Pediatric Extracorporeal Cardiopulmonary Resuscitation: Development of a Porcine Model and the Influence of Cardiopulmonary Resuscitation Duration on Brain Injury

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Abstract
Background: The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22‐ to 24‐hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results: Ten‐kilogram, 4‐week‐old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof‐of‐concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0–6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra‐abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group ( P =0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4–7.4] versus CPR30: 7.5 [IQR 7.4–7.5], P =0.022), higher lactate (CPR60: 6.8 [IQR 6.8–11] versus CPR30: 4.2 [IQR 4.1–4.3] mmol/L; P =0.012), and higher ICP (CPR60: 19.3 [IQR 11.7–29.3] versus CPR30: 7.9 [IQR 6.7–9.3] mm Hg; P =0.037). Both groups had greater mitochondrial injury than shams (CPR60: P P <0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions: A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24‐hour survival with more severe lactic acidosis in the 60‐minute cohort.

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