Cooling to Hypothermic Circulatory Arrest by Immersion vs. Cardiopulmonary Bypass (CPB): Worse Outcome After Rewarming in Immersion Cooled Pigs

Abstract

Introduction: Cooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO₂) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism.

Materials and methods: Total sixteen healthy, anesthetized juvenile (2-3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMM _c , n = 8), or cooling by CPB (CPB _c , n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia.

Results: Survival rates at 2 h after completed rewarming were 4 out of 8 in the IMM _c group, and 8 out of 8 in the CPB _c group. Compared with the CPB _c -group, IMM _c animals showed significant reduction in DO₂, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPB _c animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMM _c vs. CPB _c animals.

Conclusion: Our data indicate that, although global O₂ consumption was independent of DO₂, regional ischemic damage may have taken place during cooling in the brain of IMM _c animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.

Keywords: cardiac index; cardiopulmonary bypass; hypothermia accidental; hypothermia induced; immersion cooling; rewarming.

FIGURE 1

Temperatures at various body locations. (A) Immersion cooled animals (IMM_c group), and (B) in animals cooled by CPB (CPB_c group). Data presented as mean and SEM. ^#n was reduced to 4 animals at the end of experiments (End exp.) in IMM_c group.

FIGURE 2

Time-dependent changes in temperature in esophagus (A) and urinary bladder (B). ↓ denotes start of cooling in either group. Data presented as mean and SEM. ^‡Statistically significant difference between groups (p < 0.05). ^#n was reduced to 4 animals at end of the experiments (End exp.) in IMM_c group.

FIGURE 3

Blood flow and pressures. (A) Cardiac output and CPB flow (CO/CPB flow). (B) Mean arterial pressure (MAP). (C) Systemic vascular resistance (SVR). (D) Intracranial pressure (ICP). (E) Cerebral perfusion pressure (CPP). Data presented as mean and SEM. ^‡Statistically significant difference between groups (p < 0.05). ^#n was reduced to 5 animals after termination of CPB (Post CPB) and to 4 animals at end of experiments (End exp.) in IMM_c group.

FIGURE 4

Oxygen variables. (A) Blood hemoglobin (Hb) concentration. (B) Arterial and mixed venous blood oxygen saturation (SaO₂ and SVO₂). (C) Internal jugular venous blood oxygen saturation (SvjO₂). (D) Global delivery of oxygen (DO₂). (E) Global consumption of oxygen (VO₂). Data presented as mean and SEM. ^‡Statistically significant difference between groups (p < 0.05). ^#n was reduced to 5 animals after termination of CPB (Post CPB) and to 4 animals at end of experiments (End exp.) in IMM_c group.

FIGURE 5

Brain microdialysate analyses. (A) Brain lactate. (B) Brain pyruvate. (C) Brain lactate/pyruvate ratio. (D) Brain glucose. (E) Brain glucose/lactate ratio. (F) Brain glycerol. Data presented as mean and SEM. *Statistically significant difference from baseline within IMM_c group, and ^†within CPB_c group (p < 0.05). ^‡ Statistically significant difference between groups (p < 0.05). ^#n was reduced to 5 animals after termination of CPB (Post CPB) and to 4 animals at end of experiments (End experiment) in IMM_c group.

FIGURE 6

Cerebral blood flow. (A): forebrain, (B): cerebellum, (C): hippocampus. Data presented as mean and SEM. *Statistically significant difference from baseline within IMM_c group, and ^†within CPB_c group (p < 0.05). ^‡ Statistically significant difference between groups (p < 0.05). ^#n was reduced to 5 animals after termination of CPB (Post CPB) and to 4 animals at end of experiments (End exp.) in IMM_c group.

FIGURE 7

Biochemical analyses. (A): Albumin; (B): ASAT; (C): ALAT; (D): Troponin-T (Tn-T). Data presented as mean and SEM. *Statistically significant difference from baseline within IMM_c group, and ^†within CPB_c group (p < 0.05). ^‡Statistically significant difference between groups (p < 0.05).

FIGURE 8

Fluid administration and organ edema. (A): Fluid volume administration rate. (B): Postmortem wet/dry organ weight ratio. Data presented as mean and SEM. ^‡Statistically significant difference between groups (p < 0.05).