Functional responses to extremely high plasma epinephrine concentrations in cardiac arrest

J. Wortsman, N. A. Paradis, G. B. Martin, E. P. Rivers, M. G. Goetting, R. M. Nowak, P. E. Cryer

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23 Scopus citations


Objective: To evaluate the action of high-dose epinephrine by measuring simultaneously its vasopressor and norepinephrine releasing effects in humans during cardiac arrest. Design: A prospective study on consecutive patients admitted with cardiac arrest. Setting: Emergency Department in a large, urban hospital. Patients: Eighteen patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (CPR). Interventions: Catheterization of both the aorta and right atrium for the recording of pressure and collection of blood samples. Throughout the study period (12.5 mins), 18 patients received epinephrine at both the standard dose (1 mg, ~0.015 mg/kg) and high dose (0.2 mg/kg). Blood samples were drawn five times, every 2.5 mins. Measurements and Main Results: Plasma epinephrine and norepinephrine concentrations; aorta, right atrial, and coronary perfusion pressures. Epinephrine concentrations (normal at rest = 160 ± 10 [SEM] pmol/L) were increased at the time of the first sample (2.5 mins) by ~3,000- fold (to ~0.5 μmol/L), and, increased further to 12,000-fold (~2.0 μmol/L) during the study. Aortic pressure increased from 20 ± 3 to 28 ± 3 mm Hg (p < .001), and coronary perfusion pressure increased from 4 ± 3 to 10 ± 3 mm Hg (p < .001). Simultaneous plasma norepinephrine concentrations were 30-fold higher than the normal resting value of 1.30 ± 0.04 nmol/L, and increased by 90-fold during the study (p < .001). The spectral distributions of the individual correlations between plasma epinephrine and norepinephrine concentrations were segregated into high correlations (r > .83) in 12 of 18 patients and low r values (r = .29 to .79) in the remaining six patients. The distribution of the correlations was nonuniform by the Kolmogorov-Smirnov goodness-of-fit test with p < .001; this profile suggests that norepinephrine responsiveness to epinephrine can separate two populations, one of which (r > .83) would have preserved viability of the corresponding epinephrine receptors. The correlations between plasma epinephrine concentrations and coronary perfusion pressures were distributed more evenly, also in a nonuniform pattern (p < .02 by Kolmogorov-Smirnov goodness-of-fit test) and the relationship between the two sets of correlations was not significant. Conclusions: Despite the very high prevailing plasma epinephrine concentrations during cardiac arrest, further epinephrine increases still elicit biological responses. The present work provides physiologic support for the use of large doses of epinephrine during the course of CPR.

Original languageEnglish
Pages (from-to)692-697
Number of pages6
JournalCritical care medicine
Issue number5
StatePublished - 1993


  • cardiac arrest
  • cardiopulmonary resuscitation
  • catecholamines
  • critical illness
  • epinephrine
  • intensive care unit
  • myocardial reperfusion
  • norepinephrine
  • pharmacokinetics
  • vasopressor agents


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