Controlled pauses at the initiation of sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation

Abstract

Objective A multi-pronged approach to improve vital organ perfusion during cardiopulmonary resuscitation (CPR) that includes sodium nitroprusside (SNP), active compression-decompression (ACD)-CPR, an impedance threshold device, and abdominal pressure (SNPeCPR) has been recently shown to increase coronary and cerebral perfusion pressures and higher rates of return of spontaneous circulation (ROSC) versus standard CPR. To further reduce reperfusion injury during SNPeCPR we investigated the addition of adenosine and four 20-second controlled pauses (CP) spread throughout the first 3 minutes of SNPeCPR. The primary study endpoint was 24-hour survival with favorable neurological function after 15 minutes of untreated ventricular fibrillation. (VF) Design Randomized, prospective blinded animal investigation. Setting Preclinical animal laboratory. Subjects 32 female pigs (4 groups of 8) 32±2Kg. Interventions After 15 minutes of untreated VF isoflurane anesthetized pigs received 5 minutes of either standard CPR, SNPeCPR, SNPeCPR+adenosine or CP-SNPeCPR+adenosine. After 4 minutes of CPR all animals received epinephrine (0.5 mg) and a defibrillation shock one minute later. SNPeCPR-treated animals received SNP (2 mg) after 1 minute of CPR and 1 mg after 3 minutes of CPR. After 1 minutes of SNPeCPR, adenosine (24 mg) was administered in two groups. Measurements and Main Results A veterinarian blinded to the treatment assigned a cerebral performance category score of 1–5 (normal, slightly disabled, severely disabled but conscious, vegetative state, dead, respectively) 24 hours after ROSC. SNPeCPR, SNPeCPR+adenosine, CP-SNPeCPR+adenosine resulted in significantly higher 24-hour survival rate compared to standard CPR (7/8, 8/8, 8/8 versus 2/8, respectively p<0.05). The mean CPC scores for standard CPR, SNPeCPR, SNPeCPR+adenosine or CP-SNPeCPR+adenosine were 4.6 ±0.7, 3±1.3, 2.5±0.9 and 1.5±0.9 (p<0.01 for CP-SNPeCPR+adenosine compared to all other groups). Conclusions Reducing reperfusion injury and maximizing circulation during CPR significantly improved functional neurological recovery after 15 minutes of untreated VF. These results suggest that brain resuscitation after prolonged cardiac arrest is possible with novel non-invasive approaches focused on reversing the mechanisms of tissue injury.

Ischemic post-conditioning and vasodilator therapy during standard cardiopulmonary resuscitation to reduce cardiac and brain injury after prolonged untreated ventricular fibrillation

“…SNP was given as a 2mg bolus at minute 1 and a second 1mg bolus at minute 3 of CPR. 6 Adenosine was given as a single 24mg bolus after the first SNP bolus (after preliminary studies demonstrated superiority of this dose in improving post-resuscitation left ventricular (LV) dysfunction. 9 Epinephrine was administered in all groups in a 0.5mg (~15 μg/kg) bolus at minute 4 of CPR, 60 seconds before first defibrillation.…”

“…5 IPC with four, 20 seconds pauses during the first 3 minutes of CPR have been shown to be synergistic with sodium nitroprusside “enhanced” CPR (SNPeCPR) which utilizes active compression and decompression CPR with an inspiratory impedance threshold device and abdominal binding. 6 …”

Sodium Nitroprusside–Enhanced Cardiopulmonary Resuscitation Facilitates Intra-Arrest Therapeutic Hypothermia in a Porcine Model of Prolonged Ventricular Fibrillation*

“…The surgical preparation, anesthesia, data monitoring, and recording procedures used in this study have been previously described (14, 15). Under aseptic surgical conditions, we used initial sedation with intramuscular ketamine (10 mL of 100 mg/mL, Ketaset, Fort Dodge Animal Health, Fort Dodge, Iowa) followed by inhaled isoflurane at a dose of 0.8–1.2%.…”

Novelties in pharmacological management of cardiopulmonary resuscitation

“…In a porcine model of ventricular fibrillation arrest involving 15 min of untreated ventricular fibrillation, adenosine was added to SNPeCPR-treated animals. Adenosine-treated SNPeCPR animals had further increased cerebral blood flow after 5 min of CPR [41]. Arterial blood pressure and coronary perfusion pressure were similar.…”