Malignant hyperthermia (MH) is generally thought of in its fulminant from, manifesting as severe hypercapnia, uncontrollable hyperthermia, and accompanied by hyperkalemia with cardiac dysrhythmias. We report a case of an adult surgical patient who developed severe postoperative rhabdomyolysis without other symptoms and who was subsequently found by muscle biopsy to be MH susceptible.

A 50-yr-old, 100-kg male was scheduled for a radical prostatectomy for prostatic adenocarcinoma. Medical history included depression, chronic left upper extremity weakness for 23 yr, and peptic ulcer disease. Surgical and anesthetic history included general anesthesia for cholecystectomy, hemorrhoidectomy, and three procedures on his left lower extremity (for vein stripping). Halothane and succinylcholine were used in at least one of the anesthetics, without recorded complications. Family history was unremarkable. Medications included nortriptyline, naproxen, cimetidine, valproic acid, and isoxsuprine. The patient had not used tobacco or alcohol since 1991 and had no allergies to medications. Preoperative physical examination was unremarkable except for some dystrophic changes and lessened motor strength (3/5) in the left upper extremity. Laboratory data 6 days before surgery were normal except for an incomplete right bundle branch block on his electrocardiogram.

The patient received no premedication for sedation or analgesia until his arrival to the preoperative holding area where he received 2 mg of intravenous midazolam during placement of an epidural catheter. Standard monitors were placed, along with a radial artery catheter. The patient was placed in the supine position, and general anesthesia was induced with midazolam, fentanyl, sodium thiopental, d-tubocurare, and succinylcholine. No masseter muscle rigidity was noted during direct laryngoscopy. Maintenance of anesthesia was conducted with isoflurane, nitrous oxide, and fentanyl during the 8-h period. Positioning for the surgical procedure was supine with a 30 [degree sign] flexed back and an elevated kidney rest. Hemodynamic values remained within 30% of the preoperative values. Serial arterial blood gas analysis indicated consistent normocapnia and a pH between 7.33 and 7.37. The capnograph display indicated a PETCO2between 28 and 35 mmHg. The arterial oxygen tension ranged from 110 to 148 mmHg while the patient received an FIO2of 0.35–0.44. A serum potassium measured 45 min after induction was 4.0 mEq/l. The potassium value remained stable throughout the case.

The blood loss was estimated to be 3000 ml. Fluids administered included 6% hetastarch, autologous blood, 0.9% saline, and lactated Ringer's solution. At the end of the surgical procedure, neuromuscular blockade was reversed, the endotracheal tube was removed, and the patient was taken to the postanesthesia care unit (PACU). Vital signs remained within preoperative range during this time. The patient was awake and expressed no specific complaints. Results of a blood gas analysis were normal. He was discharged from the PACU to the intensive care unit, and an epidural infusion of morphine and bupivacaine was initiated for analgesia. Postoperative vital signs remained within normal limits until approximately 13 h postoperatively when he became febrile to an oral temperature of 37.6 [degree sign] Celsius. The oral temperature remained close to 37.8 [degree sign] Celsius throughout the postoperative course.

During the first postoperative day, the patient felt well, had return of bowel sounds, and had his nasogastric tube withdrawn. He experienced some left lower extremity numbness, and because of plans to ambulate, the bupivacaine was withheld from his epidural infusion. During the second postoperative day, the patient began to complain of lumbar pain. Physical examination of the lumbar region revealed paravertebral muscle tenderness bilaterally. Also during the second postoperative day, his abdomen became slightly distended, and oral intake was withheld because of the possibility of an ileus. Blood was drawn to analyze multiple enzymes levels to determine if an abnormal intraabdominal process was occurring. The serum glutamic oxaloacetic transaminase (SGOT) and lactic dehydrogenase (LDH) levels were elevated (505 U/1 and 1143 U/l, respectively).

On postoperative day three, the patient continued to complain of lumbar pain, and despite adequate analgesia of his wound pain, he requested withdrawal of his epidural catheter. He was then placed on intravenous patient-controlled analgesia (PCA) with morphine. His lumbar pain increased in severity after withdrawal of epidural analgesia. Serum gamma-glutamyl transferase (GGT), serum glutamic pyruvic transaminase (SGPT), and creatine kinase (CK) levels were ordered to delineate any abnormal gastrointestinal processes and rule out a muscle source of the increased SGOT and LDH. The SGPT was 245 mU/l, the GGT was normal, and the CK level was > 285,000 U/l. A diagnosis of rhabdomyolysis was made. At this time, the serum creatinine was 1.3 mg/dl. Further examination revealed no sign of compartment syndrome in any extremity. A nephrologist was then consulted, who suggested institution of intravenous normal saline, mannitol, and sodium bicarbonate to prevent acute renal failure from myoglobinuria (urine myoglobin = 226 mg/l). He was transferred to the intensive care unit.

A computed tomographic scan was performed to determine whether an abnormal intraabdominal or pelvic process was present. There were no abdominal or pelvic abnormalities noted, except for expected postoperative changes from his prostatectomy. The scan revealed edema surrounding the latissimus dorsi muscles and overlying the external oblique abdominal muscles bilaterally. There was also slight decreased attenuation of the paraspinal muscles.

Over the balance of his hospitalization, the patient's serum muscle enzyme levels gradually dropped to CK, 7,486; LDH, 880; and SGOT, 234 (Table 1) by the time of discharge. His serum creatinine level remained stable. Although he continued to have lumbar pain, he experienced no other problems and was discharged 10 days after his surgical procedure. Laboratory analysis obtained during a postoperative clinic visit 1 week after discharge continued to indicate elevation of muscle enzymes (SGOT, 59; LDH, 411) and mild hyperkalemia (K sup +, 5.3 mEq/l).

Table 1. Sequence of Laboratory Values over Time 

Table 1. Sequence of Laboratory Values over Time 
Table 1. Sequence of Laboratory Values over Time 

Approximately 4 months after his surgical procedure, the patient was referred to our Malignant Hyperthermia Center for evaluation. Because strong signs of MH were lacking, the value of a muscle biopsy was questioned, but because of the severity of his rhabdomyolysis, we decided to obtain a muscle biopsy to test for MH. Vastus lateralis muscle was obtained during general anesthesia, performed with a non-triggering anesthetic technique. Three muscle fascicles were tested with caffeine, and contractures were initiated in each at 0.5 mM concentration, exhibiting an abnormal response. Two of these fascicles had isometric contracture tensions of 0.33 g and 0.75 g when exposed to 2.0 mM caffeine, exceeding the MH diagnostic threshold of 0.2 g. [1]Three other fascicles were tested for halothane-induced contracture response, and in two of these, tensions of 0.5 g and 0.7 g exceeded the diagnostic threshold range of 0.2–0.7 g. Other fascicles tested with caffeine plus halothane also produced abnormal responses. These results indicated MH susceptibility for this patient as judged by diagnostic testing standards set forth by the North American MH Protocol. The patient was counseled regarding the implications of the results for himself and his family. To our knowledge, he has not undergone any further surgical procedures requiring anesthesia.

The clinical presentation of MH can be highly variable and may present anytime perioperatively. [2]Other cases of anesthetic-associated myoglobinuria reported as episodes of MH demonstrated myoglobinuria as the only presenting sign. [3–8]As in our case, MH has been reported to occur in subjects who have received several anesthetics that produced no complications. [9,10]Rhabdomyolysis has also been reported in patients undergoing surgical procedures in whom pressure necrosis of muscle occurs from positioning. [11,12]A case of idiopathic rhabdomyolysis not related to surgery has also been reported in an adult male in whom no precipitating cause could be determined. [13] 

The differential diagnoses for his rhabdomyolysis included:(1) MH, (2) compression of musculature leading to muscle ischemia, (3) dermatomyositis, (4) one of several enzyme deficiencies (glucose-6-phosphodiesterase, phosphofructokinase, carnitine palmityl transferase, muscle phosphorylase), and (5) familial periodic paralysis. The first two etiologies were deemed most likely because of the abrupt nature and timing of his rhabdomyolysis. Moreover, the other etiologies occur rarely. The likelihood of MH was considered less likely because of the patient's lack of perioperative tachycardia, hypercapnia, acidemia, and the low level of his postoperative hyperthermia. On the other hand, a review of the literature had revealed that reported levels of CK after intraoperative pressure muscle ischemia were much lower (< 75,000 U/l) than observed in our patient.

Previous authors have described a syndrome of anesthesia-induced myoglobinuria as an abortive form of MH. [5]Because of the lack of reports that analyze series of cases of perioperative rhabdomyolysis, no judgment can be made on the validity of this phenomenon as an expression of MH. The question of what exactly triggered rhabdomyolysis in this particular case remains unanswered. The patient had a muscle type that tested positive for MH and was given triggering agents. Also his weight, duration of surgery, and positioning could potentially lead to pressure ischemia.

Although the existence of false-positive MH diagnostic test results is unproven, one possible explanation for our finding is that the MH-like muscle responses represent a false-positive diagnosis. Another explanation for the findings in this patient is that some other underlying myopathic process has predisposed the muscle to the clinical and in vitro test responses. Neither histologic nor histochemical examination of the muscle tissue was performed to rule out specific or non-specific myopathy. However, false-positive MH contracture results in patients with specific muscle disease, e.g., myotonia congenita, is an unproven entity. Hence, even finding a specific myopathy in this patient cannot rule out MH. [14] 

In summary, we describe a patient, who later tested positive for MH, who developed severe postoperative rhabdomyolysis after a general anesthetic for radical prostatectomy. The patient demonstrated no signs or symptoms indicating MH intraoperatively. We believe that other cases of MH may occur that also go unrecognized. When patients demonstrate symptoms or laboratory evidence of significant muscle injury perioperatively, the possibility of MH should be considered.

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