Experimental cardiac arrest treatment with adrenaline, vasopressin, or placebo

Abstract

Background: The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified.

Objectives: To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC).

Methods: A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC.

Results: Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019).

Conclusion: The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate.

Figure 1

Protocol design of experimental cardiac arrest and cardiopulmonary resuscitation (CPR).

Figure 2

Return of spontaneous circulation (ROSC) rate and survival curve adaptation of pigs in ventricular fibrillation, potentially alive during resuscitation efforts and with all deaths occurring at 37 minutes, according to randomized and blinded treatment

Figure 3

Coronary perfusion pressure (CPP) mean ± standard error, pre-cardiac arrest at time zero, and during cardiopulmonary resuscitation (CPR) initiated at 7 minutes of ventricular fibrillation (VF), according to randomized and blinded treatment applied (T) repeatedly. Asterisks indicate timepoints of pressure increase with vasoconstrictors, wich remained significant with vasopressin. The pigs count decreases until 14 animals that not resuscitated: adrenaline 2/12, vasopressin 6/12, and placebo 6/8.

Figure 4

Return of spontaneous circulation (ROSC) rate accumulated until the last resuscitated pig in each treatment group.

Figure 5

Parameters: mean ± stardard error of pressures, expired carbon dioxide (ETCO2), and respiratory rate, pre-cardiac arrest at time zero, and during cardiopulmonary resuscitation started at 7 minutes, according to randomized and blinded treatment applied in pigs electrically induced to ventricular fibrillation. Manual chest compression rate was similar (99.5 ± 0.1). Following vasoconstrictors treatment at 9 minutes, there was significant effect (compared with placebo) on the aortic pressure only