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.

Figure 1

Study protocol. After 12 min of ventricular fibrillation (VF) and 3 min of basic life support (BLS) up to three 275 joules, biphasic defibrillatory shocks were delivered (Lifepak 15; Physio-Control, Redmond, WA). If return of spontaneous circulation (ROSC) was not achieved after 1–3 defibrillations, advanced life support (ALS) was started based on a randomization plan that was unblinded after induction of VF. In all groups, epinephrine (Epi) was administered as a 0.5 mg (~15 μg/kg) bolus 15 s after starting ALS through the jugular vein. A bolus of 25 mg of amiodarone was also administered in all groups after epinephrine injection. After 2 min of ALS, 1–3 shocks were delivered, as needed. As a secondary endpoint, when ROSC was not achieved in animals in group A using standard cardiopulmonary resuscitation (CPR) during ALS, then active compression-decompression (ACD) plus intrathoracic pressure regulator (ITPR) was initiated as a rescue therapy along with a second dose of 0.5 mg of epinephrine. A defibrillatory shock was delivered every 2 min thereafter until ROSC was achieved or for up to the point in time when a total of 15 min of CPR had been performed. ITD = impedance threshold device.

Figure 2

Twenty-four-hour Cerebral Performance Category (CPC) score (1= normal, 2 = mild deficit, 3 = severe deficit, 4 = coma, and 5 = dead). CPC is significantly different between groups (p = 0.001). ACD = active compression-decompression, ALS = advanced life support, BLS = basic life support, CPR = cardiopulmonary resuscitation, ITD = impedance threshold device, ITPR = intrathoracic pressure regulator.

Figure 3

Representative example of pressure curve during the study. ACD = active compression-decompression, ALS = advanced life support, BLS = basic life support, CPR = cardiopulmonary resuscitation, ITD = impedance threshold device, ITPR = intrathoracic pressure regulator.