The optimal dose of epinephrine during CPR in human beings is unknown. We studied ten prehospital cardiac arrest patients (six men and four women; mean age, 54 +/- 5 years) to determine the vasopressor response and change in the end-tidal carbon dioxide concentration (PetCO2) after incremental (1-, 3-, and 5-mg) doses of IV epinephrine given five minutes apart during closed-chest CPR. All patients were in ventricular fibrillation on arrival of the paramedics and did not respond to standard advanced cardiac life support. CPR was performed with a computerized Thumper; all patients were intubated and ventilated at 12 times a minute at an FiO2 of 0.8. Radial artery pressure was measured with a 20 angiocath inserted by radial artery cutdown. Paramedic response time was 4.3 +/- 0.5 minutes; elapsed time to emergency department arrival was 40.0 +/- 9.5 minutes. Initial blood gases were paO2, 241 +/- 50 mm Hg; pH, 7.23 +/- 0.08; paCO2, 27 +/- 5 mm Hg; and HCO3, 11 +/- 2 mEq/L. Baseline systolic and diastolic blood pressures were 47 +/- 5 mm Hg and 18 +/- 2 mm Hg, respectively. Systolic blood pressure was directly related to the dose of epinephrine (P less than .0001), rising to 69 +/- 7 mm Hg, 74 +/- 8 mm Hg, and 85 +/- 8 mm Hg after 1-, 3-, and 5-mg doses of epinephrine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)