Abstract 249: Sodium Nitroprusside Combined with Intrathoracic Pressure Regulation Increases Neurologically Favorable 24-Hour Survival in a Porcine Model of Prolonged Ventricular Fibrillation

Abstract

Introduction: Use of epinephrine and standard (S) CPR has not been shown to improve neurologically-sound survival after cardiac arrest. Treatment with the potent vasodilator sodium nitroprusside (SNP) improves neurologically intact survival rates in animals when combined with abdominal compression, active compression decompression (ACD) CPR, and an impedance threshold device (ITD). We recently observed that SNP combined with ACD-CPR and a new intrathoracic pressure regulator (IPR), which provides continuous negative intrathoracic pressure after each positive pressure ventilation, increases blood flow to the heart and brain in the absence of epinephrine or abdominal compression. We hypothesized that this combination of SNP plus ACD CPR plus IPR (S-A-I) would improve 24h survival with favorable neurologic function compared with S-CPR. Method: After 12 minutes of untreated ventricular fibrillation (VF), 14 pigs received 3 minutes of S-CPR and were then randomized to a) a bolus of epinephrine (0.05mcg/kg), 2 more minutes of S-CPR and up to 3 defibrillation shocks or b) S-A-I and up to 3 shocks 2 minutes later. All resuscitated animals received therapeutic hypothermia for 4 hours. The primary endpoint was favorable neurologic outcome 24h after resuscitation defined by a Cerebral Performance Category score ≤ 2 (CPC with 1 for no deficit and 5 as dead or unable to resuscitate) as determined by a blinded veterinarian. Hemodynamic parameters and left ventricular ejection fraction were recorded. Data are presented as mean±SEM. Results: At 24 hours, 0/7 pigs in the S-CPR group vs. 5/7 pigs in S-A-I had favorable outcome (p=0.02). One pig survived 24 hours in the S-CPR group with a CPC of 4 vs. 5 in the S-A-I group with a CPC of 1.4±0.2. Carotid blood flow and ETCO2 were higher with S-A-I_vs. S-CPR and epinephrine (127±32 vs. 22±4 ml/min, p=0.005, and 46±5 vs. 22±3 mmHg, respectively, p=0.001). Conclusion: After prolonged VF in pigs, treatment with the combination of ACD CPR, an intrathoracic pressure regulator and SNP, in the absence of epinephrine, significantly increased carotid flow, ETCO2 levels, and neurologically-favorable 24 hour survival rates compared with S-CPR and epinephrine. This novel and promising approach should be considered for a Phase 1 human trial.