IV Epinephrine for Anaphylaxis Associated with Increased Cardiovascular Risk Compared with Intramusclar Epinephrine

New research indicates that doctors who treat anaphylaxis with intravenous epinephrine rather than intramuscular or subcutaneous injections are increasing the risk that patients will suffer overdoses or other adverse reactions. The findings, which were published by The Journal of Allergy and Clinical Immunology: In Practice, come from an observational cohort study undertaken by researchers from the Mayo Clinic’s Department of Emergency Medicine.

“Analysis of the data supports the safety of IM epinephrine and a need for extreme caution and further education about IV bolus epinephrine in anaphylaxis,” the authors concluded. “The risk of overdose and adverse CV events is significantly higher with IV bolus epinephrine administration.”

The study team searched more than four years of records from one hospital emergency department (ED) for patients who met diagnostic criteria for anaphylaxis and then collected information about patient demographics, triggers, epinephrine administration, and subsequent cardiovascular events such as arrhythmia, cardiac ischemia, stroke, angina, and hypertension.

Among the 573 patients in the final cohort, 301 (57.6%) received at least 1 dose of epinephrine. This finding alone provides yet more support to the well-established observation that EDs frequently fail to live up to guidelines that recommend epinephrine for nearly all cases of anaphylaxis.

More than two thirds (67.7%) of all 361 doses of epinephrine were given to patients with intramuscular (IM) autoinjectors. Administration of the remaining doses was divided among IM injection (19.6%), subcutaneous injection (8.3%), intravenous (IV) bolus (3.3%), and IV continuous infusion (1.1%).

The records showed that 8 patients suffered adverse cardiovascular events and that 4 of them also suffered overdoses.

Adverse cardiovascular events took place after 3 of 30 doses (10%) of IV bolus epinephrine compared with 4 of 316 doses (1.3%) of IM epinephrine (odds ratio [OR], 8.7; 95% confidence interval [CI], 1.8-40.7; P = .006).

Overdose occurred after 4 of 30 doses (13.3%) of IV bolus epinephrine compared with 0 of 316 doses (0%) of IM epinephrine (OR, 61.3; 95% CI, 7.5 to infinity; P < .001).

The study authors noted several potential limitations in their findings beyond the retrospective nature of their work. The relatively small number of adverse events, for example, prevented the researchers from narrowing down their estimates of effect sizes.

Still, they noted, the effects were strong enough to reach the certain conclusion that IV bolus epinephrine was associated with significantly more negative events than any form of injection.

Current guidelines already recommend epinephrine injections over IV administration for most patients. IV bolus epinephrine is typically recommended only for patients in cardiorespiratory arrest who have failed to respond to intramuscular epinephrine or for profoundly hypotensive patients.

Unlike autoinjectors, which all provide 0.3 or 0.5 cc of medication in a 1:1,000 concentration, IV applications force caregivers to make their own dosing choices. No standards have been established, though there is widespread agreement that epinephrine should be considerably more diluted for IV administration than for IM injection. Concentrated doses increase the risk of lethal arrhythmias.

Several sources say that it’s highly desirable to have hemodynamic monitoring in place for those cases that necessitate the use of IV epinephrine.