FUNCTIONAL-RESPONSES TO EXTREMELY HIGH PLASMA EPINEPHRINE CONCENTRATIONS IN CARDIAC-ARREST

Objective. To evaluate the action of high-dose epinephrine by measurin g simultaneously its vasopressor and norepinephrine releasing effects in humans during cardiac arrest. Design: A prospective study on consec utive patients admitted with cardiac arrest. Setting. Emergency Depart ment in a large, urban hospital. Patients: Eighteen patients with out- of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (C PR). Interventions: Catheterization of both the aorta and right atrium for the recording of pressure and collection of blood samples. Throug hout the study period (12.5 mins), 18 patients received epinephrine at both the standard dose (1 mg, approximately 0.015 mg/kg) and high dos e (0.2 mg/kg). Blood samples were drawn five times, every 2.5 mins. Me asurements and Main Results: Plasma epinephrine and norepinephrine con centrations; aorta, right atrial, and coronary perfusion pressures. Ep inephrine concentrations (normal at rest = 160 +/- 10 [SEM] pmol/L) we re increased at the time of the first sample (2.5 mins) by approximate ly 3,000-fold (to approximately 0.5 mumol/L), and, increased further t o 12,000-fold (approximately 2.0 mumol/L) during the study. Aortic pre ssure increased from 20 +/- 3 to 28 +/- 3 mm Hg (p < .001), and corona ry perfusion pressure increased from 4 +/- 3 to 10 +/- 3 mm Hg (p <.00 1). Simultaneous plasma norepinephrine concentrations were 30-fold hig her than the normal resting value of 1.30 +/- 0.04 nmol/L, and increas ed by 90-fold during the study (p < .001). The spectral distributions of the individual correlations between plasma epinephrine and norepine phrine concentrations were segregated into high correlations (r > .83) in 12 of 18 patients and low r values (r = .29 to.79) in the remainin g six patients. The distribution of the correlations was nonuniform by the Kolmogorov-Smirnov goodness-of-fit test with p < .001; this profi le suggests that norepinephrine responsiveness to epinephrine can sepa rate two populations, one of which (r > .83) would have preserved viab ility of the corresponding epinephrine receptors. The correlations bet ween plasma epinephrine concentrations and coronary perfusion pressure s were distributed more evenly, also in a nonuniform pattern (p <.02 b y Kolmogorov-Smirnov goodness-of-fit test) and the relationship betwee n the two sets of correlations was not significant. Conclusions. Despi te the very high prevailing plasma epinephrine concentrations during c ardiac arrest, further epinephrine increases still elicit biological r esponses. The present work provides physiologic support for the use of large doses of epinephrine during the course of CPR.