Propofol Linearly Reduces the Vasoconstriction and Shivering Thresholds 

1995 ◽  
Vol 82 (5) ◽  
pp. 1169-1180 ◽  
Author(s):  
Takashi Matsukawa ◽  
Andrea Kurz ◽  
Daniel I. Sessler ◽  
Andrew R. Bjorksten ◽  
Benjamin Merrifield ◽  
...  

Background Skin temperature is best kept constant when determining response thresholds because both skin and core temperatures contribute to thermoregulatory control. In practice, however, it is difficult to evaluate both warm and cold thresholds while maintaining constant cutaneous temperature. A recent study shows that vasoconstriction and shivering thresholds are a linear function of skin and core temperatures, with skin contributing 20 +/- 6% and 19 +/- 8%, respectively. (Skin temperature has long been known to contribute approximately 10% to the control of sweating). Using these relations, we were able to experimentally manipulate both skin and core temperatures, subsequently compensate for the changes in skin temperature, and finally report the results in terms of calculated core-temperature thresholds at a single-designated skin temperature. Methods Five volunteers were each studied on 4 days: (1) control; (2) a target blood propofol concentration of 2 micrograms/ml; (3) a target concentration of 4 micrograms/ml; and (4) a target concentration of 8 micrograms/ml. On each day, we increased skin and core temperatures sufficiently to provoke sweating. Skin and core temperatures were subsequently reduced to elicit peripheral vasoconstriction and shivering. We mathematically compensated for changes in skin temperature by using the established linear cutaneous contributions to the control of sweating (10%) and to vasoconstriction and shivering (20%). From these calculated core-temperature thresholds (at a designated skin temperature of 35.7 degrees C), the propofol concentration-response curves for the sweating, vasoconstriction, and shivering thresholds were analyzed using linear regression. We validated this new method by comparing the concentration-dependent effects of propofol with those obtained previously with an established model. Results The concentration-response slopes for sweating and vasoconstriction were virtually identical to those reported previously. Propofol significantly decreased the core temperature triggering vasoconstriction (slope = -0.6 +/- 0.1 degrees C.micrograms-1.ml-1; r2 = 0.98 +/- 0.02) and shivering (slope = -0.7 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.95 +/- 0.05). In contrast, increasing the blood propofol concentration increased the sweating threshold only slightly (slope = 0.1 +/- 0.1 degrees C.micrograms -1.ml-1; r2 = 0.46 +/- 0.39). Conclusions Advantages of this new model include its being nearly noninvasive and requiring relatively little core-temperature manipulation. Propofol only slightly alters the sweating threshold, but markedly reduces the vasoconstriction and shivering thresholds. Reductions in the shivering and vasoconstriction thresholds are similar; that is, the vasoconstriction-to-shivering range increases only slightly during anesthesia.

1995 ◽  
Vol 82 (5) ◽  
pp. 1160-1168 ◽  
Author(s):  
Christi Cheng ◽  
Takashi Matsukawa ◽  
Daniel I. Sessler ◽  
Ozaki Makoto ◽  
Andrea Kurz ◽  
...  

Background The contribution of mean skin temperature to the thresholds for sweating and active precapillary vasodilation has been evaluated in numerous human studies. In contrast, the contribution of skin temperature to the control of cold responses such as arteriovenous shunt vasoconstriction and shivering is less well established. Accordingly, the authors tested the hypothesis that mean skin and core temperatures are linearly related at the vasoconstriction and shivering thresholds in men. Because the relation between skin and core temperatures might vary by gender, the cutaneous contribution to thermoregulatory control also was determined in women. Methods In the first portion of the study, six men participated on 5 randomly ordered days, during which mean skin temperatures were maintained near 31, 34, 35, 36, and 37 degrees C. Core hypothermia was induced by central venous infusion of cold lactated Ringer's solution sufficient to induce peripheral vasoconstriction and shivering. The core-temperature thresholds were then plotted against skin temperature and a linear regression fit to the values. The relative skin and core contributions to the control of each response were calculated from the slopes of the regression equations. In the second portion of the study, six women participated on three randomly ordered days, during which mean skin temperatures were maintained near 31, 35, and 37 degrees C. At each designated skin temperature, core hypothermia sufficient to induce peripheral vasoconstriction and/or shivering was again induced by central venous infusion of cold lactated Ringer's solution. The cutaneous contributions to control of each response were then calculated from the skin- and core-temperature pairs at the vasoconstriction and shivering thresholds. Results There was a linear relation between mean skin and core temperatures at the response thresholds in the men: r = 0.90 +/- 0.06 for vasoconstriction and r = 0.94 +/- 0.07 for shivering. Skin temperature contributed 20 +/- 6% to vasoconstriction and 19 +/- 8% to shivering. Skin temperature in the women contributed to 18 +/- 4% to vasoconstriction and 18 +/- 7% to shivering, values not differing significantly from those in men. There was no apparent correlation between the cutaneous contributions to vasoconstriction and shivering in individual volunteers. Conclusions These data indicate that skin and core temperatures contribute linearly to the control of vasoconstriction and shivering in men and that the cutaneous contributions average approximately 20% in both men and women. The same coefficients thus can be used to compensate for experimental skin temperature manipulations in men and women. However, the cutaneous contributions to each response vary among volunteers; furthermore, the contributions to the two responses vary within volunteers.


1997 ◽  
Vol 86 (5) ◽  
pp. 1046-1054 ◽  
Author(s):  
Andrea Kurz ◽  
Takehiko Ikeda ◽  
Daniel I. Sessler ◽  
Merlin D. Larson ◽  
Andrew R. Bjorksten ◽  
...  

Background Meperidine administration is a more effective treatment for shivering than equianalgesic doses of other opioids. However, it remains unknown whether meperidine also profoundly impairs other thermoregulatory responses, such as sweating or vasoconstriction. Proportional inhibition of vasoconstriction and shivering suggests that the drug acts much like alfentanil and anesthetics but possesses greater thermoregulatory than analgesic potency. In contrast, disproportionate inhibition would imply a special antishivering mechanism. Accordingly, the authors tested the hypothesis that meperidine administration produces a far greater concentration-dependent reduction in the shivering than vasoconstriction threshold. Methods Nine volunteers were each studied on three days: 1) control (no opioid); 2) a target total plasma meperidine concentration of 0.6 microgram/ml (40 mg/h); and 3) a target concentration of 1.8 micrograms/ml (120 mg/h). Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds (at a designated skin temperature of 34 degrees C) were computed using established linear cutaneous contributions to control sweating (10%) and vasoconstriction and shivering (20%). The dose-dependent effects of unbound meperidine on thermoregulatory response thresholds was then determined using linear regression. Results are presented as means +/- SDs. Results The unbound meperidine fraction was approximately 35%. Meperidine administration slightly increased the sweating threshold (0.5 +/- 0.8 degree C.microgram-1.ml; r2 = 0.51 +/- 0.37) and markedly decreased the vasoconstriction threshold (-3.3 +/- 1.5 degrees C.microgram-1.ml; r2 = 0.92 +/- 0.08). However, meperidine reduced the shivering threshold nearly twice as much as the vasoconstriction threshold (-6.1 +/- 3.0 degrees C.microgram-1.ml; r2 = 0.97 +/- 0.05; P = 0.001). Conclusions The special antishivering efficacy of meperidine results at least in part from an uncharacteristically large reduction in the shivering threshold rather than from exaggerated generalized thermoregulatory inhibition. This pattern of thermoregulatory impairment differs from that produced by alfentanil, clonidine, propofol, and the volatile anesthetics, all which reduce the vasoconstriction and shivering thresholds comparably.


1976 ◽  
Vol 40 (5) ◽  
pp. 701-706 ◽  
Author(s):  
J. A. Downey ◽  
C. E. Huckaba ◽  
P. S. Kelley ◽  
H. S. Tam ◽  
R. C. Darling ◽  
...  

Studies of central and peripheral heating of a resting spinal man (T6) were performed under various ambient temperatures (20–34 degrees C). It was found that at a constant core temperature, sweating could not be initiated by sentient skin heating alone, but skin cooling alone did produce a rapid decrease in sweating response. Central heating alone induced sweating responses and the central temperature thresholds of sweating were inversely related to the ambient (sentient skin) temperatures. The local and mean sweating rates were found to be linearly related to the core temperature. The slopes of local sweating rates versus the core temperature vary increasingly with the following locations: chest, forearm, and forehead; but the slopes of mean sweating rates versus core temperature were essentially constant.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
D Aronson ◽  
Y Nitzan ◽  
S Petcherski ◽  
E Bravo ◽  
M Habib ◽  
...  

Abstract Background Current treatment of fluid retention in heart failure (HF) relies primarily on diuretics. However, adequate decongestion is not achieved in many patients. Purpose To study the feasibility and short-term performance of a novel approach to remove fluids and sodium directly from the interstitial compartment by enhancing sweat rate. Methods We used a device designed to enhance fluid and salt loss via the eccrine sweat glands. Skin temperature in the lower body was increased to 35–38°, where the slope of the relationship between temperature and sweat production is linear. With this wearable device, the sweat evaporates instantaneously, thus avoiding the awareness of perspiration. The primary efficacy endpoint was the ability to increase skin temperature to the desired range without elevating the core temperature above normal range. A secondary efficacy endpoint was a clinically meaningful hourly sweat output, defined as ≥150 mL/h. The primary safety endpoint was any procedure-related adverse events. Results We studied 6 normal subjects and 10 HF patients with clinical evidence of congestion and median NT-proBNP of 602 pg/mL [interquartile range 427 to 1719 pg/mL]. Participants underwent 3 treatment sessions of up to 4h. Skin temperature increased to a median of 37.5°C (interquartile range 37.1–37.9°C) with the core temperature remaining unchanged. The median total weight loss during treatment was 219±67 g/h (Figure) with a range of 100–338 g/h. In 77% of cases, the average sweat rate was ≥150 mL/h. Systolic (P=0.25) and diastolic (P=0.48) blood pressure and heart rate (P=0.11) remained unchanged during the procedure. There were no significant changes in renal function and no procedure-related adverse events. Conclusion Enhancing sweat rate was safe and resulted in a clinically meaningful fluid removal and weight loss. Further evaluation of this concept is warranted. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): AquaPass Inc Weight loss due to sweat


1997 ◽  
Vol 86 (3) ◽  
pp. 603-612 ◽  
Author(s):  
Takehiko Ikeda ◽  
Daniel I. Sessler ◽  
Danielle Marder ◽  
Junyu Xiong

Background Recently, liquid crystal skin-surface thermometers have become popular for intraoperative temperature monitoring. Three situations during which cutaneous liquid-crystal thermometry may poorly estimate core temperature were monitored: (1) anesthetic induction with consequent core-to-peripheral redistribution of body heat, (2) thermoregulatory vasomotion associated with sweating (precapillary dilation) and shivering (minimal capillary flow), and (3) ambient temperature variation over the clinical range from 18-26 degrees C. Methods The core-to-forehead and core-to-neck temperature difference was measured using liquid-crystal thermometers having an approximately 2 degrees C offset. Differences exceeding 0.5 degree C (a 1 degree C) temperature range) were a priori deemed potentially clinically important. Seven volunteers participated in each protocol. First, core-to-peripheral redistribution of body heat was produced by inducing propofol/desflurane anesthesia; anesthesia was then maintained for 1 h with desflurane. Second, vasodilation was produced by warming unanesthetized volunteers sufficiently to produce sweating; intense vasoconstriction was similarly produced by cooling the volunteers sufficiently to produce shivering. Third, a canopy was positioned to enclose the head, neck, and upper chest of unanesthetized volunteers. Air within the canopy was randomly set to 18, 20, 22, 24, and 26 degrees C. Results Redistribution of body heat accompanying induction of anesthesia had little effect on the core-to-forehead skin temperature difference. However, the core-to-neck skin temperature gradient decreased approximately 0.6 degree C in the hour after induction of anesthesia. Vasomotion associated with shivering and mild sweating altered the core-to-skin temperature difference only a few tenths of a degree centigrade. The absolute value of the core-to-forehead temperature difference exceeded 0.5 degree C during approximately 35% of the measurements, but the difference rarely exceeded 1 degree C. The core-to-neck temperature difference typically exceeded 0.5 degree C and frequently exceeded 1 degree C. Each 1 degree C increase in ambient temperature decreased the core-to-fore-head and core-to-neck skin temperature differences by less than 0.2 degree C. Conclusions Forehead skin temperatures were better than neck skin temperature at estimating core temperature. Core-to-neck temperature differences frequently exceeded 1 degree C (a 2 degrees C range), whereas two thirds of the core-to-forehead differences were within 0.5 degree C. The core-to-skin temperature differences were, however, only slightly altered by inducing anesthesia, vasomotor action, and typical intraoperative changes in ambient temperature.


1995 ◽  
Vol 83 (2) ◽  
pp. 293-299. ◽  
Author(s):  
Andrea Kurz ◽  
Janice C. Go ◽  
Daniel I. Sessler ◽  
Klaus Kaer ◽  
Merlin D. Larson ◽  
...  

Background Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. Methods Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. Results In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] + 37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C) = -0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 = 0.70). Conclusions The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a slight increase in the sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.


1996 ◽  
Vol 80 (2) ◽  
pp. 422-429 ◽  
Author(s):  
C. E. Johnston ◽  
M. D. White ◽  
M. Wu ◽  
G. K. Bristow ◽  
G. G. Giesbrecht

Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation.


1995 ◽  
Vol 82 (4) ◽  
pp. 870-876. ◽  
Author(s):  
Andrea MD Kurz ◽  
Daniel I. Sessler ◽  
Franz Birnbauer ◽  
Udo M. Illievich ◽  
Christian K. Spiss

Background Many clinicians now consider hypothermia indicated during neurosurgery. Active cooling often will be required to reach target temperatures < 34 degrees C sufficiently rapidly and nearly always will be required if the target temperature is 32 degrees C. However, the efficacy even of active cooling might be impaired by thermoregulatory vasoconstriction, which reduces cutaneous heat loss and constrains metabolic heat to the core thermal compartment. The authors therefore tested the hypothesis that the efficacy of active cooling is reduced by thermoregulatory vasoconstriction. Methods Patients undergoing neurosurgical procedures with hypothermia were anesthetized with either isoflurane/nitrous oxide (n = 13) or propofol/fentanyl (n = 13) anesthesia. All were cooled using a prototype forced-air cooling device until core temperature reached 32 degrees C. Core temperature was measured in the distal esophagus. Vasoconstriction was evaluated using forearm minus fingertip skin-temperature gradients. The core temperature triggering a gradient of 0 degree C identified the vasoconstriction threshold. Results In 6 of the 13 patients given isoflurane, vasoconstriction (skin-temperature gradient = 0 degrees C) occurred at a core temperature of 34.4 +/- 0.9 degree C, 1.7 +/- 0.58 h after induction of anesthesia. Similarly, in 7 of the 13 patients given propofol, vasoconstriction occurred at a core temperature of 34.5 +/- 0.9 degree C, 1.6 +/- 0.6 h after induction of anesthesia. In the remaining patients, vasodilation continued even at core temperatures of 32 degrees C. Core cooling rates were comparable in each anesthetic group. However, patients in whom vasodilation was maintained cooled fastest. Patients in whom vasoconstriction occurred required nearly an hour longer to reach core temperatures of 33 degrees C and 32 degrees C than did those in whom vasodilation was maintained (P < 0.01). Conclusions Vasoconstriction did not produce a full core temperature "plateau," because of the extreme microenvironment provided by forced-air cooling. However, it markedly decreased the rate at which hypothermia developed. The approximately 1-h delay in reaching core temperatures of 33 degrees C and 32 degrees C could be clinically important, depending on the target temperature and the time required to reach critical portions of the operation.


2018 ◽  
Vol 02 (01) ◽  
pp. 019-024
Author(s):  
Muralidhar Kanchi ◽  
Prashanth Menon

Abstract Introduction Unintentional hypothermia in patients undergoing off pump coronary artery bypass grafting (OPCABG) under general anesthesia (GA) is a known complication. The wide sternotomy wound as well as low ambient operating room temperature further promotes heat loss. The changes in temperature could further be affected by the use of various vasoactive drugs by affecting the thermoregulatory response. This study is aimed to detect the temperature changes and the influence of vasoactive infusions on the temperature in the patients undergoing OPCABG under GA. Aims The main purpose of this article is to assess the core and skin temperature changes during OPCABG surgery and to assess the effect of vasoactive infusion used intraoperatively on the core temperature Settings and Design Single center, nonrandomized, open label, observational study. Methods and material After informed consent and ethical clearance from institutional review board, 151 adult patients undergoing elective OPCABG surgeries under GA were included in the study. A common anesthetic protocol and warming strategy was used in all patients. The core temperature measured with a nasopharyngeal probe and the skin temperature measured at the palmar surface of the right index finger were recorded at induction, at 30 minutes intervals thereafter, and at end surgery. The demographic variables and the duration of surgery were also recorded. The type and dose of vasoactive agents used intraoperatively were also recorded. The study population was divided post hoc into groups and subgroups for further analysis. Results All the patients showed a decrease in core temperature at end surgery. The temperature changes showed an initial exponential decrease in the first hour followed by a gradual decrease subsequently. The peripheral temperature showed a gradual increase from induction to end surgery. The temperature gradients showed a linear decrease with the core temperature and peripheral skin temperature reaching equilibrium at end surgery. The study population was divided into four groups depending on the type of vasoactive drugs received intraoperatively: vasoconstrictor (V), vasodilator (D), mixed vasoconstrictor and vasodilator (M), and no vasoactive drugs (N) group. The patients in the vasoconstrictor group had a higher core temperature at end surgery when compared with vasodilator group. Conclusions OPCABG under GA results in decrease in core temperature. The decrease in temperature is exponential in the initial 1 hour followed by a more gradual decrease. The temperature changes are possibly affected by the vasoactive drugs used intraoperatively. The effect of vasoactive drugs on core temperature is higher when used during the initial exponential decrease in temperature. However, further adequately powered randomized controlled trials may be required to establish these findings.


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