Original Article
Epinephrine in Anaphylaxis: Higher Risk of Cardiovascular Complications and Overdose After Administration of Intravenous Bolus Epinephrine Compared with Intramuscular Epinephrine

https://doi.org/10.1016/j.jaip.2014.06.007Get rights and content

Background

Epinephrine is the drug of choice for the management of anaphylaxis, and fatal anaphylaxis is associated with delayed epinephrine administration. Data on adverse cardiovascular (CV) complications and epinephrine overdose are limited.

Objective

To compare rates of CV adverse events and epinephrine overdoses associated with anaphylaxis management between various routes of epinephrine administration among patients with anaphylaxis in the emergency department.

Methods

This was an observational cohort study from April 2008 to July 2012. Patients in the emergency department who met diagnostic criteria for anaphylaxis were included. We collected demographics; route of epinephrine administration; trigger; overdose; and adverse CV events, including arrhythmia, cardiac ischemia, stroke, angina, and hypertension.

Results

The study cohort included 573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine. A total of 362 doses of epinephrine were administered to 301 patients: 67.7% intramuscular (IM) autoinjector, 19.6% IM injection, 8.3% subcutaneous injection, 3.3% intravenous (IV) bolus, and 1.1% IV continuous infusion. There were 8 CV adverse events and 4 overdoses with 8 different patients. All the overdoses occurred when epinephrine was administered IV bolus. Adverse CV events were associated with 3 of 30 doses of IV bolus epinephrine compared with 4 of 316 doses of IM epinephrine (10% vs 1.3%; odds ratio 8.7 [95% CI, 1.8-40.7], P = .006). Similarly, overdose occurred with 4 of 30 doses of IV bolus epinephrine compared with 0 of 316 doses of IM epinephrine (13.3% vs 0%; odds ratio 61.3 [95% CI, 7.5 to infinity], P < .001).

Conclusion

The risk of overdose and adverse CV events is significantly higher with IV bolus epinephrine administration. 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.

Section snippets

Study design

We conducted an observational cohort study of patients who presented to the ED from April 2008 through July 2012.

Setting and participants

This study was conducted at Mayo Clinic Hospital, Saint Marys campus ED, a tertiary care academic ED that has a patient volume of 73,000 annual patient visits, including both pediatric and adult patients of all ages. Patients who presented with anaphylaxis as defined per the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network diagnostic criteria

Results

The study cohort included 573 patients, of whom, 301 (57.6%) received at least 1 dose of epinephrine (Table I). Overall, 341 patients were women (60%) and the median age was 34.5 years (interquartile range, 18.6-51.5 years). A total of 362 doses of epinephrine were administered to 301 patients: 245 IM autoinjector (67.7%), 71 IM injection (19.6%), 30 SC injection (8.3%), 12 IV bolus (3.3 %), and 4 IV continuous infusion (1.1%). There was no difference by sex, age, or race in the frequency of

Discussion

To our knowledge, this is the first study to systematically compare the risk of CV complications and overdose with various routes of epinephrine administration for anaphylaxis. We found a significantly higher risk of CV complications (10% vs 1.3%) and overdose (13.3% vs 0%) with IV bolus epinephrine compared with IM epinephrine administration. In addition, our results confirmed the relative safety of IM epinephrine administration. Although numerous case reports have established the link between

Conclusions

Our results underscore the risks associated with the use of IV bolus epinephrine in the management of anaphylaxis. Furthermore, they demonstrate the relative safety of the use of the IM autoinjector, given that overdose is much less likely with this design and that there were no associated major CV adverse events. When taken together, these findings support current guidelines that recommend initial use of IM epinephrine and avoidance of IV bolus epinephrine except in extreme circumstances.

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No funding was received for this work.

Conflicts of interest: The authors declare that they have no relevant conflicts of interest.

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