Malignant hyperthermia

A 12-year-old, 40-kg boy was scheduled for strabismus corrective surgery of the right eye. He had no significant past medical history and no family history of anesthetic problems or muscle or nerve disease. He had never received general anesthesia before. Physical examination was normal. The preoperative vital signs were blood pressure 100/60 mm Hg, heart rate 92 beats per minute, and axillary temperature 36.7° C. Because the patient was needle-phobic, an inhalation induction of anesthesia was achieved with sevoflurane 4.0 vol% in a mixture of nitrous oxide and oxygen (fraction of inspired oxygen 0.4). After induction, an intravenous catheter was placed, and rocuronium bromide, 20 mg, and fentanyl, 50 μg, were administered. Direct laryngoscopy was performed, and the trachea was intubated easily with a 6.0-mm cuffed tube. The patient’s heart rate suddenly increased 60 minutes after intubation from 130 to 190 beats per minute. Over the next 10 minutes, the end-tidal carbon dioxide (ETCO 2 ) tension increased from 35 to 65 mm Hg, and the axillary temperature increased from 35° C to 38.9° C. An esophageal temperature probe showed a temperature of 39.5° C.

What is malignant hyperthermia?

Malignant hyperthermia (MH) is a life-threatening familial hypermetabolic disorder of skeletal muscle that can be precipitated by specific anesthetic agents. MH was first reported in the 1960s and is characterized by tachycardia, tachypnea, hyperthermia, generalized muscle rigidity, acidosis, and increasing ETCO 2 levels. The incidence of MH is 1 in 15,000 anesthetics in children and 1 in 50,000–100,000 anesthetics in adults. Children <15 years old account for >50% of all reported MH cases, with most cases reported in boys. MH can be described as a spectrum, ranging from the classic life-threatening reaction to mild presentations.

What is the pathophysiology of malignant hyperthermia?

In the normal state, depolarization of skeletal muscle fiber membranes leads to calcium ion release from the sarcoplasmic reticulum (SR). After calcium diffusion into thin filaments, calcium binds to calcium-regulatory sites on troponin, leading to normal excitation-contraction coupling. In MH, calcium is released from the SR at very high rates, leading to a sustained hypermetabolic state and subsequent loss of cellular integrity. This hypermetabolic state produces increased lactate levels, high adenosine triphosphate (ATP) consumption, increased carbon dioxide release, increased oxygen consumption, and increased muscle heat accumulation secondary to sustained muscle contractions. Later in the clinical course, ATP production ceases, causing failure of intracellular membrane pumps. Cellular leakage of electrolytes follows, including potassium and calcium, enzymes such as creatine phosphokinase, large amounts of metabolic acids, and myoglobin. Fatal arrhythmias, end-organ damage, and eventually death may ensue.

The ryanodine receptor has been implicated in the pathogenesis of MH. Ryanodine receptors are a group of high-conductance SR calcium channels in muscles and endoplasmic reticulum in other cells. Mutations impairing function of ryanodine receptors occur in central core disease, an autosomal dominant congenital myopathy, and King-Denborough syndrome, a congenital myopathy. Both conditions are associated with an increased susceptibility to MH.

What are the clinical characteristics of malignant hyperthermia?

MH episodes are characterized by sinus tachycardia, muscle contractures, arrhythmias, increased core temperature, increased serum creatine kinase levels, myoglobinuria, and eventually cardiac arrest. All of these changes combine with hypoxemia, hypercapnia, metabolic acidosis, respiratory acidosis, and hyperkalemia. Early recognition and treatment of MH are essential if an adverse outcome is to be avoided. The earliest signs are usually masseter muscle rigidity, tachypnea (if spontaneously breathing), tachycardia, and increasing ETCO 2 (but not inspired carbon dioxide). The sequence of clinical events during an episode of MH is summarized in Table 25-1 . None of these signs are specific for MH, and a broad differential diagnosis should always be considered ( Box 25-1 ).

TABLE 25-1

Clinical Features of Malignant Hyperthermia

Early Signs Late Signs
Musculoskeletal Sustained jaw rigidity Generalized muscle rigidity
Cardiovascular Tachycardia Severe cardiac arrhythmias
PVCs Cardiovascular collapse
Unstable blood pressure
Respiratory Tachypnea (spontaneously breathing)
Rising ETCO 2 (despite increased minute ventilation)
Metabolic Rising temperature Rapidly increasing temperature
Hypoxia (increased oxygen consumption) Life-threatening hyperkalemia
Acidosis (respiratory and metabolic) Increased CPK
Hyperkalemia DIC

CPK, Creatine phosphokinase; DIC, disseminated intravascular coagulation; ETCO 2 , end tidal carbon dioxide; PVCs, premature ventricular contraction.

BOX 25-1

Differential Diagnosis of Suspected Malignant Hyperthermia Event

  • Inadequate anesthesia/analgesia

  • Insufficient ventilation/fresh gas flow

  • Overwarming

  • Exothermic reaction in absorber (sevoflurane + Baralyme)

  • Anesthesia machine malfunction

  • Anaphylactic reaction

  • Sepsis

  • Antimuscarinics

  • Neuromuscular disorders

  • Neuroleptic malignant syndrome

  • Thyroid crisis

  • Pheochromocytoma

  • Carcinoid

  • Cocaine toxicity

  • Laparoscopic associated hypercarbia

Discuss masseter muscle rigidity during induction.

Children and adults can exhibit decreased mouth-opening and increased jaw stiffness when succinylcholine is administered after exposure to halogenated volatile anesthetics. Masseter muscle rigidity (MMR) is the inability to open the jaw (trismus). The exact incidence of MMR after succinylcholine administration is unknown but has been estimated to range from 1 in 1000 to 1 in 100,000 patients. MMR may be an early indicator of, but is not pathognomonic for, MH. Differential diagnosis for MMR includes inadequate dose of succinylcholine, outdated succinylcholine, rapid succinylcholine hydrolysis, underlying myotonic dystrophy, trismus secondary to facial trauma, and MMR as an early sign of MH.

When MMR occurs, MH could ensue. Consequently, all triggering agents should be discontinued, 100% oxygen should be delivered, monitoring should be continued for evidence of other signs of MH, and an arterial blood gas (ABG) should be drawn. Combined respiratory and metabolic acidosis indicates MH, and if present, the patient should be treated appropriately. If the ABG does not show a combined respiratory and metabolic acidosis, and other signs of MH are absent, the anesthesiologist has two options. One is to postpone surgery, awaken the patient, and continue monitoring in the postanesthesia care unit. The second option is to convert to a nontriggering anesthetic and proceed with surgery, monitoring carefully for any signs of MH. In the case of emergency surgery that cannot be delayed, the only option is to convert to a nontriggering anesthetic while maintaining a heightened vigilance for MH. In all cases, the patient should be referred for further evaluation of MH susceptibility.

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Jul 14, 2019 | Posted by in ANESTHESIA | Comments Off on Malignant hyperthermia

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