Apical Ballooning Syndrome After Administration of Intravenous Epinephrine During an Anaphylactic Reaction

To the Editor: First described in Japan, apical ballooning syndrome (ABS), or Takotsubo cardiomyopathy, is an acquired, reversible cardiomyopathy. Catecholamine-induced myocardial stunning is the leading hypothesis for its pathophysiology.1 Epinephrine is the treatment of choice for patients with anaphylaxis.2 Prompt intramuscular administration is recommended because adverse reactions are more likely with intravenous dosing.3 We describe a case of a woman who developed ABS after intravenous administration of epinephrine. A 41-year-old woman developed itching, hives, lip and tongue swelling, and shortness of breath after a bee sting. After self-administration of diphenhydramine, she presented to a local emergency department. Her vital signs were as follows: blood pressure, 116/93 mm Hg; pulse, 98 beats/min; respiratory rate, 24 breaths/min; oxygen saturation, 98%; and temperature, 36.7°C. She was given intravenous fluids and diphenhydramine. Oral edema appeared to be increasing. Records from the referring emergency department indicate that the physician ordered 0.5 mL of intravenous epinephrine (1:10,000), but nursing notes indicate that 0.5 mg (1:10,000) of epinephrine was administered intravenously. The patient became hypotensive. The physician ordered another 0.5-mL dose of intravenous epinephrine (1:10,000). Again, nursing records indicate that a 0.5-mg dose (1:10,000) of intravenous epinephrine was administered instead. The patient developed chest pain and wide complex tachycardia. Electrocardiography revealed ST-segment elevation in leads I and aVL and ST-segment depression in leads III and aVF, consistent with myocardial infarction. While still receiving nitroglycerin therapy, the patient was transferred to a tertiary center (Mayo Clinic). On arrival, she was treated with dexamethasone and antihistamines. She had a troponin T level of 0.49 ng/mL (reference ranges provided parenthetically) (≤0.01 ng/mL) and a creatine kinase-MB level of 11.4 ng/mL (≤6.2 ng/mL). Cardiac angiography revealed normal coronary arteries. Left ventriculography showed akinesis of posterolateral, lateral, anterolateral, diaphragmatic, and basal septal segments of the left ventricle (ejection fraction, 48%) (Figure). Follow-up echocardiography after 22 days showed less extensive wall motion abnormalities and an ejection fraction of 60%. FIGURE. Diastolic and systolic freeze frames from a left ventriculogram of the patient demonstrating basal contraction but akinesis of the anterolateral wall (arrows). Testing for IgE yellow jacket venom was positive (1.08 kU/L [<0.35 kU/L]). Catechol O-methyltransferase genotype testing showed that the patient was a heterozygote and an intermediate metabolizer. Skin tests showed positive reactions to wasp, yellow jacket, yellow hornet, and white-faced hornet venom. The clinical presentation of our patient met the Mayo Clinic ABS diagnostic criteria.1 To our knowledge, this case is the first to implicate intravenous epinephrine administration during anaphylaxis as a cause of ABS. Intravenous epinephrine is indicated in patients with severe hypotension or cardiac arrest unresponsive to intramuscular epinephrine and fluid resuscitation. A 0.2 μg/kg intravenous bolus is recommended for hypotension and a 0.1- to 0.5-mg dose for cardiovascular collapse.4 This patient's hypotension appeared to occur after the first dose of epinephrine. The hypotension likely represented the initiation of adverse cardiac response to epinephrine. The temporal relationship between administration of epinephrine and onset of findings consistent with ABS supports the hypothesis of catecholamine-induced myocardial stunning as the mechanism for left ventricular dysfunction. The patient's catechol O-methyltransferase genotype may have also increased her predisposition to ABS. Our case illustrates that administration of intravenous epinephrine, especially at high doses, may be a trigger for ABS and underscores the risk of inappropriate epinephrine dosing during anaphylaxis.5