Abstract
Purpose
This study was conducted to test the hypothesis that clonidine produces a dose-dependent increase in the sweating threshold and dose-dependent decreases in vasoconstriction and shivering thresholds.
Methods
Six healthy subjects (two female) were studied on four days after taking clonidine in oral doses of either 0 (control). 3. 6 or 9 μg · kg. The order followed a balanced design in a double-blind fashion. Oesophageal temperature and mean skin temperature (from 12 sites) were measured. Subjects were seated in 37°C water which was gradually warmed until sweating occurred (sweat rate increased above 50 g · m 2 · h−1). The water was then cooled gradually until thresholds for vasoconstnction (onset of sustained decrease in fingertip blood flow) and shivering (sustained elevation m metabolism) were determined. Thresholds were then referred to as the core temperature, adjusted to a designated mean skin temperature of 33°C.
Results
High dose clonidine similarly decreased the adjusted core temperature thresholds for vasoconstriction by 1. 16 ± 0.30°C and for shivenng by 1.63 ± 0.23°C (P< 0.01). The dose response effects were linear for both cold responses with vasoconstriction and shivenng thresholds decreasing by 0.13 ± 0.05 and 0.19 ± 0.09°C · μg−1 respectively (P < 0.0001). The sweating threshold was unaffected by clonidine, however the interthreshold range between sweating and vasoconstnction thresholds increased from control (0.19 ± 0.48°C) to high dose donidine (1.31 ±0.54°C).
Conclusion
The decreases in core temperature thresholds for cold responses and increased interthreshold range are consistent with the effects of several anaesthetic agents and opioids and is indicative of central thermoregulatory inhibition.
Résumé
Objectif
Vérifier si la clonidine provoque une augmentation du seuil de sudation et une diminution des seuls de vasoconstnction et de fnsson proportionnellement à la dose.
Méthodes
Six patients en bonne santé (dont deux femmes) qui avaient reçu des doses orales de clonidine de 0 (contrôle). 3. 6 et 9 μg· kg ont été étudiés pendant quatre jours. Létude suivait un plan équilibré et en double insu. Les températures moyennes oesophagiennes et cutanées (à 12 endroits) ont été mesurées. Les sujets étaient assis dans l’eau à 37°C réchauffée graduellement jusqu’à l’apparition de la sudation (un taux de sudation à50 g · m2 · h−1). Leau était par la suite refroidie progressivement jusqu’aux seuils de vasoconstnction (début de la diminution du flux sanguin à l’extrémité des doigts) et de frissonnement. Ces seuils ont été reconnus comme la température centrale ajustée à une température cutanée désignée de 33°C.
Résultats
Les hautes doses de clonodine abaissent également les seuils de vasoconstriction ajustés à la température centrale de 1. 16 ± 0.30°C et du frissonnement de 1,63 ± 0.23C (P < 0,01). Les effets dose-réponse sont linéaires pour les deux réponses au froid avec des seuils de vasoconstnction et de frissonnement diminuant respectivement de 0,13 ± 0,05 et de 0.19 ± 0.09°C μg−1 (P < 0,0001). Le seuil de sudation n’est pas affecté par le donodine; toutefois l’écart entre les seuils de sudation et de vasoconstriction s’élargit entre le contrôle (0,19 ± 0,48°C) et la clonodine à haute dose (1.31 ± 0.54°C).
Conclusion
La baisse des seuils de la température centrale pour les réponses au froid et l’augmentation de l’écart entre les seuils sont consistants avec les effets de plusieurs agents anesthésiques et morphmiques et démontrent une inhibition de la thermorégulation centrale.
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References
Maze M, Tmnquilli W. Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology 1991; 74: 581–605.
Stoelting BJC. Pharmacology and Physiology in Anesthesic Practice, 2nd ed. Philadelphia, JB Lippincott Co. 1991.
Omoigui S. The Anesthesia Drugs Handbook, 2nd ed. St. Louis: Mosby, 1995.
Joris J, Banacbe M, Bonnet F, Sessler DI, Lamy M. Clonidine and ketanserin both are effective treatment for postanesthetic shivering. Anesthesiology 1993; 79: 532–9.
Delaunay L, Bonnet F, Liu N, Beydon L, Catoire P, Sessler DI. Clonidine comparably decreases the thermoregulatory thresholds for vasoconstriction and shivering in humans. Anesthesiology 1993; 79: 470–4.
Washington DE, Sessler DI, Moayeri A, et al. Thermoregulatory responses to hyperthermia during isoflurane anesthesia in humans. J Appl Physiol 1993; 74: 82–7.
Stoen R, Sessler DI. The thermoregulatory threshold is inversely proportional to isoflurane concentration. Anesthesiology 1990; 72: 822–7.
Lopez M, Ozaki M, Sessler DI, Valdes M. Physiologic responses to hyperthermia during anesthesia and combined epidural/enflurane anesthesia in women. Anesthesiology 1993; 78: 1046–54.
Washington DE, Sessler DI, McGuire J, Hynson J, Schroeder M, Moayeri A. Painful stimulation minimally increases the thermoregulatory threshold for vasoconstriction during enflurane anesthesia in humans. Anesthesiology 1992;77: 286–90.
Matsukawa T, Kurz A, Sessler DI, Bjorksten AR, Merrifield B, Cheng C. Propofol linearly reduces the vasoconstriction and shivering thresholds. Anesthesiology 1995; 82: 1169–80.
Kurz A, Go JC, Sessler DI, Kaer K, Larson MD, Bjorksten AR. Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds. Anesthesiology 1995; 83: 293–9.
Kurz A, Sessler DI, Annadata R, et al. Meperidine slightly increases the sweating threshold, but markedly decreases the vasoconstriction and shivering thresholds. Anesthesiology 1995; 83: A169.
Mekjavic IB, Rempel ME. Determination of esophageal probe insertion length based on standing and sitting height. J Appl Physiol 1990; 69: 376–9.
Hayward JS, Eckerson JD, Kemna D. Thermal and cardiovascular changes during three methods of resuscitation from mild hypothermia. Resuscitation 1984; 11: 21–33.
Ozaki M, Sessler DI, Lopez M, Walter K. Pulse oximeter-based flow index correlates well with fingertip volume plethysmography. Anesthesiology 1993; 79: A542.
Layton RP, Mints WH Jr, Annis JF, Rack MJ, Webb P. Calorimetry with heat flux transducers: comparison with a suit calorimeter. J Appl Physiol 1983; 54: 1361–7.
Lopez M, Sessler DI, Walter K, Emerick T, Ayyalapu A. Reduced sweating threshold during exercise-induced hypothermia. Pflüegers Arch 1995; 430: 606–11.
Mekjavi IB, Sundberg CJ, Linnarsson D. Core temperature “null zone.” J Appl Physiol 1991; 71: 1289–95.
Nadel ER, Mitchell JW, Stolwijk JAJ. Control of local and total sweating during exercise transients. Int J Biometerol 1971; 15: 201–16.
Cheng C, Matsukawa T, Sessler DI, et al. Increasing mean skin temperature linearly reduces the core-temperature thresholds for vasoconstriction and shivering in humans. Anesthesiology 1995; 82: 1160–8.
Thorn S, Hayes R, Calvete J, Sever PS. In vivo and in vitro studies of2-adrenoceptor responses in human vascular smooth muscle. J Cardiovasc Pharmacol 1985; 7: S137–43.
Boehringer-Ingelheim. Clonidine HCl.In: MC Gillis (Ed.). Compendium of Pharmaceuticals and Specialties, 31st ed. Ottawa: Canadian Pharmaceutical Association, 1996: 232–3.
Nance PW, Shears AH, Nance DM. Reflex changes induced by clonidine in spinal cord injured patients. Paraplegia 1989; 27: 296–301.
Unnerstall JR, Kopajtic TA, Kahar MJ. Distribution of a2 agonist binding sites in the rat and human central nervous system: analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents. Brain Res Rev 1984; 7: 69–101.
Langer SZ, Cavero I, Massingham R. Recent developments in noradrenergjc neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents. Hypertension 1980; 2: 373–82.
Leslie K, Sessler DI, Bjorksten AR, et al. Propofol causes a dose-dependent decrease in the thermoregulatory threshold for vasoconstriction, but has little effect on sweating. Anesthesiology 1994; 81: 353–60.
Lopez M, Sessler DI, Walter K, Emerick T, Ozaki M. Rate and gender dependence of the sweating, vasoconstriction, and shivering thresholds in humans. Anesthesiology 1994; 80: 780–8.
Just B, Delva E, Camus Y, Lienhart A. Oxygen uptake during recovery following naloxone. Relationship with intraoperative heat loss. Anesthesiology 1992; 76: 60–4.
Bunker JP, Goldstein R. Coagulation during hypothermia in man. Proc Soc Exp Biol Med 1958; 97: 199–202.
Heier T, Caldwell JE, Sessler DI, Miller RD. Mild intraoperative hypothermia increases duration of action and spontaneous recovery of vecuronium blockade during nitrous oxide-isoflurane anesthesia in humans. Anesthesiology 1991; 74: 815–9.
Sheffield CW, Sessler DI, Hunt TK, Scheuenstuhl H. Mild hypothermia during halothane-induced anesthesia decreases resistance tostaphylococcus aureus dermal infection in guinea pigs. Wound Repair and Regeneration 1994; 2: 48–56.
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Supported by the Natural Science and Engineering Research Council of Canada,Manitoba Health Research Council, and Augustine Medical Inc.
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Nicolaou, G., Chen, A.A., Johnston, C.E. et al. Clonidine decreases vasoconstriction and shivering thresholds, without affecting the sweating threshold. Can J Anaesth 44, 636–642 (1997). https://doi.org/10.1007/BF03015448
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DOI: https://doi.org/10.1007/BF03015448