Important Determinants of Neurological Outcome after 20 Minutes No Flow Time and Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model

Objectives: Controlled automated reperfusion of the whole body (CARL) may limit ischemia-reperfusion injury after cardiac arrest (CA) when applied in pigs. CARL represents a therapy bundle based on extracorporeal circulation with targeted therapy to enhance reperfusion quality of the whole body after prolonged periods of CA. In the presented set of animal experiments, we investigated variables within the CARL therapy that might predict neurologic recovery after CA. The known confounder “head position” was examined via subgroup analysis.

Methods: A retrospective analysis of 42 pigs that received CARL treatment after 20 minutes of CA and follow-up treatment for up to 7 days was performed. Two groups were formed with respect to head position during reperfusion. One group had an elevated head position (HUP, N = 24), the other group had a flat-supine head position (SUP, N = 18). The neurological state was assessed daily based on a species-specific neurological deficit score (NDS). A favorable neurological outcome was defined as an NDS of less than 50 on day 7 (outcome+). Three parameters for superior neurologic outcome were tested: (1) high blood flow (cardiac index > 6 L/min/m²), (2) low serum calcium concentration (arterial ionized calcium < 0.8 mM), and (3) physiological hemoglobin (Hb) (Hb > 8 g/dL). We hypothesized that all three parameters had to be met to enhance the likelihood of a favorable neurological outcome (test+).

Results: Overall, the test had a sensitivity (SEN) of 79.2% and a specificity (SPE) of 94.4% accompanied by a positive predictive value (PPV) of 95% and a negative predictive value (NPV) of 77.3%. In group SUP, all animals were correctly identified by the test. In group HUP, SEN and SPE fell to 75% resulting in a PPV of 93.7% and an NPV of 37.5%. Disregarding the hypothesis of a cardiac index > 6 L/min/m² in group HUP, increased SEN to 90%, PPV to 94.7%, and NPV to 60% with SPE remaining at 75%.

Overall (HUP + SUP)	Outcome+	Outcome−	Total	HUP	Outcome+	Outcome−	Total
Abbreviations: HUP, elevated head position; SUP, flat-supine head position.
Note: Overall test results (left) and test results for HUP (right).
Test+	19	1	20	Test+	15	1	16
Test−	5	17	22	Test−	5	3	8
Total	24	18	42	Total	20	4	24

Conclusion: The identified parameters Hb, cardiac index, and arterial ionized calcium were crucial for the prognosis of the neurological outcome after CARL in this animal model. In pigs with SUP, a cardiac index < 6 L/min/m² was associated with an unfavorable neurological outcome. In pigs with HUP, the required minimal blood flow appeared to be lower than 6 L/min/m².