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Anesth Analg 2001;93:934-938
© 2001 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Induction of Anesthesia with Ketamine Reduces the Magnitude of Redistribution Hypothermia

Takehiko Ikeda, MD*, Tomiei Kazama, MD{dagger}, Daniel I. Sessler, MD{ddagger}, Sumiko Toriyama, MD*, Kazuya Niwa, MD*, Chiaki Shimada, MD*, and Shigehito Sato, MD{dagger}

*Department of Anesthesia, Nagoya Ekisaikai Hospital, Nagoya, Japan; the {dagger}Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Japan; and the {ddagger}Outcomes ResearchTM Institute and Department of Anesthesiology, University of Louisville, Louisville, Kentucky

Address correspondence to Takehiko Ikeda, MD, Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan. Address e-mail to tikeda{at}nyc.odn.ne.jp


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Hypothermia after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Both central inhibition of tonic thermoregulatory vasoconstriction in arteriovenous shunts and anesthetic-induced arteriolar and venous dilation contribute to this redistribution. Ketamine, unique among anesthetics, increases peripheral arteriolar resistance; in contrast, propofol causes profound venodilation that other anesthetics do not. We therefore tested the hypothesis that induction of anesthesia with ketamine causes less core hypothermia than induction with propofol. Twenty patients undergoing elective surgery were randomly assigned to anesthetic induction with either 1.5 mg/kg ketamine (n = 10) or 2.5 mg/kg propofol (n = 10). Anesthesia in both groups was subsequently maintained with sevoflurane and 60% nitrous oxide in oxygen. Forearm minus finger, skin-temperature gradients <0°C were considered indicative of significant arteriovenous shunt vasodilation. Ketamine did not cause vasodilation just after induction, whereas propofol rapidly induced vasodilation. Core temperatures in the patients given ketamine remained significantly greater than those in the patients induced with propofol. These data suggest that maintaining vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia.

IMPLICATIONS: Core hypothermia during the first hour of anesthesia was less after induction of anesthesia with ketamine than propofol. Maintaining arteriovenous shunt vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Mild intraoperative hypothermia is associated with serious adverse outcomes, including coagulopathy and increased allogeneic transfusion requirement (1), surgical wound infection and prolonged hospitalization (2), delayed postanesthetic recovery (3), and morbid cardiac events (4). Much core hypothermia develops during the first hour after induction of general anesthesia (5). Hypothermia results from a core-to-peripheral redistribution of body heat that is caused by anesthetic-induced inhibition of tonic vasoconstriction.

Consistent with this theory, nifedipine, a calcium-channel blocker, aggravates redistribution hypothermia (6), whereas phenylephrine, a pure {alpha}-adrenergic agonist, reduces redistribution hypothermia (7). Redistribution hypothermia is also modified by induction anesthetics. For example, induction of anesthesia with inhaled sevoflurane causes less redistribution hypothermia than induction with IV propofol, presumably because sevoflurane causes less vasodilation than propofol (8).

Most induction anesthetics produce vasodilation, which facilitates core-to-peripheral redistribution of heat (5,6,9). Ketamine is unique among anesthetics in producing sympathetic nervous system stimulation. Augmented arteriolar peripheral resistance (10) is mediated by increased plasma concentrations of norepinephrine (11). Ketamine may decrease core-to-peripheral redistribution of heat to the extent that it induces vasoconstriction during induction of general anesthesia or at least prevents the vasodilation that accompanies induction with propofol and other anesthetics. Accordingly, we tested the hypothesis that induction of anesthesia with ketamine causes less core hypothermia than induction with propofol.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After institutional ethics committee approval and informed consent, we studied 20 ASA physical status I-II patients undergoing elective oral and superficial surgery. None of the patients were obese, were taking medication, or had a history of thyroid disease, dysautonomia, Raynaud’s syndrome, diabetes mellitus, or hypertension.

Protocol
Patients fasted for 10 h before arriving at the operating room. They were premedicated IM with 50 mg hydroxyzine, 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 to anesthetic induction with 1.5 mg/kg ketamine (n = 10) or 2.5 mg/kg propofol (n = 10). Endotracheal intubation was facilitated by IV administration of 0.1 mg/kg vecuronium bromide.

Anesthesia was subsequently maintained with {approx}2% 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 at approximately 25°C–26°C. Patients were covered with a single cotton blanket and surgical drapes during surgery.

Measurements
Ambient temperature was measured by a thermocouple (Mallinckrodt Anesthesiology Products, Inc., St. Louis, MO) positioned at the level of the patient, well away from any heat-producing equipment. Forearm and finger skin temperatures were measured by thermistors (Nikkiso-YSI CO, Ltd, Tokyo, Japan) to determine forearm minus finger, skin-surface temperature gradients that were used as an index of hand arteriovenous shunt perfusion (12). As in previous studies, we considered a gradient below 0°C to indicate vasodilation (13).

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 was securely taped in place, and a gauze bandage was 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 mea-sured from the distal esophagus with thermocouples.

Heart rate was measured from a three-lead electrocardiogram. Blood pressure was determined oscillometrically at the left arm. End-tidal sevoflurane and carbon dioxide concentrations were recorded from a 5250 RGM monitor (Ohmeda, Louisville, CO). Oxyhemoglobin saturation (SpO2) was monitored by pulse oximetry. Most values were recorded at 15-min intervals, starting immediately before induction of anesthesia (elapsed time zero). Forearm minus finger, skin-surface temperature gradients were recorded before induction of anesthesia, 3 min after administering ketamine or propofol (just before endotracheal intubation), and at 15-min intervals after induction of anesthesia. End-tidal sevoflurane and carbon dioxide concentrations were recorded at 15-min intervals after induction of anesthesia.

Data Analysis
Hemodynamic responses, end-tidal sevoflurane and carbon dioxide concentrations, and ambient temperature were first averaged within each patient; the resulting values were then averaged among patients. Differences between the treatment groups were evaluated with two-tailed, unpaired Student’s t-tests. All results are presented as means ± SDs; P < 0.05 was considered statistically significant.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Morphometric characteristics were comparable in the two groups. Duration of surgery, fluid replacement, ambient temperature, end-tidal sevoflurane and carbon dioxide concentrations, heart rate, and mean blood pressure were also similar in the two groups (Table 1).


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  		Table 1.  Morphometric and Anesthetic Data
 
Initial core temperatures were virtually identical in the two groups. However, core temperatures in the patients induced with ketamine subsequently remained significantly greater than core temperatures in the patients given propofol (Fig. 1). Core temperature during the first hour of anesthesia decreased 1.4 ± 0.4°C in the propofol patients but only 0.5 ± 0.2°C in patients given ketamine.



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  		Figure 1. Core temperatures in the patients induced with ketamine were consistently and significantly greater than those in the patients induced with propofol. Elapsed time-0 = immediately before induction of anesthesia. Asterisks identify values differing significantly between groups; results are presented as means ± SDs.

 
The patients in both groups demonstrated intense arteriovenous shunt vasoconstriction before induction of anesthesia, with forearm minus finger, skin-temperature gradients near 2.5°C. Induction of anesthesia with propofol induced immediate arteriovenous shunt vasodilation even before administration of sevoflurane and nitrous oxide. These patients subsequently remained vasodilated during maintenance of anesthesia with sevoflurane and nitrous oxide. In contrast, patients remained vasoconstricted after induction of anesthesia with ketamine. Arteriovenous shunt constriction in these patients persisted through endotracheal intubation and did not dissipate until after administration of sevoflurane and nitrous oxide maintenance anesthesia. After 15 min of anesthesia, patients in both groups were similarly dilated (Fig. 2).



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  		Figure 2. Forearm minus fingertip, skin-temperature gradients are an index of hand arteriovenous shunt perfusion; a gradient <0°C indicates vasodilation. Elapsed time-0 = just before induction of anesthesia; the second set of values was recorded 3 min after induction of anesthesia. The patients in both groups were intensely vasoconstricted before induction of anesthesia. Propofol rapidly induced vasodilation, whereas vasoconstriction persisted 3 min after ketamine administration. Subsequent maintenance of anesthesia with sevoflurane and nitrous oxide produced vasodilation. Results are presented as means ± SDs.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Temperature is rarely evenly distributed within body tissues. Instead, tissue temperature is increased in core rather than peripheral tissues. This normal core-to-peripheral temperature gradient is maintained by tonic thermoregulatory vasoconstriction. Most general anesthetics impair central thermoregulatory control, thus inhibiting normal tonic thermoregulatory vasoconstriction (14–17). This allows redistribution of body heat from core to peripheral tissues. Consequently, core temperature usually decreases 0.5°C–1.5°C during the first hour after induction of general anesthesia (5).

All previously studied anesthetics decrease the vasoconstriction threshold in humans (9,14,15,18), thus inducing arteriovenous shunt vasodilation. Many al-so produce locally mediated arteriolar dilation (19); in addition, propofol produces venodilation (20,21). Ketamine differs from other anesthetics in increasing the plasma concentration of norepinephrine (11) and arteriolar peripheral resistance (10).

We measured skin-temperature gradients (12), our index of vasomotor status, before induction of anesthesia, 3 min after administering ketamine or propofol (just before endotracheal intubation), and at 15-min intervals after induction of anesthesia. The critical measurement was the one just before intubation. This timing of this measurement was important because after endotracheal intubation, the values would have been confounded by the vasodilating effect of sevoflurane (8,16) and nitrous oxide (17) that were used to maintain anesthesia. Furthermore, noxious stimulus of endotracheal intubation may augment shunt tone because painful stimulation slightly increases the vasoconstriction threshold (22).

As might thus be expected from their respective pharmacologies, the vasomotor response to anesthetic induction with ketamine and propofol differed markedly; arteriovenous shunt vasoconstriction was well maintained with ketamine, whereas propofol provoked immediate vasodilation. Our theory was that maintaining vasoconstriction during induction of anesthesia would reduce the extent to which core-to-peripheral redistribution of body heat decreases core temperature. Our major finding was indeed that core temperature during the first hour of anesthesia decreased three times as much after induction with propofol than ketamine. Because anesthesia after intubation was maintained with sevoflurane and nitrous oxide in all patients, the observed temperature difference presumably results exclusively from the choice of induction drug. Reduced redistribution hypothermia with ketamine is consistent with our previous report that phenylephrine, a pure {alpha}-adrenergic agonist, reduces the magnitude of redistribution hypothermia (7).

Skin-temperature gradients 15, 30, 45, and 60 min after induction of anesthesia were virtually identical in the two groups, and indicated consistent arteriovenous shunt dilation. This vasodilation apparently results from the administration of sevoflurane and nitrous oxide for maintenance of anesthesia. Although gradients were virtually identical after induction of anesthesia, core temperatures after induction of anesthesia differed significantly in the two treatment groups. This suggests that maintaining arteriovenous vasoconstriction during the minutes of anesthetic induction markedly decreases the magnitude of redistribution hypothermia.

Skin-temperature gradients are relatively specific measures of arteriovenous shunt vasomotor status (12). Thus, our results only indicate that ketamine and propofol have a markedly different effect on arteriovenous shunts. Skin-temperature gradients, however, cannot be considered as an index of systemic vasomotor status. Furthermore, we did not directly measure extremity perfusion or core-to-peripheral flow of heat. More importantly, induction with propofol was our only reference treatment. This is important because propofol apparently produces more systemic vasodilation (including venodilation) than other anesthetics. It thus remains possible that well-preserved core temperature was as much a result of propofol-induced dilation as preserved vasoconstriction with ketamine. This possibility is consistent with our previous observation that anesthetic induction with propofol aggravates redistribution hypothermia compared with induction with inhaled sevoflurane (8).

Ketamine increases cardiac output (23,24). Shitara et al. (25) have demonstrated that dobutamine infusion aggravates intraoperative hypothermia after induction of anesthesia. The mechanism, apparently, is an increase in cardiac output that in turn augments convective transfer of heat from core to peripheral tissues. Thus, heat constraint by ketamine-induced vasoconstriction may, to some extent, counter heat transfer augmented by the increased cardiac output by ketamine. The net effect, in our patients, was to reduce the overall magnitude of redistribution hypothermia.

In conclusion, arteriovenous shunt tone was well maintained after anesthetic induction with ketamine, but decreased after induction with propofol. As a result, core temperature during the first hour of anesthesia was far better maintained after induction of anesthesia with ketamine than propofol. These data suggest that maintaining vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia.


   Acknowledgments
 
Supported, in part, by National Institutes of Health Grant GM 58273, the Joseph Drown Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund.

Mallinckrodt Anesthesiology Products, Inc. (St. Louis, MO) loaned the thermometers used in this study.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication May 22, 2001.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press