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Effects of combined administration of vasopressin, epinephrine, and norepinephrine during cardiopulmonary resuscitation in pigs*

Objective:Synergistic effects of epinephrine and vasopressin may be of benefit during cardiopulmonary resuscitation. However, cerebral perfusion was decreased when epinephrine was combined with vasopressin compared with vasopressin alone. Although a combined infusion of norepinephrine and vasopressin improves hemodynamic variables compared with norepinephrine alone during sepsis, it is unknown whether norepinephrine in addition to vasopressin and epinephrine changes vital organ perfusion during cardiopulmonary resuscitation. Design:Prospective, randomized animal study. Setting:University hospital research laboratory. Subjects:Twenty-one domestic pigs. Interventions:After 4 mins of ventricular fibrillation and 3 mins of basic life support, the pigs were randomly assigned to receive either 200 &mgr;g/kg epinephrine, 0.4 units/kg vasopressin alone, or 45 &mgr;g/kg norepinephrine plus 45 &mgr;g/kg epinephrine plus 0.4 units/kg vasopressin before defibrillation. Measurements and Main Results:Organ perfusion was determined by radiolabeled microspheres. Myocardial blood flow (mean ± sem) before and 90 secs and 5 mins after drug administration was 8 ± 2, 25 ± 6, and 7 ± 1 mL/min/100 g after high-dose epinephrine, 12 ± 1, 75 ± 7, and 60 ± 10 mL/min/100 g after vasopressin, and 9 ± 2, 95 ± 26, and 46 ± 15 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). At the same time points, cerebral blood flow was 8 ± 2, 23 ± 3, and 17 ± 3 mL/min/100 g after epinephrine, 11 ± 3, 55 ± 7, and 52 ± 7 mL/min/100 g after vasopressin, and 11 ± 4, 67 ± 13, and 53 ± 12 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p < .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). Two of seven animals in the epinephrine group, four of seven animals in the vasopressin/epinephrine/norepinephrine group, and seven of seven animals in the vasopressin group could be successfully resuscitated (p < .05 vasopressin vs. epinephrine). Conclusions:Vasopressin with or without epinephrine and norepinephrine resulted in higher myocardial and cerebral perfusion than epinephrine alone, but there was no benefit in adding norepinephrine to vasopressin and epinephrine with regard to cardiac and cerebral blood flow during cardiopulmonary resuscitation.