Enhanced Perfusion During Advanced Life Support Improves Survival With Favorable Neurologic Function in a Porcine Model of Refractory Cardiac Arrest

Abstract

Objective To improve the likelihood for survival with favorable neurologic function after cardiac arrest, we assessed a new advanced life support approach using active compression-decompression cardiopulmonary resuscitation plus an intrathoracic pressure regulator. Design Prospective animal investigation. Setting Animal laboratory. Subjects Female farm pigs (n = 25) (39 ± 3 kg). Interventions Protocol A: After 12 minutes of untreated ventricular fibrillation, 18 pigs were randomized to group A—3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with standard cardiopulmonary resuscitation; group B—3 minutes of basic life support with standard cardiopulmonary resuscitation, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator; and group C—3 minutes of basic life support with active compression-decompression cardiopulmonary resuscitation plus an impedance threshold device, defibrillation, and if needed 2 minutes of advanced life support with active compression-decompression plus intrathoracic pressure regulator. Advanced life support always included IV epinephrine (0.05 μg/kg). The primary endpoint was the 24-hour Cerebral Performance Category score. Protocol B: Myocardial and cerebral blood flow were measured in seven pigs before ventricular fibrillation and then following 6 minutes of untreated ventricular fibrillation during sequential 5 minutes treatments with active compression-decompression plus impedance threshold device, active compression-decompression plus intrathoracic pressure regulator, and active compression-decompression plus intrathoracic pressure regulator plus epinephrine. Measurements and Main Results Protocol A: One of six pigs survived for 24 hours in group A versus six of six in groups B and C (p = 0.002) and Cerebral Performance Category scores were 4.7 ± 0.8, 1.7 ± 0.8, and 1.0 ± 0, respectively (p = 0.001). Protocol B: Brain blood flow was significantly higher with active compression-decompression plus intrathoracic pressure regulator compared with active compression-decompression plus impedance threshold device (0.39 ± 0.23 vs 0.27 ± 0.14 mL/min/g; p = 0.03), whereas differences in myocardial perfusion were not statistically significant (0.65 ± 0.81 vs 0.42 ± 0.36 mL/min/g; p = 0.23). Brain and myocardial blood flow with active compression-decompression plus intrathoracic pressure regulator plus epinephrine were significantly increased versus active compression-decompression plus impedance threshold device (0.40 ± 0.22 and 0.84 ± 0.60 mL/min/g; p = 0.02 for both). Conclusion Advanced life support with active compression-decompression plus intrathoracic pressure regulator significantly improved cerebral perfusion and 24-hour survival with favorable neurologic function. These findings support further evaluation of this new advanced life support methodology in humans.

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation

“…This is consistent with our prior published work in prolonged resuscitation with open arteries where SNPeCPR led to higher carotid blood flow, 24-hour survival with good neurological function as well as significant improvement in post resuscitation left ventricular global function. 13–17 In essence, we believe that the beneficial effects of SNPeCPR are mediated by an increase in “redirected” blood flow to the heart and brain and potentially through direct pharmacological effect of nitric oxide on the ischemic endothelium.…”

“…Sodium Nitroprusside enhanced CPR (SNPeCPR) has been shown to improve CPR generated blood flow to the heart and brain, 13–17 improve cardiac function after pulseless electrical activity (PEA) and VF arrest, and cerebral recovery in prolonged CPR and prolonged untreated VF porcine models of cardiac arrest. 14,15,18 …”

Personalized physiology-guided resuscitation in highly monitored patients with cardiac arrest—the PERSEUS resuscitation protocol

“…In addition to the primarily vascular activity, it may also have antioxidant effects through the release of NO, which is a potent antioxidant and is capable of rendering neuroprotection against oxidative stress-induced neurotoxicity [23]. Besides nitroglycerin, sodium nitroprusside-enhanced CPR has been shown to improve myocardial, carotid, and cerebral blood flow, postresuscitation left ventricular global function, and 24-h survival with good neurological function in porcine models of cardiac arrest [24,25]. Also, the addition of inhaled NO to hemodynamic-directed CPR may improve short-term survival and intra-arrest hemodynamics [26].…”

Effects of mechanical ventilation with expiratory negative airway pressure on porcine pulmonary and systemic circulation: mechano-physiology and potential application

“…Indeed, "inspiratory" negative airway pressure with impedance threshold device has been shown to increase the cardiac output during cardiac arrest resuscitation with cardiac massage [10][11][12][13]. More recently, another technology with an intrathoracic pressure regulator was developed, which actively creates a continuous low level of negative intrathoracic pressure during cardiac massage following each inspiratory positive pressure breath [14][15][16]. Accordingly, short term use of "expiratory" negative airway pressure (ENAP) ventilation has been shown to improve spontaneous systemic circulation during clinical as well as experimental non-cardiac arrest shock like hemorrhagic hypovolemic states [17][18][19].…”