Increased blood glucose variability during therapeutic hypothermia and outcome after cardiac arrest

OBJECTIVE:Hypothermia impairs blood glucose homeostasis and insulin sensitivity. However, the impact of therapeutic hypothermia on blood glucose levels and insulin requirements is unknown. We analyzed blood glucose variability during therapeutic hypothermia in patients with coma after cardiac arrest and examined its impact on outcome. DESIGN:Prospective observational study. SETTING:Two university hospital medical/surgical intensive care units. PATIENTS:Comatose cardiac arrest patients treated with therapeutic hypothermia (33°C, 24 hrs). INTERVENTIONS:Insulin therapy (blood glucose target 6–8 mmol/L [110–150 mg/dL]), according to a written algorithm, with nurse-driven adjustment of insulin dose. MEASUREMENTS AND MAIN RESULTS:Two-hundred and twenty patients (median age 61 yrs, median time to return of spontaneous circulation 20 min) were studied. Two time periods, comparable in duration, were categorizedtherapeutic hypothermia (stable maintenance phase) and normothermia (after rewarming). Blood glucose variability was defined as the difference between maximum and minimum blood glucose concentration during each time period. Mean blood glucose (8.3 ± 2.3 vs. 7.1 ± 1.3 mmol/L), blood glucose variability (5.7 ± 3.9 vs. 3.7 ± 3.6 mmol/L), and insulin dose (2 ± 2 vs. 1 ± 1 U/h) were higher during therapeutic hypothermia compared to normothermia (all p < .001). Higher mean blood glucose (7.9 ± 1.8 mmol/L in survivors vs. 8.7 ± 2.6 mmol/L in nonsurvivors, p = .02) and increased blood glucose variability (4.9 ± 3.5 vs. 6.5 ± 4.1 mmol/L, p = .003) during therapeutic hypothermia were associated with mortality. After adjusting for time to return of spontaneous circulation, initial arrest rhythm, and cardiac arrest etiology, increased blood glucose variability during therapeutic hypothermia, but not mean blood glucose level, was an independent predictor of inhospital mortality (odds ratio for death 1.10 [confidence interval 1.02–1.19], p = .016). CONCLUSIONS:Mild therapeutic hypothermia is associated with higher blood glucose levels, increased blood glucose variability, and greater insulin requirements compared to the postrewarming normothermic phase. Increased blood glucose variability during therapeutic hypothermia is a predictor of inhospital mortality after cardiac arrest, independent of injury severity and mean blood glucose levels.