May 2013 • Volume 116 • Number 5 www.anesthesia-analgesia.org 1001 O rexin neurons contribute to a wide range of physiological functions, including regulation of arousal, wakefulness, cardiovascular function, res- piration, autonomic responses, the fight-or-flight response, and feeding. 1 The role of orexin neurons in regulating wakefulness is of particular interest for researchers and clinicians because degeneration of orexin neurons is implicated in the pathological dysregulation of wakefulness observed in narcolepsy, 2,3 and these neurons may also participate in the regulation of wakefulness during anesthesia. In animal experiments, orexin neurons have been proposed to drive emergence from a variety of anesthesias, 4–9 whereas orexin neurons exert a minimal influence on anesthesia induction. In human studies, the role of orexin neurons in induction and emergence from anesthesia remains controversial. Plasma orexin levels have been observed to increase after (but not before) emergence in patients undergoing general anesthesia. 10 Prolonged emergence time from general anesthesia in a narcolepsy patient has also been reported, 11 although information detailing the perioperative outcome and management for narcolepsy patients remains scarce. Theoretical complications for these patients include postoperative hypersomnia, prolonged emergence after general anesthesia, 11 apnea with sleep paralysis, 12 and interactions with medications. 13,14 However, the actual frequency of these complications has not been documented, and one study suggests that their narcoleptic patients undergoing anesthesia experienced no increased risk for postoperative complications or difference in time The Impact of Hypothermia on Emergence from Isoflurane Anesthesia in Orexin Neuron-Ablated Mice Chiharu Kuroki, MD,*† Yoshiko Takahashi, MD,*† Youichirou Ootsuka, PhD,* Yuichi Kanmura, MD, PhD,† and Tomoyuki Kuwaki, PhD* Copyright © 2013 by the International Anesthesia Research Society. DOI: 10.1213/ANE.0b013e31828842f0 From the Departments of *Physiology and †Anesthesiology, Kagoshima Uni- versity Graduate School of Medical and Dental Sciences, Kagoshima, Japan. Accepted for publication January 8, 2013. Funding: Supported, in part, by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Tomoyuki Kuwaki, PhD, Department of Physiol- ogy, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890–8544, Japan. Address e-mail to kuwaki@ m3.kufm.kagoshima-u.ac.jp. BACKGROUND: Orexin neurons regulate the sleep/wake cycle and are proposed to inluence general anesthesia. In animal experiments, orexin neurons have been shown to drive emer- gence from general anesthesia. In human studies, however, the role of orexin neurons remains controversial, owing at least, in part, to the fact that orexin neurons are multifunctional. Orexin neurons regulate not only the sleep/wake cycle, but also body temperature. We hypothesized that orexin neurons do not directly regulate emergence from anesthesia, but instead affect emergence indirectly through thermoregulation because anesthesia-induced hypothermia can greatly inluence emergence time. To test our hypothesis, we used simultaneous measurement of body temperature and locomotor activity. METHODS: We used male orexin neuron-ablated (ORX-AB) mice and their corresponding wild- type (WT) littermates to investigate the role of orexin neurons in emergence. Body tempera- ture was recorded using an intraperitoneally implanted telemetric probe, and locomotor activity was measured using an infrared motion sensor. Induction of anesthesia and emergence from anesthesia were deined behaviorally as loss and return, respectively, of body movement. Mice received general anesthesia with 1.5% isolurane in 100% oxygen for 30 minutes under 3 condi- tions. In the irst experiment, the anesthesia chamber was warmed (32°C), ensuring a constant body temperature of animals during anesthesia. In the second experiment, the anesthesia chamber was maintained at room temperature (25°C), allowing body temperature to luctuate. In the third experiment in WT mice, the anesthesia chamber was cooled (23°C) so that their body temperature would decrease to the comparable value to that obtained in the ORX-AB mice during room temperature condition. RESULTS: In the warmed condition, there were no signiicant differences between the ORX-AB and control mice with respect to body temperature, locomotor activity, induction time, or emer- gence time. In the room temperature condition, however, anesthesia-induced hypothermia was greater and longer lasting in ORX-AB mice than that in WT mice. Emergence time in ORX-AB mice was signiicantly prolonged from the warmed condition (14.2 ± 0.8 vs 6.0 ± 1.1 minutes) whereas that in WT mice was not different (7.4 ± 0.8 vs 4.9 ± 0.2 minutes). When body tem- perature was decreased by cooling in WT mice, emergence time was prolonged to 12.4 ± 1.3 minutes. Induction time did not differ among temperature conditions or genotypes. CONCLUSIONS: The effect of orexin deiciency to impair thermoregulation during general anesthesia is of suficient magnitude that body temperature must be appropriately controlled when studying the role of orexin neurons in emergence from anesthesia. (Anesth Analg 2013;116:1001–5)