SHAPIRO syndrome , first described in 1969, 1is an extremely rare condition consisting of the clinical triad of recurrent hypothermia, sweating, and chills in the presence of agenesis of the corpus callosum. The periodicity of the hypothermic episodes ranges from hours to years, and episodes may last hours to weeks. 2Typically, but not invariably, there are associated central nervous system abnormalities affecting structures, particularly in the hypothalamus, that are related to thermoregulation. 2Although the effect of anesthesia and surgery on thermoregulation are well-known, 3such an effect has never been described in patients with Shapiro syndrome. In this report, we describe the clinical course and perioperative temperature changes of a patient with Shapiro syndrome who underwent elective cholecystectomy. The temperature changes in a group of normal patients undergoing the same procedure are compared.

A 49-yr-old man presented for elective laparoscopic cholecystectomy for treatment of cholelithiasis. He was diagnosed with Shapiro syndrome approximately 11 yr previously when he experienced attacks of flushing and profuse, drenching diaphoresis that were sometimes followed by the sensation of cold and shivering. The patient was treated with phenobarbital, and, over several weeks, the attacks diminished in frequency and finally stopped.

The attacks resumed, without any obvious precipitating event, 13 months before scheduled cholecystectomy and continued for 8 months. The episodes occurred 10–20 times per day and lasted 20–120 min. During the initial phase of the attacks, examination revealed profuse sweating and vasodilatation. Later, the skin was cold to touch and body temperature was as low as 31°C. Rigidity in the extremities was noted, although this may have been secondary to shivering. In addition, he seemed to be inattentive. Blood analysis indicated a normal complete blood count and blood chemistry. Cortisol (am), thyroid stimulating hormone, free T4, and prolactin concentrations were normal. Imaging studies revealed agenesis of the corpus callosum. Electroencephalographic recording during an attack indicated generalized disturbances compatible with cortical and subcortical grey matter dysfunction but no epileptiform activity. Autonomic testing demonstrated minimal heart rate changes during deep breathing or tilting, although blood pressure changes were within the normal range during the latter maneuver. A variety of medications (phenobarbital, procyclidine, carbidopa–levodopa, clonidine, carbamazepine, divalproex, and chlorpromazine) were tried without any obvious benefit. As with the first series of attacks, they gradually diminished in frequency and then stopped.

At the time of surgery, the patient had not experienced hypothermic episodes for 5 months and was not taking any medication. General anesthesia was induced with 2 mg midazolam, 200 mg propofol, and 150 μg fentanyl, and muscle paralysis was achieved with 50 mg rocuronium. Anesthesia was maintained with desflurane (3.2–6.0%) in an O2–N2O (40%:60%) mixture, and fentanyl was administered in 50-μg bolus doses as needed (total 250 μg). Cefazolin, 1 g, was administered shortly after induction, and muscle paralysis was reversed at the end of surgery with 2.5 mg neostigmine and 0.6 mg glycopyrrolate. Monitoring consisted of electrocardiography (leads II and V), pulse oximetry, capnography, and a nerve stimulator. Oral temperature was recorded before induction and in the postanesthesia care unit using an IVAC TEMP.PLUS II thermometer (San Diego, CA). Ambient operating room and nasopharyngeal temperatures were recorded using a Datex-Engstrom AS/3 anesthesia monitor and temperature probe (Helsinki, Finland). Invasive systemic arterial pressure was recorded via  a catheter inserted into a radial artery. Routine thermal care was used, which consisted of standard surgical draping. Intravenous fluid (normal saline) was not heated. After induction, intravenous fluid was administered throughout the procedure at a maintenance rate (4 ml · kg1· h1[first 10 kg]+ 2 ml · kg1· h1[second 10 kg]+ 1 ml · kg1· h1[remainder]= 136 ml · kg1· h1) via  a catheter inserted into an upper extremity.

In a subsequent series of 10 control patients undergoing elective laparoscopic cholecystectomy, the perioperative temperature changes were recorded for comparison. These patients were anesthetized using the same drugs and received identical thermal care.

The patient with Shapiro syndrome had an uneventful perioperative course. Blood pressure and heart rate were within limits normally observed. The ambient operating room temperature was 22°C. The nasopharyngeal temperature decreased rapidly from a baseline of 37.2 to 36.2°C during the first 10 min and then gradually decreased to a plateau of 36.0°C at 40 min (fig. 1A) during the operation. For the controls, the ambient operating room temperature was 21.6°C ± 1.3 (mean ± SD, n = 10). They demonstrated a similar rapid initial decrease in temperature, from a baseline of 36.7 ± 0.3 to 36.4 ± 0.7°C in the first 10 min, and their temperatures continued to decrease throughout the procedure (fig. 1A). In the postanesthesia care unit, the temperature of the Shapiro syndrome patient gradually increased and reached baseline by 50 min (fig. 1B). The temperature of the controls also increased gradually in the postanesthesia care unit but remained lower at any given time period compared with that of the Shapiro syndrome patient and did not return to baseline by 60 min (time of discharge). The Shapiro syndrome patient had an uneventful postoperative course and did not experience subsequent hypothermic episodes.

Fig. 1. Temperature (ordinate) as a function of time (abscissa) is plotted during the intraoperative (A ) and postoperative (B ) periods. Data were obtained from a patient with Shapiro syndrome (filled circles) and from normal patients (filled squares) undergoing laparoscopic cholecystectomy. The temperature recorded at time zero during the intraoperative period (A ) was obtained just before induction, whereas that recorded during the postoperative period (B ) was obtained immediately after arrival in the postanesthesia care unit. Error bars indicate SDs.

Fig. 1. Temperature (ordinate) as a function of time (abscissa) is plotted during the intraoperative (A ) and postoperative (B ) periods. Data were obtained from a patient with Shapiro syndrome (filled circles) and from normal patients (filled squares) undergoing laparoscopic cholecystectomy. The temperature recorded at time zero during the intraoperative period (A ) was obtained just before induction, whereas that recorded during the postoperative period (B ) was obtained immediately after arrival in the postanesthesia care unit. Error bars indicate SDs.

Close modal

Shapiro syndrome, or spontaneous periodic hypothermia, is an extremely rare neurologic disorder with previously unreported anesthetic considerations. We present the case of a patient with this disorder in whom abnormal thermoregulatory responses were not observed during anesthesia and surgery.

Reduction in temperature observed during anesthesia and surgery is common and is attributed to increased heat loss (radiation, convection, evaporation, and conduction) and altered thermoregulation. Volatile and intravenous anesthetic drugs reduce, in a dose-dependent manner, the threshold temperature that triggers heat-conserving mechanisms, such as vasoconstriction and shivering. 3This results in a predictable pattern of change in core temperature.

It is thought that the fluctuating body temperature observed in Shapiro syndrome is produced by an altered balance between the anterior hypothalamic heat-dissipating and the posterior hypothalamic heat-conserving centers. 2This results in an abnormal lower core temperature set point; the thermoregulatory mechanisms that defend this new set point still function normally, with an intact autonomic nervous system controlling the temperature-regulating effectors. The underlying cause for this altered balance is unknown. Suggested mechanisms include central nervous system structural abnormalities, degenerative processes, neurochemical dysfunction, inflammatory processes, and seizure activity. 2 

With the Shapiro syndrome patient described in this report, there were no signs of disturbed thermoregulation during the preoperative period, and temperature fluctuations were similar to those observed in the controls. Importantly, anesthesia did not trigger a hypothermic episode typical of Shapiro syndrome. This is consistent with the notion that anesthetics do not alter the hypothalamic temperature set point but instead change thermoregulatory threshold values, whereas hypothermia in Shapiro syndrome is a result of an abnormal set point.

It is interesting to consider the approach one should take had this patient experienced hypothermic attacks at the time of surgery. Perioperative hypothermia, even when mild, may be associated with adverse effects. These include impaired wound healing, increased surgical blood loss, cardiac arrhythmia and ischemia, shivering, discomfort, and decreased drug metabolism. 3For elective surgery, delaying the case until the patient is symptom-free seems prudent. In the event of emergency surgery during a symptomatic period, profound hypothermia should be treated appropriately to avoid its adverse effects. Because of the abnormally low thermoregulatory set point, active rewarming could be hindered by the patient’s normally functioning heat dissipating mechanisms, and a temperature value closer to the lowered set point may have to be accepted. However, because anesthetics inhibit thermoregulatory control, the ability to defend the lowered set point may be reduced. Hypothermia should be avoided in patients with Shapiro syndrome who are symptom-free, as in any other type of patient. Evidence from one patient with this disorder suggests that changes in body temperature per se  do not act as a trigger. 4Obviously, with this type of patient, it is important that temperature is recorded during the perioperative period and that appropriate equipment is available for active rewarming.

Abnormal cardioregulatory responses have been reported with patients experiencing episodic hypothermia. These include paroxysmal hypertension, 2hypotension, 4bradycardia, 5,6tachycardia 4and electrocardiographic abnormalities. 1Conceivably, the marked increase in peripheral blood flow and diaphoresis associated with the hypothermic attacks could contribute to a reduction in central volume. Therefore, consideration should be given to invasive monitoring.

In summary, we describe an uneventful anesthetic procedure for a patient with Shapiro syndrome undergoing cholecystectomy. The anesthetic agents described in this report were not observed to precipitate a profound hypothermic episode.

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