The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period.

BACKGROUND: Studies evaluating the dose of epinephrine required to optimize return of spontaneous circulation and survival after CPR have shown that doses greater than recommended by advanced cardiac life support (ACLS) improve coronary perfusion pressure and short-term resuscitation rates. Since survival has not improved, it is possible that higher doses of epinephrine may be physiologically detrimental in the postresuscitation period.

OBJECTIVE: The object of this study is to measure the effect of the total cumulative dose of epinephrine given during ACLS on the hemodynamic, oxygen transport, and utilization variables in the postresuscitation period.

DESIGN: A prospective nonrandomized control trial of inception cohorts.

SETTING: A large urban emergency department and intensive care unit.

PATIENTS: Forty-nine successfully resuscitated witnessed, normothermic, nontraumatic, out-of-hospital patients, who had suffered cardiac arrests.

INTERVENTIONS: All patients were treated according to ACLS guidelines; however, the epinephrine dose (0.01 to 0.2 mg/kg or 1 to 14 mg) was selected at the clinician's discretion and given through central venous access every 3 to 5 min. Hemodynamic, oxygen transport, and utilization variables were measured on a return of spontaneous circulation, and at least every 30 min thereafter under a standardized postresuscitation protocol.

MAIN OUTCOME MEASURES: Hemodynamic, oxygen transport/utilization variables, and mortality in patients resuscitated from cardiac arrest. The total cumulative dose of epinephrine given during ACLS until a return of spontaneous circulation was recorded.

RESULTS: A total cumulative epinephrine dose of 15 mg was found to best predict 24-h mortality. Of the 49 patients, 20 received less than 15 mg (group 1) and 29 received greater than 15 mg (group 2). Age, premorbid health status, sex, presenting rhythm, and duration of cardiac arrest were similar in both groups. The 24-h survival was 17 of 20 (85%) and 12 of 29 (41%) in group 1 and 2, respectively (p < 0.002). Over the first 6 h of the postresuscitation period, both groups had similar mean arterial pressure (MAP), mixed venous oxygen saturation, and systemic oxygen extraction ratio (all p > 0.1). Group 2, however, had a significantly lower cardiac index (CI), systemic oxygen consumption (VO2), and systemic oxygen delivery (DO2) (all p < 0.01). Systemic vascular resistance index (SVRI), initial and 6-h lactic acid levels were significantly higher in group 2 (all p < 0.03).

CONCLUSIONS: The administration of all doses of epinephrine during the resuscitation of out-of-hospital cardiac arrest is associated with impairment of DO2 and VO2 in the postresuscitation period. Both duration and severity of these impairments correlate with the total cumulative epinephrine dose given during the resuscitation. Thus, inadvertent catecholamine toxicity represents a further complicating factor in the production of postresuscitation disease. Diagnostic and therapeutic interventions addressed toward mitigating these potentially reversible adverse effects may impact morbidity and mortality in out-of-hospital cardiac arrests.