AimTo determine if controlled head and thorax elevation, active compression-decompression cardiopulmonary resuscitation (CPR), and an impedance threshold device combined, termed automated head-up positioning CPR (AHUP-CPR), should be initiated early, as a basic (BLS) intervention, or later, as an advanced (ALS) intervention, in a severe porcine model of cardiac arrest. MethodsYorkshire pigs (n = 22) weighing ∼40 kg were anesthetized and ventilated. After 15 minutes of untreated ventricular fibrillation, pigs were randomized to AHUP-CPR for 25 minutes (BLS group) or conventional CPR for 10 minutes, followed by 15 minutes of AHUP-CPR (ALS group). Thereafter, epinephrine, amiodarone, and defibrillation were administered. Neurologic function, the primary endpoint, was assessed 24-hours later with a Neurological Deficit Score (NDS, 0 = normal and 260 = worst deficit score or death). Secondary outcomes included return of spontaneous circulation (ROSC), cumulative survival, hemodynamics and epinephrine responsivity. Data, expressed as mean ± standard deviation, were compared using Fisher's Exact, log-rank, Mann-Whitney U and unpaired t-tests. ResultsROSC was achieved in 10/11 pigs with early AHUP-CPR versus 6/11 with delayed AHUP-CPR (p = 0.14), and cumulative 24-hour survival was 45.5% versus 9.1%, respectively (p < 0.02). The NDS was 203 ± 80 with early AHUP-CPR versus 259 ± 3 with delayed AHUP-CPR (p = 0.035). ETCO2, rSO2, and responsiveness to epinephrine were significantly higher in the early versus delayed AHUP-CPR. ConclusionWhen delivered early rather than late, AHUP-CPR resulted in significantly increased hemodynamics, 24-hour survival, and improved neurological function in pigs after prolonged cardiac arrest. Based on these findings, AHUP-CPR should be considered a BLS intervention.