Our Patient Safety Tip of the Week for December 4, 2012 “Unintentional Perioperative Hypothermia: A New Twist” discussed unintentional hypothermia occurring during surgical procedures, primarily cesarean deliveries, performed under spinal anesthesia using morphine. The “twist” was that some of these patients had paradoxical sweating (or vasodilation or feeling “hot”) despite profound hypothermia.
Three articles in the January 2018 issue of Anesthesia & Analgesia discuss the issue of unintentional hypothermia in obstetrics. Using an intestinal telemetric sensor, a rapid decrease in core temperature was documented during cesarean delivery under spinal anesthesia (du Toit 2018). Fifty percent of participants in this study became hypothermic. Although the surgical procedure is typically of short duration, women undergoing spinal anesthesia for cesarean delivery experience significant hypothermic exposure and compromised thermoregulation for several hours.
Participants reached their intestinal temperature nadir after a median of 1 hour. The majority of participants experienced a continued decrease in intestinal temperature after leaving the operating room. Interestingly, despite the significant decrease in core temperature, the median thermal comfort score remained zero (neutral) at all but the late afternoon measurement time.
In another study, Munday and colleagues found that a short period of preoperative warming is not effective in preventing intraoperative temperature decline for women receiving intrathecal morphine (Munday 2018). This was a prospective, single-blinded, randomized controlled trial compared 20 minutes of forced air warming (plus intravenous fluid warming) versus no active preoperative warming (plus intravenous fluid warming) in 50 healthy American Society of Anesthesiologists graded II women receiving intrathecal morphine as part of spinal anesthesia for elective cesarean delivery.
Allen and Habib (Allen 2018), in their editorial accompanying the two new articles on unintentional hypothermia, lament the relative lack of proven interventions to prevent or treat hypothermia in obstetrical patients. They note that current core temperature monitoring practices and temporary management guidelines will need to be updated. They also emphasize the need to extend the duration of temperature monitoring well beyond the early recovery period.
Interestingly, none of the 3 new articles even mentions the phenomenon we highlighted in our Patient Safety Tip of the Week for December 4, 2012 “Unintentional Perioperative Hypothermia: A New Twist”. Specifically, there appears to be a syndrome related to cases (most often obstetrical) in which spinal anesthesia with morphine is used and patients develop hypothermia with paradoxical sweating (Ryan 2012, Hess 2005). Though most cases in the literature have followed cesarean sections, the case described by Ryan et al. was in a patient who underwent a knee arthroplasty. Spinal anesthesia was used with 11 mg of isobaric 0.5% bupivacaine, 15 micrograms of fentanyl, and 150 micrograms of morphine. The patient’s temperature reached a low point of 33.6 degrees C four hours after surgery, though at times her temperature could not be recorded by any route. Despite the hypothermia she felt hot and was diaphoretic without shivering. Warming efforts using forced air warming blankets, infusion of warmed intravenous fluids, and hourly bladder irrigation with warm saline were not successful in elevating her temperature. But a quick literature search by the authors showed the syndrome often responds to benzodiazepines and their patient rapidly became normothermic after receiving a small sublingual dose (0.5 mg) of lorazepam. The authors go on to discuss the cases in the literature and the current theory of the pathogenesis of this syndrome. The theory is that enough of the morphine ascends in the subarachnoid space to reach the hypothalamus where it interacts with receptors important in thermoregulation. Essentially this leads to alteration of the hypothalamic thermoregulatory set point causing the body to feel hot and sweat in attempt to adapt to heat. Benzodiazepine receptors are also found in the hypothalamus and are probably also involved in thermoregulation.
Hess et al had reported on 14 patients who developed hypothermia following cesarean sections in which they had received spinal anesthesia with bupivacaine, morphine and fentanyl (Hess 2005). All had diaphoresis and felt hot. Four of the 14 were given lorazepam and had prompt resolution of symptoms and rapid increase in temperature. The remainder, who received conventional management of hypothermia, were hypothermic and symptomatic for 6 hours on average. The authors subsequently observed 100 consecutive patients and found 6% developed symptomatic hypothermia lasting for several hours.
Another article (Giladi 2015) discussed the differential diagnosis of prolonged hypothermia following cesarean delivery and concluded the patient likely had the syndrome of hypothermia with paradoxical sweating induced by spinal anesthesia with morphine.
There is some evidence suggesting that this phenomenon might be dose-related. In a randomized controlled trial Hui and colleagues randomized patients undergoing elective cesarean section to receive either 150 micrograms of morphine or normal saline along with the bupivacaine in their spinal anesthesia (Hui 2006). They found that both groups developed hypothermia but that the maximum decrease in temperature was greater in the morphine group and of longer duration. This suggests that even a low dose of morphine may intensify the hypothermic effect of spinal anesthesia. However, they point out that many of the cases in the literature had much higher doses of morphine. In fact, they note that larger doses are avoided because they are often associated with nausea, vomiting, pruritis and shivering.
In at least 3 cases hypothermia after intrathecal morphine has improved promptly after administration of naloxone. In one case (Sayyid 2003) the patient’s temperature had dropped to 33.6 degrees C after a cesarean section and the patient was sweating excessively despite the hypothermia. She also had nausea, vomiting, pruritis and some sedation. Following naloxone administration all the above symptoms disappeared and she developed shivering and cessation of sweating concomitant with rising body temperature. In the other case (Mangus 2011) a patient developed hypothermia unresponsive to usual warming measures several hours after a cesarean section in which she received intrathecal morphine. Severe pruritis and lethargy were also present. Naloxone was administered intravenously in incremental doses and her temperature began to rise within 5 minutes. The pruritis and lethargy also improved and her pain control was never compromised. In another case profound hypothermia followed intrathecal injection of an unintended high dose of morphine for a cesarean delivery (Kanazawa 2015). Within 2 hours after completion of surgery, the patient’s axillary temperature decreased to 35.0°C despite an ambient temperature of 25°C. Despite active warming with a forced-air warming device, her temperature continued to drop to 34.0°C over the next 3 hours. The patient was not aware of hypothermia. In fact, she felt hot and was perspiring profusely. After review of the anesthesia record revealed that 1 mg of morphine had been injected intrathecally, 0.2 mg of naloxone was administered intravenously over a 10-minute period. Soon after starting the naloxone injection, the patient felt cold and demonstrated extensive shivering, while her axillary temperature rapidly rose to 35.5°C over the next hour. Nausea and respiratory depression also subsided thereafter.
Another article demonstrated that atropine could stop the excessive sweating associated with intrathecal morphine or fentanyl administration (Mazy 2016). Excessive sweating was observed in three cases among 217 consecutive patients wo underwent lower limb orthopedic surgery under spinal anesthesia using intrathecal morphine or fentanyl administration. The sweating began about 3 hours after spinal injection. Atropine promptly stopped the sweating in 3 cases, followed by slow rise in body temperature. The Mazy article has an excellent discussion about the potential mechanisms. The delayed onset was explained as the time elapsed until cephalad spread of morphine to the hypothalamic opioid receptors involved in temperature regulation.
Admittedly, many of the patients in the 3 new articles were said to have shivering, and sweating was not mentioned. Therefore, those patients may have had different mechanisms responsible for the hypothermia than the mechanism postulated in the Ryan and Hess articles. Nevertheless, it is very important to recognize the hypothermia with paradoxical sweating phenomenon since, as in the case described by Ryan, there may be prompt resolution after a small sublingual dose of lorazepam.
Perioperative hypothermia can have serious adverse consequences, including increased risk of surgical site infections, myocardial ischemia, prolongation of drug effects, bleeding diatheses, shivering, pressure ulcers, poor patient satisfaction, and increased economic effects due to things like increased length of stay (Hart 2011). This excellent review of unintended perioperative hypothermia by Hart and colleagues at the Ochsner Clinic does not mention the “hypothermia with paradoxical sweating” phenomenon. Nor did it consider spinal anesthesia with opioids as a risk factor for hypothermia.
Likewise, this phenomenon also receives little or no attention in most of the major guidelines and other resources on perioperative hypothermia (ASPAN 2010, PPSA 2008, NICE 2008, NICE 2017, AORN 2007, AORN 2013, AORN 2017).
But another study by Munday and colleagues (Munday 2017) refutes the association between perioperative hypothermia and use of intrathecal morphine. That study was a retrospective case controlled study of patients undergoing spinal anesthesia for cesarean delivery, comparing 179 who received intrathecal morphine and 179 without intrathecal morphine (control group). Administration of intrathecal morphine (combined with intrathecal fentanyl and hyperbaric bupivacaine) is standard care in their institution; therefore, the no morphine group was selected first by identifying patients who, because of clinical reasons such as allergy, did not receive intrathecal morphine. This group was then matched with patients who did receive intrathecal morphine. There was no significant difference in mean postoperative temperature for the morphine group (mean postanesthesia care unit arrival temperature, 35.91°C) and the no morphine group (mean postanesthesia care unit arrival temperature, 35.88°C). However, paradoxical sweating was noted in only 3 patients in the morphine group and 1 in the no morphine group. This study did show that there was a decline in core temperature in both groups preoperatively to postoperatively that was statistically and clinically significant. However, overall the fall in temperature was considerably less than that described in the published cases of “unintentional hypothermia with paradoxical sweating”.
Quite frankly, given the difficulties maintaining normothermia in this patient population and given that the timeframe and duration of hypothermia would be compatible with the theoretical “resetting of the hypothalamic thermostat”, we are surprised that no one seems to have tried either lorazepam or naloxone in those cases even though they lacked paradoxical sweating.
Undoubtedly, there would be concern about exposing a neonate to the effects of lorazepam or naloxone or any other drug. However, since the hypothermia extends long after the cesarean delivery, use of lorazepam to reverse hypothermia would be an option after the delivery.
As we noted in our original column, the importance of recognizing the “hypothermia with paradoxical sweating” is twofold. First, you may want to limit the dose of intrathecal morphine used. Second, you need to amend your hypothermia management protocols to take this phenomenon into account. Specifically, there should be a prompt to consider the phenomenon if the expected improvement in hypothermia is not occurring within a reasonable amount of time after conventional warming procedures have been instituted. Perhaps even a prompt at the beginning of your protocol to look for signs you would not expect with hypothermia (i.e. sweating, hot feeling, vasodilation) might suggest this unusual etiology for the hypothermia. The presence of nausea and pruritis might be an additional clue. In either case the prompt should remind you to consider a trial of either low dose benzodiazepine or naloxone.
You probably should have a formal protocol you follow for prevention and management of perioperative hypothermia. Use one of the above mentioned guidelines to start with. But make sure that whatever protocol you choose you add that prompt we noted above to at least consider the possibility of the morphine-induced syndrome because its management requires additional considerations.
Some of our previous columns on maternal and ob/gyn issues:
February 5, 2008 “Reducing Errors in Obstetrical Care”
February 2010 “Joint Commission Sentinel Event Alert on Maternal Deaths”
April 2010 “RCA: Epidural Solution Infused Intravenously”
July 20, 2010 “More on the Weekend Effect/After-Hours Effect”
August 2010 “Surgical Case Listing Accuracy”
September 7, 2010 “Patient Safety in Ob/Gyn Settings”
January 2011 “Surgical Fires Not Just in High Risk Cases”
February 8, 2011 “”
April 2011 “Ob/Gyn Patient Safety Programs”
April 24, 2012 “Fire Hazard of Skin Preps Oxygen”
July 2012 “WHO Safe Childbirth Checklist”
December 4, 2012 “Unintentional Perioperative Hypothermia: A New Twist”
September 2013 “Full-Time Laborists Reduce C-Section Rates”
October 2013 “Challenging the 39-Week Campaign”
November 2013 “The Weekend Effect: Not One Simple Answer”
January 2014 “It MEOWS But Doesn’t Purr”
May 13, 2014 “Perioperative Sleep Apnea: Human and Financial Impact”
August 19, 2014 “Some More Lessons Learned on Retained Surgical Items”
November 3, 2015 “Medication Errors in the OR - Part 2”
February 7, 2017 “”
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Journal of PeriAnesthesia Nursing 2017; article in press