In this article, Lysa Pam Posner DVM DACVAA addresses the issue of perianesthetic hyperthermia in cats, including: why do some cats develop temperatures exceeding 105°F (40.5°C); what are the precipitating factors; and when should you intervene and how?
Introduction
Transient severe hyperthermia >105°F (40.5°C) occurs in some cats during recovery from general anesthesia (Niedfeldt & Robertson 2006; Posner et al. 2007; Killos et al. 2010). The upper range of normal body temperature for domestic cats is 102.5°F (39.2°C). Cats with severe post anesthetic hyperthermia have body temperatures that can exceed 42.2°C (108°F). Moderate and severe hyperthermia can be associated with tissue damage, abnormal physiologic functions, organ damage (including the brain), and tissue hypoxia; however cats seem more resistant to the syndrome of heat stroke than dogs. Most clinicians do not intervene until body temperature exceeds 103.5°F (39.7°C).
Thermoregulation
Cats are “warm-blooded” and maintain their body temperature between 100.5-102.5°F (38.1°C and 39.2°C). The range between upper and lower normal temperatures is referred to as the interthreshold range. When body temperature is within that range, no thermoregulatory responses are triggered.
Thermoregulation is a complex interaction between thermal sensing, central processing by the hypothalamus, and behavioral and physiologic responses. Heat and cold thermal receptors are widely distributed throughout the body. Cold information is transmitted primarily along Aδ fibers, whereas heat information is conducted along c-fibers and relayed via the spinal cord to the hypothalamus. The hypothalamus then “compares” these values with the threshold temperatures that trigger thermoregulatory responses. If body temperature has exceeded the threshold temperatures (either above or below), a series of behavioral and physiologic responses are triggered. Behavioral responses can include changing postures to minimize or maximize exposed surface area or heat seeking or avoidance behaviors. Autonomic responses can include vasomotor responses to preserve or release heat and activation of the sympathetic nervous system, which increases thermogenesis.
Thermogenesis
Thermogenesis is the process of heat production. In mammals thermogenesis can occur by increased muscle activity such as shivering or exercise or and nonshivering mechanisms such as diet/metabolism associated thermogenesis. Shivering increases body temperature by converting chemical energy (ATP) into kinetic energy, which creates heat. Shivering can increase metabolic rate 2 to 3 times normal and the release of thyroid hormones and catecholamines can increase metabolic rate and contribute to thermogenesis. Hyperthermia can occur from nonpyogenic mechanisms such as an inability to adequately dissipate heat or the inability to sense or react to body temperature changes.
Anesthesia and Thermoregulation
The effects of anesthesia on thermoregulation are multifactorial and additive. General anesthesia causes the loss of normal behavioral responses, decreases the hypothalamic response, enlarging the interthreshold range, inhibits shivering, and promotes peripheral vasodilation. In general, anesthetics inhibit thermoregulation in a dose-dependent manner and this predictably results in hypothermia.
Regional anesthesia (local blocks) also cause the loss of thermoregulatory control due alterations in vasomotor tone at blocked sites (potentially large surface areas), loss of ability to shiver, altered thermal sensing at the blocked sites and an increase in interthreshold range.
Post Anesthetic Hyperthermia in Cats
While some cats demonstrate a transient severe hyperthermia (> 105°F) following from general anesthesia, the cause of the abnormal thermoregulation remains unclear. To date, there has been no association with breed, sex, or underlying disease reported.
What Do We Know (from evidence-based medicine)?
● Opioids alter thermoregulation by resetting the threshold point controlled by the hypothalamus (Cox et al. 1976).
● Hydromorphone, morphine, buprenorphine, butorphanol, and fentanyl affect thermoregulation in cats. When studied as individual agents, they rarely cause more than mild hyperthermia (Posner et al. 2010)
● Administration of buprenorphine at 0.24mg/kg (Simbadol) is associated with mild to moderate hyperthermia for up to 20 hrs (Cannarozzo et al 2020).
● Severe hyperthermia in cats is consistently associated with some type of opioid.
● Severe hyperthermia occurs in cats anesthetized with and without inhalant anesthesia.
● Severe hyperthermia has been associated with cats anesthetized with and without ketamine (Niedfeldt et al, 2006; Posner et al. 2007).
● Severe hyperthermia has been associated with cats anesthetized with and without hydromorphone.
● Severe hyperthermia (108°F [42.2 °C]) can occur following administration of butorphanol in combination of with midazolam and ketamine.
● Administration of NSAIDs does not attenuate hyperthermia.
● Cats with severe hyperthermia often appear restless or agitated.
● No cats with severe hyperthermia showed signs or complications of heat stroke.
What Do We Think We Know (from anecdotal reports)
● Cat with severe post anesthesia hyperthermia are generally hypothermic immediately before recovery. Cats with the lowest body temperatures at the beginning of recovery had the highest body temperatures during recovery. One hypothesis is that the thermogenesis triggered by hypothermia coupled with the increased interthreshold range results in excessive thermogenesis and subsequent hyperthermia.
● Cats that are administered ketamine and hydromorphone appear to have a higher incidence of severe hyperthermia than cats administered other anesthetic protocols.
● Administration of naloxone quickly attenuates hyperthermia, implicating opioids as a precipitating factor.
Presumptive Conclusions
● Post-anesthetic hyperthermia in cats is likely multifactorial; including the effects of opioids on the hypothalamus altering the interthreshold range, exaggerated thermogenesis following hypothermia, as well as the effects of other anesthetic agents.
● Anesthetic protocols that include opioids put cats at risk to develop severe post-anesthetic hyperthermia.
● Post-anesthetic hyperthermia persists as long as the duration of action of opioid used (up to 20 hrs for Simbadol).
● The incidence of severe hyperthermia appears to increase when ketamine is a co-anesthetic.
● The incidence of severe hyperthermia appears to increase inversely proportional to hypothermia immediately before recovery.
● Antagonism (reversal) of opioids attenuates hyperthermia in cats during recovery.
● Minimal morbidity has been reported in cats affected by post-anesthetic hyperthermia
Personal recommendations
Based on what we know (and don’t know).
● I routinely check body temperature in cats during and following anesthesia. The SOP in our hospital is to check body temperature in animals recovering from anesthesia until their body temperature returns to normal. I do not increase my vigilance in cats administered opioids.
● Any cat recovering from anesthesia that shows agitation or hypermobility will have its body temperature measured since those behaviors have been associated with severe post anesthetic hyperthermia in cats.
● I routinely use mu (full and partial) and kappa opioid drugs in cats. I choose the opioid based on the appropriateness of the drug to manage pain, not whether I am worried about the risk of hyperthermia.
● It has not been reported, and I have not seen a cat demonstrate severe hyperthermia while on a fentanyl CRI, so do not hesitate to use it when appropriate.
● I do not attempt to treat mild or moderate hyperthermia; <104.0°F/ 40°C. The elevated body temperature is transient and does not appear to cause any morbidity.
● I treat cats demonstrating behaviors associated with severe hyperthermia and temperatures >104.0°F(40°C) in an escalating fashion based on the severity of hyperthermia. Treatment can include: removing heating devices, acting cooling (fan, wetting paws), antagonism of opioids, cool IV fluids.
● There is not clear evidence on what is the best reversal agent. I have seen and it has been reported that naloxone administration quickly results in the return to normal body temperature. Since butorphanol has been associated with severe hyperthermia, I do not use it as a mu antagonist reversal to treat post anesthetic hyperthermia.
● I do not administer NSAIDs to attempt to decrease the body temperature. There is no evidence that the elevation in body temperature is associated with inflammation, and there is evidence that is not effective.
Dr. Posner is a Professor of Veterinary Anesthesiology in the College of Veterinary Medicine (CVM) at NC State University. She completed a B.S. degree in biochemistry from Purdue University and a Doctor of Veterinary Medicine (DVM) degree from Cornell University. Following graduation from veterinary school, she practiced as a general practice veterinarian for 8 years before returning to Cornell University to complete a Residency in Veterinary Anesthesiology. She is a Board Certified Specialist in Veterinary Anesthesia and Analgesia.
References
1. Cannarozzo CJ, Kirch P, Campoy L, et al: Retrospective investigation of an association between high-dose buprenorphine and perpetuation of post-anesthesia hyperthermia in cats following ovariohysterectomy. Journal of Feline Medicine and Surgery:1098612X20976207, 2020.
2. Killos MB, Graham LF, Lee J: Comparison of two anesthetic protocols for feline blood donation. Veterinary anaesthesia and analgesia 37:230-239, 2010.
3. Niedfeldt RL, Robertson SA: Postanesthetic hyperthermia in cats: a retrospective comparison between hydromorphone and buprenorphine. Veterinary Anaesthesia and Analgesia 33:381-389, 2006.
4. Posner LP, Gleed RD, Erb HN, et al: Post-anesthetic hyperthermia in cats. Veterinary anaesthesia and analgesia 34:40-47, 2007.
5. Posner LP, Pavuk AA, Rokshar JL, et al: Effects of opioids and anesthetic drugs on body temperature in cats. Veterinary anaesthesia and analgesia 37:35-43, 2010.
6. Cox B, Ary M, Chesarek W, et al: Morphine hyperthermia in the rat: An action of the central thermostats. European journal of pharmacology 36:33-39, 1976.