WE report an unusual case of myoglobin-induced acute renal failure occurring on the third postoperative day in a patient receiving a general anesthetic.
Case Report
A 48-yr-old man (weight, 109 kg; height, 182 cm) presented for elective umbilical hernia repair. His medical history was significant for gastroesophageal reflux and mild mitral valve prolapse. There was no personal or family history for myopathy or malignant hyperthermia (MH). The patient reported having a tonsillectomy performed when he was a child during general anesthesia without incident. He was not taking any outpatient medications and had no history of drug allergies. The results of preoperative laboratory testing, including a complete blood count, coagulation studies, and a chemistry panel, were within normal limits.
The patient was taken to the operating room, and a rapid sequence induction was performed. The patient received 180 mg succinylcholine and 200 mg propofol for induction. A defasciculating dose of a nondepolarizing muscle relaxant was not administered, and no fasciculations were observed. His trachea was easily intubated, with no evidence of increased masseter tone. The patient was maintained with oxygen–isoflurane–nitrous inhalational anesthesia in addition to fentanyl. The concentration of isoflurane administered was approximately 0.5 minimum alveolar concentration. Muscle relaxation was maintained with rocuronium after 4/4 twitches with normal height returned.
The patient remained in the supine position for the surgical procedure, which lasted approximately 1 h. No urinary catheter was placed intraoperatively. The patient remained hemodynamically stable throughout the procedure with no dysrhythmias. His heart rate ranged from 62–75 beats/min, and his blood pressure ranged from 85/50 mmHg immediately after induction to a maximum of 140/82 mmHg, with a mean reading of 120/72 mmHg. His nasal temperature remained constant at 35.9 ± 0.2°C. He received a total of 1 l Ringer's lactate during the procedure, with minimal surgical blood loss. Muscle relaxation was reversed, and the patient underwent extubation while awake in the operating room without incident. An arterial blood gas measurement was not obtained perioperatively in this patient.
The patient recovered uneventfully in the postanesthetic care unit. His vitals signs throughout his stay in the postanesthesia care unit were unremarkable. He was discharged to home within 4 h of completion of the surgery, with no complaints.
The patient returned to the hospital on the third postoperative day, reporting general malaise, myalgias, and nausea and vomiting of 2 days’ duration. He denied fevers, sweats, palpitations, or rigidity. He did report that his urine was dark in color on the evening of surgery but reported that this had improved over the next 2 days. He maintained normal urinary output until the day of presentation, when he noted a moderate decrease. A routine chemistry panel performed in the emergency room revealed a serum creatinine concentration of 7.8 mg/dl and a blood urea nitrogen concentration of 56 mg/dl. The patient's urine tested positive for myoglobin.
The patient was admitted to the intensive care unit with a preliminary diagnosis of rhabdomyolysis with myoglobin-induced acute renal failure. Examination of his extremities revealed no evidence of compartment syndrome. The concentration of creatine kinase taken on the evening of his readmission was 12,041 U/l. The calcium concentration was 8.7 mg/dl, phosphate was 6.3 mg/dl, and uric acid was 13.4 mg/dl. Liver function test results revealed an aspartate aminotransferase concentration of 195 U/l, an alanine aminotransferase concentration of 128 U/l, and a lactate dehydrogenase concentration of 1,411 U/l. Nephrology was consulted, and the patient was hydrated and alkalinized to maintain a urine pH of 7.5–7.8. A urinary catheter was placed. The creatine kinase concentration decreased to 4,049 U/l within 24 h and was down to 757 U/l 72 h after readmission.
Over the next 14 days, the patient's renal function eventually recovered, and he was discharged to home with normal blood urea nitrogen and creatinine concentrations. The remainder of his electrolyte panel and liver function test results were normalized. Dialysis was not required.
Approximately 4 months later, the patient underwent vastus lateralis muscle biopsy during spinal anesthesia. Muscle samples underwent caffeine–halothane contracture testing (CHCT) at the Uniformed Services University of the Health Sciences Malignant Hyperthermia Testing Center in Bethesda, Maryland. Diagnosis of MH was performed according to the North American CHCT protocol. 1Individuals are considered MH susceptible if any one of the six muscle strips exceeds diagnostic criteria (3% halothane—increased basal contracture of at least 0.7 g; 2 mm caffeine—increased basal tension of at least 0.3 g).
All three muscle strips tested with 3% halothane exhibited an abnormal response: 1.1, 0.9, and 1.3 g. At 2.0 mm caffeine concentration, another three strips exhibited an abnormal increase in tension: 0.5, 0.5, and 1.0 g.
Histopathologic and histoenzymatic analyses for myopathies were conducted at the Armed Forces Institute of Pathology in Washington, DC. Adenosine monophosphate deaminase, myofibrillary adenosine triphosphatase at pH 10.4, nicotinamide adenine dinucleotide tetrazolium reductase, alkaline phosphatase, and nonspecific esterase test results were all normal. Modified Gomori trichrome, periodic acid-Schiff, and hematoxylin and eosin stains performed on the frozen muscle sample were normal.
The formalin-fixed tissue was processed in paraffin, and sections were stained with hematoxylin and eosin and trichrome. Under microscopy, the sections revealed normal fiber size and configuration without evidence of atrophy, degeneration, regeneration, inflammation, or fibrosis. Oxidative enzyme stains revealed no abnormalities of the intermyofibrillary network. The perimysium and its neurovascular contents were unremarkable.
Genetic analysis of 18 known mutations in the ryanodine receptor (RYR) type 1 was conducted at the Uniformed Services University of the Health Sciences. The presence or absence of mutations was determined by the polymerase chain reaction–based restriction fragment polymorphism method using genomic DNA extracted from stored muscle tissue. None of the 18 mutations screened for was identified in this patient. 2
Discussion
Classically, MH presents perioperatively with tachycardia, tachypnea, fever, rigidity, metabolic acidosis, cardiac dysrhythmias, cyanosis, or mottling. Although none of these signs were evident, myoglobinuria developed in the patient, leading to nonoliguric, acute renal failure postoperatively. Case reports of patients with rhabdomyolysis postoperatively after administration of succinylcholine, inhalation agents, or both are usually associated with undiagnosed myopathies in children rather than MH. 3However, histologic–histochemical analysis of the patient's muscle was normal. Further, his increased creatine kinase concentration and myoglobinuria returned to normal rapidly with treatment, making the diagnosis of latent myopathy unlikely. Lack of significant fasciculations or myalgias does not support a diagnosis of succinylcholine-induced rhabdomyolysis.
The patient's lack of clinical signs may be explained by the relatively short exposure to isoflurane. MH triggering with isoflurane has been associated with a delayed onset of MH triggering. 4
Phenotypically, MH presents in a highly variable fashion. Some perioperative episodes have only subtle signs, and up to 50% of MH-susceptible patients have been exposed to triggering agents without development of any clinical signs of MH. 5A recently published genetic study of patients with exertional rhabdomyolysis found 3 of 10 CHCT-positive patients had RYR type I mutations typical of MH. 6A possible link between exertional heat stroke and MH has also been reported. 7CHCT using North American guidelines is reported to be 97% sensitive and 78% specific. 8Although the differential diagnosis of rhabdomyolysis is extensive, 9in light of the history, test results, and recent publications mentioned, we diagnosed this patient as MH susceptible.
In summary, the nature of this subacute but clinically significant presentation of MH suggests that the incidence of MH may be higher than currently reported. 10This patient did not have an acute MH episode; however, given his CHCT results, perioperative myoglobinuria, and acute renal failure, there is little doubt that another exposure to volatile anesthetics, depolarizing muscle relaxants, or both would be unwise.
