Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia.

OBJECTIVE: Therapeutic temperature modulation is recommended after cardiac arrest (CA). However, body temperature (BT) regulation has not been extensively studied in this setting. We investigated BT variation in CA patients treated with therapeutic hypothermia (TH) and analyzed its impact on outcome. METHODS: A prospective cohort of comatose CA patients treated with TH (32-34°C, 24h) at the medical/surgical intensive care unit of the Lausanne University Hospital was studied. Spontaneous BT was recorded on hospital admission. The following variables were measured during and after TH: time to target temperature (TTT=time from hospital admission to induced BT target <34°C), cooling rate (spontaneous BT-induced BT target/TTT) and time of passive rewarming to normothermia. Associations of spontaneous and induced BT with in-hospital mortality were examined. RESULTS: A total of 177 patients (median age 61 years; median time to ROSC 25 min) were studied. Non-survivors (N=90, 51%) had lower spontaneous admission BT than survivors (median 34.5 [interquartile range 33.7-35.9]°C vs. 35.1 [34.4-35.8]°C, p=0.04). Accordingly, time to target temperature was shorter among non-survivors (200 [25-363]min vs. 270 [158-375]min, p=0.03); however, when adjusting for admission BT, cooling rates were comparable between the two outcome groups (0.4 [0.2-0.5]°C/h vs. 0.3 [0.2-0.4]°C/h, p=0.65). Longer duration of passive rewarming (600 [464-744]min vs. 479 [360-600]min, p<0.001) was associated with mortality. CONCLUSIONS: Lower spontaneous admission BT and longer time of passive rewarming were associated with in-hospital mortality after CA and TH. Impaired thermoregulation may be an important physiologic determinant of post-resuscitation disease and CA prognosis. When assessing the benefit of early cooling on outcome, future trials should adjust for patient admission temperature and use the cooling rate rather than the time to target temperature.

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 categorized: therapeutic 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.