Marc Schroeder

Heat flow and distribution during induction of general anesthesia

Background Core hypothermia after induction of general anesthesia results from an internal core‐to‐peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution. Methods Six minimally clothed male volunteers in an [nearly equal] 22 degrees Celsius environment were evaluated for 2.5 control hours before induction of general anesthesia and for 3 subsequent hours. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, 10 skin temperatures, and “deep” foot temperature. To separate the effects of redistribution and net heat loss, we multiplied the change in overall heat balance by body weight and the specific heat of humans. The resulting change in mean body temperature was subtracted from the change in distal esophageal (core) temperature, leaving the core hypothermia specifically resulting from redistribution. Results Core temperature was nearly constant during the control period but decreased 1.6 plus/minus 0.3 degrees Celsius in the first hour of anesthesia. Redistribution contributed 81% to this initial decrease and required transfer of 46 kcal from the trunk to the extremities. During the subsequent 2 h of anesthesia, core temperature decreased an additional 1.1 plus/minus 0.3 degrees Celsius, with redistribution contributing only 43%. Thus, only 17 kcal was redistributed during the second and third hours of anesthesia. Redistribution therefore contributed 65% to the entire 2.8 plus/minus 0.5 degrees Celsius decrease in core temperature during the 3 h of anesthesia. Proximal extremity heat content decreased slightly after induction of anesthesia, but distal heat content increased markedly. The distal extremities thus contributed most to core cooling. Although the arms constituted only a fifth of extremity mass, redistribution increased arm heat content nearly as much as leg heat content. Distal extremity heat content increased [nearly equal] 40 kcal during the first hour of anesthesia and remained elevated for the duration of the study. Conclusions The arms and legs are both important components of the peripheral thermal compartment, but distal segments contribute most. Core hypothermia during the first hour after induction resulted largely from redistribution of body heat, and redistribution remained the major cause even after 3 h of anesthesia.

Heat Flow and Distribution during Epidural Anesthesia

Background Core hypothermia after induction of epidural anesthesia results from both an internal core‐to‐peripheral redistribution of body heat and a net loss of heat to the environment. However, the relative contributions of each mechanism remain unknown. The authors thus evaluated regional body heat content and the extent to which core hypothermia after induction of anesthesia resulted from altered heat balance and internal heat redistribution.

Propofol blood concentration and the bispectral index predict suppression of learning during propofol/epidural anesthesia in volunteers

Propofol is often used for sedation during regional anesthesia.We tested the hypothesis that propofol blood concentration, the Bispectral Index and the 95% spectral edge frequency predict suppression of learning during propofol/epidural anesthesia in volunteers. In addition, we tested the hypothesis that the Bispectral Index is linearly related to propofol blood concentration. Fourteen healthy, male volunteers were studied on three randomly ordered days: no propofol, target propofol blood concentration 1 micro gram/mL, and target propofol blood concentration 2 micro gram/mL. Each day, epidural anesthesia (approximate equals T11 level) was induced using 2% 2-chloroprocaine. Propofol was infused by a computer-controlled pump, and propofol concentration measured in central venous blood. We administered a Trivial Pursuit Registered Trademark-type question task on all 3 days. The electroen-cephalogram was monitored continuously (Fp1, Fp2; reference, Cz; ground, mastoid). Propofol caused concentration-related impairment of learning. The propofol blood concentration suppressing learning by 50% was 0.66 +/- 0.1 micro gram/mL. The Bispectral Index value when learning was suppressed by 50% was 91 +/- 1. In contrast, the 95% spectral edge frequency did not correlate well with learning. The Bispectral Index decreased linearly as propofol blood concentration increased (Bispectral Index = -7.4 centered dot [propofol] + 90; r2 = 0.47, n = 278). There was no significant correlation between the 95% spectral edge frequency and propofol concentration. In order to suppress learning, propofol blood concentrations reported to produce amnesia may be targeted. Alternatively, the Bispectral Index may be used to predict anesthetic effect during propofol sedation. (Anesth Analg 1995;81:1269-74)

Thermoregulatory thresholds during epidural and spinal anesthesia.

BackgroundThere are significant physiologic differences between spinal and epidural anesthesia. Consequently, these two types of regional anesthesia may influence thermoregulatory processing differently. Accordingly, in volunteers and in patients, we tested the null hypothesis that the core-temperature thresholds triggering thermoregulatory sweating, vasoconstriction, and shivering are similar during epidural and spinal anesthesia. MethodsSix male volunteers participated on three consecutive study days: epidural or spinal anesthesia were randomly assigned on the 1st and 3rd days (± T10 level); no anesthesia was given on the 2nd day. On each day, the volunteers were initially warmed until they started to sweat, and subsequently cooled by central venous infusion of cold fluid until they shivered. Mean skin temperature was kept constant near 36°C throughout each study. The tympanic membrane temperatures triggering a sweating rate of 40 g · m−2 · h−1, a finger flow less than 0.1 ml/min, and a marked and sustained increase in oxygen consumption (± 30%) were considered the thermoregulatory thresholds for sweating, vasoconstriction, and shivering, respectively. Twenty-one patients were randomly assigned to receive epidural (n = 10) or spinal (n = 11) anesthesia for knee and calf surgery (± T10 level). As in the volunteers, the shivering threshold was defined as the tympanic membrane temperature triggering a sustained increase in oxygen consumption. ResultsThe thresholds and ranges were similar during epidural and spinal anesthesia in the volunteers. However, the sweating-to-vasoconstriction (interthreshold) range, the vasoconstriction-to-shivering range, and the sweating-to-shivering range all were significantly increased by regional anesthesia. The shivering thresholds in patients assigned to epidural and spinal anesthesia were virtually identical. ConclusionsComparable sweating, vasoconstriction, and shivering thresholds during epidural and spinal anesthesia suggest that thermoregulatory processing is similar during each type of regional anesthesia. However, thermoregulatory control was impaired during regional anesthesia, as indicated by the significantly enlarged interthreshold and sweating-to-shivering ranges.

optimal Duration and Temperature of Prewarming

Background Core hypothermia developing immediately after induction of anesthesia results largely from an internal core‐to‐peripheral redistribution of body heat. Although difficult to treat, redistribution can be prevented by prewarming. The benefits of prewarming may be limited by sweating, thermal discomfort, and efficacy of the warming device. Accordingly, the optimal heater temperature and minimum warming duration likely to substantially reduce redistribution hypothermia were evaluated. Methods Sweating, thermal comfort, and extremity heat content were evaluated in seven volunteers. They participated on two study days, each consisting of a 2‐h control period followed by 2 h of forced‐air warming with the heater set on “medium” ([nearly equal] 40 degrees Celsius) or “high” ([nearly equal] 43 degrees Celsius). Arm and leg tissue heat contents were determined from 19 intramuscular needle thermocouples, ten skin temperatures, and “deep” foot temperature. Results Half the volunteers started sweating during the second hour of warming. None of the volunteers felt uncomfortably warm during the first hour of heating, but many subsequently did. With the heater set on “high,” arm and leg heat content increased 69 kcal during the first 30 min of warming and 136 kcal during the first hour of warming, representing 38% and 75%, respectively, of the values observed after 2 h of warming. The increase was only slightly less when the heater was set to “medium.” Conclusions Neither sweating nor thermal discomfort limited heat transfer during the first hour of warming. Thirty minutes of forced‐air warming increased peripheral tissue heat content by more than the amount normally redistributed during the first hour of anesthesia. The large increase in arm and leg heat content during prewarming thus explains the observed efficacy of prewarming.

Thermoregulatory response thresholds during spinal anesthesia

Reportedly, during spinal anesthesia, the shivering threshold is reduced approximately 1 degree C but the vasoconstriction threshold remains normal. Such divergence between the shivering and vasoconstriction thresholds is an unusual pattern of thermoregulatory impairment and suggests that the mechanisms of impairment during regional anesthesia may be especially complex. Accordingly, we sought to define the pattern of thermoregulatory impairment during spinal anesthesia by measuring response thresholds. Seven healthy women volunteered to participate on two study days. On one day, we evaluated thermoregulatory responses to hypothermia and hyperthermia during spinal anesthesia; on the other day, responses were evaluated without anesthesia. Upper body skin temperature was kept constant throughout the study. The volunteers were warmed via the lower body and cooled by central venous infusion of cold fluid. The core temperatures triggering a sweating rate of 40 g.m-2 x h-1, a finger flow of 0.1 mL/min, and a marked and sustained increase in oxygen consumption were considered the thermoregulatory thresholds for sweating, vasoconstriction, and shivering, respectively. Spinal anesthesia significantly decreased the thresholds for vasoconstriction and shivering, and the decrease in each was approximately 0.5 degree C. The range of temperatures not triggering thermoregulatory responses (those between sweating and vasoconstriction) was 0.9 +/- 0.6 degree C during spinal anesthesia. The synchronous decrease in the shivering and vasoconstriction thresholds during spinal anesthesia is consistent with thermoregulatory impairment resulting from altered afferent thermal input.

Naloxone, Meperidine, and Shivering

BackgroundMeperidine, which binds both μ and k opioid receptors, is reportedly more effective in treating shivering than are equianalgesic doses of morphine (a nearly pure μ-receptor agonist). Furthermore, butorphanol, a k-receptor agonist/antagonist, treats shivering better than does fentanyl, which mostly binds μ receptors. These data Indicate that much of meperidines special antishivering activity may be mediated by its k activity. Accordingly, the authors tested the hypothesis that the antishivering activity of meperidine will be minimally Impaired by low-dose naloxone (blocking most μ-receptors), but largely prevented by high-dose naloxone (blocking all μ and most k receptors). MethodsTwelve volunteers each participated on 2 days. On both days, shivering was induced by central venous Infusion of cold fluid. Twenty minutes later, six volunteers were given a placebo infusion of saline on one day, or an Infusion of 0.5 μg ± kg−1 ± min−1 naloxone hydrochloride (“low-dose,” designed to block μ receptors) on the other. The second group of six volunteers was given a saline bolus and infusion on one day, or a bolus of 11.5 μg/kg naloxone hydrochloride followed by an infusion of naloxone at 5 μg ± kg−1 ± min−1 (“high-dose,” designed to block both μ and k receptors) on the other day. The infusions were continued for the duration of the study. The order of the treatment days (saline vs. naloxone) was randomly assigned, and the study was double blinded. Fifteen minutes after the test infusion was started, all 12 volunteers were given an intravenous bolus of 1 mg/kg meperidine hydrochloride. Pupillary diameter and light reflex amplitude were used to quantify opioid-receptor agonist activity; shivering intensity was evaluated using oxygen consumption. ResultsAdministration of naloxone alone did not alter oxygen consumption, pupil size, or the pupillary light reflex. No pupillary constriction was detected in either group when naloxone and meperidine were combined; in contrast, meperidine alone decreased pupil size and amplitude of the light reflex 30%. The meperidine bolus decreased oxygen consumption nearly to control values when the volunteers were given saline placebo. Combined administration of meperidine and low-dose naloxone also significantly reduced oxygen consumption, but the reduction and the duration of the reduction was less than during saline. When the volunteers were given high-dose naloxone, meperidine only slightly reduced oxygen consumption, and the values rapidly returned to premeperidine levels. ConclusionsThese data Indicate that the antishivering property of meperidine is not fully mediated by μ-receptors. Although meperidine has well-known nonopioid actions, stimulation of k receptors seems a likely alternative explanation for much of the drugs antishivering action.

Centrally and locally mediated thermoregulatory responses alter subcutaneous oxygen tension

Mild perianesthetic hypothermia decreases resistance to infections. Decreased resistance likely results in part from direct immune inhibition. However, decreased tissue oxygen partial pressure also decreases resistance to infection by impairing oxidative killing by neutrophils and collagen deposition. Thermoregulatory vasoconstriction decreases skin blood flow and may also decrease subcutaneous tissue oxygen tension. Accordingly, we determined the influence of centrally and locally mediated thermoregulatory vasomotion on subcutaneous oxygen tension. We also compared subcutaneous oxygen tension to other potential markers of tissue perfusion: laser Doppler flowmetry and transcutaneous oxygen tension. Arterial oxygen tension was maintained near 325 mm Hg in five volunteers. Control subcutaneous oxygen tension values were recorded after 1 hour of euthermia (no sweating or vasoconstriction). Volunteers were then cooled with a circulating‐water mattress positioned under the trunk and legs. After 1.5 hours of cooling sufficient to produce shivering, the right upper arm was covered for 1 hour with a small circulating water blanket set to 40° C while systemic cooling continued. The volunteers were then systematically warmed to produce sweating, and the right arm was locally cooled. There was no correlation among laser Doppler flowmetry, transcutaneous oxygen tension, and subcutaneous oxygen tension. Systemic cooling significantly decreased subcutaneous oxygen tension, but subcutaneous oxygen tension in the right arm returned to control values during local heating. Systemic warming significantly increased subcutaneous oxygen tension, and 1 hour of local cooling failed to fully reverse the increase. These data indicate that thermoregulatory vasoconstriction significantly decreases tissue oxygen availability. Decreased subcutaneous oxygen tension may be one mechanism by which mild perianesthetic hypothermia facilitates development of surgical wound infections.

Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium.

Background The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action. Methods Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0°C, 35.0–35.9°C, 36.0–36.9°C, and ≥ 37.0°C. With temperature stabilized, vecuronium was infused at 5 &mgr;g · kg−1 · min−1 until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 &mgr;g · kg−1 · min−1, was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics. Results Decreasing core temperature over 38.0–34.0°C decreases the plasma clearance of vecuronium (11.3% per °C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min−1 per °C), and increases the slope of the concentration–response relationship (0.43 per °C). Conclusions Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature.

Leg Heat Content Continues to Decrease during the Core Temperature Plateau in Humans Anesthetized with Isoflurane

Background:Sufficient hypothermia during anesthesia provokes thermoregulatory responses, but the clinical significance of these responses remains unknown. Nonshivering thermogenesis does not increase metabolic heat production in anesthetized adults. Vasoconstriction reduces cutaneous heat loss, but the initial decrease appears insufficient to cause a thermal steady state (heat production equaling heat loss). Accordingly, the authors tested the hypotheses that: 1) thermoregulatory vasoconstriction prevents further core hypothermia; and 2) the resulting stable core temperature is not a thermal steady state, but, instead, is accompanied for several hours by a continued reduction in body heat content. Methods:Six healthy volunteers were anesthetized with isoflurane (0.8%) and paralyzed with vecuronium. Core hypothermia was induced by fan cooling, and continued for 3 h after vasoconstriction in the legs was detected. Leg heat content was calculated from six needle thermocouples and skin temperature, by integrating the resulting parabolic regression over volume Results:Core temperature decreased 1.0 ± 0.2°C in the 1 h before vasoconstriction, but only 0.4 ± 0.3° C in the subsequent 3 h. This temperature decrease, evenly distributed throughout the body, would reduce leg heat content 10 kcal. However, measured leg heat content decreased 49 ± 18 kcal in the 3 h after vasoconstriction Conclusions:These data thus indicate that thermoregulatory vasoconstriction produces a clinically important reduction in the rate of core cooling. This core temperature plateau resulted, at least in part, from sequestration of metabolic heat to the core which allowed core temperature to remain nearly constant, despite a continually decreasing body heat content.