VOLUME 36, ISSUE 1

Subarachnoid blocks are frequently associated with modest degrees of hypothermia related to their peripheral vasodilating effects leading to redistribution of heat from the core to the periphery. However, rarely, the hypothermia can be profound and refractory. Refractory intrathecal opioid induced hypothermia (OIH) is a presumed uncommon side effect of neuraxial opioids. A literature review of intrathecal OIH revealed several case reports, case series, and a randomized controlled study describing this effect. The overarching theme described for intrathecal OIH included refractory hypothermia following intrathecal morphine. Hess et al described a case series of 14 patients with presumed intrathecal OIH following spinal anesthesia with bupivacaine, fentanyl, and morphine.1 Symptomatically, all the patients described feeling hot and exhibited diaphoresis. Four of these patients were treated with conservative measures and warming techniques. The other 10 patients were treated with lorazepam in doses ranging from 1 to 2 mg. The conservatively treated group had an average of 6 hours of hypothermia refractory to standard treatments while the 10 treated with lorazepam had “rapid cessation” of their hypothermia with normalization of temperature.

Additionally, four case reports described presumed OIH following intrathecal opioids. All had similar presentations with refractory hypothermia unresponsive to typical conservative measures.2, 3, 4, 5 All were eventually treated by unconventional methods and all described rapid resolution of the hypothermia. One of the patients was treated with sublingual lorazepam,2 one with a single low dose of intravenous midazolam,3 one with mixed opioid partial agonist/antagonist, nalbuphine,4 and one with naloxone.5

Although most GABA receptors are located in the cerebral cortex, they are also found in the hypothalamus. The effect of binding of these receptors in the hypothalamus by benzodiazepines is not completely understood, but it has been postulated that this may modulate thermoregulation. Similarly, it has been postulated that opioid antagonists can effectively reverse intrathecal OIH by antagonism of the opioid receptors. Animal studies have suggested that the hypothermia effect of opioids may be modulated by a nitric oxide pathway, as inhibitors of nitric oxide have been shown to block the hypothermic response to opioids.

A randomized, double-blind study of intrathecal OIH was conducted by Hui, et al, evaluating patients for hypothermia after intrathecal morphine.6 The control group had saline added to the intrathecal bupivacaine instead of morphine. They found significant decreases in body temperature in both the morphine and saline control groups but the maximum decrease in temperature was significantly more pronounced in the morphine group. The lowest recorded temperature being 93.7 degrees Fahrenheit.

The patient in the clinical vignette was successfully treated with low-dose lorazepam and demonstrated a rapid normalization of her core temperature to within normal range. Two months following the patient in the vignette, another patient had similar refractory hypothermia presumed to be intrathecal OIH. However, this patient did not demonstrate normalization of temperature following two doses of lorazepam. Interestingly, she did respond rapidly to a dose of 0.04mg of naloxone with normalization of temperature 25 minutes later.

Intrathecal OIH appears to be a side effect of intrathecal opioids, most likely morphine. It may be more common than once thought and has been well described in the published literature. Although the mechanism does not appear to be well understood, successful treatment has been described using benzodiazepines and opioid antagonists when conventional therapies fail.

Hypothermia can lead to many potential harmful effects in the perioperative phase. Therefore, recognition and treatment of intrathecal OIH is clinically important in patients who have received intrathecal opioids and the techniques to address this are not part of our standard workflow. It is important to consider intrathecal OIH in patients who exhibit refractory hypothermia following neuraxial opioids so that potential alternative treatments, as described above, may be considered when conventional rewarming techniques prove unsuccessful.

Since a moderate degree of hypothermia is an expected and common side effect of subarachnoid blocks due to vasodilation and thermal redistribution, it is challenging to clearly delineate the true incidence of intrathecal IOH and if it is truly different from the routine hypothermia associated with subarachnoid blocks. Certainly, further study of the true nature of this more profound hypothermic response to intrathecal opioids would be helpful to better understand it. Until we know more about this response, we should remain vigilant in monitoring these patients closely for any signs of refractory hypothermia.