BJA Advance Access originally published online on July 23, 2009
British Journal of Anaesthesia 2009 103(4):554-560; doi:10.1093/bja/aep199
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Hypothermic responses to infection are inhibited by 
2-adrenoceptor agonists with possible clinical implications
1 Department of Anaesthesia, Frenchay Hospital, North Bristol NHS Trust, Frenchay, Bristol, UK.
2 Department of Anatomy and
3 Psychopharmacology Unit, University of Bristol, UK.
4 Department of Medicine, United Bristol Healthcare Trust, Bristol Royal Infirmary, Bristol, UK.
* Corresponding author. E-mail: stevetolchard{at}yahoo.co.uk
Background: 
2-Adrenoceptor agonists are currently used as primary sedative agents in high dependency patients who are at high risk of sepsis. Clinical surveillance of such patients relies in part on their ability to mount appropriate responses to infection, in particular thermal responses. Thermoregulatory responses to infection are well studied in the rat and in this species, and humans, infection can induce febrile, hypothermic, or mixed hypothermic and febrile responses. The involvement of noradrenergic systems in thermal responses to infection prompted the hypothesis that ligands that act on adrenoceptors may interfere with the normal thermal responses to infection.
Methods: In this study on rats, the effect of infusion of the selective 2-agonist, mivazerol, on hypothermic and plasma corticosterone responses induced by bacterial lipopolysaccharide (LPS) was investigated.
Results: Clinically effective doses of mivazerol (4.8 and 10 µg kg–1 h–1) had no effect on body temperature alone. However, mivazerol significantly inhibited the typical thermoregulatory response to bacterial LPS in a dose-dependent manner. This effect was mimicked by the selective 2-agonist, UK14304-18 (6 µg kg–1 h–1), and antagonized by the 2-antagonist, RX811059A (7 µg kg–1 h–1). The 2-ligands had no effect on basal or LPS-induced corticosterone levels.
Conclusions: These data suggest that early thermoregulatory responses to infection can be selectively antagonized by ligands that activate 2-adrenoreceptors. High dependency patients receiving 2-adrenoceptor agonists may not be capable of mounting a normal thermal response to infecting organisms and clinical monitoring using core temperature to detect infection may therefore be unreliable in these vulnerable patients.
Keywords: adrenergic receptors; bacterial infection; temperature
5 Present address: The Orchard Medical Centre, Macdonald Walk, Kingswood, Bristol BS15 8NJ, UK