Journal: Paediatr Anaesth 18(2):100-106, 2008
Reprint: The Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8
Faculty Disclosure: Abstracted by R. Klotz, who has nothing to disclose.
Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy, with an incidence of approximately one in 3500 live male births. Patients with DMD suffer from progressive degeneration of skeletal, cardiac and smooth muscle beginning at 3-5 years of age. The progression of muscle weakness is rapid, resulting in a failure to walk by adolescence and eventual death before the end of the third decade. Dilated cardiomyopathy occurs in over 50% of patients by 15 years of age.
Perioperative adverse events are not common. Acute rhabdomyolysis is believed to be triggered primarily by the administration of succinylcholine. Potent inhalation anesthetic agents have also been implicated in rhabdomyolysis as well as perioperative metabolic reactions that resemble malignant hyperthermia (MH). Controversy exists as to whether inhalational agents can be safely administered in DMD patients. The authors present a hypothetical clinical scenario as well as a review of the perioperative metabolic reactions that resemble MH. These reactions are grouped into three categories according to clinical presentation, and the etiology and underlying pathophysiological process responsible for these reactions is discussed.
A review of the literature found a total of 13 patients, ages 2-18 yr, who had sudden hyperkalemic cardiac arrest with no obvious preceding signs of hyper¬metabolism; 8 patients had, or were suspected of having, DMD. The remainder were diagnosed with Becker muscular dystrophy (BMD). For 7 of the DMD and one of the BMD patients, hyperkalemic cardiac arrest was the initial presentation of the underlying myopathy. Halothane was administered to over half the patients, with the others receiving isoflurane, sevoflurane, or a combination of the two. The timing of the cardiac arrest was unpredictable, varying from 10 minutes after induction to 20 minutes following arrival in the PACU. Plasma potassium levels were elevated. All patients developed massive rhabdo¬myolysis with myoglobinuria, and plasma CK levels were significantly elevated. Six patients had an elevated body temperature and/or arterial pCO2 level.
Two articles described 9 patients with DMD who developed unexplained hyperthermia and tachycardia during or after anesthesia with halothane. In 7 patients the onset occurred within a few hours of anesthesia and resolved spontaneously. Two patients developed intraoperative hyperthermia and tachycardia that resolved once halothane was discontinued.
Significant muscle cell breakdown has been reported in 6 patients following exposure to halothane, sevoflurane, and enflurane; 5 of the 6 had a diagnosis of DMD, and one patient had BMD. Rhabdomyolysis resulted in elevated plasma CK levels in 5 patients. The patient who received a "trigger-free" anesthetic did not have an elevated CK level. One patient had sinus tachycardia and a perioperative elevation in body temperature despite the use of dantrolene. A long¬standing view is that MH is the underlying mechanism responsible for these reactions. The combination of clinical signs such as tachycardia, raised arterial pCO2 levels, and rhabdomyolysis are suggestive of MH. Additionally, many DMD and BMD patients have tested positive for MH using skeletal muscle in vitro contracture tests.
The Malignant Hyperthermia Clinical Grading Scale is a method for estimating the qualitative likelihood of an MH reaction in a given patient using a standardized point system based on diagnostic criteria grouped into 6 processes: muscle rigidity, muscle breakdown, respiratory acidosis, temperature increase, cardiac involvement and a family history of MH.
The lack of evidence to support an association between DMD or BMD and MH has led to the proposal of an alternative mechanism termed anesthesia-induced rhabdomyolysis (AIR). The supporting evidence for AIR is the same as that against MH: the reactions are atypical for MH despite some similar characteristics, and most caffeine-halothane contracture test results are negative, and probably unreliable, in muscular dystrophy patients.
Although only a small proportion of DMD patients develop AIR after exposure to inhalational anesthetic agents, the question is: should we continue to use inhalational anesthetic agents when total intravenous anesthesia (TIVA) is a safe and readily available alternative? The evidence says "no", and the authors suggest a trigger-free anesthetic and "clean" anesthesia machine be used, similar to that for MH susceptible patients. This recommendation is based on the fact that the minimum triggering concentration of inhalational agent remains unknown.
In the event that AIR is suspected, the inhalational anesthetic agent should be discontinued immediately. Serial serum potassium levels should be measured and immediately treated with IV sodium bicarbonate and insulin with 10% dextrose. The patient should be hyperventilated to produce a respiratory alkalosis. Serial plasma CK, plasma myoglobin and urine myoglobin levels should be measured to detect rhabdomyolysis. If present, the patient should be treated with IV hydration and mannitol to maintain the urine output > 1 mL/kg/hr. The role of dantrolene in the management of AIR is unknown.
Perioperative hyperkalemic cardiac arrest in an asymptomatic young male patient may be the initial presentation of occult muscular dystrophy. The AHA Guidelines recommend the immediate administration of IV calcium chloride to antagonize the myocardial effects of hyperkalemia and help restore a spontaneous cardiac rhythm.
Differentiation between AIR and MH may be difficult, especially if the patient is not known to have DMD. However, acute hyperkalemic cardiac arrest or isolated rhabdomyolysis with no signs of systemic hyper¬metabolism strongly suggests AIR. Conversely, the present of rapidly rising end-tidal CO2, unexplained metabolic acidosis, inappropriate tachycardia or tachypnea in a spontaneously breathing patient, muscle rigidity and increasing body temperature are consistent with MH. |
