Induction and maintenance of mild hypothermia by surface cooling in non-intubated subjects

Mild induced hypothermia holds promise as an effective therapy for acute ischemic stroke. We developed a novel strategy to rapidly induce and maintain mild hypothermia in unanesthetized, non-intubated subjects as a model for the treatment of acute stroke patients. We induced and maintained mild hypothermia (tympanic membrane temperature 34 degrees C-35 degrees C) for over 5 hours in 10 healthy volunteers. All subjects received 1000 mg of acetaminophen orally and meperidine intravenously for comfort and suppression of shivering. In phase 1, subjects (n=5) were cooled using Arctic Sun Energy Transfer Pads (Medivance, Inc., Louisville, CO) with manual temperature control. In phase 2, subjects (n=5) were cooled using the Arctic Sun Energy Transfer Pads connected to the Arctic Sun Model 200 Temperature control module (Medivance, Inc.). Core temperatures were measured at the tympanic membrane and rectum. All subjects reached the target tympanic temperature range. The mean time to reach a tympanic temperature of 35 degrees C was 90+/-53 minutes (1.4 degrees C/hour) in phase 2. The most common side effect was nausea, observed in 30% of subjects. There was no statistically significant change in heart rate, blood oxygenation, or diastolic blood pressure compared with baseline; systolic blood pressure was significantly elevated for the 180 minute time point only (140+/-20 mm Hg v 122+/-13 mm Hg; P = .042). We developed a method to rapidly and comfortably induce and maintain mild hypothermia in unanesthetized, non-intubated humans. Further study to optimize the pharmacologic inhibition of thermoregulation and to assess tolerability over longer durations is warranted.