1. Fever during Anesthesia Speaker: Guo, Shu-Lin Date: 2003-12-09

2. Thermoregulation Thermoregulatory response: a core temperature that triggers physiological defenses against excessive heat or cold Inter-threshold range: the difference between the sweating and vasoconstriction thresholds

3. Thermoregulation Setpoint: the normal inter-threshold range is only a few tenths of a degree centigrade

4. Role of Fever Pathphysiology: the pyrogenic stimulation activates hypothalamic thermoregulatory control centers Elevation of setpoint: a synchronous elevation in the cold- response and warm-response threshold

6. Role of Fever Kluger et al. Science. 1975 Method: the desert iguana infected with bacteria Result: a clear correlation between the increase in body temperature after bacterial infection and the host survival rate

7. Role of Fever Vaughum et at. Brain Research Bulletin 1998 Method: rabbit with fever Result: antipyretic use reduced body temperature and significantly decreased the host survival rate

8. Role of Fever Disadvantage: Increasing cardiac output, oxygen consumption and energy consumption Antipyretic use timing: the elderly or patients with poor cardiac or pulmonary function

9. Process of Fever Thermoregulatory control Neuron-mediated primarily Vagal afferent pathways Humoral mediators The major endogenous pyrogens Interlukin-1 Interlukin-6 Tumor necrosis factor (TNF-alpha) Interferon-alpha

10. Process of Fever Process of fever The core temperature elevates All thermoregulatory response thresholds also elevate Cold-defenses are strongly augmented The maximal temperature usually dose not exceed 42°C

11. Process of Fever Antipyretics: Pyrogens vs. antipyretics (cryogens) Endogenous antipyretics: Interleukin-10 Glucocorticoids Vasopression Melanocyte-stimulating hormone (alpha- MSH) Nitric oxide

13. Fever during Anesthesia Thermoregulatory control during anesthesia Volatile anesthetics, propofol, opioids and sedatives: Slightly increase the sweating threshold Markedly decreasing the vasoconstriction and shivering thresholds Inter-threshold range increases to 2-4°C

14. Volatile Anesthesia And Fever Fever is relatively rare during general anesthesia The general anesthesia attenuates fever by the lowering of thermoregulatory threshold of cold defences

15. Volatile Anesthesia And Fever Negishi et al. Anesthesiology 1998 Method: desflurane and IL-2 induced fever Result: 1.0 MAC essentially obliterating the temperature increase by IL-2

17. Volatile Anesthesia And Fever Lenhardt et al. Anesthesiology 1999 Methods: measure the thresholds of IL-2 induced fever and general anesthesia Result: the combination of IL-2 administration and desflurane increased the sweating threshold and reduced the vasoconstriction threshold compared to IL-2 alone

19. Volatile Anesthesia And Fever Peripherally mediated inhibition by desflurane anesthesia Desflurane did not affect the plasma concentrations of the circulating cytokines induced by IL-2 Desflurane decreases the thermoregulatory thresholds of cold defenses via central action

20. Intravenous Anesthesia And Fever Roytblat et al. A&A 1998 Before cardiac pulmonary bypass, ketamine (0.25mg/kg) reduces serum IL-6 concentration during and post surgery Crozier et al. BJA 1994 Alfentil and propofol diminishes release of IL-6 during abdominal surgery

21. Opioids And Fever Opioids administration increases warm-response thresholds and decreases cold-response thresholds The pattern of inhibition is similar to that produced by general anesthesia though the magnitude is somewhat low

22. Opioids And Fever Opioids also suppress fever in a dose- dependent fashion Opioids use in ICU or during the post- operation period need to be aware

23. Neuraxial anesthesia and Fever Re-distribution is a major cause of core hypothermia during epidural and spinal anesthesia The BT loss rate is determined by the inequality between heat loss and heat productions well as block level

24. Neuraxial anesthesia and Fever With neuraxial anesthesia peripheral nerve block is a more important cause of hypothermia Sufficient core hypothermia will trigger vasoconstriction and shivering even during neuraxial anesthesia, but only in the unblocked areas

25. Neuraxial anesthesia and Fever Epidural analgesia is frequently associated with hyperthermia, especially during labor and post- operative period The paradoxical hyperthermia often prompts clinical interventions such as work-up for infection and newborn sepsis

26. Neuraxial anesthesia and Fever During epidural analgesia, the sweating threshold slightly increases Epidural pain control vs intravenous pain control

28. Paralysis And Fever Paralysis prevents shivering and the associated increase in metabolic heat production Paralysis can reduce the magnitude of fever, but clinically its effect seems to be less important than anesthetic- induced inhibition of fever

29. Post-operative Fever A positive relationship between the post-operative increase in core temperature and plasma IL-6 concentration

31. Treatment of Fever Most febrile patients are treated with antipyretic, mainly for patients comfort Fever should be treated in patients with cardiopulmonary dysfunction, acute brain stroke or injury, or in those whose temperature above 40°C

32. Treatment of Fever Active cooling does not reduce core temperature, but increases the metabolic rate, activates the autonomic system, and provokes thermal discomfort

33. Treatment of Fever Fever occurs in almost half of the patients with acute brain stroke or injury Mild brain hyperthermia worsens the functional outcome by enhancing neurotransmitter release, exaggerating oxygen radical production, and extending blood-brain barrier breakdown

34. Any Questions?