Skip to main content
Log in

Physiology and clinical relevance of induced hypothermia

  • New Perspectives In Management Of Brain Injury
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Experimental evidence and clinical experience suggest that mild hypothermia protects numerous tissues from damage during ischemic insult. However, the extent to which hypothermia becomes a valued therapeutic option will depend on the clinician’s ability to rapidly reduce core body temperature and safely maintain hypothermia. To date, general anesthesia is the best way to block autonomic defenses during induction of mild-to-moderate hypothermia; unfortunately, general anesthesia is not an option in most patients likely to benefit from therapeutichy pothermia. Induction of hypothermia in a wake humans is complicated by both the technical difficulties related to thermal manipulation and the remarkable efficacy of thermoregulatory defenses, especially vasoconstriction and shivering. The most effective thermal manipulation devices are generally invasive and, therefore, more prone to complications than surface methods. In an effort to inhibit thermoregulation in awake humans, several agents have been tested either alone or in combination with each other. For example, the combination of meperidine and buspirone has already been applied to faciltate induction of hypothermia in human trials. However, pharmacological induction of thermoregulatory tolerance to cold without excessive sedation, respiratory depression, or other serious toxicity remains a major focus of current therapeutic hypothermia research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sakai F, Amaha K. The effects of hypothermia on a cloned human brain glutamate transporter (hGLT-1) expressed in Chinese hamster ovary cells: -[3H]L-glutamate uptake study. Anesth Analg 1999;89:1546–1550.

    Article  PubMed  CAS  Google Scholar 

  2. Schwartz LM, Verbinski SG, Vander Heide RS, Reimer KA. Epicardial temperature is a major predictor of myocardial infarct size in dogs. J Mol Cell Cardiol 1997;29:1577–1583.

    Article  PubMed  CAS  Google Scholar 

  3. Churn SB, Taft WC, Billingsley MS, et al. Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils. Stroke 1990;21:1715–1721.

    PubMed  CAS  Google Scholar 

  4. Busto R, Dietrich WD, Globus MY-T, et al. Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J of Cerebral Blood Flow Metabolism 1987;7:729–738.

    CAS  Google Scholar 

  5. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–563.

    Article  PubMed  Google Scholar 

  6. Group THACAS. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–556.

    Article  Google Scholar 

  7. Hajat C, Hajat S, Sharma P. Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients. Stroke 2000;31:410–414.

    PubMed  CAS  Google Scholar 

  8. Doufas AG, Akça O, Barry A, et al. Initial experience with a novel heat-exchanging catheter inneurosurgical patients. Anesth Analg 2002;95:1752–1756.

    Article  PubMed  Google Scholar 

  9. Plattner O, Kurz A, Sessler DI, et al. Efficacy of intraoperative cooling methods. Anesthesiology 1997;87:1089–1095.

    Article  PubMed  CAS  Google Scholar 

  10. Kurz A, Sessler DI, Lenhardt RA, Study of wound infections and temperature group. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med 1996;334:1209–1215.

    Article  PubMed  CAS  Google Scholar 

  11. Schmied H, Kurz A, Sessler DI, et al. Mild intraoperative hypothermia increases blood loss and allogeneic transfusion requirements during total hip arthroplasty. Lancet 1996;347:289–292.

    Article  PubMed  CAS  Google Scholar 

  12. Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review. Crit Care Med 2003;31:2041–2051.

    Article  PubMed  Google Scholar 

  13. Doufas AG. Consequences of inadvertent perioperative hypothermia. Best Practice & Research Clinical Anaesthesiology 2003;17:535–549.

    Article  Google Scholar 

  14. Sessler DI. Complications and treatment of mild hypothermia. Anesthesiology 2001;95:531–543.

    Article  PubMed  CAS  Google Scholar 

  15. Crawshaw LI, Wollmuth LP, O’Connor CS, et al. Body temperature regulation in vertebrates: Comparative aspects and neuronal elements. In: Thermoregulation: physiology and biochemistry. (Schönbaum E, Lomax P, eds.). Pergamon Press, New York, 1990,209–220.

    Google Scholar 

  16. Fuller BJ. Gene expression in response to low temperatures in mammalian cells: a review of current ideas. Cryo Letters 2003;24:95–102.

    PubMed  CAS  Google Scholar 

  17. Marks LI, Gonzalez RR. Skin temperature modfies the pleasantness of thermal stimuli. Nature 1974;247:473–475.

    Article  PubMed  CAS  Google Scholar 

  18. Johnson KG, Cabanac M. Human thermoregulatory behavior during a conflict between cold discomfort and money. Physiol Behav 1983;30:145–150.

    Article  PubMed  CAS  Google Scholar 

  19. Taylor NA, Allsopp NK, Parkes DG. Preferred room temperature of young vs aged males: the influence of thermal sensation, thermal comfort, and affect. J Gerontol A Biol Sci Med Sci 1995;50:M216-M221.

    PubMed  CAS  Google Scholar 

  20. Johnston CE, Bristow GK, Elias DA, Giesbrecht GG. Alcohol lowers the vasoconstriction threshold in humans without affecting core cooling rate during mild cold exposure. Eur J Appl Physiol Occup Physiol 1996;74:293–295.

    Article  PubMed  CAS  Google Scholar 

  21. Zweifler RM, Sessler DI, Zivin JA. Thermoregulatory vasoconstriction and shivering impede therapeutic hypothermia in acute ischemic stroke victims. J Stroke Cerebrovasc Dis 1997;6:100–104.

    Article  Google Scholar 

  22. Lopez M, Sessler DI, Walter K, et al. Rate and gender dependence of the sweating, vasoconstriction, and shivering thresholds in humans. Anesthesiology 1994;80:780–788.

    Article  PubMed  CAS  Google Scholar 

  23. Sessler DI, Moayeri A, Støen R, et al. Thermoregulatory vasoconstriction decreases cutaneous heat loss. Anesthesiology 1990;73:656–660.

    Article  PubMed  CAS  Google Scholar 

  24. Sessler DI, McGuire J, Sessler AM. Perioperative thermal insulation. Anesthesiology 1991;74:875–879.

    Article  PubMed  CAS  Google Scholar 

  25. Matsukawa T, Sessler DI, Christensen R, et al. Heat flow and distribution during epidural anesthesia. Anesthesiology 1995;83:961–967.

    Article  PubMed  CAS  Google Scholar 

  26. Kurz A, Sessler DI, Christensen R, Dechert M. Heat balance and distribution during the core-temperature plateau in anesthetized humans. Anesthesiology 1995;83:491–499.

    Article  PubMed  CAS  Google Scholar 

  27. Jessen K. An assessment of human regulatory nonshivering thermogenesis. Acta Anaesthesiol Scand 1980;24:138–143.

    PubMed  CAS  Google Scholar 

  28. Jessen K, Rabøl A, Winkler K. Total body and splanchnic thermogenesis in curarized man during a short exposure to cold. Acta Anaesthesiol Scand 1980;24:339–344.

    PubMed  CAS  Google Scholar 

  29. Hynson JM, Sessler DI, Moayeri A, McGuire J. Absence of nonshivering thermogenesis in anesthetized humans. Anesthesiology 1993;79:695–703.

    Article  PubMed  CAS  Google Scholar 

  30. Just B, Delva E, Camus Y, Lienhart A. Oxygen uptake during recovery following naloxone. Relationship with intraoperative heat loss. Anesthesiology 1992;76:60–64.

    Article  PubMed  CAS  Google Scholar 

  31. Eyolfson DA, Tikuisis P, Xu X, et al. Measurement and prediction of peak shivering intensity in humans. Eur J Appl Physiol 2001;84:100–106.

    Article  PubMed  CAS  Google Scholar 

  32. Horvath SM, Spurr GB, Hutt BK, Hamilton LH. Metabolic cost of shivering. J Appl Physiol 1956;8:595–602.

    PubMed  CAS  Google Scholar 

  33. De Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology 2002;96:467–484.

    Article  PubMed  Google Scholar 

  34. Plattner O, Ikeda T, Sessler DI, et al. Postanesthetic vasoconstriction slows postanesthetic peripheral-to-core transfer of cutaneous heat, thereby isolating the core thermal compartment. Anesth Analg 1997;85:899–906.

    Article  PubMed  CAS  Google Scholar 

  35. Frank SM, Cattaneo CG, Wieneke-Brady MB, et al. Threshold for adrenomedullary activation and increased cardiac work during mild core hypothermia. Clin Sci (Lond) 2002;102:119–125.

    Article  CAS  Google Scholar 

  36. Frank SM, Fleisher LA, Breslow MJ, et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. JAMA 1997;277:1127–1134.

    Article  PubMed  CAS  Google Scholar 

  37. Greif R, Laciny S, Rajek A, et al. Blood pressure response to thermoregulatory vasoconstriction during isoflurane and desflurane anesthesia. Acta Anaesthesiol Scand; 47:847–852.

  38. 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;82:1160–1168.

    Article  PubMed  CAS  Google Scholar 

  39. Sweney MT, Sigg DC, Tahvildari S, Iaizzo PA. Shiver suppression using focal hand warming in unanesthetized normal subjects. Anesthesiology 2001;95:1089–1095.

    Article  PubMed  CAS  Google Scholar 

  40. Iaizzo PA, Jeon YM, Sigg DC. Facial warming increases the threshold for shivering. J Neurosurg Anesthesiol 1999;11:231–239.

    Article  PubMed  CAS  Google Scholar 

  41. Mekjavic IB, Eiken O. Inhibition of shivering in man by thermal stimulation of the facial area. Acta Physiol Scand 1985;125:633–637.

    PubMed  CAS  Google Scholar 

  42. Murphy MT, Lipton JM, Loughran P, Giesecke Jr AH. Postanesthetic shivering in primates: Inhibition by peripheral heating and by taurine. Anesthesiology 1985;63:161–165.

    Article  PubMed  CAS  Google Scholar 

  43. Sharkey A, Lipton JM, Murphy MT, Giesecke AH. Inhibition of postanesthetic shivering with radiant heat. Anesthesiology 1987;66:249–252.

    Article  PubMed  CAS  Google Scholar 

  44. Sharkey A, Gulden RH, Lipton JM, Giesecke AH. Effect of radiant heat on the metabolic cost of postoperative shivering. Br J Anaesth 1993;70:449–450.

    Article  PubMed  CAS  Google Scholar 

  45. Doufas AG, Wadhwa A, Lin CM, et al. Neither arm nor face warming reduces the shivering threshold in unanesthetized humans. Stroke 2003;34:1736–1740.

    Article  PubMed  Google Scholar 

  46. Delaunay L, Bonnet F, Liu N, et al. Clonidine comparably decreases the thermoregulatory thresholds for vasoconstriction and shivering in humans. Anesthesiology 1993;79:470–474.

    Article  PubMed  CAS  Google Scholar 

  47. Delaunay L, Bonnet F, Duvaldestin P. Clonidine decreases postoperative oxygen consumption in patients recovering from general anaesthesia. Br J Anaesth 1991;67:397–401.

    Article  PubMed  CAS  Google Scholar 

  48. Horn E-P, Sessler DI, Standl T, et al. Non-thermoregulatory shivering in patients recovering from isoflurane or desflurane anesthesia. Anesthesiology 1998;89:878–886.

    Article  PubMed  CAS  Google Scholar 

  49. Matsukawa T, Kurz A, Sessler DI, et al. Propofol linearly reduces the vasoconstriction and shivering thresholds. Anesthesiology 1995;82:1169–1180.

    Article  PubMed  CAS  Google Scholar 

  50. Sessler DI. Perioperative hypothermia. N Engl J Med 1997;336:1730–1737.

    Article  PubMed  CAS  Google Scholar 

  51. Kurz A, Go JC, Sessler DI, et al. Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds. Anesthesiology 1995;83:293–299.

    Article  PubMed  CAS  Google Scholar 

  52. Talke P, Tayefeh F, Sessler DI, et al. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly reduces the vasoconstriction and shivering thresholds. Anesthesiology 1997;87:835–841.

    Article  PubMed  CAS  Google Scholar 

  53. Annadata RS, Sessler DI, Tayefeh F, et al. Desflurane slightly increases the sweating threshold, but produces marked, non-linear decreases in the vasoconstriction and shivering thresholds. Anesthesiology 1995;83:1205–1211.

    Article  PubMed  CAS  Google Scholar 

  54. Ozaki M, Kurz A, Sessler DI, et al. Thermoregulatory thresholds during spinal and epidural anesthesia. Anesthesiology 1994;81:282–288.

    Article  PubMed  CAS  Google Scholar 

  55. Pollock JE, Neal JM, Liu SS, et al. Sedation during spinal anesthesia. Anesthesiology 2000;93:728–734.

    Article  PubMed  CAS  Google Scholar 

  56. Hodgson PS, Liu SS, Gras TW. Does epidural anesthesia have general anesthetic effects? A prospective, randomized, doubleblind, placebo-controlled trial. Anesthesiology 1999;91:1687–1692.

    Article  PubMed  CAS  Google Scholar 

  57. Rajek A, Greif R, Sessler DI. Effects of epidural anesthesia on thermal sensation. Reg Anesth Pain Med 2001;26:527–531.

    Article  PubMed  CAS  Google Scholar 

  58. Leslie K, Sessler DI, Bjorksten A, et al. Propofol causes a dose-dependent decrease in the thermoregulatory threshold for vasoconstriction, but has little effect on sweating. Anesthesiology 1994;81:353–360.

    Article  PubMed  CAS  Google Scholar 

  59. Nemoto EM, Klementavicius R, Melick JA, Yonas H. Norepinephrine activation of basal cerebral metabolic rate for oxygen (CMRO2) during hypothermia in rats. Anesth Analg 1996;83:1262–1267.

    Article  PubMed  CAS  Google Scholar 

  60. Harrison G. Control of the malignant hyperpyrexic syndrome in MHS swine by dantrolene sodium. Br J Anaesth 1975;47.

  61. Goulon M, de Rohan-Chabot P, Elkharrat D, et al. Beneficial effects of dantrolene in the treatment of neuroleptic malignant syndrome: a report of two cases. Neurology 1983;33:516–518.

    PubMed  CAS  Google Scholar 

  62. Granato JE, Stern BJ, Ringel A, et al. Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine. Ann Neurol 1983;14:89,90.

    Article  PubMed  CAS  Google Scholar 

  63. Lin C-M, Neeru S, Doufas AG, et al. Dantrolene reduces the threshold and gain for shivering. Anesth Analg 2004;98:1318–1324.

    Article  PubMed  CAS  Google Scholar 

  64. Gordon CJ. Thermoregulation in laboratory mammals and humans exposed to anticholinesterase agents. Neuro Toxicol Teratol 1994;16:427–453.

    Article  CAS  Google Scholar 

  65. Lyons B, Taylor A, Power C, Casey W. Postanaesthetic shivering in children. Anaesthesia 1996;51:442–445.

    Article  PubMed  CAS  Google Scholar 

  66. Baxendale BR, Mahajan RP, Crossley AWA. Anticholinergic premedication influences the incidence of postoperative shivering. Br J Anaesth 1994;72:291–294.

    Article  PubMed  CAS  Google Scholar 

  67. Greif R, Laciny S, Rajek AM, et al. Neither nalbuphine nor atropine posses special antishivering activity. Anesth Analg 2001;93:620–627.

    Article  PubMed  CAS  Google Scholar 

  68. Johnson KG. Thermoregulatory changes induced by cholinomimetic substances introduced into the cerebral ventricles of sheep. Br J Pharmacol 1975;53:489–497.

    PubMed  CAS  Google Scholar 

  69. Nikki P. Influence of some cholinomimetic and cholinolytic drugs on halothane shivering in mice. Ann Med Exp Biol Fenn 1968;46:521–530.

    PubMed  CAS  Google Scholar 

  70. Horn E-P, Standl T, Sessler DI, et al. Physostigmine prevents postanesthetic shivering as does meperidine or clonidine. Anesthesiology 1998;88:108–113.

    Article  PubMed  CAS  Google Scholar 

  71. Kurz A, Sessler DI, Annadata R, et al. Midazolam minimally impairs thermoregulatory control. Anesth Analg 1995;81:393–398.

    Article  PubMed  CAS  Google Scholar 

  72. Matsukawa T, Hanagata K, Ozaki M, et al. I.M. midazolam as premedication produces a concentration dependent decrease in core temperature in male volunteers. Br J Anaesth 1997;78:396–399.

    PubMed  CAS  Google Scholar 

  73. Alfonsi P, Sessler DI, Du Manoir B, et al. The effects of meperidine and sufentanil on the shivering threshold in postoperative patients. Anesthesiology 1998;89:43–48.

    Article  PubMed  CAS  Google Scholar 

  74. Joris J, Banache M, Bonnet F, et al. Clonidine and ketanserin both are effective treatments for postanesthetic shivering. Anesthesiology 1993;79:532–539.

    Article  PubMed  CAS  Google Scholar 

  75. Piper SN, Suttner SW, Schmidt CC, et al. Nefopam and clonidine in the prevention of postanaesthetic shivering. Anaesthesia 1999;54:695–699.

    Article  PubMed  CAS  Google Scholar 

  76. Singh P, Dimitriou V, Mahajan RP, Crossley AW. Double-blind comparison between doxapram and pethidine in the treatment of postanaesthetic shivering. Br J Anaesth 1993;71:685–688.

    Article  PubMed  CAS  Google Scholar 

  77. Sarma V, Fry EN. Doxapram after general anaesthesia. Its role in stopping shivering during recovery. Anaesthesia 1991;46:460,461.

    Article  PubMed  CAS  Google Scholar 

  78. De Witte J, Deloof T, De Veylder J, Housmans PR. Tramadol in the treatment of postanesthetic shivering. Acta Anaesthesiol Scand 1997;41:506–510.

    Article  PubMed  Google Scholar 

  79. Doufas AG, Lin CM, Suleman MI, et al. Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke 2003;34:1218–1223.

    Article  PubMed  CAS  Google Scholar 

  80. De Witte JL, Kim J-S, Sessler DI, et al. Tramadol reduces the sweating, vasoconstriction, and shivering thresholds. Anesth Analg 1998;87:173–179.

    Article  PubMed  Google Scholar 

  81. Heel RC, Brogden RN, Pakes GE, et al. Nefopam: a review of its pharmacological properties and therapeutic efficacy. Drugs 1980;19:249–267.

    PubMed  CAS  Google Scholar 

  82. Guirimand F, Dupont X, Bouhassira D, et al. Nefopam strongly depresses the nociceptive flexion (R(III)) reflex in humans. Pain 1999;80:399–404.

    Article  PubMed  CAS  Google Scholar 

  83. Ohkubo Y, Nomura K, Yamaguchi I. Involvement of dopamine in the mechanism of action of FR64822, a novel non-opioid antinociceptive compound. Eur J Pharmacol 1991;204:121–125.

    Article  PubMed  CAS  Google Scholar 

  84. Fuller RW, Snoddy HD. Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice. Neuropharmacology 1993;32:995–999.

    Article  PubMed  CAS  Google Scholar 

  85. Buritova J, Besson JM. Effects of nefopam on the spinal nociceptive processes: a c-Fos protein study in the rat. Eur J Pharmacol 2002;441:67–74.

    Article  PubMed  CAS  Google Scholar 

  86. Gray AM, Nevinson MJ, Sewell RD. The involvement of opioidergic and noradrenergic mechanisms in nefopam antinociception. Eur J Pharmacol 1999;365:149–157.

    Article  PubMed  CAS  Google Scholar 

  87. Dordoni PL, Della Ventura M, Stefanelli A, et al. Effect of ketorolac, ketoprofen and nefopam on platelet function. Anaesthesia 1994;49:1046–1049.

    Article  PubMed  CAS  Google Scholar 

  88. Bhatt AM, Pleuvry BJ, Maddison SE. Respiratory and metabolic effects of oral nefopam in human volunteers. Br J Clin Pharmacol 1981;11:209–211.

    PubMed  CAS  Google Scholar 

  89. Alfonsi P, Adam F, Passard A, et al. Nefopam, a non-selective benzoxazocine analgesic, selectively reduces the shivering threshold. Anesthesiology 2004;100:37–43.

    Article  PubMed  CAS  Google Scholar 

  90. Kranke P, Eberhart LH, Roewer N, Tramer MR. Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg 2002;94:453–460.

    Article  PubMed  CAS  Google Scholar 

  91. Tsai Y-C, Chu K-s. A comparison of tramadol, amitrptyline, and meperidine for postepidural anesthetic shivering in pParturients. Anesth Analg 2001;93:1288–1292.

    Article  PubMed  CAS  Google Scholar 

  92. Wang JJ, Ho ST, Lee SC, Liu YC. A comparison among nalbuphine, meperidine, and placebo for treating postanesthetic shivering. Anesth Analg 1999;88:686–689.

    Article  PubMed  CAS  Google Scholar 

  93. Burks L, Aisner J, Fortner CL, Wiernik PH. Meperidine for the treatment of shaking chills and fever. Arch Intern Med 1980;140:483,484.

    Article  PubMed  CAS  Google Scholar 

  94. Kurz A, Ikeda T, Sessler DI, et al. Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. Anesthesiology 1997;86:1046–1054.

    Article  PubMed  CAS  Google Scholar 

  95. Magnan J, Paterson SJ, Tavani A, Kosterlitz HW. The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn-Schmiedeberg’s Arch Pharmacol 1982;319:197–205.

    Article  CAS  Google Scholar 

  96. Kurz M, Belani K, Sessler DI, et al. Naloxone, meperidine, and shivering. Anesthesiology 1993;79:1193–1201.

    Article  PubMed  CAS  Google Scholar 

  97. Adler MW, Bradley E, Martinez R, Geller EB. Production of hypothermia in the guinea pig by a kappa-agonist opioid alone and in combination with chlorpromazine. Pharmacol Biochem Behav 1991;40:129–132.

    Article  PubMed  CAS  Google Scholar 

  98. Votava Z, Elliott HW. The effect of morphine, meperidine, and methadone on the cholinergic EEG and behavioral activation in rabbits. In: Chemical Modulation of Brain Function (Sabelli HC, ed.). Raven Press, New York, 1973,123–135.

    Google Scholar 

  99. Mackenzie JE, Frank LW. Influence of pretreatment with a monoamine oxidase inhibitor (phenelzine) on the effects of buprenorphine and pethidine in the conscious rabbit. Br J Anaesth 1988;60:216–221.

    Article  PubMed  CAS  Google Scholar 

  100. Wynn RL, Bergman SA, Rudo FG, Leventer M. GABA mimetics diminish antinociception of meperidine under conditions which enhance other opioid μ-agonists. Arch Int Pharmacodyn 1990;304:136–146.

    PubMed  CAS  Google Scholar 

  101. Wagner LE, 2nd, Eaton M, Sabnis SS, Gingrich KJ. Meperidine and lidocaine block of recombinant voltage-dependent Na+ channels: evidence that meperidine is a local anesthetic. Anesthesiology 1999;91:1481–1490.

    Article  PubMed  CAS  Google Scholar 

  102. Takada K, Clark DJ, Davies MF, et al. Meperidine exerts agonist activity at the alpha(2B)-adrenoceptor subtype. Anesthesiology 2002;96:1420–1426.

    Article  PubMed  CAS  Google Scholar 

  103. Latta KS, Ginsberg B, Barkin RL. Meperidine: a critical review. Am J Ther 2002;9:53–68.

    Article  PubMed  Google Scholar 

  104. Mokhtarani M, Mahgob AN, Morioka N, et al. Buspirone and meperidine synergistically reduce the shivering threshold. Anesth Analg 2001;93:1233–1239.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anthony G. Doufas MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Doufas, A.G., Sessler, D.I. Physiology and clinical relevance of induced hypothermia. Neurocrit Care 1, 489–498 (2004). https://doi.org/10.1385/NCC:1:4:489

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/NCC:1:4:489

Key Words

Navigation