Malignant hyperthermia (MH) is commonly regarded as a fulminant hypermetabolic response of patients to specific triggering anaesthetic drugs. However, it can be insidious in onset as illustrated in this case report. Many factors were involved that confused the presentation, may have precipitated the event and possibly delayed the diagnosis and treatment.
The patient was a 36-year-old man scheduled for resection of a retroperitoneal teratoma. He had undergone a right orchidectomy under uneventful general anaesthesia 6 months previously (spontaneous respiration with enflurane) for an anaplastic teratoma with spermatocytic seminoma. A computer assisted tomography scan at that time revealed a bulky abdominal mass and two lung metastases. Six courses of chemotherapy (bleomycin, etoposide and cisplatin) resolved the pulmonary lesions.
Past medical history included mild asthma and emergency laparotomy for perforated duodenal ulcer 3 years previously in Holland (notes unavailable but uneventful anaesthetic according to the patient). The patient had no known allergies and was not on medication. There was no family history of illness or anaesthetic problems. He was of normal muscular build. Routine blood investigations were normal.
The patient was premedicated with temazepam 30 mg. Anaesthesia was induced with morphine, thiopentone and vecuronium and maintained by ventilation with 40% oxygen in nitrous oxide and 0.5-1.0% enflurane. He was easy to ventilate with a facemask but developed bronchospasm when intubated; however, this quickly resolved by deepening anaesthesia. Cardiorespiratory parameters were stable throughout and he was transferred to the operating table. Heat conservation measures included a water mattress, aluminium foil body insulation, blood warmer, low-flow ventilator circuit with heat and moisture exchange device and a raised theatre temperature of 24°C. Surgery commenced with minimal cardiac response, anaesthesia was supplemented with increments of morphine and vecuronium and was uneventful for the next 6 h. After this time (Table 1) there was a gradual increase in heart rate and end-tidal CO2 (PetCO2) which was only temporarily abated by increments of morphine and increasing the minute ventilation and depth of anaesthesia (end-tidal enflurane up to 1.2%). The ventilator intermittently indicated spurious tidal volumes due to endotracheal secretions and water condensation which required endotracheal suction on several occasions.
Eight hours after induction the tachycardia suddenly increased to 140 beats min−1. The patient was warm peripherally and an oesophageal probe was inserted which recorded a temperature of 37.6°C. Heat conserving measures were removed or switched off. At this stage it was thought this might just be a case of simple overheating in combination with some effects from tumour mobilization. The SpO2 remained stable at 96-98%. An arterial line was inserted and blood samples taken. During this 20 min period his temperature rapidly increased, accompanied by a tachycardia of 160 min−1, PetCO2 of 12 kPa, and a drop in blood pressure to 70/40 mmHg. The SpO2 remained at 95%, but he developed a large gradient between the inspired oxygen fraction (0.45) and the expired oxygen fraction (0.3) implying a large consumption. A diagnosis of MH was made (8.5 h after induction) and enflurane was discontinued and flushed out with high-flow oxygen. The maximum recorded temperature was 40.1°C. Muscle spasm was not apparent at any time. Active cooling was instituted with topical ice packs, cold (4°C) intravenous (i.v.) fluids and lavage of the stomach, bladder and peritoneal cavities. Dantrolene 100 mg and propanolol 1 mg were administered. The blood pressure returned to normal within 10 min and the PetCO2 and temperature gradually decreased over the next half hour. Anaesthesia was maintained with fentanyl and midazolam. A central line was inserted and central venous pressure (CVP) was recorded as 5 mmHg. Cooling measures continued until his temperature stabilized at 35.3°C. Blood results (Table 2) confirmed a combined metabolic and respiratory acidosis, mild coagulopathy and a mild hyperkalaemia. No bicarbonate or insulin/dextrose were administered due to his continuing clinical improvement. After completion of bladder lavage, urine output continued at 100-150 mL h−1 and so forced diuresis was not pursued.
Surgery was continued as the MH crisis appeared to have resolved 80 min after the diagnosis was made. The operation was completed a further 2 h and 40 min later. He was transferred to the intensive care unit (ITU) and ventilated overnight. He received morphine and midazolam for analgesia and sedation. The following morning (23 h after induction) he developed a mild pyrexia (37.5°C) and tachycardia of 130 min−1. He was given a further 60 mg of dantrolene which reduced the temperature although the tachycardia persisted. The highest level of creatine kinase was recorded at this time [18 030 UL−1, normal range 10-171]. He was extubated soon after this and made an uneventful recovery.
Subsequent investigation at the Leeds Malignant Hyperthermia Unit revealed that both the patient and his son are MH susceptible with normal histology, his daughter is MH normal.
Only 10% of MH syndromes present are the fulminant type, with rapid onset of pyrexia and hypermetabolism[1,2]. Most present as abortive MH which is subdivided into three groups with an equal frequency of incidence: (a) masseter spasm and mild metabolic signs, (b) masseter spasm only or (c) mild metabolic signs without masseter spasm. The development of MH in this patient was delayed (7-8 h) and was initially mild and gradual (probably over 2 h) until the rapid exacerbation typical of the fulminant presentation of the syndrome. If surgery had finished sooner or the syndrome detected earlier this patient may not have gone on to develop fulminant MH and would have been classified as abortive MH, subgroup c.
More than 75% of MH cases occur after the combined use of a potent volatile agent, usually halothane, and suxamethonium. Neither of these agents were used in this patient. The only known trigger agent used was enflurane which is less likely to trigger MH . The use of a non-depolarizing muscle relaxant may inhibit the presentation of MH. Animal experiments have shown that pancuronium can protect against the response to halothane perhaps by either reducing muscle activity and therefore intracellular free ionized calcium or by some mechanism linked to the compound's amino-steroid configuration . The combination of exposure to weak triggering agents and the use of vecuronium may have delayed the onset in this patient.
The diagnosis was delayed because the gradual hypercarbia and increasing airway pressures were thought to be due to a combination of mechanical problems with the ventilator and the patient's airway disease from smoking and asthma. 'Chest tightness' due to muscle rigidity and not asthma has been reported as a pre-operative symptom in a patient who went on to develop fulminant MH after receiving three anaesthetics(including suxamethonium and halothane) within a 36-h period .
Temperature measurement in this case was not established until after a clinical suspicion of MH had been aroused. We doubt that earlier measurement would have led to an earlier diagnosis as the diagnostic criteria of temperature rise greater than 2°C per hour is usually preceded by clinical signs of acidosis. MH should be considered early in cases of unexplained tachycardia or rising PetCO2.
Recrudescence is another characteristic of MH which can occur many hours after the initial presentation and so demands that the patient should be closely monitored in an appropriate area during the post-operative period. Our patient developed a tachycardia and mild pyrexia 23 h after induction of anaesthesia which may have been early signs of a recrudescence. His temperature, but not his heart rate, quickly returned to normal following the dantrolene. Mathieu et al. report two cases that developed fatal recrudescence 30 h after an anaesthetic using suxamethonium and halothane, both of which were associated with marked muscle rigidity which they suggest to be an ominous sign . Muscle rigidity was not a feature of our patient at any time which may have explained his rapid response to treatment and subsequent good recovery.
MH has resulted following use of all the available volatile agents . It has even been reported when a 'safe' anaesthetic technique has been employed and after the use of prophylactic dantrolene [8,9]. The presentation of MH in these cases was abortive (muscle rigidity was not mentioned) and delayed (occurred in the recovery room an average of 4.5 h after surgery). The precipitating factors were postulated to be 'stress' induced by either pain or mild hypothermia.
Cytokines play a role in the body's thermoregulatory processes resulting in pyrexia [10,11]. Release of these mediators from necrotic tumour results in fever and a mild sepsis syndrome . There may be release of cytokines during extensive surgical dissection of necrotic tumour. It is common to see a tachycardia during surgery on inflamed or necrotic tissue and this would certainly confuse the diagnosis in the early phase and may also have played a role in triggering the syndrome. Surgery was completed in our patient as the bulk of the tumour had been removed and the risk of retriggering the MH was thought to be low. A literature search by us has not found any other reports of surgery being continued after initial presentation of MH.
In summary we present a patient who developed the MH syndrome 6-8 h into anaesthesia using enflurane. The onset was delayed and gradual before becoming fulminant; muscle rigidity was not a feature. Tachycardia and a rising PetCO2 were attributed to ventilation problems and mobilization of the tumour. These signs should prompt early consideration of a diagnosis of MH as a rise in temperature is often a variable and late sign. The crisis responded rapidly to treatment and surgery was completed uneventfully apart from mild signs of recrudescence 18 h later.
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