Confusion About Epinephrine Dosing Leading to Iatrogenic Overdose: A Life-Threatening Problem With a Potential Solution

Epinephrine is indicated for various medical emergencies, including cardiac arrest and anaphylaxis, but the dose and route of administration are different for each indication. For anaphylaxis, it is given intramuscularly at a low dose, whereas for cardiac arrest a higher dose is required intravenously. We encountered a patient with suspected anaphylaxis who developed transient severe systolic dysfunction because of inappropriately received cardiac arrest dose, ie, larger dose given as an intravenous push. Three additional patients who experienced potentially lethal cardiac complications after receiving inappropriately higher doses intravenously were also identified. These iatrogenic errors resulted from underlying confusion by physicians about proper dosing of epinephrine for anaphylaxis. The risk of error was amplified by the need for rapid decisionmaking in critically ill anaphylactic patients. An e-mail survey of local hospitals in southeast Michigan revealed that 6 of 7 hospitals did not stock prefilled intramuscular dose syringes for emergency use in anaphylaxis. At our institution, we have introduced prefilled and appropriately labeled intramuscularly dosed epinephrine syringes in crash carts, which are easily distinguished from intravenously dosed epinephrine syringes. In this Concepts article, we describe the clinical problem of inadvertent epinephrine overdose and propose a potential solution. Epinephrine must be clearly packaged and labeled to avoid inappropriate usage and unnecessary, potentially lethal complications in patients with anaphylaxis.

Introduction

Epinephrine is a catecholamine administered for life-threatening conditions of anaphylaxis and cardiac arrest. It is available in different doses and concentrations, to be delivered by various routes for appropriate indications (Table). Intramuscular (IM) dose of 0.3 to 0.5 mg (1:1,000) is recommended for use in anaphylaxis, whereas 0.1 mg (1:10,000) intravenous (IV) epinephrine injected slowly during 5 minutes is reserved for anaphylaxis symptoms refractory to IM doses or anaphylactic shock.¹ This is significantly lower than the dose recommended for cardiac arrest, in which the recommended first dose is a 1-mg (1:10,000) IV push.² Confusion concerning proper dosing and concentrations for different indications has been reported.3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Also, epinephrine is available in differing concentrations (1:1,000 and 1:10,000) in multidose vials, which can create another source of drug errors. Numerous case reports of inadvertent epinephrine overdose causing coronary dissection and infarction, cardiomyopathy, transient left ventricular dysfunction, and ventricular arrhythmias have been reported worldwide.3, 4, 5, 6, 7, 8, 9, 10, 11 During a 5-year period at our hospital, there have been 4 cases of patients developing serious cardiovascular complications from accidental epinephrine overdose, caused by confusion over appropriate dose and route.

In this Concepts article, our objective is to present 4 cases of potentially lethal complications resulting from inappropriate epinephrine dosing and then to discuss potential causes of this possibly underreported error and present solutions to eliminate this error.

A 23-year-old woman with history of asthma was admitted to our hospital for respiratory distress triggered by ingestion of seafood. On presentation, she was found to be tachypneic at 22 breaths/min, with mild inspiratory stridor. She was treated for possible seafood allergy with inhaled racemic epinephrine, IV antihistamines, and corticosteroids, with no improvement of symptoms. During the next few hours, she developed another episode of acute respiratory distress, this time unprovoked by seafood ingestion. Her physical examination was again unremarkable except for inspiratory stridor. Because her working diagnosis at the time was “possible anaphylaxis,” a decision was made to administer epinephrine. However, she was erroneously given 2 doses of 1 mg (1:10,000) epinephrine IV push per physician-written order. Subsequently, she developed cardiogenic shock with severe left ventricular dysfunction (ejection fraction of 15%). She was treated with intubation and ventilator support, along with diuretics, after which she had rapid clinical improvement. Repeated echocardiograms after 4 days showed normal ventricular function, with ejection fraction of 60%, confirming our diagnosis of reversible catecholamine cardiomyopathy from epinephrine overdose. Further evaluation revealed paradoxic vocal cord dysfunction as the cause of her stridor and respiratory events.

A 52-year-old woman was admitted to the emergency department (ED) for shortness of breath and throat constriction after ingestion of catfish. Her physical examination was consistent with angioedema, and given her respiratory distress, a decision was made to administer epinephrine. A 0.3-mg 1:1,000 concentration dose was ordered, but the route was not specified in the written order by the physician. The nurse drew the ordered dose from a multidose vial and delivered it IV. Minutes later, the patient developed severe left-sided chest pain, with new-onset ST elevations in leads II, III, and aVF. Her symptoms resolved after 2 doses of 0.4 mg sublingual nitroglycerine and 4 mg IV morphine, with return of ST elevations to baseline. The patient underwent cardiac catheterization, which did not reveal significant coronary artery disease.

A 33-year-old woman was admitted for observation for suspected anaphylaxis to IV iron sulfate. She was hemodynamically stable but had noticeable throat angioedema, as evidenced by tongue swelling. She was erroneously given 0.3 mg (1:1000) IV epinephrine by the nurse, instead of the requested IM injection. Subsequent to this, she developed severe chest pain and ST elevations in her II, III, and aVF leads. Because she continued to complain of chest pain despite 3 mg of IV morphine and 2 doses of 0.4 mg sublingual nitroglycerine, she was taken for an emergency cardiac catheterization, which revealed right-sided coronary artery dissection. She underwent stenting of the vessel, with uneventful recovery.

A 34-year-old man presented with anaphylaxis after ingestion of seafood. His presenting blood pressure was 90/60 mm Hg, and he was tachypneic (26 beats/min), tachycardic (104 beats/min), and in acute distress. IV epinephrine was considered appropriately, but instead of the anaphylactic dose of 0.1 mg (1:10,000) slow IV, he was given the cardiac arrest dose of 1 mg (1:10,000) IV push. Apparently, there was confusion between the verbal and written order for the drug by the physician per nursing notes. He subsequently became symptomatic, with dizziness and worsening hypotension. Telemetry revealed sustained ventricular tachycardia, which resolved spontaneously. He was observed in the ICU, with no recurrent arrhythmia. Echocardiogram and stress test results were unremarkable.

To determine the total number of admissions for this diagnosis during a 5-year period (2002 to 2007), we extracted the International Statistical Classification of Diseases and Related Health Problems codes for anaphylaxis syndromes and angioedema (995.0, 995.1, 995.6, and 999.4) from our hospital admission database. There were 166 admissions through our ED for anaphylaxis or angioedema, of which we have presented complications in 4 patients (incidence of 2.4%). These 4 patients' cases were presented in our cardiology morbidity and mortality conferences during the 5-year period. We also conducted an informal inpatient pharmacy survey by sending out e-mails to 15 neighboring hospitals in southeast Michigan, with an inquiry about the method of stocking epinephrine in hospital crash carts. Of the 7 hospitals that responded to our survey, only 1 hospital carried prefilled syringes for IM administration in their crash carts. All hospitals had the 1-mg (1:10,000 concentration) IV dose syringe, appropriate for use in cardiac arrest, readily available. The review of collected data and patient information for this report was approved by St. John Hospital and Medical Center Investigational Review Board.