Anesth Analg 1999;89:462
© 1999 International Anesthesia Research Society
GENERAL ARTICLES
Intraoperative Phenylephrine Infusion Decreases the Magnitude of Redistribution Hypothermia
Takehiko Ikeda, MD*,
Makoto Ozaki, MD
,
Daniel I. Sessler, MD
,
Tomiei Kazama, MD*,
Kazuyuki Ikeda, MD, FRCA*, and
Shigehito Sato, MD*
*Department of Anesthesiology and Intensive Care and
Outcomes ResearchTM Group, Hamamatsu University School of Medicine, Hamamatsu;
Department of Anesthesia, Tokyo Women’s Medical University, Tokyo, Japan;
Department of Anesthesia and Perioperative Care, University of California-San Francisco, California;
Ludwig Boltzmann Institute for Clinical Anesthesia and Intensive Care; and
Department of Anesthesia and General Intensive Care, University of Vienna, Vienna, Austria
Address correspondence and reprint requests to Dr. Takehiko Ikeda, Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan. Address e-mail to tikeda{at}hama-med.ac.jp
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Abstract
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Core hypothermia during the first hour after induction of general anesthesia results largely from an internal core-to-peripheral redistribution of body heat. This redistribution results from both central inhibition of tonic thermoregulatory vasoconstriction in the arteriovenous shunt and anesthetic-induced vasodilation. We therefore tested the hypothesis that acute administration of phenylephrine, a pure 
-adrenergic agonist, reduces the magnitude of anesthetic-induced core-to-peripheral redistribution of body heat. Patients undergoing minor oral surgery were randomly assigned to an infusion of 0.5 µg · kg-1 · min-1 phenylephrine IV or no treatment (control). The phenylephrine infusion was started immediately before anesthesia was induced with 2.5 mg/kg propofol IV. Subsequently, anesthesia was maintained with sevoflurane and 60% nitrous oxide in oxygen. Calf minus toe, skin-temperature gradients <0°C were considered indicative of significant arteriovenous shunt vasodilation. Ambient temperature and end-tidal concentrations of maintenance sevoflurane were comparable in each group. Although there were no significant differences in skin-temperature gradients, core temperatures in the untreated patients decreased significantly more (1.2 ± 0.4°C) than in those given phenylephrine (0.5 ± 0.2°C, P < 0.001). These data suggest that maintaining precapillary vasoconstriction of blood vessels, not in the arteriovenous shunt reduces the magnitude of redistribution hypothermia.
Implications: Core hypothermia immediately after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Core temperature reduction during the first hour of anesthesia decreased less in patients given phenylephrine than in untreated controls. These data suggest that maintaining precapillary vasoconstriction possibly reduces the magnitude of redistribution hypothermia.
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Introduction
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Intraoperative hypothermia is common, and is associated with adverse outcomes including coagulopathy and increased allogeneic transfusion requirement (1), surgical wound infection and prolonged hospitalization (2), delayed postanesthetic recovery (3), and morbid cardiac complications (4). Core hypothermia during the first hour after induction of general anesthesia results largely from an internal core-to-peripheral redistribution of body heat (5). This redistribution results in part from central anesthetic-induced (6–8) inhibition of tonic thermoregulatory vasoconstriction in the arteriovenous shunt.
Most anesthetics produce arterial and venous dilation as well as thermoregulatory vasodilation in the arteriovenous shunt (9,10). This direct vasodilation contributes to the central inhibition of thermoregulatory control and aggravates core-to-peripheral redistribution of body heat (11). The importance of vasomotor tone is illustrated by studies showing that acute vasodilation induced by nifedipine augments redistribution hypothermia (12). We therefore tested the corollary hypothesis that acute administration of phenylephrine, a pure -adrenergic agonist, reduces the magnitude of anesthetic-induced core-to-peripheral redistribution of body heat.
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Methods
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With approval of the Ethics Committee at the Hamamatsu University School of Medicine and written informed consent, we studied 18 ASA physical status I-II patients undergoing minor oral surgery. None was obese, was taking medication, or had a history of thyroid disease, dysautonomia, or Raynaud’s syndrome.
Patients fasted for 10 h before arriving at the operating room. They were premedicated IM with 0.5 mg atropine and 20 mg famotidine 30 min before induction of anesthesia. A 20-gauge catheter was inserted into a left forearm vein for fluid and drug administration. The patients were randomly assigned, based on computer-generated codes, to an IV infusion of phenylephrine (0.5 µg · kg-1 · min-1) or no treatment (control). The patients were blinded to group assignment and treatment, but the investigator was not. The phenylephrine infusion was started immediately before induction of anesthesia.
Anesthesia in both groups was induced with 2.5 mg/kg propofol IV. Endotracheal intubation was facilitated by IV administration of 0.1 mg/kg vecuronium bromide. Anesthesia was subsequently maintained with \F2% end-tidal sevoflurane and 60% nitrous oxide in oxygen at a 6-L/min fresh-gas flow. Ventilation was controlled to maintain end-tidal carbon dioxide partial pressure near 35 mm Hg. Heat- and moisture-exchanging filters were positioned between the endotracheal tube and breathing circuit. IV fluids were warmed to 37°C and ambient temperature was maintained near 25–26°C. Patients were covered with a single cotton blanket and one layer of surgical drape.
Ambient temperature was measured by a thermocouple positioned at the level of the patient, well away from any heat-producing equipment. Mean skin temperature was calculated from four sites: 0.3 (Tchest + Tarm) + 0.2 (Tthigh + Tcalf) (13). Calf minus toe skin-surface temperature gradients were used as an index of foot arteriovenous shunt perfusion. As in previous studies, we considered a leg gradient <0°C to indicate vasodilation (14).
Core temperature was measured at the tympanic membrane before induction of anesthesia using thermocouples. The aural probes were inserted by patients until they felt the thermocouple touch the tympanic membrane; appropriate placement was confirmed when patients easily detected a gentle rubbing of the attached wire. The aural canal was occluded with cotton, the probe securely taped in place, and a gauze bandage positioned over the external ear. All skin and tympanic membrane temperature probes were positioned on the patients’ right sides. After induction of anesthesia, core temperature was measured from the distal esophagus. All temperatures were measured using Mon-a-Therm® thermocouples (Mallinckrodt Anesthesiology Products, Inc., St. Louis, MO).
Heart rate was measured from a three-lead electrocardiogram. Blood pressure was determined oscillometrically at the left ankle. End-tidal sevoflurane and carbon dioxide concentrations were recorded from an Ultima monitor (Datex, Helsinki, Finland). Oxyhemoglobin saturation (SpO2) was monitored by pulse oximetry. All values were recorded at 15-min intervals, starting immediately before induction of anesthesia (elapsed time zero).
Hemodynamic responses, end-tidal sevoflurane and carbon dioxide concentrations, ambient temperature, and mean skin temperatures were first averaged within each patient, the resulting values were then averaged among patients. Differences between two groups were compared using two-tailed, unpaired t tests. All results are presented as means ± SDs, P < 0.05 was considered statistically significant.
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Results
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Morphometric characteristics were comparable in the two groups. Duration of surgery, fluid replacement, ambient temperature, end-tidal sevoflurane and carbon dioxide partial pressure, and mean skin temperature were also similar in the two groups. Heart rate was somewhat less in the patients given phenylephrine (although not significantly so) whereas mean blood pressure was significantly greater (Table 1).
Initial core temperatures were virtually identical in the two groups. However, core temperatures in the patients given phenylephrine subsequently remained significantly higher than those in the patients without phenylephrine (Fig. 1). Core temperature during the first hour of anesthesia decreased 1.2 ± 0.4°C in the control patients, but only 0.5 ± 0.2°C in those given phenylephrine. (P < 0.01).
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Figure 1. Core temperatures in the patients given phenylephrine 0.5 µg · kg-1 · min-1 were significantly greater than those in the patients without phenylephrine. Elapsed time-zero indicates immediately before induction of anesthesia. Asterisks (*) identify values differing significantly between groups; results are presented as means ± SDs.
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The patients in both groups were intensely vasoconstricted in the arteriovenous shunt before induction of anesthesia, with calf minus toe, skin-temperature gradients near 7°C. Induction of anesthesia in both groups produced arteriovenous shunt vasodilation, as indicated by negative skin-temperature gradients. There were, however, no statistically significant differences in calf minus toe skin-surface temperature gradients between the two groups (Fig. 2).
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Figure 2. Calf minus toe skin-surface temperature gradients as an index of foot arteriovenous shunt perfusion. A gradient <0°C indicates vasodilation. Elapsed time-zero indicates immediately before induction of anesthesia. There were no statistically significant differences between groups. Results are presented as means ± SDs.
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Discussion
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Hypothermia during general anesthesia develops with a characteristic pattern consisting of three distinct phases: 1) an initial rapid decrease in core temperature, resulting largely from an internal core-to-peripheral redistribution of body heat (5); 2) a slower, linear decrease in core temperature that results from heat loss exceeding metabolic heat production (15); and, 3) a core-temperature plateau resulting from decreased cutaneous heat loss (16) and constraint of metabolic heat to the core thermal compartment in patients becoming sufficiently hypothermic to trigger thermoregulatory vasoconstriction (17).
Our major finding is that core temperature during the first hour of anesthesia decreased significantly less in the patients given phenylephrine. Hypothermia during this period is known to result from central anesthetic-induced (6–8) inhibition of tonic thermoregulatory vasoconstriction in the arteriovenous shunt (5) combined with anesthetic-induced arterial and venous vasodilation (11,18).
Interestingly, though, calf minus toe, skin-temperature gradients were similar in both the phenylephrine and placebo groups. Gradients are relatively specific for shunt flow of the skin. These data thus indicate that arteriovenous shunts in both groups were constricted before induction of anesthesia, but subsequently dilated. Dilation is consistent with the central thermoregulatory inhibition caused by propofol (6), sevoflurane (19,20), and nitrous oxide (21,22).
Because arteriovenous shunt flow seems to have been virtually identical in the two groups, differing core temperatures suggest that phenylephrine modulated heat balance and/or distribution by producing vasoconstriction at another site (23). The most likely site is precapillary arterioles. This location is consistent with the drug’s known mechanism of action and the fact that it increases systemic vascular resistance. It is also consistent with the observed increase in mean arterial pressure. We did not, however, directly measure extremity perfusion or flow or core-to-peripheral flow of heat. Methods exist to evaluate both (5,17,24), but none is easy to implement during surgery.
Precapillary vasoconstriction induced by phenylephrine administration will, to some extent, counter the vasodilating effects of general anesthetics. This will not prevent the core-to-peripheral redistribution associated with arteriovenous shunt dilation, but will reduce the effect of anesthetic-induced precapillary dilation (11), because core temperature decreased after induction of anesthesia even during phenylephrine infusion. The net effect then, as in our patients, is to reduce the overall magnitude of redistribution hypothermia. It is likely that the difference in core temperatures during the first hour of anesthesia is almost entirely due to reduced redistribution of heat in the phenylephrine-treated patients.
An additional potential effect of phenylephrine is reduced cutaneous perfusion which would decrease flow of metabolic heat to the environment (23). There is some support for this possibility, in that core temperature continued to decrease after the first hour of anesthesia in the control patients, whereas it reached a core-temperature plateau in the others. However, redistribution is hardly complete after just one hour of anesthesia. Instead, it continues for up to three hours and contributes significantly to core hypothermia throughout this period (17). It is thus impossible to determine from our data alone the extent to which continued hypothermia in the control patients resulted from additional redistribution or whether the core-temperature plateau in the treated patients resulted in part from reduced cutaneous heat loss.
Phenylephrine decreases cardiac output by increasing afterload and reducing heart rate (25). This may be important because Shitara et al. (26) have demonstrated that dobutamine infusion aggravates intraoperative hypothermia after induction of anesthesia. The mechanism, apparently, is an increase in cardiac output which in turn augments convective transfer of heat from core to peripheral tissues. To the extent that phenylephrine reduces cardiac output, it may restrict transfer of heat to the periphery.
In summary, core hypothermia immediately after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Core temperature reduction during the first hour of anesthesia decreases less in patients given phenylephrine than in untreated controls. These data suggest that maintaining precapillary vasoconstriction possibly reduces the magnitude of redistribution hypothermia.
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Acknowledgments
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Supported by NIH Grant GM58273, the Joseph Drown Foundation (Los Angeles, CA), and the Fonds zur Förderung der wissenschaftlichen Forschung (Vienna, Austria).
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Footnotes
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The authors do not consult for, accept honoraria from, or own stock or stock options in any anesthesia-related company.
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References
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Schmied H, Kurz A, Sessler DI, et al. Mild intraoperative hypothermia increases blood loss and allogeneic transfusion requirements during total hip arthroplasty. Lancet 1996;347:289–92.[Web of Science][Medline]
-
Kurz A, Sessler DI, Lenhardt RA, et al. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med 1996;334:1209–15.[Abstract/Free Full Text]
-
Lenhardt R, Marker E, Goll V, et al. Mild intraoperative hypothermia prolongs postoperative recovery. Anesthesiology 1997;87:1318–23.[Web of Science][Medline]
-
Frank SM, Fleisher LA, Breslow MJ, et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events: a randomized clinical trial. JAMA 1997;277:1127–34.[Abstract/Free Full Text]
-
Matsukawa T, Sessler DI, Sessler AM, et al. Heat flow and distribution during induction of general anesthesia. Anesthesiology 1995;82:662–73.[Web of Science][Medline]
-
Matsukawa T, Kurz A, Sessler DI, et al. Propofol linearly reduces the vasoconstriction and shivering thresholds. Anesthesiology 1995;82:1169–80.[Web of Science][Medline]
-
Annadata RS, Sessler DI, Tayefeh F, et al. Desflurane slightly increases the sweating threshold, but produces marked, non-linear decreases in the vasoconstriction and shivering thresholds. Anesthesiology 1995;83:1205–11.[Web of Science][Medline]
-
Kurz A, Ikeda T, Sessler DI, et al. Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. Anesthesiology 1997;86:1046–54.[Web of Science][Medline]
-
Schwinn DA, McIntyre RW, Reves JG. Isoflurane-induced vasodilation: role of the alpha-adrenergic nervous system. Anesth Analg 1990;71:451–9.[Abstract/Free Full Text]
-
Sellgren J, Ponten J, Wallin BG. Percutaneous recording of muscle nerve sympathetic activity during propofol, nitrous oxide, and isoflurane anesthesia in humans. Anesthesiology 1990;73:20–7.[Web of Science][Medline]
-
Plattner O, Ikeda T, Sessler DI, et al. Postanesthetic vasoconstriction slows postanesthetic peripheral-to-core transfer of cutaneous heat, thereby isolating the core thermal compartment. Analg 1997;85:899–906.[Abstract]
-
Vassilieff N, Rosencher N, Sessler DI, et al. Nifedipine and intraoperative core body temperature in humans. Anesthesiology 1994;80:123–8.[Web of Science][Medline]
-
Ramanathan NL. A new weighting system for mean surface temperature of the human body. J Appl Physiol 1964;19:531–3.[Abstract/Free Full Text]
-
Belani K, Sessler DI, Sessler AM, et al. Leg heat content continues to decrease during the core temperature plateau in humans. Anesthesiology 1993;78:856–63.[Web of Science][Medline]
-
Hynson J, Sessler DI. Intraoperative warming therapies: a comparison of three devices. J Clin Anesth 1992;4:194–9.[Medline]
-
Sessler DI, Hynson J, McGuire J, et al. Thermoregulatory vasoconstriction during isoflurane anesthesia minimally decreases heat loss. Anesthesiology 1992;76:670–5.[Web of Science][Medline]
-
Kurz A, Sessler DI, Christensen R, et al. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology 1995;83:491–9.[Web of Science][Medline]
-
Altura BM, Altura BT, Carella A, et al. Vascular smooth muscle and general anesthetics. Fed Proc 1980;39:1584–91.[Web of Science][Medline]
-
Ozaki M, Sessler DI, Suzuki H, et al. The threshold for thermoregulatory vasoconstriction during nitrous oxide/sevofluruane anesthesia is reduced in elderly patients. Anesth Analg 1997;84:1029–33.[Abstract]
-
Hanagata K, Matsukawa T, Sessler DI, et al. Isoflurane and sevoflurane produce a dose-dependent reduction in the shivering threshold in rabbits. Anesth Analg 1995;81:581–4.[Abstract]
-
Ozaki M, Sessler DI, Suzuki H, et al. Nitrous oxide decreases the threshold for vasoconstriction less than sevoflurane or isoflurane. Anesth Analg 1995;80:1212–6.[Abstract]
-
Passias TC, Mekjavic IB, Eiken O. The effect of 30% nitrous oxide on thermoregulatory responses in humans during hypothermia. Anesthesiology 1992;76:550–9.[Web of Science][Medline]
-
Silverman DG, Jotkowitz AB, Freemer M, et al. Peripheral assessment of phenylephrine-induced vasoconstriction by laser Doppler flowmetry and its potential relevance to homeostatis mechanisms. Circulation 1994;90:23–6.[Abstract/Free Full Text]
-
Tayefeh F, Kurz A, Sessler DI, et al. Thermoregulatory vasoconstriction decreases the venous partial pressure of oxygen. Anesth Analg 1997;85:657–62.[Abstract]
-
Brooker RF, Butterworth JFt, Kitzman DW, et al. Treatment of hypotension after hyperbaric tetracaine spinal anesthesia: a randomized, double-blind, cross-over comparison of phenylephrine and epinephrine. Anesthesiology 1997;86:797–805.[Web of Science][Medline]
-
Shitara T, Wajima Z, Ogawa R. Dobutamine infusion modifies thermoregulation during general anesthesia. Anesth Analg 1996;83:1154–9.[Abstract]
Accepted for publication April 16, 1999.
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Abstract
Introduction
