626 Anesthesiology 1999; 91:626–32 ©1999AmericanSocietyofAnesthesiologists,Inc. Lippincott Williams & Wilkins, Inc. Thermoregulatory Thresholds for Vasoconstriction in Patients Anesthetized with Various 1-Minimum Alveolar Concentration Combinations of Xenon, Nitrous Oxide, and Isoflurane Takahisa Goto, M.D.,* Takashi Matsukawa, M.D.,† Daniel I. Sessler, M.D.,‡ Shoichi Uezono, M.D.,§ Yoshiki Ishiguro, M.D.,§ Makoto Ozaki, M.D.,ʈ Shigeho Morita, M.D.# Background: Nitrous oxide limits intraoperative hypother- sevoflurane or isoflurane, presumably because of its stimulat- mia because the vasoconstriction threshold with nitrous oxide ing actions on the sympathetic nervous system. Xenon, in con- is higher than with equi–minimum alveolar concentrations of trast, does not cause sympathetic activation. Therefore, the au- thors tested the hypothesis that the vasoconstriction threshold during xenon–isoflurane anesthesia is less than during nitrous * Associate Professor, Department of Anesthesia, Teikyo University oxide–isoflurane anesthesia or isoflurane alone. Ichihara Hospital. Methods: Fifteen patients each were randomly assigned to † Associate Professor, Department of Anesthesia, Yamanashi Medical one of three 1-minimum alveolar concentration anesthetic reg- University. imens: (1) xenon, 43% (0.6 minimum alveolar concentration) and isoflurane, 0.5% (0.4 minimum alveolar concentration); (2) ‡ Professor, Department of Anesthesia and Perioperative Care, Uni- nitrous oxide, 63% (0.6 minimum alveolar concentration) and versity of California–San Francisco; Professor, Ludwig Boltzmann Insti- isoflurane 0.5%; or (3) isoflurane, 1.2%. Ambient temperature tute for Clinical Anesthesia and Intensive Care; Director, Outcomes was maintained near 23°C and the patients were not actively Research௢; Professor and Vice Chair, Department of Anesthesia and warmed. Thermoregulatory vasoconstriction was evaluated us- General Intensive Care, University of Vienna. ing forearm-minus-fingertip skin temperature gradients. A gra- § Assistant Professor, Department of Anesthesia, Teikyo University dient exceeding 0°C indicated significant vasoconstriction. The Ichihara Hospital. core-temperature threshold that would have been observed if ʈ Associate Professor, Department of Anesthesia, Tokyo Women’s skin had been maintained at 33°C was calculated from mean Medical University. skin and distal esophageal temperatures at the time of vasocon- # Professor and Chair, Department of Anesthesia, Teikyo University striction. Ichihara Hospital. Results: The patients’ demographic variables, preinduction core temperatures, ambient operating room temperatures, and Received from the Outcomes Research௢ Group, the Department of fluid balance were comparable among the three groups. Heart Anesthesia, Teikyo University Ichihara Hospital, Chiba, Japan; Yama- rates were significantly less during xenon anesthesia than with nashi Medical University, Yamanashi, Japan; the Department of Anes- nitrous oxide. The calculated vasoconstriction threshold was thesia and Perioperative Care, University of California–San Francisco, lowest with xenon (34.6 ؎ 0.8°C, mean ؎ SD), intermediate San Francisco, California; the Ludwig Boltzmann Institute for Clinical with isoflurane alone (35.1 ؎ 0.6°C), and highest with nitrous -Anesthesia and Intensive Care, Vienna, Austria; the Department of oxide (35.7 ؎ 0.6°C). Each of the thresholds differed signifi Anesthesia and General Intensive Care, University of Vienna, Vienna, cantly. Austria; and the Department of Anesthesia, Tokyo Women’s Medical Conclusions: Xenon inhibits thermoregulatory control more University, Tokyo, Japan. Submitted for publication December 8, 1998. than isoflurane, whereas nitrous oxide is the least effective in Accepted for publication April 12, 1999. Supported by Ministry of this respect. (Key words: Anesthesia; heat; temperature; ther- Education grants 09877310 and 09671553 (Tokyo, Japan), National moregulation.) Institutes of Health grant GM58273 (Bethesda, Maryland), the Joseph Drown Foundation (Los Angeles, California), and the Fonds zur Fo¨rde- rung der wissenschaftlichen Forschung (Vienna, Austria). Major cor- XENON has recently attracted renewed interest because porate funding for the Outcomes Research௢ Group is provided by it possesses many characteristics of an ideal anesthetic. Augustine Medical, Inc. The authors do not consult for, accept hono- For example, (1) the minimum alveolar concentration raria from, or own stock or stock options in any company related to (MAC) of xenon is 71%, so xenon alone can provide this research. anesthesia for surgery under normobaric conditions1; (2) Address reprint requests to Dr. Sessler: Department of Anesthesia, University of California–San Francisco, 374 Parnassus Avenue, 3rd xenon is analgesic, with a potency similar to that of 2,3 4 Floor, San Francisco, California 94143-0648. Address electronic mail to: nitrous oxide ; (3) the toxicity of xenon is low, be- [email protected]. On the world wide web: www.or.org cause it is chemically inert and probably does not un- Anesthesiology, V 91, No 3, Sep 1999 627 THERMOREGULATION DURING XENON, N2O, AND ISOFLURANE dergo biotransformation; (4) xenon produces minimal ml/kg unwarmed intravenous fluid. General anesthesia hemodynamic depression5,6; and (5) xenon is environ- was induced by intravenous administration of 2 mg/kg mentally friendly, because it is prepared by fractional propofol, and the lungs were ventilated with oxygen distillation of air.4 containing progressively increasing concentrations of A prominent feature of xenon is its blood–gas partition isoflurane. The patients’ tracheas were intubated after coefficient of only 0.12 to 0.14,7,8 which is smaller than muscle relaxation was induced by administration of 0.1 that of nitrous oxide. Therefore, xenon provides faster mg/kg vecuronium bromide. emergence from anesthesia than other inhalational Fifteen patients each were assigned randomly to one of 9 agents, and emergence times are not prolonged even three, 1-MAC anesthetic regimens: (1) xenon, 43% (0.6 10 after long periods of anesthesia. The primary disadvan- MAC) and isoflurane, 0.5% (0.4 MAC); (2) nitrous oxide, tage of xenon is that the gas is expensive. Fortunately, 63% (0.6 MAC), and isoflurane, 0.5%; or (3) isoflurane, the xenon requirements per hour of anesthesia decrease 1.2%.1,18 We assumed the additivity of xenon and isoflu- 10 progressively during closed-circuit anesthesia. This rane MAC fractions because those of xenon and halo- makes xenon an economically viable anesthetic choice thane are known to be additive.1 These maintenance for long operations. anesthetics were delivered via a closed-circuit breathing Inadvertent hypothermia often complicates prolonged system to limit the expenditure of xenon. During the surgery. In patients becoming sufficiently hypothermic, period between skin incision and the application of reemergence of thermoregulatory vasoconstriction usu- 11 peritoneal retractors, however, the concentration of ally prevents further core hypothermia. Nitrous oxide isoflurane was increased temporarily if mean arterial may, to some extent, restrict intraoperative hypother- pressure exceeded the preinduction value by more than mia, because its vasoconstriction threshold is higher 30%. No additional anesthetics, sedative, or opioids were than equi-MACs of sevoflurane or isoflurane.12 The rela- given subsequently until the end of surgery. tively high vasoconstriction threshold during nitrous ox- Mechanical ventilation was adjusted to maintain end- ide anesthesia is presumably related to the drug’s sym- tidal carbon dioxide partial pressure between 32 and 35 pathetic nervous system activation.13–15 Xenon, in mmHg. Supplemental vecuronium was administered as contrast, does not cause sympathetic activation5,16 and needed to maintain zero-to-two twitches in response to attenuates the hemodynamic response to skin incision supramaximal stimulation of the ulnar nerve at the wrist. more effectively than isoflurane or sevoflurane.17 At least 8 ml ⅐ kgϪ1 ⅐ hϪ1 unwarmed intravenous fluid Therefore, we tested the hypothesis that the vasocon- was administered during the study period to maintain striction threshold during xenon–isoflurane anesthesia is Ϫ1 Ϫ1 less than during isoflurane alone. We took this opportu- urine output of at least 0.5 ml ⅐ kg ⅐ h . nity to simultaneously confirm our previous observation An antimicrobial airway filter (Hygrobac S-M; Mallinck- that the threshold is higher during nitrous oxide–isoflu- rodt Medical, St. Louis, MO) was used for passive humid- rane anesthesia than when isoflurane is used alone. ification from the outset of mask ventilation, and the patients were covered with a single layer of surgical draping. No other warming measures were used during Methods the study. Ambient temperature was maintained near With institutional review board approval and written 22–23°C. informed patient consent, we studied 45 patients classi- Once significant vasoconstriction was observed (ex- fied as American Society of Anesthesiologists physical plained subsequently), patients were actively rewarmed status 1 and 2. All were aged 32 to 65 yr and were using appropriate measures, including forced air and undergoing elective abdominal surgery. Potential partic- circulating water. Subsequent anesthetic management ipants were excluded if they had a history of thyroid was left to the discretion of the responsible anesthetist. disease, dysautonomia, Raynaud’s syndrome, malignant If vasoconstriction had not occurred within 1.5 h of the