While it may be argued that any elevation of CO2 should have Dantrolene, it is important to understand it is the presence of elevated CO2 that is not reducible via hyperventilation accompanied by other symptoms and signs are used to make a presumptive diagnosis of MH. In this case, ultimately it turned out there were two events occurring simultaneously that mimicked MH: overheating of the patient via convection warmer and dead volume of the LMA. The ETCO2 was reducible via hyperventilation but not all the way back to normal. The core temperature was 100.0 (37.77 deg C) after being under a heating blanket that was set to deliver 109.4 degrees warmed air and this certainly resulted in skin temperatures of 105 deg C (a red herring). Fever may rise late in the course of MH, but the patient had been under general anesthesia for 2 hours 15 min and there was no significant core temperature rise. A long tourniquet time and the use of fentanyl may have exacerbated the ETCO2 elevation. There was no masseter spasm, no generalized rigidity, no cardiac dysrhythmias, no mottling or flushing of the skin, no elevation or decline in BP, no sweating in parts of the body outside the heating blanket and the temperature began to decline as soon as the heating blanket was removed (something that is not seen with MH). The cases reported with MH have the entire canister of absorbent blue and warm to touch. The blood gas was available in 4 minutes- sooner than the dantrolene could be obtained and mixed. By this time, there were more signs the patient was not suffering from MH. The recovery was uneventful.
The differential diagnosis for MH includes:
Anesthesia/surgery-related issues
●Insufficient anesthesia/analgesia – Patients with insufficient anesthesia/analgesia can have tachycardia, hypertension, and tachypnea (in a spontaneously-breathing patient), causing hypocarbia; muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) and hypercarbia would not be present.
●Insufficient ventilation/fresh gas flow – Patients with insufficient ventilation/fresh gas flow commonly have hypercarbia, respiratory acidosis, and, possibly, tachycardia and hypertension; metabolic acidosis and muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present.
●Anesthesia machine malfunction – A malfunctioning expiratory valve on the anesthesia machine will lead to rebreathing of exhaled CO2, with similar findings as for insufficient ventilation. A malfunctioning temperature probe may indicate hyperthermia that is not present.
●Overheating – Fever alone, no matter how high, is not a useful indicator of acute MH. This may occur as a result of an infectious process or iatrogenic warming; the clinical situation should be taken into account. Postoperative fever is relatively common; in the absence of other signs and symptoms of MH, alternate diagnoses should be sought.
●Increased CO2 absorption during laparoscopy – Hypercarbia resistant to increases in minute ventilation may be due to continuous CO2 absorption during laparoscopy. The presence of subcutaneous emphysema, or known insufflation of CO2 into tissues, makes this a likely explanation. Occasionally the insufflating trochar may back out to the point subcutaneous insufflation is occurring resulting in hypercarbia both inspired and expired and subcutaneous CO2 with crepitance of the skin. Tachycardia and hypertension are often noted during laparoscopy; muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) and metabolic acidosis would not be present.
Drug-related issues
●Anaphylaxis – Reduced blood pressure may be seen in both anaphylaxis and MH. Anaphylaxis leads to bronchospasm, wheezing, and increased airway pressures, causing lower minute ventilation and thus increased PaCO2; MH-related hypercarbia persists despite higher minute ventilation (from tachypnea or increasing ventilator settings). Ninety percent of anaphylactic episodes include skin symptoms and signs. Muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present with anaphylaxis.
●Transfusion reaction – Signs common to both transfusion reaction and MH may include fever, brown urine, hypotension, and signs of hyperkalemia. Concomitant transfusion of blood products should raise this possibility.
●Drugs of abuse – A number of drugs of abuse may cause signs that overlap with MH:
•Cocaine acute administration within 2 hours may cause tachycardia, cardiac arrhythmias, hypertension, and rhabdomyolysis. Chronic cocaine on the other hand depletes catecholamines and results in hypotension unresponsive to fluids, ephedrine, and phenylephrine.
•MDMA (ecstasy) acute administration (usually within 6 hours) may cause tachycardia, cardiac arrhythmias, hypertension, hyperthermia, and rhabdomyolysis. It may also lead to serotonin syndrome.
•Methamphetamine (acute administration within 6 hours) may lead to tachycardia, hypertension, sudden cardiovascular collapse, and tachypnea.
●Alcohol withdrawal – Delirium tremens generally begins 48 to 96 hours after the last drink, and may include tachycardia, hypertension, and fever.
●Neuroleptic malignant syndrome – The slow onset of neuroleptic malignant syndrome (NMS) (heralded by mental status changes evolving over one to three days) generally distinguishes it from MH. Both syndromes may include fever, rigidity, and autonomic instability, but NMS does not generally occur during administration of general anesthesia.
●Serotonin syndrome – This can result from excess ingestion or inadvertent interactions of the many drugs that increase serotonergic activity. It has many signs in common with MH (tachycardia, volatile blood pressure, hyperthermia, and muscle rigidity), as well as elevated CK and metabolic acidosis; but serotonin syndrome may also have signs not seen in MH (tremor, clonus, hyperreflexia, akathisia, and dilated pupils).
●Extrapyramidal side effects of antipsychotic medications – These can include muscle spasms, but rapid onset and characteristic localization (usually neck, tongue, or jaw) distinguish them from MH.
●Pyrogenic contaminants – Pyrogenic contaminants to intravenous solutions can cause fever.
Coexisting medical conditions
●Infection/septicemia – Sepsis may be accompanied by fever, metabolic acidosis, and elevations in CK; this makes it difficult to distinguish from MH. Generalized rigidity would not be seen in sepsis. Other perioperative causes of fever are much more common than acute MH. Patients undergoing surgery involving endothelial surfaces (gastrointestinal tract, urogenital tract, etc) are particularly prone to develop fever, which can be due to transient bacteremia or the effects of anesthetics and/or surgery on the hypothalamic thermoregulatory system .
●Pheochromocytoma – Undiagnosed pheochromocytoma may present during surgery with episodic severe hypertension and tachycardia
●Thyroid storm – Thyroid storm may occur in patients with untreated hyperthyroidism, precipitated by surgery or trauma. Symptoms which overlap with MH include tachycardia, cardiac arrhythmia, and hyperthermia to 104 to 106°F. Hypotension and cardiovascular collapse may develop. Muscular signs (generalized rigidity, masseter spasm, rhabdomyolysis, and hyperkalemia) would not be present with thyroid storm. Mental status changes and gastrointestinal symptoms of thyroid storm are not apparent under general anesthesia.
●Cerebral pathology – Fever may result from hypoxic encephalopathy, intracranial bleed, traumatic brain injury, or meningitis.
●Neuromuscular disorders – Patients with various muscular disorders, including Duchenne and Becker muscular dystrophy, may develop rhabdomyolysis or hyperkalemia when exposed to volatile anesthetics or SCH; this is not fulminant MH (although these drugs are contraindicated in patients with these conditions). Other disorders (myotonias, osteogenesis imperfecta) may have increased muscular symptomatology or fever during anesthesia without other signs of MH.
●Rhabdomyolysis – Rhabdomyolysis may occur from other causes and must be distinguished from MH by the clinical situation.
