Nitrous Oxide Decreases the Threshold for Vasoconstriction Less Than Sevoflurane or Isoflurane Makoto Ozaki, MD*, Daniel I. Sessler, Mm, Hidehiro Suzuki, MD*, Kyoko Ozaki, MD*, Chiharu Tsunoda, MD*, and Kenji Atarashi, MD* *Department of Anesthesia, Tokyo Women’s Medical College, Tokyo, Japan, and the tThermoregulation Research Laboratory, Department of Anesthesia, University of California, San Francisco, California The core temperature triggering thermoregulatory (1%); 2) sevoflurane alone (2%); 3) N,O (60%) and 0.5 arteriovenous shunt constriction is designated the MAC isoflurane (0.6%); and, 4) isoflurane alone threshold for vasoconstriction. High thresholds are (1.2%). A forearm minus fingertip, skin temperature generally desirable because vasoconstriction helps gradient 20°C was considered significant vasocon- prevent further core hypothermia by decreasing cu- striction; the esophageal temperature triggering va- taneous heat loss and constraining metabolic heat to soconstriction identified the threshold. Morphomet- the core thermal compartment. Previous studies sug- ric characteristics were comparable in each group. gest that nitrous oxide (N,O) may inhibit thermoreg- The threshold for vasoconstriction was 35.8 + 0.3”C ulatory vasoconstriction less than comparable doses in the patients given 50% N,O combined with 0.5 of volatile anesthetics. To confirm this impression, MAC sevoflurane, which was significantly greater we tested the hypothesis that 0.5 minimum alveolar than that in those given 1.0 MAC sevoflurane: 35.1 2 anesthetic concentration (MAC) N,O combined with 0.4”C. Similarly, the threshold for vasoconstriction 0.5 MAC sevoflurane or isoflurane would reduce the was 35.9 + 0.3”C in the patients given 60% N,O com- vasoconstriction threshold less than 1.0 MAC bined with 0.5 MAC isoflurane, which was signifi- sevoflurane or isoflurane. With institutional review cantly greater than that in those given 1.0 MAC board approval, we studied 40 patients, aged 20-60 isoflurane: 35.0 + 0.5”C. We thus conclude that N,O yr, undergoing open abdominal surgery. No premed- impairs thermoregulation less than sevoflurane or ication was given. Ten patients each were anesthe- isoflurane. tized with: 1) N,O (50%) and 0.5 MAC sevoflurane (Anesth Analg 1995;80:1212-6) ntraoperative hypothermia is common, and causes All general anesthetics so far tested significantly de- potentially serious complications (l-7). The reduc- crease the thermoregulatory threshold for vasoconstic- I tion in core temperature immediately after in- tion (i.e., the core temperature triggering vasoconstric- duction of general anesthesia results largely from tion) (8-11). Because vasoconstriction is effective in anesthetic-induced inhibition of tonic thermoregula- minimizing additional core hypothermia (15), anesthetic tory vasoconstriction (8 -1 l), and subsequent core-to- combinations causing less-than-typical thermoregula- peripheral redistribution of body heat (12). Heat loss tory inhibition may be preferable in some patients. exceeding metabolic heat production then typically Nitrous oxide (N,O) (60%) combined with fentanyl continues to reduce body temperature for several ad- (4 pg -kg-’ *h-l) decreases the threshold to 34.2 + ditional hours (13). Finally, reemergence of thermo- 0.5”C (16). Similarly, 30% N,O decreases the shivering regulatory vasoconstriction (in patients becoming threshold -1°C (17), thus nearly doubling the normal sufficiently hypothermic) moderates further core hy- sweating-to-shivering range (18). However, adding pothermia by decreasing cutaneous heat loss (14) N20 to enflurane decreases the vasoconstriction and constraining metabolic heat to the core thermal threshold less than expected (191, suggesting that N,O compartment (15). may impair thermoregulation less than comparable doses of other anesthetics. To confirm this impression, This study was supported by the Joseph Drown Foundation and we tested the hypothesis that 0.5 minimum alveolar National Institutes of Health Grant GM49670. anesthetic concentration (MAC) N20 combined with Accepted for publication January 31, 1995. 0.5 MAC sevoflurane or isoflurane would reduce the Address correspondence and reprint requests to Daniel I. Sessler, MD, Thermoregulation Research Laboratory, University of Califor- vasoconstriction threshold less than 1 .O MAC sevoflu- nia, San Francisco, CA 94143-0648. rane or isoflurane alone. 01995 by the International Anesthesia Research Society 1212 An&h Analg 1995;80:12124 0003-2999/95/$5.00 ANESTH ANALG OZAKI ET AL. 1213 1995;80:1212-6 NITROUS OXIDE AND THERMOREGULATION Methods inserted until the patients felt the thermocouple touch the tympanic membrane; appropriate placement was With institutional review board approval and in- confirmed when they easily detected a gentle rubbing formed consent, we studied 40 ASA physical status of the attached wire. The probe was then taped in I-II patients. They were aged 20-60 yr, and undergo- place, the aural canal occluded with cotton, and the ing elective abdominal surgery. None of the partici- external ear covered with a gauze pad. Tympanic pants had a history of thyroid disease, dysautonomia, membrane temperatures correlate well with distal Raynaud’s syndrome, or malignant hyperthermia. esophageal temperatures in the perioperative period Surgery started near 8:30 AM in nearly all of the pa- (24,25). After induction of anesthesia, core tempera- tients, and typically finished near noon. Twenty initial ture was recorded from the distal esophagus. patients were given sevoflurane; subsequently, 20 oth- Mean skin temperature was calculated from four sites: ers were studied during isoflurane anesthesia. 0.3&m + Tam) + O.p(Tthigh + Tcaif) (26). Fingertip Upon arrival to the operating suite, 10 mL/kg of perfusion was evaluated using forearm minus fingertip unwarmed intravenous (IV) fluid was administered. skin temperature gradients. Perfusion was recorded Without any premeditation, anesthesia was induced from an arm exposed to the operating room environ- by inhalation of 70% N,O and progressively greater ment and not having a blood pressure cuff or IV catheter. concentrations of sevoflurane or isoflurane. Intubation There is an excellent correlation between skin tempera- of the trachea was facilitated by administration of ture gradients and volume plethysmography (27). vecuronium bromide (0.1 mg/kg). Mechanical venti- Temperatures were recorded from Mon-a-Therm@ lation was maintained with a circle system having a thermocouples (Mallinckrodt Anesthesia Products, fresh gas flow of 6 L/min, and adjusted to maintain Inc., St. Louis, MO). They were connected to a cali- end-tidal Pco, near 35 mm Hg. No airway heating or brated Iso-Thermex@ 16-channel electronic thermom- humidification was provided. No thiopental or opioid eter (Columbus Instruments International, Corp., Co- was administered. lumbus, OH) having an accuracy of O.l”C and a Patients given sevoflurane were then randomly as- precision of O.Ol”C. signed to maintenance anesthesia consisting of: 1) 50% Heart rate was monitored continuously using three- N,O (-0.5 MAC) and 0.5 MAC sevoflurane (1%); or 2) lead electrocardiography. Blood pressure was deter- 1.0 MAC sevoflurane (2%) (20,21). Patients given mined oscillometrically at 5-min intervals. We used isoflurane were then randomly assigned to mainte- oscillometric rather than direct arterial blood pressure nance anesthesia consisting of: 1) 60% N,O (eO.5 measurements to minimize the artifact induced by MAC) and 0.5 MAC isoflurane (0.6%); or 2) 1.0 MAC thermoregulatory vasoconstriction (28,29). Respira- isoflurane (1.2%) (20,22). The concentration of N,O tory gas concentrations were quantified using a cali- was increased in the second series because there is still brated end-tidal gas analyzer (Datex Medical Instru- some controversy about the MAC of this drug in mentation, Inc., Tewksbury, MA). Data were recorded humans. at lo-min intervals, starting immediately before induc- Supplemental vecuronium was administered as tion of anesthesia (“initial” values). needed to maintain one to two twitches in response to As in previous studies (151, we considered a gradi- supramaximal stimulation of the ulnar nerve at the ent of 0°C to indicate significant thermoregulatory wrist. At least 10 mL * kg-i . h-i fluid was given IV vasoconstriction. The distal esophageal temperature and blood products were replaced to maintain the triggering significant vasoconstriction was considered hematocrit between 25%-32%. Administered fluids the thermoregulatory threshold. The preinduction were warmed to 37°C. fluid bolus was not considered part of the intraoper- The patients were covered with a single layer of ative fluid balance. Fluid administered to the time of surgical draping (23); no other warming measures vasoconstriction was divided by the time to vasocon- were taken during the study period. Twenty min- striction to produce the fluid administration rate. Am- utes after significant vasoconstriction was observed, bient temperature in each case was averaged over time patients were actively rewarmed using a forced-air from induction of anesthesia until vasoconstriction. system (Bair Hugger@; Augustine Medical, Inc., Morphometric data, initial core temperatures, am- Eden Prairie, MN). Subsequent anesthetic manage- bient temperatures, and fluid administration rates in ment was left to the discretion of the responsible the patients given each volatile anesthetic were com- anesthesiologist. pared using Mann-Whitney U-tests. Anesthetic con- Ambient