Malignant hyperthermia (MH) is an inherited syndrome in which a defective gene alters calcium movement (Heller, 2009; Rosenberg, Sambuughin, & Dirksen, 2010). MH was first identified in the 1960s with a mortality of 80%. (Christiansen & Collins, 2004). Today, with increased awareness of this condition, preoperative screening, and policies in place to handle this critical emergency, mortality has decreased to 5% (Rosenberg, Antognini, & Muldoon, 2002). This article will address the incidence, triggers of and testing for MH, the pathophysiology of MH, and the role of the operating room personnel in the treatment of MH, including the preparation of dantrolene.
INCIDENCE, TESTING, AND TRIGGERS
The incidence of MH occurs in 1 of 50,000 cases in adult general anesthetic procedures and 1 of 15,000 cases in pediatric general anesthetic procedures (Christiansen & Collins, 2004; Rosenberg et al., 2010). Larach, Gronert, Allen, Brandom, and Lehman (2010) investigated 286 episodes of MH in North America between 1987 and 2006 and reported that 74.8% of the cases occurred in males. Larach et al. (2010) also reported that 77% of these cases of MH had at least two prior unremarkable general anesthetics. To date, two genetic mutations have been identified predisposing to MH, and up to 70% of MH cases are caused by mutations in gene RYR1 (Rosenberg et al., 2010). Molecular genetic testing for RYR1 and CACNA1S is available. Screening tests in suspected cases include caffeine-halothane contracture test. This process involves exposure of 2 gm of muscle from the thigh through a small incision and exposing it to halothane and or caffeine and comparing contraction of muscle against non-MH muscle (Christiansen & Collins, 2004; Rosenberg et al., 2010). According to the Malignant Hyperthermia Association of the United States (2008), caffeine-halothane contracture test may be performed at only six designated testing centers throughout North America as this test must be performed on fresh tissue.
Known agents used in the operating room to potentially cause MH in the susceptible patient are the muscle relaxant succinylcholine and volatile inhaled agents; such as: deslurane, enflurane, halothane, isoflurane, and sevoflurane (Rosenberg et al., 2010). In the susceptible patient, reports include the onset of MH being triggered by extreme emotional and or exposure to hot environments (Rosenberg et al., 2010).
PATHOPHYSIOLOGY
There is a cascade of signs and symptoms that occur in a patient experiencing malignant hyperthermia related to the pathophysiology (see Table 1). The release of excessive amounts of calcium from intracellular storage sites in the cytoplasm of the muscle cells leads to a chain of events that, if not caught early, is associated with a high mortality. According to Rosenberg et al. (2010) the first indications of MH are usually tachycardia and tachypnea in the operating room. In the analysis conducted by Larach et al. (2010) of 286 cases of MH between 1987 and 2006, increased carbon dioxide (hypercarbia), sinus tachycardia, or masseter spasm were the frequent initial MH signs. In 63.5%, temperature increases was the first to third sign (Larach et al., 2010). MH may also occur in the early postoperative period (Rosenberg et al., 2010).
Due to the defective gene, there is an increased concentration of calcium in the muscle cell leading to a rapid rise in metabolic rate, with an increased production of heat, hypercarbia, and lactic acid leading to respiratory and metabolic acidosis (Larach et al., 2010). In the 286 cases analyzed by Larach et al. (2010), 78.6% of the MH cases presented with both muscular abnormalities and respiratory acidosis; whereas, metabolic acidosis occurred in only 26.6% of the cases. Muscle contraction and masseter muscle rigidity results when the muscle cells are incapable of reprocessing calcium and returning it to storage areas within the cell; therefore, the skeletal muscles remain contracted. Muscle ineffectively uses its adenosine triphosphate stores attempting to reprocess the calcium and end the muscle contraction resulting in generation of excess heat and hyperthermia. The body temperature may rise by 0.6 8 C/min. The likelihood of any complication increased 1.6 times per 30-min delay in dantrolene use (Larach et al., 2010). The resulting excess consumption of oxygen results in hypoxia and decreased oxygen delivery to vital organs and tissues. Disruption of the skeletal muscle cell membranes leads to leaking of the following into the blood stream: myoglobin, electrolytes, and creatinine kinase. Myoglobin obstructs the renal tubules and may result in acute renal failure. The electrolyte imbalance associated with MH is hyperkalemia that results in cardiac dysrhythmia including ventricular irritability and ventricular fibrillation. Creatinine kinase leaking into the blood stream results in prolonged skeletal muscle contraction and muscle destruction, known as rhabdomyolysis (Christiansen & Collins, 2004; Heller, 2009).
TREATMENT AND RESPONSIBILITIES
When a known or high-risk patient is identified preoperatively, the MH cart and resuscitative equipment need to be readily available. In the situation of a MH case, the nurse is to obtain 3 L of refrigerated normal saline and ice. The patient is to be cooled using refrigerated normal saline intravenously, cold lavage to any available body cavity, cooling blanket, and ice packs to the axilla, groin, and head in attempts to reduce the rapid rise in body temperature (American Operating Room Nurses, 2000; Hotel Dieu Hospital/Kingston General Hospital, 2005). Urinary output needs to be carefully monitored via a foley catheter. Venous blood work is to be drawn regularly throughout the crisis for electrolytes, blood sugar, and pH. Vital signs are also to be regularly monitored. An order to reconstitute dantrolene will likely be given by the anesthesiologist and the nurse will prepare this medication, to be described later.
Once a high-risk patient with known MH or a family history of MH has been identified preoperatively, they should be listed first on the operating room schedule. The anesthesia machine must be fitted with a new circuit and soda lime prior to a case with a suspected MH patient. Triggering agents need to be avoided. There are a variety of safe preoperative and intraoperative medications that may be used. See Table 2. For the patient deemed high risk or who has previously experienced a full-blown MH episode, the anesthesiologist may use prophylactic dose of dantrolene 2 mg/kg 30-60 min preoperatively.
In the patient who experiences signs and symptoms of MH, triggering agents need to be discontinued immediately. If surgery cannot be aborted, the anesthetic agent should be changed to a nontriggering one. Hyperventilation with 100% oxygen will help offset the rapid increase in retained carbon dioxide that leads to respiratory acidosis. Dantrolene may be administered via a large bore intravenous or central venous line. A nasogastric tube should be inserted with administration of cold saline gastric lavage to reduce the rapid increase in body temperature. If possible, a radial arterial line should be inserted. With the development of lactic acidosis, intravenous sodium bicarbonate should be given at a dose of 2 mEq/kg initially and then according to arterial blood gases. For documented hyperkalemia and the potentially lethal cardiac dysrhythmia associated with this, administration of 10-20 units of regular insulin combined with 50 cc of 50% dextrose will promote the flow of potassium out of the blood and into the cells. For pediatrics, the dose of regular insulin is 0.25 units per kilogram in 50% dextrose. Maintaining high urine output to prevent the accumulative and negative effects of myoglobin to the kidneys is critical. Administration of cold intravenous fluids at a rate of 2-8 cc/kg initially with subsequent amounts based on the central venous pressure and urine output will help prevent tubular damage in the kidneys. If required, intravenous furosemide or mannitol may also be infused to promote diuresis. The patient will be ventilated at this time with the manual resuscitator. Blood work needs to be drawn frequently during and after the crisis, including: arterial blood gases, calcium, electrolytes, creatinine kinase every 6 hr for 24 hr, coagulation studies, myoglobin blood, myoglobin urine every 6 hr for 24 hr.
DANTROLENE
Dantrolene sodium reduces muscle tone and metabolism by preventing the ongoing release of calcium from the sarcoplasmic reticulum and by enhancing the reuptake of calcium. It does not reduce the muscle calcium to render the muscle flaccid and without tone, as it is not a muscle relaxant, as pancuronium bromide, and it does not potentiate the effects on nondepolarizing muscle relaxants or prevent the ability to reverse curariform drugs with anticholinersterase agents (Larach et al., 2010). It may cause significant muscle weakness in patients with preexisting muscle disease and should be used with extreme caution in those patients. The recommended initial dose of dantrolene is 2.5-4 mg/kg intravenous push, with repeats every 5-10 min until maximum of 10 mg/kg or MH is controlled, followed by a bolus of dantrolene 1 mg/kg every 4-6 hr for 24 to 48 hr (Fortunato-Phillips, 2000; Larach et al., 2010). Most MH crises respond to 2.5-4 mg/kg of dantrolene initially, but some may need significantly more to bring the episode under control. Once a patient has been treated successfully with dantrolene intravenously, oral dantrolene may be given for several days. The recurrence of MH exists for up to 48 hours after the initial crisis; therefore, continued treatment for at least 48 hr after MH at a dose of 1 mg/kg every 4 hr is recommended (Larach et al., 2010). Have 18 vials immediately available in the operating room suite. Mix each 20 mg vials of Dantrium with 60 cc of preservative-free sterile water. Have a total of 36 vials stocked. The concomitant use of a calcium channel blocker such as diltiazem or verapamil may produce significant hyperkalemia and myocardial depression and should be avoided.
CONCLUSION
Malignant hyperthermia is a hereditary condition often triggered by the use of succinylcholine or volative inhaled agents. The mechanism related to the rapid deterioration of the patient results from a chain of events starting with an excessive amount of intracellular calcium leading to cardiac dysrhythmias, respiratory acidosis, muscle ridigity hypoxia, a rapid rise in temperature, myoglobinemia, rhabdomolysis, acute renal failure, and death. Fortunately with preoperative screening for high-risk patients and institution of policies to handle this life-threatening emergency, the fatality once associated with MH has been greatly reduced.
POSTARTICLE QUIZ
1. Malignant hyperthermia is characterized by:
1. Sustained muscle rigidity
2. Tachycardia, tachypnea
3. Fever
4. All of the above
2. MH results in release of excessive amounts of calcium from the skeletal muscle intracellular storage sites.
1. True
2. False
3. Management of acute MH includes all of the following except:
1. Administration of Dantrium
2. Cold normal saline bolus
3. Administration of succinylcholine
4. Insulin and dextrose administration
5. Sodium bicarbonate administration
4. An MH susceptible patient may safely be discharged home when the home discharge criteria have been met and a minimum of ____ hours of observation and monitoring have been completed.
1. 2
2. 4
3. 6
5. Treatment of Acute MH involves IV administration of Dantrium. What solution is used to mix this?
1. Normal saline
2. D5W
3. Ringers Lactate
4. Preservative free sterile water
6. What volume of the above solution must be added to a vial of Dantrium?
1. 10 ml
2. 20 ml
3. 40 ml
4. 60 ml
7. Intravenous diltiazem or verapamil may be used to treat cardiac arrhythmias occurring in the setting of MH?
1. True
2. False
8. A patient weighs 100 kg. The anesthesiologist wants to give 3 mg/kg of Dantrium. Knowing each vial contains 20 mg of Dantrium, how many vials would be required for this patient initially?
1. 5
2. 10
3. 15
4. 18
REFERENCES