Pharmacokinetics of Epinephrine During Cardiac Arrest: A Pilot Study

Abstract

Aim of the study: Epinephrine has been recommended for several decades for the treatment of cardiac arrest. However, although this potent medicament has a documented impact on the return of spontaneous circulation, it does not improve long-term survival. Decreased cerebral blood flow, one of the side effects of epinephrine, indicates that the use of this drug is a two-edged sword. Despite clinical recommendations, no study has investigated epinephrine pharmacokinetics in a setting of cardiac arrest. Therefore, in a pilot setting, we measured the plasma concentrations of epinephrine following a single administration.

Methods: Nine patients with cardiac arrest were included in our study. A single dose of 1 mg epinephrine was administered into a peripheral vein. Simultaneously, blood samples were withdrawn every minute from the jugular vein to determine the plasma concentration. A mixed effects model was used to estimate the T_1/2 following the peak concentration.

Results: One patient did not achieve a peak concentration during observation and was hence excluded. The remaining eight patients had 26 measurements suitable for modelling. In a stable model, the decline is estimated to be -0.259 [95% CI (-0.361, -0.157) (p<0.001)]. This implies a half-time for epinephrine of 2.6 (1.9, 4.4) minutes.

Conclusion: Our study indicates that elimination of epinephrine during cardiac arrest is prolonged and that repeated doses of epinephrine may lead to increased plasma levels. Further and larger studies are warranted to determine the optimal plasma concentration during resuscitation.

Keywords: Cardiac arrest; adrenaline; epinephrine; half-time; pharmacokinetic.