showing a subarach-
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noid hemorrhage in the right sylvian and inter hemispheric fissures. From the patient's family and his physician we learned that the patient had taken an antihypertensive medication for 4 years but that he had not taken the drugs for several months. Three days before admission the patient had visited his physician for a cough and was given terfenadine (Seldane) and promethazine with codeine. He had gained 60 pounds over the preceding 6 months and complained of shortness of breath of a week's duration. However, he had not been restarted on his antihypertensive medications. While at work in his office on the day of admission he had begun having difficulty breathing and noticed a rash. At this point 911 had been called. In the ICU, echocardiography showed mild global hypokinesis with a shortening fraction of 23% but no areas of akinesis, suggesting chronic hypertension. Diuresis yielded 7 L of fluid, with stabilization of pulmonary function. Serial creatine kinase-MB fractions were normal. Neurologic function did not improve, however, and the patient was pronounced brain dead and allowed to die. Postmortem examination was not performed. DISCUSSION
Epinephrine-induced morbidity in prehospital care is rare. Karch 9 reported a case of medication error in which 2 mg of epinephrine was administered intravenously when 2 mg of naloxone had actually been ordered. The patient sustained transient coronary vasospasrn but recovered. Our case is instructive in that it is the first reported fatality associated with prehospital administration of a standard subcutaneous dose of epinephrine. In this patient, cardiovascular collapse occurred after a single dose of subcutaneous epinephrine, and the patient was subsequently found to have a subarachnoid hemorrhage. In this case the paramedic did not recognize an extremely increased blood pressure of 220/160 mm Hg as a local protocol contraindication to giving epinephrine on standing orders. Because the paramedics on the scene did not discuss this case with on-line medical control, an opportunity to avoid epinephrine administration was missed. The patient was also given highdose epinephrine later in the resuscitation attempt. We cannot establish whether any of these doses was the cause of central nervous system bleeding. Immediately after resuscitation the patient was again severely hypertensive. It is unfortunate that the patient's physician failed to recognize symptoms suggesting congestive heart failure (CHF) when the patient presented with a cough 3 days before admission. Weight gain, pitting edema, and noncom-
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pliance with the prescribed antihypertensive regimen indicated left ventricular dysfunction. Although the patient probably was exhibiting an allergic reaction to one of his medications when he was seen by the paramedics, it was in the setting of decompensated CHE The wheezes heard on examination may have been those of "cardiac asthma," n o t allergic bronchospasm. In the setting of the failing left ventricle, epinephrine is clearly contraindicated because vasoconstriction increases the afterIoad and may cause the heart to fail further. We will never know whether this acute decompensation of the left ventricle or the sudden onset of intercranial hemorrhage caused the patient's cardiopulmonary collapse, ahhough the immediate deterioration with hypertension and bradycardia suggests a Cushing reflex associated with sudden increased intracrania] pressure. Paramedics are hindered in their ability to diagnose complicated respiratory complaints in the field by limited diagnostic modalities, incomplete patient histories, and, sometimes, erroneous assumptions. In previous studies Tresch 6 showed that pulmonary edema was misdiagnosed by paramedics in 11% of cases in the Milwaukee EMS system and 5chaider r found a 18% misdiagnosis rate in the Denver EMS system. Wuerz s found a 15% misdiagnosis rate in the Hershey, Pennsylvania, EMS system and demonstrated increased, mortality in a group of patients with chronic obstructive pulmonary disease (COPD) who were treated according to a CHF protocoI (13.6% versus 3.8%). CHF patients mistakenly treated according to a COPD protocol showed no morbidity, hut only nine such patients were mismanaged in this way it is unclear whether any of these patients received epinephrine, as did our patient. Although epinephrine has long been used in asthma and allergic reactions by subcutaneous administration 1°, studies have not been performed to establish its pharrnacodynamics after subcutaneous administration. However, Emerman 11 has shown that epinephrine levels do not increase in patients with asthma or COPD who are treated with albuterol or glycopyrrolate aerosols. This finding suggests that these agents create less adrenergic release in the treatment of acute bronchospasm and that they should remain the first-line agent for both asthma and COPD. The standard treatment of anaphylactic reactions has included the use of subcutaneous epinephrine. Although advanced life support protocols allow the use of epinephrine for suspected anaphylaxis, the revised curriculum for EMT-Is also recommends the assisted administration of the patient's own epinephrine in cases of anaphylaxis. 4 Some EMS systems are investigating the use of epinephrine by basic life support providers when the patient does not possess an anaphylaxis kit. 3,4 Although we report only an a s s o c -
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iationbetween subcutaneous epinephrine and our patient's death, not causation, we believe this case should serve as a caution to any EMS system contemplating standing-order use of epinephrine for allergic reactions. The rash, history of a "new" medicine, and physical signs of bronchospasm led the paramedics in our case to diagnose anaphylaxis. Clues to the correct diagnosis, although subtle, were overlooked. The greatly increased blood pressure and pitting edema, both common in acute pu]monary edema, should have been a warning. Had these findings been relayed to the base station physician, the diagnosis of CHF might have been further explored and epinephrine withheld. REFERENCES 1. Cummins RO {ed): Textbookof AdvancedCardiacL/fe Support.Dallas: American Heart Association, t994:72-74. 2. Paradis NA, KoscoveEM: Epinephrinein cardiac arrest: A critical review. Ann EmergMed 1990;19:1288-1301. 3. FortenberryJE, Laine J, Shalit M: Use of epinephrine for anaphylaxis by emergencymedical technicians in a wilderness setting, Ann EmergMed 1995;25:785-787. 4. Lindbeck GH, Burns DM, Rockwell DD; Out-of-hospital provider use of epinephrine for allergic reactions: Pilot program. AcadEmergMed 1985;2:592-596. 5. Shuster M, ChongJ: Pharmacologicintervention in prehospital care: A critical appraisal. Ann EmergMed1989;18:192-196. 6. Tresch DD, Dabrowski RC, Fioretti GP, et al: Out-of-hospital pulmonary edema: Diagnosis and treatment. Ann EmergMed 1983;12:533-537. 7. Schaider J, Riccio J, Rvdman R, et ah Paramedicdiagnostic accuracy in patients with chest pain or shortness of breath [abstract]. Prehospita/DisasterMed 1991;5:392. 8. Wuerz RC, Meader SA: Effects of prehospitai medications on mortality and length of stay in congestive heart failure. Ann EmergMeal1992;21:669-674. 9. Karch SB: Coronaryartery spasm induced by intravenous epinephrine overdose.Am J Emerg Med 1989;7:485-488. 10. Heilpern KL: The treacherous clinical spectrum of allergic emergencies: Diagnosis, treatment, and prevention. EmergMed Reports1994;15:211-222. 11. Emerman CL, Cydulka RK: Changesin serum cathecholamine levels during acute bronchospasm. Ann EmergMed 1993;22:1836-1841.
Reprint no. 47/1/77587 Address for reprints: 8 ZaneHorowitz,MD
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