Fast Hypothermia Induced by Continuous Renal Replacement Therapy Alleviates Renal and Intestinal Injury after Cardiac Arrest in Swine

Abstract

Background: Renal and intestinal damage lead to multiple organ dysfunction and death after cardiopulmonary resuscitation (CPR), and can be partly mitigated by therapeutic hypothermia. Currently, continuous renal replacement therapy (CRRT) was demonstrated to be an effective way to induce hypothermia. In the present study, we aimed to investigate the influence of CRRT cooling on renal and intestinal damage after CPR based on a porcine model.Methods: 32 swine were subjected to ventricular fibrillation for 8 min, while defibrillation was performed at 5 min of CPR. All pigs were randomly allocated to receive CRRT (n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (Control, n = 5) at 5 min post resuscitation. In the CRRT group, the pigs were cooled by the combination of 8-hr CRRT and 16-hr SC, a rate of 180 ml/min of blood flow was initially set with the infusion line submerged in 4 °C of ice water. In the SC group, pigs were cooled by the 24-hr SC. As to the NT and Control groups, the temperatures were maintained at a normal range. The levels of creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured at baseline and at 1, 3, 6, 12, 24 and 30h post resuscitation. Additionally, tissues of kidney and intestine were harvested, from which the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the contents of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and the apoptosis levels were analyzed. Results: After resuscitation, the blood temperature decreased significantly more rapidly in the CRRT group than in the SC group (9.8 ± 1.6 vs. 1.5 ± 0.4 ℃/h, P < 0.01). The levels of Cr, BUN, IFABP and DAO after resuscitation were significantly lower in the two hypothermic groups compared with the NT group. Furthermore, from pathological evidence, cooling induced by CRRT alleviated post-resuscitation renal and intestinal injury compared to SC.Conclusion: Fast hypothermia induced by continuous renal replacement therapy was superior to surface cooling in mitigating renal and intestinal injury post resuscitation.