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Biomedical subjects

M Schroeder

Publications and source records attributed to M Schroeder.

At least 91 records · Page 5Linked to original sources
PubMed1994

From ill-defined extracts to the immunomodulatory lectin: will there be a reason for oncological application of mistletoe?

There is an obvious discrepancy between the popularity of mistletoe extracts and their classification as a non-conventional treatment modality with unproven efficacy in oncology. The commercial preparations suffer from several major drawbacks: lack of precise declarations for the molecular characteristics and the concentrations of diverse extract constituents; the composition of extracts can even be influenced by the different methods of preparation, the time of harvest, and the type of host tree; lack of experimentally substantiated instructions for the dose of supposedly effective substance(s) and the schedule of applications to clinically trigger an undisputably documented antitumoral activity; lack of thorough clinical studies according to the generally accepted criteria as the measure for responsible recommendations. To provide the indispensable set of data for a rational decision, the immunomodulatory galactoside-specific lectin was biochemically characterized and its antitumoral/antimetastatic activity was documented in three murine tumor model systems, occurring within a narrow dose range. Biweekly treatment with s.c. injections of a lectin dose of 1 ng/kg caused no notable harmful side-effects in patients, who showed modulation of selected immune parameters. In a group of 23 patients with advanced cancer no at least partial remission was seen. In principle, enhancement of factors like cytokine availability or NK-cell activity is not necessarily linked to therapeutic benefit. Factors such as growth promotion of certain tumor cell lines by cytokines, occurrence of respective insensitivity in advanced stages or varying levels of target sensitivity to cell-mediated cytotoxicity with significant interindividual differences deserve attention. Each tumor class has to be considered separately for its responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1994

Epidural anesthesia impairs both central and peripheral thermoregulatory control during general anesthesia.

BACKGROUND: The authors tested the hypotheses that: (1) the vasoconstriction threshold during combined epidural/general anesthesia is less than that during general anesthesia alone; and (2) after vasoconstriction, core cooling rates during combined epidural/general anesthesia are greater than those during general anesthesia alone. Vasoconstriction thresholds and heat balance were evaluated under controlled circumstances in volunteers, whereas the clinical importance of intraoperative thermoregulatory vasoconstriction was evaluated in patients. METHODS: Five volunteers were each evaluated twice. On one of the randomly ordered days, epidural anesthesia (approximately T9 dermatomal level) was induced and maintained with 2-chloroprocaine. On both study days, general anesthesia was induced and maintained with isoflurane (0.7% end-tidal concentration), and core hypothermia was induced by surface cooling and continued for at least 1 h after fingertip vasoconstriction was observed. Patients undergoing colorectal surgery were randomly assigned to combined epidural/enflurane anesthesia (n = 13) or enflurane alone (n = 13). In appropriate patients, epidural anesthesia was maintained by an infusion of bupivacaine. The core temperature that triggered fingertip vasoconstriction identified the threshold. RESULTS: In the volunteers, the vasoconstriction threshold was 36.0 +/- 0.2 degrees C during isoflurane anesthesia alone, but significantly less, 35.1 +/- 0.7 degrees C, during combined epidural/isoflurane anesthesia. Cutaneous heat loss and the rates of core cooling were similar 30 min before vasoconstriction with and without epidural anesthesia. In the 30 min after vasoconstriction, heat loss decreased 33 +/- 13 W when the volunteers were given isoflurane alone, but only 8 +/- 16 W during combined epidural/isoflurane anesthesia. Similarly, the core cooling rates in the 30 min after vasoconstriction were significantly greater during combined epidural/isoflurane anesthesia (0.8 +/- 0.2 degrees C/h) than during isoflurane alone (0.2 +/- 0.1 degrees C/h). In the patients, end-tidal enflurane concentrations were slightly, but significantly, less in the patients given combined epidural/enflurane anesthesia (0.6 +/- 0.2% vs. 0.8 +/- 0.2%). Nonetheless, the vasoconstriction threshold was 34.5 +/- 0.6 degrees C in the epidural/enflurane group, which was significantly less than that in the other patients, 35.6 +/- 0.8 degrees C. When the study ended after 3 h of anesthesia, patients given combined epidural/enflurane anesthesia were 1.2 degrees C more hypothermic than those given general anesthesia alone. The rate of core cooling during the last hour of the study was 0.4 +/- 0.2 degrees C/h during combined epidural/enflurane anesthesia, but only 0.1 +/- 0.3 degrees C/h during enflurane alone. CONCLUSIONS: These data indicate that epidural anesthesia reduces the vasoconstriction threshold during general anesthesia. Furthermore, the markedly reduced rate of core cooling during general anesthesia alone illustrates the importance of leg vasoconstriction in maintaining core temperature.

Adolescent↗
PubMed1994

Thermoregulatory thresholds during epidural and spinal anesthesia.

BACKGROUND: There 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. METHODS: Six male volunteers participated on three consecutive study days: epidural or spinal anesthesia were randomly assigned on the 1st and 3rd days (approximately 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 degrees 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 (approximately 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 (approximately T10 level). As in the volunteers, the shivering threshold was defined as the tympanic membrane temperature triggering a sustained increase in oxygen consumption. RESULTS: The thresholds and ranges were similar during epidural and spinal anesthesia in the volunteers. However, the sweating-to-vasoconstriction (inter-threshold) 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. CONCLUSIONS: Comparable 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 inter-threshold and sweating-to-shivering ranges.

Adult↗
PubMed1994

Epidural anesthesia increases apparent leg temperature and decreases the shivering threshold.

BACKGROUND: Lower core temperatures than usual are required to trigger shivering during epidural and spinal anesthesia, but the etiology of this impairment remains unknown. In this investigation, we propose and test a specific mechanism by which a peripheral action of regional anesthesia might alter centrally mediated thermoregulatory responses. Conduction anesthesia blocks all thermal sensations; however, cold signals are disproportionately affected because at typical leg temperatures mostly cold receptors fire tonically. It thus seems likely that epidural and spinal anesthesia increase the leg temperature perceived by the thermoregulatory system. Because skin temperature reportedly contributes 5-20% to thermoregulatory control, increased apparent (as distinguished from actual) leg temperature would produce a complimentary decrease in the core temperature triggering thermoregulatory shivering. Accordingly, we tested the hypothesis that abnormal tolerance for hypothermia during epidural anesthesia coincides with an increase in apparent leg temperature. We defined apparent temperature as the leg-skin temperature required to induce a reduction in the shivering threshold comparable to that produced by epidural anesthesia. METHODS: Six women were studied on 4 randomly ordered days: (1) leg-skin temperature near 32 degrees C; (2) leg-skin temperature near 36 degrees C; (3) leg-skin temperature near 38 degrees C; and (4) epidural anesthesia without leg-warming (leg-skin temperature approximately 34 degrees C). At each designated leg temperature, core hypothermia sufficient to evoke shivering was induced by central venous infusion of cold fluid. Upper-body skin temperature was kept constant throughout. In each volunteer, linear regression was used to calculate the correlation between the shivering thresholds on the 3 non-epidural days and concurrent leg temperatures. The slope of these regression equations thus indicated the extent to which leg-warming increased thermoregulatory tolerance for core hypothermia, and was expressed as a percentage leg-skin and leg-tissue contribution to total thermal afferent input. The skin and tissue temperatures that would have been required to produce the observed shivering threshold during epidural anesthesia, the apparent temperatures, were then interpolated from the regression. RESULTS: There was a good linear relation between the shivering threshold and leg-skin temperature (r2 = 0.94 +/- 0.06). The contribution of leg-skin temperature to the shivering threshold was 11 +/- 3% of the total thermal input. Apparent leg-skin temperature during epidural anesthesia was 37.8 +/- 0.5 degrees C, which exceeded actual leg-skin temperature by approximately 4 degrees C. The contribution of leg-tissue temperature to the shivering threshold was 19 +/- 7% of the total. Apparent leg-tissue temperature during epidural anesthesia was 37.1 +/- 0.4 degrees C, which exceeded actual leg-skin temperature by approximately 2 degrees C. CONCLUSIONS: Because leg-skin contributed approximately 11% to the shivering threshold, it is unlikely that the entire skin surface contributes at much less than 20%. These data suggest that the shivering threshold during epidural anesthesia is reduced by a specific mechanism, namely that conduction block significantly increases apparent (as distinguished from actual) leg temperature.

Adult↗
PubMed1994

Propofol causes a dose-dependent decrease in the thermoregulatory threshold for vasoconstriction but has little effect on sweating.

BACKGROUND: Volatile anesthetics increase the core temperature required to trigger sweating and decrease the core temperature required to trigger vasoconstriction. However, little is known about the effects of intravenous anesthetics on thermoregulation. We therefore tested the hypothesis that propofol increases the sweating threshold and decreases the vasoconstriction threshold, thereby increasing the inter-threshold range (core temperatures not triggering autonomic thermoregulatory responses). The study was conducted using a new model in which thermal manipulations were restricted to insensate skin, and sensate skin temperature was controlled. METHODS: Six healthy, male volunteers were studied on 3 randomly ordered days: no propofol, target propofol blood concentration 2 micrograms/ml, and target blood propofol concentration 4 micrograms/ml. Each day, epidural anesthesia (approximately T11 level) was induced, using 2% 2-chloroprocaine (one volunteer received bupivacaine). Thermal manipulations were confined to the legs, and we attempted to maintain upper-body (sensate) skin temperature constant. Propofol was infused by a computer-controlled infusion pump. Volunteers were heated until sweating was observed, then cooled until fingertip vasoconstriction was observed. The sweating threshold was defined as the tympanic membrane temperature triggering sustained evaporative heat loss > 40 g.m-2.h-1. Similarly, the vasoconstriction threshold was defined as the tympanic membrane temperature triggering a sustained reduction in fingertip blood flow to < 0.25 ml/min. Central venous blood was assayed for propofol blood concentration. RESULTS: Increasing propofol concentration produced a linear decrease the vasoconstriction threshold (slope = -0.53 +/- 0.34 degrees C.microgram-1.ml-1; R2 = 0.98 +/- 0.04 [mean +/- SD]), but had little effect on the sweating threshold. The inter-threshold range was 0.51 +/- 0.46 degrees C during epidural anesthesia alone, and increased significantly, by 0.49 +/- 0.31 degrees C.microgram-1.ml-1 during propofol administration. CONCLUSIONS: Like volatile anesthetics, propofol reduces the vasoconstriction threshold and increases the inter-threshold range. However, propofol differs in leaving the sweating threshold unchanged.

Adult↗
PubMed1994

A small GTP-binding protein from Arabidopsis thaliana functionally complements the yeast YPT6 null mutant.

A clone designated A.t.RAB6 encoding a small GTP-binding protein was isolated from a cDNA library of Arabidopsis thaliana leaf tissue. The predicted amino acid sequence was highly homologous to the mammalian and yeast counterparts, H.Rab6 and Ryh1/Ypt6, respectively. Lesser homology was found between the predicted Arabidopsis protein sequence and two small GTP-binding proteins isolated from plant species (44% homology to Zea mays Ypt1 and 43% homology to Nicotiana tabacum Rab5). Conserved stretches in the deduced amino acid sequence of A.t.Rab6 include four regions involved in GTP-binding, an effector region, and C-terminal cysteine residues required for prenylation and subsequent membrane attachment. Northern blot analysis demonstrated that A.t.Rab6 mRNA was expressed in root, leaf, stem, and flower tissues from A. thaliana with the highest levels present in roots. Escherichia coli produced histidine-tagged A.t.Rab6 protein-bound GTP, whereas a mutation in one of the guanine nucleotide-binding sites (asparagine122 to isoleucine) rendered it incapable of binding GTP. Functionally, the A.t.RAB6 gene was able to complement the temperature-sensitive phenotype of the YPT6 null mutant in yeast. The isolation of this gene will aid in the dissection of the machinery involved in soluble protein sorting at the trans-Golgi network of plants.

Amino Acid Sequence↗
PubMed1994

Treatment of mild immersion hypothermia by direct body-to-body contact.

Body-to-body contact is often recommended for rewarming mildly hypothermic victims in the field. This procedure involves a euthermic individual donating heat to the recipient by direct contact in an insulated bag. However, this technique has not been critically evaluated and may not be beneficial because there is limited direct contact between recipient and donor, peripheral vasoconstriction may impair heat transfer to the core, skin warming may blunt the recipient's shivering response, and cold stress to the donor may be excessive. The present study was designed to evaluate whether donation of heat by a donor would be sufficient to enhance rewarming of a hypothermic subject (recipient). Six pairs of recipients (5 men, 1 woman) and donors (2 men, 4 women) participated in the study. Esophageal and skin temperatures, cutaneous heat flux, and oxygen consumption were measured. Recipients were immersed in 8 degrees C water until esophageal temperature decreased to a mean of 34.6 +/- 0.7 degrees C (SD). They then were rewarmed by one of three methods: rewarming by the endogenous heat generated by shivering only (SH), body-to-body rewarming (BB), or rewarming with a constant-heat source manikin (MAN). Mean afterdrop for the three conditions was 0.54 +/- 0.2, 0.54 +/- 0.2, and 0.57 +/- 0.2 degrees C for SH, BB, and MAN, respectively (NS), and the rate of rewarming was 2.40 +/- 0.8, 2.46 +/- 1.1 and 2.55 +/- 0.9 degrees C/h for SH, BB, and MAN, respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Treatment of mild immersion hypothermia by forced-air warming.

Forced-air warming is used for prevention or reversal of hypothermia in surgical patients. In the present study, the efficacy of this system for treatment of immersion hypothermia was evaluated. Six men and two women were twice immersed in 8 degrees C water until hypothermic. They were then rewarmed by either: 1) shivering-only inside a sleeping bag; or 2) forced-air warming. Esophageal and skin temperature, cutaneous heat flux and metabolism were measured. Afterdrop (+/- SD) during forced-air warming (0.43 +/- 0.26 degrees C) was approximately 30% less than during shivering (0.61 +/- 0.26 degrees C) (p < 0.001). Rewarming rate during forced-air warming (3.26 +/- 1.8 degrees C.h-1) was not significantly different from shivering (3.02 +/- 1.2 degrees C.h-1). Skin temperature was higher during forced-air warming by 3.7 degrees C early and 4.5 degrees C after 35 min of warming. Heat production increased by 77 W over the initial 20 min of shivering, and subsequently declined, compared to an immediate decrease with forced-air warming. During shivering heat flux ranged from 30 W early in rewarming, to 50 W after 35 min, compared to -237 W and -163 W respectively, for forced-air warming. Forced-air warming attenuated afterdrop and the metabolic stress of shivering while maintaining an average rate of rewarming comparable to shivering. Forced-air warming is a safe, simple, noninvasive treatment and could be used effectively in an emergency medical facility, and possibly in some rescue/emergency vehicles or marine vessels.

Adult↗
PubMed1993

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 degrees C in the 1 h before vasoconstriction, but only 0.4 +/- 0.3 degrees 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.

Anesthesia, Inhalation↗
PubMed1993

The pupillary light reflex. Effects of anesthetics and hyperthermia.

BACKGROUND: The pupillary light reflex often is evaluated in the perianesthetic period to assess drug effects and brainstem function. Mild hypothermia alone or combined with isoflurane does not impair pupillary responses. Although perioperative hyperthermia is less common than hypothermia, abnormal increases in core temperature remain an important thermal disturbance. Accordingly, the pupillary effects of hyperthermia alone and hyperthermia combined with isoflurane and enflurane were evaluated. Additionally, the effects of nitrous oxide on pupillary responses were determined. METHODS: The pupillary light reflex was evaluated in 31 non-surgical volunteers participating in concurrent thermoregulatory studies. Pupillary reflexes were quantified using a portable infrared pupillometer during (1) hyperthermia alone (n = 9), (2) hyperthermia with 0.8% and 1.2% end-tidal isoflurane (n = 8), (3) hyperthermia with 1.7% end-tidal enflurane (n = 5), and (4) inhalation of 60% N2O (n = 9). RESULTS: Mild hyperthermia alone (core temperature 38.5 +/- 0.3 degrees C) produced no clinically significant change in the pupillary light reflex. Pupillary responses were decreased markedly with 0.8% isoflurane, 1.2% isoflurane, and 1.7% enflurane when the volunteers were normothermic. Mild hyperthermia combined with isoflurane or enflurane dilated the pupil and increased the amplitude of the light reflex. Sixty-percent nitrous oxide decreased the pupillary reflex only 26 +/- 4%. CONCLUSIONS: Anesthetic-induced inhibition of the pupillary response to light is reversed partially by core hyperthermia. In contrast to enflurane and isoflurane, 60% N2O has little effect on the pupil.

Adult↗
PubMed1993

Pupillary assessment of sensory block level during combined epidural/general anesthesia.

BACKGROUND: Currently, no reliable method exists to determine the level of sensory block during combined epidural/general anesthesia. However, the pupil dilates markedly in response to noxious electrical stimulation during general anesthesia. Presumably, sensory block produced by epidural anesthesia decreases or obliterates this autonomic response. Accordingly, we tested the hypothesis that pupillary dilation in response to noxious stimulation would predict the level of sensory block achieved during combined epidural/general anesthesia. METHODS: We studied eight volunteers and ten patients during combined epidural/general anesthesia. The volunteers were given an epidural infusion of 2% 2-chloroprocaine while general anesthesia was maintained with 0.8% isoflurane and 60% N2O. In the patients, an epidural infusion of 0.25% bupivacaine was combined with isoflurane and vecuronium. Noxious electrical stimulation was administered to dermatomal segments in a caudal-to-rostral progression. A twofold increase in pupil size following electrical stimulation was considered the predicted block level in volunteers. In patients, an increase in pupil size exceeding 50% was considered the predicted level. After general anesthesia was discontinued, observers blinded to the pupillary measurements independently determined the actual epidural block level using pain in response to a pinprick as the criterion. RESULTS: The level predicted by pupillary responses was within two dermatomal segments of the actual level in all the volunteers. The predicted and actual block levels were within two segments in eight of the ten patients and never differed by more than four dermatomes. CONCLUSIONS: We conclude that dilation of the pupil in response to electrical stimulation is an accurate test of the sensory block level during combined epidural/general anesthesia.

Adult↗
PubMed1993

The effects of preinduction warming on temperature and blood pressure during propofol/nitrous oxide anesthesia.

BACKGROUND: Core temperature decreases rapidly after induction of anesthesia, largely because heat is redistributed to peripheral tissues. The hypothesis that warming peripheral tissues before induction of general anesthesia (prewarming) minimizes hypothermia was tested. Because circulating blood volume may be greater during exposure to heat compared to cold, the hypothesis that prewarming decreases the amount of hypotension associated with induction of anesthesia was tested also. Finally, the hypothesis that the difference between direct radial arterial blood pressure and blood pressure measured oscillometrically at the brachial artery depends on thermoregulatory and anesthetic conditions was tested. METHODS: Each of six volunteers underwent general anesthesia (propofol and nitrous oxide) twice on the same day. Each anesthetic lasted 1 h and was preceded by either 2 h of active warming with forced air or 2 h of passive cooling by exposure to a typical operating room environment. After induction of each anesthetic, volunteers were fully exposed to the ambient environment. Volunteers recovered for 2 h before starting the second preinduction treatment. RESULTS: Initial tympanic membrane temperatures were similar before each preinduction treatment: 36.7 +/- 0.4 degrees C when volunteers were not warmed and 36.7 +/- 0.6 degrees C when volunteers were warmed. Tympanic membrane temperature did not change during the preinduction period without warming but increased slightly (delta T = 0.4 +/- 0.2 degree C) during warming. After induction of anesthesia, core temperatures decreased to 36.1 +/- 0.4 degree C over 1 h when volunteers were prewarmed but decreased to 34.9 +/- 0.4 degrees C when they were not. Radial arterial systolic, diastolic, and mean blood pressures were lower before induction of anesthesia when volunteers were warmed compared to when no warming was given. Oscillometric diastolic and mean pressures also were lower during prewarming; however, oscillometric systolic pressure did not differ significantly. Prewarming did not result in less hypotension after induction. Without warming, the difference (radial arterial minus oscillometric) in systolic blood pressure measurements was approximately 17 mmHg. Warming was associated with a reversal of the systolic pressure difference to approximately -6 mmHg. After induction of anesthesia, the differences in systolic and mean pressure measurements became more negative with respect to the preinduction values regardless of preinduction warming treatment. CONCLUSIONS: These data confirm our hypothesis that redistribution hypothermia can be minimized by preinduction warming of peripheral tissues. Prewarming decreases blood pressure but does not prevent subsequent hypotension after induction. The difference between radical arterial blood pressure and oscillometric blood pressure depends on thermoregulatory vasomotor changes but also may be influenced by vasodilation associated with administration of propofol and nitrous oxide.

Adult↗
PubMed1993

Naloxone, meperidine, and shivering.

BACKGROUND: Meperidine, which binds both mu and kappa opioid receptors, is reportedly more effective in treating shivering than are equianalgesic doses of morphine (a nearly pure mu-receptor agonist). Furthermore, butorphanol, a kappa-receptor agonist/antagonist, treats shivering better than does fentanyl, which mostly binds mu receptors. These data indicate that much of meperidine's special antishivering activity may be mediated by its kappa activity. Accordingly, the authors tested the hypothesis that the antishivering activity of meperidine will be minimally impaired by low-dose naloxone (blocking most mu-receptors), but largely prevented by high-dose naloxone (blocking all mu and most kappa receptors). METHODS: Twelve 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 microgram.kg-1.min-1 naloxone hydrochloride ("low-dose," designed to block mu 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 micrograms/kg naloxone hydrochloride followed by an infusion of naloxone at 5 micrograms.kg-1.min-1 ("high-dose," designed to block both mu and kappa 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. RESULTS: Administration 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. CONCLUSIONS: These data indicate that the antishivering property of meperidine is not fully mediated by mu-receptors. Although meperidine has well-known nonopioid actions, stimulation of kappa receptors seems a likely alternative explanation for much of the drug's antishivering action.

Adult↗
PubMed1993

Thermoregulatory responses to hyperthermia during isoflurane anesthesia in humans.

The authors tested the hypotheses that isoflurane anesthesia increases the threshold for sweating but minimally decreases the gain (sensitivity) or maximum intensity of this response and that thermoregulatory responses to hyperthermia are similar in anesthetized men and women. Sweating in response to core hyperthermia was studied in five men and five women during 0, 0.8, and 1.2% end-tidal isoflurane anesthesia. Thigh sweating was quantified by measuring gas flow, relative humidity, and temperature passing over a known surface area. The distal esophageal temperature triggering sweating was considered the sweating threshold, and gain was defined as the core temperature increment required to increase sweating rate from 25 to 75% of maximum observed intensity. The sweating threshold increased linearly with isoflurane concentration from 36.6 +/- 0.1 to 38.1 +/- 0.1 degrees C in the men and from 37.1 +/- 0.3 to 38.3 +/- 0.2 degrees C in the women. The thresholds were significantly higher in women than in men. Gain and maximum sweating intensities were similar at each anesthetic concentration and in men and women. These data indicate that isoflurane anesthesia significantly increases the threshold triggering thermoregulatory sweating but that gain and maximum sweating rate are relatively well preserved.

Anesthesia↗
PubMed1993

Heat loss in humans covered with cotton hospital blankets.

We evaluated mean skin temperature, cutaneous heat loss, and perceived warmth in six volunteers covered with one or three cotton hospital blankets, warmed or unwarmed. Mean skin temperatures were significantly higher during each treatment than during the control periods preceding each blanket application. Total cutaneous heat loss during the control period was 81 +/- 11 watts. Covering the volunteers with a single warmed or unwarmed blanket for 60 min reduced heat loss 33% +/- 5%; when they were covered with three warmed or unwarmed blankets, heat loss was reduced an additional 18% +/- 6%. Warmed blankets reduced heat loss 9-16 watts more than unwarmed ones, but the benefit dissipated in approximately 10 min. The volunteers' perception of warmth was similar when they were covered with three warmed or unwarmed blankets; it also was similar when they were covered with a single warmed or unwarmed blanket. These data indicate that increasing the number of covering blankets from one to three decreases heat loss only slightly. Similarly, warming the blankets is relatively ineffective and the benefit short-lived. The reduction in heat loss, even by three warmed blankets replaced at 10-min intervals, was small compared to that provided by available active warming systems.

Adult↗
PubMed1993

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.

Adult↗
PubMed1993

The direction dependence of thermoregulatory vasoconstriction during isoflurane/epidural anesthesia in humans.

We tested the hypothesis that once thermoregulatory vasoconstriction is triggered at a given core temperature during isoflurane anesthesia, redilation starts at a substantially higher core temperature. To avoid direct perception of cutaneous cooling and warming, we used epidural anesthesia and limited our thermal manipulations to the blocked area. Seven volunteers were anesthetized with isoflurane/epidural anesthesia (approximately T9 dermatomal level). Core hypothermia was induced by surface cooling restricted to the legs. Cooling was continued until fingertip blood flow suddenly decreased (vasoconstriction threshold). The core was then rewarmed by heating the legs until fingertip flow suddenly increased toward initial values (redilation threshold). The difference between the two thresholds defined the direction-dependent hysteresis. Vasoconstriction occurred at 35.2 +/- 0.6 degrees C and vasodilation at 36.2 +/- 0.5 degrees C (P < 0.01, paired t-test); consequently, the hysteresis was 1.0 +/- 0.6 degrees C. The observed hysteresis suggests that thermoregulatory responses during combined isoflurane/epidural anesthesia are not determined simply by instantaneous thermal input to central controllers, but may also depend on the direction of core temperature change.

Adult↗