Determinants of Heat Generation in Patients Treated With Therapeutic Hypothermia Following Cardiac Arrest

BACKGROUND Therapeutic hypothermia (TH) is recommended to reduce ischemic brain injury after cardiac arrest. The variables that predict heat generation by patients receiving TH are uncertain, as is how this heat generation relates to neurologic outcome. We hypothesized that patient characteristics, medication use, inflammation, and organ injury would be associated with heat generation. We further hypothesized that neurologic outcome would be most strongly associated with heat generation. METHODS AND RESULTS Surface and intravascular cooling devices were used to provide TH in 57 consecutive cardiac arrest patients. Device water temperatures during the maintenance (33°C) phase were collected. Patient heat generation was quantified as the "heat index" (HI), which was the inverse average water temperature over a minimum of 2 hours of maintenance hypothermia. Variables measuring reduced ischemic injury and improved baseline health were significantly associated with HI. After controlling for presenting rhythm, a higher HI was independently associated with favorable disposition (OR=2.2; 95% CI 1.2 to 4.1; P=0.014) and favorable Cerebral Performance Category (OR=1.8; 95% CI 1.0 to 3.1; P=0.035). Higher HI predicted favorable disposition (receiver-operator area under the curve 0.71, P=0.029). HI was linearly correlated with arteriovenous CO2 (r=0.69; P=0.041) but not O2 (r=0.13; P=0.741) gradients. CONCLUSIONS In cardiac arrest patients receiving TH, greater heat generation is associated with better baseline health, reduced ischemic injury, and improved neurologic function, which results in higher metabolism. HI can control for confounding effects of patient heat generation in future clinical trials of rapid TH and offers early prognostic information.