Glycopyrrolate does not ameliorate hypothermia associated bradycardia in healthy individuals: A randomized crossover trial.

ABSTRACT

BACKGROUND: Hypothermia improves outcomes following ischemia-reperfusion injury. Shivering is common and can be mediated by agents such as dexmedetomidine. The combination of dexmedetomidine and hypothermia results in bradycardia. We hypothesized that glycopyrrolate would prevent bradycardia during dexmedetomidine-mediated hypothermia. METHODS: We randomly assigned eight healthy subjects to premedication with a single 0.4 mg glycopyrrolate intravenous (IV) bolus, titrated glycopyrrolate (0.01 mg IV every 3 min as needed for heart rate <50), or no glycopyrrolate during three separate sessions of 3 h cooling. Following 1 mg/kg IV dexmedetomidine bolus, subjects received 20 ml/kg IV 4 °C saline and surface cooling (EM COOLS, Weinerdorf, Austria). We titrated dexmedetomidine infusion to suppress shivering but permit arousal to verbal stimuli. After 3 h of cooling, we allowed subjects to passively rewarm. We compared heart rate, core temperature, mean arterial blood pressure, perceived comfort and thermal sensation between groups using Kruskal-Wallis test and ANOVA. RESULTS: Mean age was 27 (SD 6) years and most (N = 6, 75%) were male. Neither heart rate nor core temperature differed between the groups during maintenance of hypothermia (p > 0.05). Mean arterial blood pressure was higher in the glycopyrrolate bolus condition (p < 0.048). Thermal sensation was higher in the control condition than the glycopyrrolate bolus condition (p = 0.01). Bolus glycopyrrolate resulted in less discomfort than titrated glycopyrrolate (p = 0.04). CONCLUSIONS: Glycopyrrolate did not prevent the bradycardic response to hypothermia and dexmedetomidine. Mean arterial blood pressure was higher in subjects receiving a bolus of glycopyrrolate before induction of hypothermia. Bolus glycopyrrolate was associated with less intense thermal sensation and less discomfort during cooling.