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Malignant Hyperthermia
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Perioperative Critical Care
Malignant Hyperthermia Update 2000 Nancymarie Fortunato-Phillips, MEd, BSN , BA, RN , RNFA, CNOR, CPSN
What is Malignant Hyperthermia? Malignant hyperthermia (MH) is a life-threatening syndrome; it is a collection of signs and symptoms and not a single disease entity. MH is a sudden pharmacogenic hypermetabolic crisis involving uncontrolled calcium release from skeletal muscle that causes potentially fatal consequences. 1 It has been shown to occur as an autosomal dominant trait in families, although heterogenicity has been demonstrated by the variances in susceptibility to MH by individuals. Genetic differences in chromosomes 19q13.1-13.2 are seen in some mutations of the sequence. 6• 11 Both sexes can transmit the condition; therefore, it is not X linked like other types of muscular disorders, such as some muscular dystrophies. Each child of a person who is susceptible has a 50% chance of inheriting the genetic predisposition for MH. 6· 11 MH can be triggered by the administration of depolarizing muscle relaxants, such as succinylcholine, or volatile inhalation anesthetics, such as halothane, isoflurane, enflurane, methoxyflurane, sevoflurane, or desflurane. Reaction may be delayed with desflurane. 2 From the Cleveland Clinic Foundation, Cleveland; Lakeland Community College, Kirtland; and Phillips Consulting, Willoughby, Ohio
Cyclopropane, chloroform, and diethyl ether may cause an MH crisis, although they are not commonly used in modern anesthesia.5 Not every patient has the same response to the syndrome. A patient may have had triggering agents in the past without ill effects. Some patients may have had minor, undiagnosed symptoms. Each response in an individual can vary with each separate trigger administration. Some patients may have had multiple exposures without incident, which can be misleading if a full-blown MH crisis happens during a subsequent procedure. The success of the patient's outcome depends on quick recognition of an MH crisis in evolution and symptomatic treatment of the condition.1· 7, 8, 13, 1s, 18, 19, 24
History of Malignant Hyperthermia MH was first described in Germany in 1937 by Gude!. Familial relationships of the disease were reported in English literature by Denborough and Lovell in 1960, inAustralia. 8A young man who had been injured in a motor vehicle accident informed his surgeon that 10 close relatives had died during the administration of general anesthesia. The initial thought was that ether had caused his family members' deaths, so halothane was used for his proce
CRITICAL CARE NURSING CLINICS OF NORTH AMERICA I Volume 12 /Number 2 /June 2000
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came cyanotic and feverish within 10 minutes of the halothane administration. The administration of anesthetic was stopped immediately, and he was resuscitated symptomatically and cooled by ice packs. He recovered without permanent injury related to the critical episode. He later had additional surgical procedures under spinal anesthesia without subsequent problems. This ultimately led to the identification of local and regional anesthesia as safe for patients susceptible to MH.7• 8 Six years later, a symposium was held in Toronto, Ontario, where 13 cases of the same type of strange physiologic responses to anesthetic administration were presented. Most of the patients described had similar episodes, including a characteristically rapid hyperthermia. It was thought that the syndrome was probably an inborn dominant trait involving metabolism, but the association with anesthetic drugs was not clearly identified at that time. The reported mortality rate was 70%, but the rate was probably closer to 80% or 90% because it was largely an unknown entity. The literature includes one report of a family with 30 deaths associated with general anesthesia. 7· 8 Because the syndrome was predominantly fatal and involved extremely high body temperature, the name malignant hyperthermia (MH) was used to describe this condition. 7· 8 In 1969, a patient who was given succinylcholine and halothane experienced an MH crisis and died within 24 hours of the episode. His creatine kinase (CK) rose from 280 IU/ L at 3 hours to 20,500 IU/ L at 24 hours. He experienced massive rhabdomyolysis that was attributed directly to the anesthetic drugs. Analysis of his case revealed that he had undergone general anesthesia several years earlier without event; however, during this administration he had received a different form of anesthesia, which caused the MH reaction. It was determined that he was susceptible because of some type of unknown muscle disease. Several of his family members were tested and found to have an elevated CK and were diagnosed with a clinical myopathy. The link between these mysterious deaths and general anesthesia caused great concern in the medical community. Researchers throughout the world began exposing muscle tissue to gases and chemicals to observe contractile activity. It was discovered that dog
muscle contracted during exposure to chloroform, which in turn led to the use of caffeine in human muscle testing. 8 MH-susceptible individuals had an increased response to caffeine-muscle contractile testing. Halothane was found to cause the same result. Many of these early test results have led to current susceptibility testing methods.7• 9. 12• 16 The Malignant Hyperthermia Association of the United States (MHAUS) is an organization established in 1981 to bring together medical professionals, MH patients and their families, researchers, and other personnel who are concerned with or have been impacted by an MH crisis. Membership is open to all disciplines. Development and adherence to standard protocols provide the continuity necessary to serve and protect the population who is at risk for MH. MHAUS sponsors a toll-free hotline (1-800-MH-HYPER [1-800-644-9737)) for medical professionals to consult during treatment of a patient in crisis. Experienced physician consultants are available 24 hours a day to support medical personnel during crisis intervention. After resolution of the crisis and stabilization of the patient, the treating anesthesia personnel are advised to register the patient with the North American Malignant Hyperthermia Registry for follow-up. Each call is evaluated, and data are collected for application to research of early detection and future prevention of MH crisis. MHAUS publishes a quarterly newsletter, The Communicator, for dissemination of current information and education about MH. More information is available at their web site www.rnhaus.org. Nonemergent questions can be directed to 1-800-986-4287. The North American Malignant Hyperthermia Registry was established in 1987 in an effort to centralize, analyze, and disseminate clinical and scientific information about MH to researchers and physicians who care for MH-susceptible patients. The data accumulated are used to support investigative research of diagnosis, treatment, and detection of MH susceptibility in humans. The registry is located in Hershey, Pennsylvania, at the Pennsylvania State University College of Medicine, Department of Anesthesia. A patient may be registered by a treating anesthesiologist after a suspected or confirmed episode of an MH crisis. In 1995, MHAUS and the North American Malignant Hyperthermia Reg-
MALIGNANT HYPERTHERMIA
istry merged in an effort to consolidate data and focus on shared services in research and clinical intervention.
Pertinent Anatomy and Physiology Physiology of Muscle Tissue
Skeletal muscle is striated in appearance because the tissue is arranged in bundles of voluntarily contractile myofibrils. The striations of the collective myofibrils represent the contractile force of the muscle as a unified structure linked together by bands of tissue. The myofibrils are covered with a netlike sheath of sarcoplasmic reticulum that contains the bulk of the calcium needed for muscular activity. Very little calcium is stored in the cytoplasm of the muscle cell itself, but other vesicular structures within the cell can contain higher amounts. The exchange of calcium between the sarcoplasmic reticulum and the cytoplasm causes muscular contraction during physical activity. Calcium is moved through release channels, ryanodine receptors, by an active pump mechanism within the reticulum. Muscular contraction is sustained as long as the active transport continues and the calcium concentration of the intracellular compartment of skeletal muscle is high. The muscle is able to relax when the calcium returns to the reticulum. Pathophysiology of Malignant Hyperthermia
In an MH crisis, a triggering agent causes the uncontrolled release of calcium from the sarcoplasmic reticulum through the ryanodine receptors to skeletal muscle cells. The calciu~ cannot be pumped back into the sarcoplasmic reticulum. MH triggering agents are listed in Box 1.* The muscle enters a state of sustained contraction and hypermetabolism, consuming large amounts of energy and oxygen. The result of this prolonged contraction is heat production at a rate of 0.5°C to 2.0°C every 5 to 10 minutes. 1• 3• ; , 13• 24 The patient's body temperature can reach or exceed 40°C very
•References 1-3, 5, 13, 15, 22, 24, and 26-29.
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Box 1 KNOWN TRIGGERS OF MALIGNANT HYPERTHERMIA All volatile inhalation anesthetics : lsoflurane Desflurane Halothane Enflurane Sevoflurane Diethyl ether Cyclopropane Methoxyf lurane Depolarizing muscle relaxants Succinylcholine chloride Decamethonium
rapidly. Hyperthermia, however, frequently is a late sign. 1• 23 • 24 Researchers are studying the possibility of a defect in the ryanodine receptor as being the cause of susceptibility to triggering agents. During this state of hypermetabolism, oxygen consumption is extreme, causing carbon dioxide levels to increase in the blood, stimulating rapid, deep breathing if the patient is not under the influence of neuromuscular blockade. The prolonged hypermetabolic state of muscular contraction causes rhabdomyolysis (i.e., muscle breakdown at the cellular level) that causes the release of free myoglobin into the serum in excess of 170 µ,g. Myoglobin accumulates like sludge in major organs and, in particular, in the renal tubules, impairing urinary output and causing renal failure. The urine that is produced has a brownish tinge that progresses to a thick, dark oliguria followed by anuria. Urinary myoglobin measurements exceed 60 µ.,g .3 Muscle tissue releases CK into the serum in proportion to the degree of musc~lar dam~ge in process. Levels of serum CK climb rapidly above 200 U/ L and can reach levels of 20,000 U/ L or higher. 1• 7• 22 • 24 • 26 Serum potassium increases, causing myocardial irritation that results in sinus tachycardia and dysrhythmias.
Who is at Risk? Patient Populations Affected by Malignant Hyperthermia
MH is seen in patient populations rarely before the age of 3 years or after the age of 60
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years. Boys and girls are affected equally up to the age of puberty, but after puberty, the incidence of MH crisis in men is increased 1.5 : 1. It affects all races and ethnic groups. The reported incidence in children is approximately 1: 15,000 and in adults, 1: 50,000 per anesthetic administration. The actual incidence may be higher in the general population because of underdiagnosis or underreporting. Because reporting is voluntary, not all episodes of MH are reported to the MH registries located in North America and Europe. 24, 27 Pediatric patients are more likely to have inhalation anesthesia and succinylcholine administration for surgical procedures. Many children display trismus in response to anesthetic triggers, but not all are related to MH. 24 Studies have shown that patients who display trismus during anesthesia induction have a higher incidence of positive MH testing. Other considerations in pediatric patients include a higher incidence of clinical, subclinical, occult, and undiagnosed musculoskeletal defects. 24
Conditions That May Predispose the Patient to Malignant Hyperthermia Certain physiologic characteristics, such as a short, stocky build; bulky muscles; muscular hypertrophy; strabismus; hernias; club foot; pectus carinatum; joint hypermobility; and spontaneous dislocation, may indicate a predisposition for MH. A patient who reports vulnerability to heat stroke or heat exhaustion also may be at risk. 10 Patients with some physiologic conditions may experience an increased incidence of MH syndrome when exposed to triggering agents. These conditions include myotonia congenita, chronic muscle cramps, exerciseinduced rhabdomyolysis/ myoglobinuria, Duchenne muscular dystrophy (X-linked disorder), Becker muscular dystrophy, osteogenesis imperfecta, arthrogryposis, kyphoscoliosis, King- Denborough syndrome, and previous incidence of neuroleptic malignant syndrome (NMS) associated with the use of antipsychotic medication. 3· 4· 10· 13· 15· 17· 28 Of adult patients who display trismus after the administration of succinylcholine, 20% will go on to have an MH episode .24· 27' 28
Assessment of Risk Factors by History Patients should be asked about their personal and family reactions to general anesthesia. A family history of sudden unexplained perioperative deaths may be a strong indicator to avoid the use of known triggering agents during anesthetic administration. 6· 11
Diagnosis of Malignant Hyperthermia Unfortunately, most diagnoses of MH are made at the time of acute MH crisis in evolution. A sudden elevation of end-tidal C02indicated by capnographic monitoring should be highly suspect, and any incidence of unexplained sinus tachycardia suggests further observation by measuring arterial and venous blood gases. All patients having general anesthesia should have their core body temperature monitored throughout the surgical procedure.24 Most patients in the average population experience a slight downward shift of body temperature in response to general anesthesia. This can be confusing during initial evaluation of potential signs of MH involving measurement of core body temperature.21. 24, 27 Ideally, diagnosis of susceptibility to MH begins with a full history and physical examination. Physical characteristics of skeletal muscle and observation of musculoskeletal deviations from the average population may prompt the examiner to query the need for MH testing. Family physiologic and anesthetic history is explored and taken into consideration before any invasive testing is performed. Only those patients at significant risk are tested by invasive means.11 • 12· 16· 24· 26 Methods of MH diagnosis include laboratory studies for baseline chemistry and the exposure of skeletal muscle to an in vitro anesthetic challenge through fresh muscle biopsy. Genetic testing for families with known MH susceptibility is of value if many family members have the same marker gene, because each family member has a 50% chance of inheriting the suspect gene. 6· 11 • 16 Serum CK testing is not a reliable indicator for the general population but may be of value for known MH families . Early types of in vitro contracture testing required the muscle tissue to be exposed to increasing amounts of caffeine followed by a
MALIGNANT HYPERTHERMIA
bolus of halothane gas. North American testing standards do not combine halothane and caffeine in testing the same specimen because false positives have been observed. 24 Current MH muscle-testing technology is available at only 12 select centers in the United States and 20 centers in Europe and involves a more complex process for accuracy. Because fresh muscle tissue is viable for only a short time, it is procured from the patient's vastus lateralis muscle at the testing center under local or regional anesthesia or under nontriggering general anesthesia. The fresh specimen is taken directly to the laboratory and placed in a fresh tissue bath ofKreb's solution at 37°C for immediate testing. The muscle fibers are isolated into six bundles and mounted under monitored tension. Electricity is used to stimulate the muscle tissue to get a baseline contraction measured in grams. Halothane, 3% gas, is directed by vaporizer onto three bundles of prepared muscle fibers. The force of the contraction is measured and compared to baseline. If caffeine is used, it is applied to three separate muscle bundles, and contraction is measured. Muscle from MHsusceptible patients is more sensitive and contracts more forcefully than normal muscle. A contracture response by North American Standards is considered positive at a threshold of greater than 0.2 g to 0.7 g in at least one of each three bundles after halothane- and caffeine-exposure testing. False negatives are rare if these standards are followed. Patients who test positive for MH sensitivity should carry appropriate identification, such as a wallet card and MedicAlert tag.16 • 24
Malignant Hyperthermia Crisis
Triggering Agents
MH is triggered by specific chemical agents. Triggers include depolarizing muscle relaxants and volatile inhalation anesthetic gases. Specific triggering agents are listed in Box 1_1 , 2, 7, 22, 24 What Are the First Signs?
Signs and symptoms of an MH crisis may appear any time throughout the perioperative period; however, they arise most commonly during the intraoperative phase of care. Con-
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Box 2 SIGNS AND SYMPTOMS OF MALIGNANT HYPERTHERMIA CRISIS Masseter muscle rigidity Increasing end-tidal C0 2 Tachycardia Tachypnea Ventricular dysrhythmia Oxygen desaturation Unstable blood pressure Generalized muscular rigidity Mottling and cyanosis Sudden increase in temperature Unexplained acidosis Rhabdomyolysis Elevated serum CK, myoglobin, and potassium
temporary monitoring systems permit the caregiver to identify signs of an MH crisis. These are listed in Box 2. The earliest physiologic signs of a potential crisis in process include masseter muscle rigidity (trismus) during intubation, increased end-tidal C02, tachycardia, ventricular dysrhythmia, and tachypnea (if not paralyzed with muscle relaxants). Of those patients who exhibit trismus after administration of succinylcholine, 20% go on to demonstrate clinical and laboratory signs of full-blown MH. 1• 3, l3, 15, 24 Additional signs include an unexplained generalized somatic muscle rigidity and an increase of core body temperature. As the muscular contractions persist, the patient's body temperature increases because of increased metabolism. Temperature may increase as a late sign. The patient may give the appearance of becoming "light" under general anesthesia by trying to overbreathe the ventilator. The blood in the surgical field becomes darker, and the patient's skin becomes mottled and diaphoretic as the blood level of C02 increases. The blood pressure increases initially because of sympathetic stimulation, hypercarbia, and hyperkalemia but later falls as the syndrome progresses, remaining unstable. Central cyanosis increases to critical levels.• Review of Body Systems During a Malignant Hyperthermia Crisis
Each body system has a collection of signs and symptoms associated with an MH crisis. •References 1, 3, 7, 13, 15, 18, 19, 22, 24, 27, and 29.
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Each affected body system is described below: 1. Cardiac system: tachycardia, ventricular dysrhythmia, ventricular fibrillation, and asystole 2. Peripheral vascular system: vasoconstriction, thready and rapid pulse, and elevated blood pressure followed by unstable hypotension 3. Respiratory system: tachypnea if not paralyzed, hypercarbia, and respiratory acidosis 4. Musculoskeletal system: may have generalized skeletal muscle rigidity that progresses to rhabdomyolysis and the release of free myoglobin into the serum 5. Renal system: decreasing urine production, myoglobinuria progressing to anuria, and metabolic acidosis 6. Integumentary system: erythematous flush, peripheral mottling, central cyanosis, and diaphoresis 7. Thermoregulatory system: palpable warmth of viscera, increase in measurable body temperature, and exhaled gases create heat in the soda lime canister of the anesthesia machine 8. Laboratory studies: increased CK, increased lactate, increased myoglobin, altered coagulation profile, and decreased pH. Electrolyte imbalance of increased magnesium, increased phosphate, increased calcium, and increased potassium. Arterial and venous blood gas samples show severe respiratory and metabolic acidosis. Table 1 describes the results of laboratory studies in an acute MH crisis. Syndromes and Conditions That Mimic Malignant Hyperthermia
The relationship between anesthetic- and nonanesthetic-caused hyperthermia is unclear. Chemically mediated hyperthermia is seen in such conditions as sympathomimetic poisoning, anticholinergic poisoning, serotonin syndrome, sulfasalazine, abuse of Ecstasy (methylenedioxymethamphetamine), and NMS; this type of hyperthermia commonly displays the same signs and symptoms as MH. Nonchemically mediated hyperthermia, such as exercise-induced rhabdomyolysis or myoglobinuria and heatstroke, often mani-
Table 1 LABORATORY FINDINGS IN MALIGNANT HYPERTHERMIA CRISIS ABG {I-pH {l-Po2 {t-Pco2 Electrolytes {t-K {t-Ca {t-Mg {I-Na Serum ft-Lactate {t-Pyruvate {t-CK {t-LDH {t-Aldolase {t-Myoglobin ft-Glucose {t-Creatinine {I-PT
{1-PTI {I-Platelets
Normal Ranges
7.35-745 80-100 mm Hg 35-45 mm Hg 4.0-54 mEq/L 4.5-5.5 mEq/L 1.8-24 mg/dL 138-148 mEq/L 0.7- 2.1 mmol/L 0.03-0.08 mmol/L 40-280 U/L 3.13-6.18 U/L Age specific 6-85 ng/mL 80-120 mg/dL 0.5-1.4 mg/dL
10- 12 22- 27 50,000
Reprinted with oermission from AORN Standards, Recommended Practices, and Guidelines, 1999, p 77. Copyright © AORN. Inc. , 2170 South Parker Road, Suite 300, Denver, 80231 . ABG = arterial blood gases; K = potassium; Ca = calcium, Mg = magnesium; Na = sodium; CPK = creatine phosphokinase; LOH ~~ lactate dehydrogenase; PT = prothrombin time; PTI = partial thromboplastin time.
co
fests in extremely high core temperatures and hypermetabolism. Heatstroke is manifest by elevated temperature and rhabdomyolysis but is not accompanied by skeletal muscle contraction. People who are susceptible to heatstroke during exercise accumulate higher levels of lactate, which stimulate the cell membrane sodium-potassium pump. Intracellular stores of sodium and calcium are affected, causing decreased energy stores. The elevated body temperature cannot dissipate, and the chemical imbalances cause rhabdomyolysis. Studies of armed forces personnel who have experienced exertional\ heatstroke have demonstrated negative caffeine contracture testing but positive halothane testing. The possibility of a relationship between hyperpyrexic states and inherited skeletal muscle defects was demonstrated when family members of the service members underwent the same testing with positive results. Heatstroke is unaffected by dantrolene administration during treatment, suggesting that although
MALIGNANT HYPERTHERMIA
it resembles MH, it is different in pathology. 4, 10, 17, zs
Treatment During a Malignant Hyperthermia Crisis Initial Resuscitation During a Malignant Hyperthermia Crisis
Teamwork during an MH crisis is critical to the outcome of the patient. Intraoperatively, each person in the operating room has a role in the treatment and resuscitative effort. The leader of the team is an anesthesiologist, who should be assisted by a support anesthesia provider. Usually, it is the anesthesiologist or anesthesia provider who detects the impending MH crisis in evolution and starts the cycle of treatment and resuscitative events. Specific protocols are observed. All inhalation anesthetics and depolarizing muscle relaxants are stopped, and the patient is immediately hyperventilated with 100% oxygen. According to recommendations of MHAUS, the breathing circuit, C0 2 absorbant (soda lime canister) , and anesthesia machine do not have to be changed. 19 The sterile team should remain sterile, rapidly end the procedure, and close the surgical site as quickly as possible. If the patient is hyperthermic, the open body cavity should be lavaged with cool saline. Lactated Ringer's solution is avoided both intravenously and intracavitarily because it accelerates metabolic acidosis. 3• 19 The scrub person should remain sterile until the patient's sterile dressing is applied. If the procedure cannot be stopped or if the patient has become stable, surgery may proceed under nontriggering anesthesia agents. 1• 3• 7• 13• 24 • 29 Nontriggering anesthetics are described in Box 3.9. 13, 24 MHAUS has published an emergency treatment poster that outlines immediate treatment of an acute MH episode. The poster is available from the organization. AORN, the Association of Perioperative Registered Nurses, has developed an MH flowchart for patient assessment that is presented in Figure 1. The circulator should summon help to the room and send for the MH supplies. Some facilities use a tackle-style box; others use a cart system. Suggested contents of an MH cart are listed in Box 4. The circulator assists the anesthesia personnel in mixing, preparing,
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Box 3 NONTRIGGERING AGENTS USED IN ANESTHESIA ADMINISTRATION
Inhalation agents: Nitrous oxide Barbiturates : Methohexital sodium Thiopental sodium Benzodiazepines: Diazepam Lorazepam Midazolam hydrochloride Intravenous induction agents: Etomidate Ketamine hydrochloride Propofol Neuromuscular blocking agents nondepolarizing: Atracurium besylate Doxacurium chloride Mivacurium chloride Pancuronium bromide Pipecuronium bromide Rocuronium bromide Vecuronium bromide Narcotic and opioid analgesia: Fentanyl citrate Hydromorphone hydrochloride Meperidine hydrochloride Morphine sulfate Sufentanil citrate Alfentanil hydrochloride Local anesthetic agents: Lidocaine hydrochloride Bupivacaine hydrochloride Chloroprocaine hydrochloride Tetracaine hydrochloride
and administering dantrolene sodium at an initial bolus rate of 2.5 mg/kg. Some patients may require up to 10 mg/kg for stabilization. 20, 25, 29, 30 Dantrolene sodium for injection (Dantrium), introduced in 1979, has proved to be the only drug effective in the treatment of MH. The death rate from MH has dropped to less than 10% since its discovery. It can be given prophylactically or during a crisis. A minimum of 36 vials with adequate sterile water (2500 mL without bacteriostatic agent) for diluant should be kept in close proximity to the operating room. A patient weighing 70 kg requires 9 vials to attain a dosage of 2.5 mg/ kg. If the same size patient requires 10 mg/ kg for stabilization, he or she can rapidly use 35 vials in attainment of this therapeutic dosage. Dantrolene administration is continued
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At increased risk?
Assess
~ Minimal risk
/
Yes / MH susceptible
y/
/ Prevention
Treatme nt of symptoms
!
!
Muscle testing
Monitor physical pa rameters
~ Family involvement
Yes
!
Acute unexpected event
Dantrolene
Lab values, oxygenation/ ventilation, fl uid balance, tempe rature
Cont inue t reatment of symptoms
l Patie nt/fami ly teaching
48-72 hours postoperative
Figure 1. Malignant hyperthermia flow chart. (Reprinted with permission from AORN Standards, Recommended Practices, and Guidelines. 1999, p 79. Copyright © AORN, Inc., 2170 South Parker Road, Suite 300, Denver, co 80231 .)
into the critical care unit postoperatively for 48 to 72 hours after stabilization at a rate of 1 mg/kg as prophylaxis for recurrence. 20 Dantrolene should be protected from direct light after mixing and used within 6 hours. The main ingredients of each vial of Dantrium are dantrolene sodium, 20 mg, and mannitol, 3 g. Dantrolene is supplied in powder form that is mixed with 60 mL sterile water without preservative and shaken until clear before use. The diluted solution may appear yellowish to orange. Normal saline is not used for reconstitution because of the potential for precipitation of free dantrolene caused by ionic effects of the solution. Dextrose, 5% in water (D 5W), is not used because the differences in pH between reconstituted dantrolene sodium (pH 9.5) and D 5W (3.5 to 6.5) also can cause precipitation of the drug. The molecular weight of the dextrose can prevent adequate mixing of the dantrolene in solution because the drug is not highly water soluble.
Shelf-life of dantrolene is 3 years from the date of manufacture. Maintenance of an adequate stock of 36 vials of dantrolene costs an average of $600 per year, according to MHAUS. 20 Dantrolene interferes with the release of calcium from the sarcoplasmic reticulum of skeletal muscle, minimizing contraction and excitation. It does not potentiate or prevent reversal of nondepolarizing relaxants. Dantrolene is not compatible w ith calcium channel blockers, such as verapamil. This combination can cause severe hyperkalemia and myocardial depression. 20• 25, 30 Managing and Monitoring a Malignant Hyperthermia Crisis
Simultaneously with the initial resuscitation steps directed by anesthesia personnel, other personnel in the operating room have specific tasks to perform. The registered nurse (RN) in charge should be available to delegate each
MALIGNANT HYPERTHERMIA
Box 4 SUGGESTED CONTENTS FOR A MALIGNANT HVPERTHERMIA CART
2 breathing circuit adapters 2 pressure bags 2 soda lime canisters
Suggested Medication and Equipment
Miscellaneous
36 ampules dantrolene sodium (i.e. , Dantrium) IV (20-mg vials) 4 500-ml bottles sterile water (preservative free) 6 50-mEq syringes sodium bicarbonate 2 50-ml syringes 50% dextrose 2 4-ml vials furosemide (10 mg/ml) 2 500-ml bottles 20% mannitol 2 prefilled syringes 2% lidocaine 6 20-ml ampules procainamide (1 g) 3 10-ml vials heparin (1000 U) 2 semiautomatic dispensing syringes 2 stopcocks (3-way) 4 60-ml syringes
1 2 1 1
Other Equipment
6 6 6 1 2 2 2 1 1 2 2 2 10 2
10-ml syringes 18-gauge needles alcohol prep pads 4-oz bottle povidone-iodine paint 10-each boxes 4 x 4 sterile gauze tourniquets radial artery catheters arterial line monitoring kit central venous pressure line kit sets cassette tubing for IV pumps sets of IV tubing (pediatric and adult) sets IV extension tubing medication labels wrist splints (1 each , pediatric and adult sizes)
Tubes for Laboratory Tests
6 5-ml heparinized blood gas syringes or ABG kits 2 urine specimen containers 1 bottle urine test strips for myoglobin 6 light blue tubes (pediatric and adult sizes) 6 lavender tubes (pediatric and adult sizes) 1O gold tubes with gel 10 red stopper tubes Cooling Equipment
2 nasogastric tubes (pediatric and adult sizes) 2 30-ml balloon, 3-way Foley catheters (several pediatric and adult sizes) 2 closed-system Foley catheter trays 2 peritoneal lavage trays 2 sets cystoscopy tubing 2 60-ml catheter tip syringes 2 5-in-1 connectors 2 Y connectors 2 plastic buckets to hold ice 10 medium- and large-size plastic bags Anesthesia Equipment
(Have on cart or immediately available) 2 breathing circuits (pediatric and adult sizes)
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sharps container Ambu bags (pediatric and adult sizes) MH cart medications/supplies checklist MHAUS label on front of cart listing hotline telephone number (i.e., [800] 644-9737; ask for Index Zero)
At the Time Cart Is Requested, Add:
Refrigerated IV normal saline solution (1000ml bags) Refrigerated normal saline for irrigation (3000ml bags) Refrigerated regular insulin Ice IV = intravenous; ABG = arterial blood gas. Reprinted with permission from AORN Standards, Recommended Practices, and Guidelines, 1999, p 80. Copyright © AORN, Inc., 2170 South Parker Road, Suite 300, Denver, co 80231 .
support person's role and to facilitate communications throughout the perioperative environment.13· 15 One RN should be assigned to record the drugs and dosages, intake and output, and any treatment given during the MH crisis. Additional RNs should be on hand to assist in mixing the dantrolene and in preparing other drugs as needed by the anesthesiologist. 3· 13• 15· 20• 30 Patient care technicians or other unlicensed assistive personnel should be delegated to obtain supplies and ice, take blood gases to the laboratory, and perform other essential tasks during the stabilization process. A Foley catheter should be placed in the patient's bladder. Physiologic monitoring is essential during an MH crisis. Each body system should be monitored and symptomatically treated until all functions are under control. Arterial blood gas (ABG) analysis will guide the use of bicarbonate. In the absence of ABG testing capabilities, administer 1 to 2 mEq/ kg of bicarbonate to treat acidosis. 19 End-tidal C0 2, oxygen saturation, potassium, calcium, and electrolyte monitoring for baselines and status checks are recommended at frequent intervals during crisis management and physiologic maintenance .19· 24 Hyperkalemia is treated with hyperventilation with 100% oxygen, bicarbonate administration, and intravenous glucose and insulin
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FORTUNATO-PHILLIPS
(0.15 U/kg regular insulin in 1 mL/ kg 50% glucose or 10 U regular insulin in 50 mL 50% glucose titrated to potassium level). Blood glucose levels should be checked every 2 hours if insulin is given. Life-threatening hyperkalemia can be treated with calcium chloride, 2 to 5 mg/kg, according to MHAUS recommendations.19· 24 Hyperthermia is not always an early sign of an MH crisis; however, the patient's temperature can rise suddenly and rapidly. Temperatures as high as 1l4°F have been recorded in the literature.7· 8· 22· 23· 26· 28 Brain damage or death can result from prolonged hyperthermia; therefore, temperature monitoring is vital. Thermal monitoring routes include esophageal, tympanic membrane, nasopharynx, and pulmonary artery for core temperatures. 21 ·24·27 Other routes include mouth, axilla, rectum, and bladder. The least reliable is the skin surface, because the patient usually is diaphoretic and the evaporative process causes surface cooling. 13· 21 Patients in active hyperthermia require rapid cooling. The patient should be undraped and the spotlights should be turned off or directed away from the surgical field. The room temperature can be lowered to facilitate the cooling effort. A hypothermia blanket can be used. Intravenous solutions should be cool. Performing saline lavages of the rectum and abdominal cavity, packing the patient in ice, or both can help to lower body temperature. Continued thermal monitoring is important because vigorous cooling efforts can lead to hypothermia as the patient stabilizes.19 Cardiac dysrhythmias respond to the treatment of hyperkalemia and acidosis. If treatment of a dysrhythmia is necessary, avoid calcium channel blockers as they may cause full cardiovascular collapse from a hyperkalemic state .19, 25 Fluid balance should be closely observed because rapid fluid shifts will occur. The patient is at high risk for pulmonary edema. A central venous or pulmonary artery monitor is recommended because of hemodynamic instability. Adequate fluid hydration and administration of furosemide or mannitol can help promote urinary output. Irrigation of the bladder as a cooling measure could interfere with urinalysis for myoglobinuria and with accurate measurement of urinary output. Pa-
tients in MH crisis are at high risk for renal failure caused by myoglobin accumulation in the renal tubules. Urine output of 2 mL/kg per hour is desired but may be recorded inaccurately if the bladder is irrigated.
Post-Malignant Hyperthermia Crisis Care Post-MH crisis treatment is continued for 24 to 48 hours in an intensive care setting because an acute recurrence is possible. Dantrolene is continued intravenously at a base rate of 1 mg/kg or more as needed during this critical period, and fluid balance is closely observed through strict intake and output measurement. 19 Urinalysis is done to check for myoglobinuria. Continuous measurement of core body temperature is maintained. Serial CK, ABGs, electrolytes, clotting studies, and other blood chemistries are performed to monitor the patient's progress at 6-hour intervals until the patient returns to full baseline.19 Pain assessment is necessary because the patient will have somatic muscle aches associated with the sustained contractions experienced during the crisis period. Obstetric patients should be advised that dantrolene is secreted in breast milk with a half-life of 9.02 hours, and breastfeeding is not advised. 14 The family should have MH risk assessment counseling to determine the extent of the familial inheritance. Medical evaluators will determine the selection of patients and MH testing modalities such as muscle biopsy or genetic marker comparisons. Registration with the No1th American Malignant Hyperthermia Registry is recommended. Prevention of MH Crisis
All efforts are directed to determine MH susceptibility before exposing any patient to potential triggers; however, some patients are not identified clearly before they experience a crisis situation. MH-susceptible patients and the patients at risk for MH are not excluded from surgical intervention under general anesthesia. Surgery can be performed using several nontriggering anesthetics. If general anesthesia is desired, the anesthesia machine should have a fresh soda lime canister and breathing circuit to prevent inadvertent exposure to residual gases that may linger in
MALIGNANT HYPERTHERMIA
the tubing. Regional and local anesthetic techniques are safe for use in the patient at risk. 1•13· 15• 24 •26•29 Postoperative temperature and EKG monitoring for 4 hours before discharge is recommended after ambulatory surgery. Oral forms of dantrolene were given to susceptible patients as preoperative prophylaxis in the past, but it was determined that therapeutic levels were variable and the practice was discontinued. 30 In select situations, the patient who has experienced an MH crisis during previous general anesthesia may be given intravenous dantrolene at 2 to 2.5 mg/ kg 30 minutes before the induction of anesthesia. 20 Intraoperatively, dantrolene can be given as needed. Prophylactic use of dantrolene is highly subjective and may be unnecessary when nontriggering anesthesia is used. 17• 20 Dantrolene can cause muscle weakness in patients with muscular disease and therefore should be used with caution as routine prophylaxis. 30 Every surgical setting wherein a potential trigger may be administered should have a plan of care for the patient in MH crisis. Dantrolene, a minimum of 36 vials with 2500 mL sterile water without bacteriostatic additives,
209
should be immediately available to the operating room and postanesthetic care unit (PACU). A refrigerator with chilled intravenous saline (6L)and1000-ml bottles of saline irrigation (12) should be in readiness and stock rotated periodically to ensure freshness. An ice machine should be easily accessible. A fully stocked MH cart or tackle box system should be assembled and checked for completeness on a routine basis (Box 4). Staff inservice training should be held periodically, and MH crisis management should be included in orientation programs offered to new personnel. Walk-through drills may be beneficial to familiarize the staff with supply location and use. Outdated dantrolene can be mixed as a demonstration of the difficulty associated with preparing the solution in an emergent situation. Familiarity with supplies and equipment can help prevent confusion in the face of a patient in MH crisis. MHAUS offers a full range of literature suitable for staff and patient education. Information about this material is available on their web site. They can be contacted via e-mail (rnhaus@norwich. net) or by calling the information number listed in this article.
SUMMARY
MH is a life-threatening crisis that can be controlled if promptly recognized and appropriately treated. Identification of patients at risk for MH is an ongoing crusade. Preparedness with needed supplies available at hand facilitates optimal treatment. All perioperative personnel should remain current in their knowledge of MH management and treatment to ensure the best possible outcome for their patients.
REFERENCES 1. Abraham RB, et al: Malignant hyperthermia. Postgrad Med J 74:867, 1998 2. Allen GC, Brubaker CL: Human malignant hyperthermia associated with desflurane anesthesia. Anesth Analg 86:6, 1998 3. Association of Operating Room Nurses: Standards, Recommended Practices, and Guidelines. Denver, Association of Operating Room Nurses, 1999 4. Balzan MV: The neuroleptic malignant syndrome: A logical approach to a patient with elevated temperature and rigidity. Postgrad Med] 74:868, 1998 5. Chan TC, Evans SD, Clark RF: Drug-induced hyperthermia. Crit Care Clin 13:4, 1997 6. Curtis S: Update for nurse anesthetists: Genetic testing for malignant hyperthermia. AANAJournal 64:6, 1996
7. Denborough M: Malignant hyperthermia. Lancet 352:9134, 1998 8. Denborough M, Lovell R: Anesthetic deaths in a family. Lancet 2:45, 1960 9. Dunn D: Malignant hyperthermia. AORN] 65:4, 1997 10. Duthie DJR: Heat-related illness. Lancet 352:9137, 1998 11. Fletcher JE, et al: Comparison of European and North American malignant hyperthermia diagnostic protocol outcomes for use in genetic studies. Anesthesiology 90:3, 1999 12. Fletcher JE, Rosenberg H, Aggarwal M: ATX II, a sodium channel toxin, sensitizes skeletal muscle to halothane, caffeine, and ryanodine. Anesthesiology 90:5, 1999 13. Fortunato NH: Berry and Kahn's Operating Room Technique, ed 9. St Louis, Mosby Year Book, 2000
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14. Fricker RM , et al: Secretion of dantrolene into breast milk after acute therapy of a suspected malignant hyperthermia crisis during cesarean section. Anesthesiology 89:4, 1998 15. Golinski M: Malignant hyperthermia: A review. Plastic Surgical Nursing 15:1, 1995 16. Islander G, Twetman ER: Comparison between the European and the North American protocols for diagnosis of malignant hyperthermia susceptibility in humans. Anesth Analg 88:5, 1999 17. Koehntop DE, Beebe DS, Belani KG: Prophylactic use of dantrolene in a patient with central core disease. Anesth Analg 86:4, 1998 18. Lampotang S, et al: Influence of pulse oximetry and capnography on time to diagnosis of critical incidents in anesthesia: A pilot study using full-scale patient simulator.] Clin Monit Comput 14:5, 1998 19. Malignant Hyperthermia Association of the United States: Emergency Therapy for Malignant Hyperthermia. Sherburne, NY, Malignant Hyperthermia Association of the United States, 1999 20. Malignant Hyperthermia Association of the United States: Malignant Hyperthermia Drugs, Equipment, and the Antidote, Dantrolene Sodium. Sherburne, NY, Malignant Hyperthermia Association of the United States, 1996
21. Malignant Hyperthermia Association of the United States: Malignant Hyperthermia Temperature Monitoring in the Perioperative Period: Why, Where, and How. Malignant Hyperthermia Association of the United States, 1997 22. Miranda AD , et al: Malignant hyperthermia. Am] Crit Care 6:5 , 1997 23. Ramirez JA, et al: Suxamethonium, masseter muscle spasm and later malignant hyperthennia. Anaesthesia 53:11 , 1998 24. Rosenberg H: An update on malignant hyperthermia. Ann Acad Med Singapore 23:6, 1994 25. Satoh M, et al: Effect of dantrolene sodium on calcium-overloaded heart. Jpn Circ J 61:10, 1997 26. Sticco SL: Clinical case conference: Malignant hyperthermia. CRNA: The Clinical Forum for Nurse Anesthetists 6: 2. 1995 27. Stolworthy C, Haas RE: Malignant hyperthermia: A potentially fatal complication of anesthesia. Seminars in Perioperative Nursing 7:1, 1998 28. Struebing VL: Differential diagnosis of malignant hyperthermia: A case report. Journal of the American Association of Nurse Anesthetists 63:5, 1995 29. Vermette E: Emergency: Malignant hyperthermia. Am ] Nurs 98:4, 1998 30. Wedel DJ, et al: Clinical effects of intravenously administered dantrolene. Mayo Clin Proc 70, 1995
Address reprint requests to Nancymarie Fortunato-Phillips, MEd, BSN, BA, RN, RNFA, CNOR, CPSN PO Box 422 Wickliffe, OH 44092-0422 e-mail: [email protected]
Perioperative Critical Care
Malignant Hyperthermia Update 2000 Nancymarie Fortunato-Phillips, MEd, BSN , BA, RN , RNFA, CNOR, CPSN
What is Malignant Hyperthermia? Malignant hyperthermia (MH) is a life-threatening syndrome; it is a collection of signs and symptoms and not a single disease entity. MH is a sudden pharmacogenic hypermetabolic crisis involving uncontrolled calcium release from skeletal muscle that causes potentially fatal consequences. 1 It has been shown to occur as an autosomal dominant trait in families, although heterogenicity has been demonstrated by the variances in susceptibility to MH by individuals. Genetic differences in chromosomes 19q13.1-13.2 are seen in some mutations of the sequence. 6• 11 Both sexes can transmit the condition; therefore, it is not X linked like other types of muscular disorders, such as some muscular dystrophies. Each child of a person who is susceptible has a 50% chance of inheriting the genetic predisposition for MH. 6· 11 MH can be triggered by the administration of depolarizing muscle relaxants, such as succinylcholine, or volatile inhalation anesthetics, such as halothane, isoflurane, enflurane, methoxyflurane, sevoflurane, or desflurane. Reaction may be delayed with desflurane. 2 From the Cleveland Clinic Foundation, Cleveland; Lakeland Community College, Kirtland; and Phillips Consulting, Willoughby, Ohio
Cyclopropane, chloroform, and diethyl ether may cause an MH crisis, although they are not commonly used in modern anesthesia.5 Not every patient has the same response to the syndrome. A patient may have had triggering agents in the past without ill effects. Some patients may have had minor, undiagnosed symptoms. Each response in an individual can vary with each separate trigger administration. Some patients may have had multiple exposures without incident, which can be misleading if a full-blown MH crisis happens during a subsequent procedure. The success of the patient's outcome depends on quick recognition of an MH crisis in evolution and symptomatic treatment of the condition.1· 7, 8, 13, 1s, 18, 19, 24
History of Malignant Hyperthermia MH was first described in Germany in 1937 by Gude!. Familial relationships of the disease were reported in English literature by Denborough and Lovell in 1960, inAustralia. 8A young man who had been injured in a motor vehicle accident informed his surgeon that 10 close relatives had died during the administration of general anesthesia. The initial thought was that ether had caused his family members' deaths, so halothane was used for his proce
CRITICAL CARE NURSING CLINICS OF NORTH AMERICA I Volume 12 /Number 2 /June 2000
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came cyanotic and feverish within 10 minutes of the halothane administration. The administration of anesthetic was stopped immediately, and he was resuscitated symptomatically and cooled by ice packs. He recovered without permanent injury related to the critical episode. He later had additional surgical procedures under spinal anesthesia without subsequent problems. This ultimately led to the identification of local and regional anesthesia as safe for patients susceptible to MH.7• 8 Six years later, a symposium was held in Toronto, Ontario, where 13 cases of the same type of strange physiologic responses to anesthetic administration were presented. Most of the patients described had similar episodes, including a characteristically rapid hyperthermia. It was thought that the syndrome was probably an inborn dominant trait involving metabolism, but the association with anesthetic drugs was not clearly identified at that time. The reported mortality rate was 70%, but the rate was probably closer to 80% or 90% because it was largely an unknown entity. The literature includes one report of a family with 30 deaths associated with general anesthesia. 7· 8 Because the syndrome was predominantly fatal and involved extremely high body temperature, the name malignant hyperthermia (MH) was used to describe this condition. 7· 8 In 1969, a patient who was given succinylcholine and halothane experienced an MH crisis and died within 24 hours of the episode. His creatine kinase (CK) rose from 280 IU/ L at 3 hours to 20,500 IU/ L at 24 hours. He experienced massive rhabdomyolysis that was attributed directly to the anesthetic drugs. Analysis of his case revealed that he had undergone general anesthesia several years earlier without event; however, during this administration he had received a different form of anesthesia, which caused the MH reaction. It was determined that he was susceptible because of some type of unknown muscle disease. Several of his family members were tested and found to have an elevated CK and were diagnosed with a clinical myopathy. The link between these mysterious deaths and general anesthesia caused great concern in the medical community. Researchers throughout the world began exposing muscle tissue to gases and chemicals to observe contractile activity. It was discovered that dog
muscle contracted during exposure to chloroform, which in turn led to the use of caffeine in human muscle testing. 8 MH-susceptible individuals had an increased response to caffeine-muscle contractile testing. Halothane was found to cause the same result. Many of these early test results have led to current susceptibility testing methods.7• 9. 12• 16 The Malignant Hyperthermia Association of the United States (MHAUS) is an organization established in 1981 to bring together medical professionals, MH patients and their families, researchers, and other personnel who are concerned with or have been impacted by an MH crisis. Membership is open to all disciplines. Development and adherence to standard protocols provide the continuity necessary to serve and protect the population who is at risk for MH. MHAUS sponsors a toll-free hotline (1-800-MH-HYPER [1-800-644-9737)) for medical professionals to consult during treatment of a patient in crisis. Experienced physician consultants are available 24 hours a day to support medical personnel during crisis intervention. After resolution of the crisis and stabilization of the patient, the treating anesthesia personnel are advised to register the patient with the North American Malignant Hyperthermia Registry for follow-up. Each call is evaluated, and data are collected for application to research of early detection and future prevention of MH crisis. MHAUS publishes a quarterly newsletter, The Communicator, for dissemination of current information and education about MH. More information is available at their web site www.rnhaus.org. Nonemergent questions can be directed to 1-800-986-4287. The North American Malignant Hyperthermia Registry was established in 1987 in an effort to centralize, analyze, and disseminate clinical and scientific information about MH to researchers and physicians who care for MH-susceptible patients. The data accumulated are used to support investigative research of diagnosis, treatment, and detection of MH susceptibility in humans. The registry is located in Hershey, Pennsylvania, at the Pennsylvania State University College of Medicine, Department of Anesthesia. A patient may be registered by a treating anesthesiologist after a suspected or confirmed episode of an MH crisis. In 1995, MHAUS and the North American Malignant Hyperthermia Reg-
MALIGNANT HYPERTHERMIA
istry merged in an effort to consolidate data and focus on shared services in research and clinical intervention.
Pertinent Anatomy and Physiology Physiology of Muscle Tissue
Skeletal muscle is striated in appearance because the tissue is arranged in bundles of voluntarily contractile myofibrils. The striations of the collective myofibrils represent the contractile force of the muscle as a unified structure linked together by bands of tissue. The myofibrils are covered with a netlike sheath of sarcoplasmic reticulum that contains the bulk of the calcium needed for muscular activity. Very little calcium is stored in the cytoplasm of the muscle cell itself, but other vesicular structures within the cell can contain higher amounts. The exchange of calcium between the sarcoplasmic reticulum and the cytoplasm causes muscular contraction during physical activity. Calcium is moved through release channels, ryanodine receptors, by an active pump mechanism within the reticulum. Muscular contraction is sustained as long as the active transport continues and the calcium concentration of the intracellular compartment of skeletal muscle is high. The muscle is able to relax when the calcium returns to the reticulum. Pathophysiology of Malignant Hyperthermia
In an MH crisis, a triggering agent causes the uncontrolled release of calcium from the sarcoplasmic reticulum through the ryanodine receptors to skeletal muscle cells. The calciu~ cannot be pumped back into the sarcoplasmic reticulum. MH triggering agents are listed in Box 1.* The muscle enters a state of sustained contraction and hypermetabolism, consuming large amounts of energy and oxygen. The result of this prolonged contraction is heat production at a rate of 0.5°C to 2.0°C every 5 to 10 minutes. 1• 3• ; , 13• 24 The patient's body temperature can reach or exceed 40°C very
•References 1-3, 5, 13, 15, 22, 24, and 26-29.
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Box 1 KNOWN TRIGGERS OF MALIGNANT HYPERTHERMIA All volatile inhalation anesthetics : lsoflurane Desflurane Halothane Enflurane Sevoflurane Diethyl ether Cyclopropane Methoxyf lurane Depolarizing muscle relaxants Succinylcholine chloride Decamethonium
rapidly. Hyperthermia, however, frequently is a late sign. 1• 23 • 24 Researchers are studying the possibility of a defect in the ryanodine receptor as being the cause of susceptibility to triggering agents. During this state of hypermetabolism, oxygen consumption is extreme, causing carbon dioxide levels to increase in the blood, stimulating rapid, deep breathing if the patient is not under the influence of neuromuscular blockade. The prolonged hypermetabolic state of muscular contraction causes rhabdomyolysis (i.e., muscle breakdown at the cellular level) that causes the release of free myoglobin into the serum in excess of 170 µ,g. Myoglobin accumulates like sludge in major organs and, in particular, in the renal tubules, impairing urinary output and causing renal failure. The urine that is produced has a brownish tinge that progresses to a thick, dark oliguria followed by anuria. Urinary myoglobin measurements exceed 60 µ.,g .3 Muscle tissue releases CK into the serum in proportion to the degree of musc~lar dam~ge in process. Levels of serum CK climb rapidly above 200 U/ L and can reach levels of 20,000 U/ L or higher. 1• 7• 22 • 24 • 26 Serum potassium increases, causing myocardial irritation that results in sinus tachycardia and dysrhythmias.
Who is at Risk? Patient Populations Affected by Malignant Hyperthermia
MH is seen in patient populations rarely before the age of 3 years or after the age of 60
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years. Boys and girls are affected equally up to the age of puberty, but after puberty, the incidence of MH crisis in men is increased 1.5 : 1. It affects all races and ethnic groups. The reported incidence in children is approximately 1: 15,000 and in adults, 1: 50,000 per anesthetic administration. The actual incidence may be higher in the general population because of underdiagnosis or underreporting. Because reporting is voluntary, not all episodes of MH are reported to the MH registries located in North America and Europe. 24, 27 Pediatric patients are more likely to have inhalation anesthesia and succinylcholine administration for surgical procedures. Many children display trismus in response to anesthetic triggers, but not all are related to MH. 24 Studies have shown that patients who display trismus during anesthesia induction have a higher incidence of positive MH testing. Other considerations in pediatric patients include a higher incidence of clinical, subclinical, occult, and undiagnosed musculoskeletal defects. 24
Conditions That May Predispose the Patient to Malignant Hyperthermia Certain physiologic characteristics, such as a short, stocky build; bulky muscles; muscular hypertrophy; strabismus; hernias; club foot; pectus carinatum; joint hypermobility; and spontaneous dislocation, may indicate a predisposition for MH. A patient who reports vulnerability to heat stroke or heat exhaustion also may be at risk. 10 Patients with some physiologic conditions may experience an increased incidence of MH syndrome when exposed to triggering agents. These conditions include myotonia congenita, chronic muscle cramps, exerciseinduced rhabdomyolysis/ myoglobinuria, Duchenne muscular dystrophy (X-linked disorder), Becker muscular dystrophy, osteogenesis imperfecta, arthrogryposis, kyphoscoliosis, King- Denborough syndrome, and previous incidence of neuroleptic malignant syndrome (NMS) associated with the use of antipsychotic medication. 3· 4· 10· 13· 15· 17· 28 Of adult patients who display trismus after the administration of succinylcholine, 20% will go on to have an MH episode .24· 27' 28
Assessment of Risk Factors by History Patients should be asked about their personal and family reactions to general anesthesia. A family history of sudden unexplained perioperative deaths may be a strong indicator to avoid the use of known triggering agents during anesthetic administration. 6· 11
Diagnosis of Malignant Hyperthermia Unfortunately, most diagnoses of MH are made at the time of acute MH crisis in evolution. A sudden elevation of end-tidal C02indicated by capnographic monitoring should be highly suspect, and any incidence of unexplained sinus tachycardia suggests further observation by measuring arterial and venous blood gases. All patients having general anesthesia should have their core body temperature monitored throughout the surgical procedure.24 Most patients in the average population experience a slight downward shift of body temperature in response to general anesthesia. This can be confusing during initial evaluation of potential signs of MH involving measurement of core body temperature.21. 24, 27 Ideally, diagnosis of susceptibility to MH begins with a full history and physical examination. Physical characteristics of skeletal muscle and observation of musculoskeletal deviations from the average population may prompt the examiner to query the need for MH testing. Family physiologic and anesthetic history is explored and taken into consideration before any invasive testing is performed. Only those patients at significant risk are tested by invasive means.11 • 12· 16· 24· 26 Methods of MH diagnosis include laboratory studies for baseline chemistry and the exposure of skeletal muscle to an in vitro anesthetic challenge through fresh muscle biopsy. Genetic testing for families with known MH susceptibility is of value if many family members have the same marker gene, because each family member has a 50% chance of inheriting the suspect gene. 6· 11 • 16 Serum CK testing is not a reliable indicator for the general population but may be of value for known MH families . Early types of in vitro contracture testing required the muscle tissue to be exposed to increasing amounts of caffeine followed by a
MALIGNANT HYPERTHERMIA
bolus of halothane gas. North American testing standards do not combine halothane and caffeine in testing the same specimen because false positives have been observed. 24 Current MH muscle-testing technology is available at only 12 select centers in the United States and 20 centers in Europe and involves a more complex process for accuracy. Because fresh muscle tissue is viable for only a short time, it is procured from the patient's vastus lateralis muscle at the testing center under local or regional anesthesia or under nontriggering general anesthesia. The fresh specimen is taken directly to the laboratory and placed in a fresh tissue bath ofKreb's solution at 37°C for immediate testing. The muscle fibers are isolated into six bundles and mounted under monitored tension. Electricity is used to stimulate the muscle tissue to get a baseline contraction measured in grams. Halothane, 3% gas, is directed by vaporizer onto three bundles of prepared muscle fibers. The force of the contraction is measured and compared to baseline. If caffeine is used, it is applied to three separate muscle bundles, and contraction is measured. Muscle from MHsusceptible patients is more sensitive and contracts more forcefully than normal muscle. A contracture response by North American Standards is considered positive at a threshold of greater than 0.2 g to 0.7 g in at least one of each three bundles after halothane- and caffeine-exposure testing. False negatives are rare if these standards are followed. Patients who test positive for MH sensitivity should carry appropriate identification, such as a wallet card and MedicAlert tag.16 • 24
Malignant Hyperthermia Crisis
Triggering Agents
MH is triggered by specific chemical agents. Triggers include depolarizing muscle relaxants and volatile inhalation anesthetic gases. Specific triggering agents are listed in Box 1_1 , 2, 7, 22, 24 What Are the First Signs?
Signs and symptoms of an MH crisis may appear any time throughout the perioperative period; however, they arise most commonly during the intraoperative phase of care. Con-
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Box 2 SIGNS AND SYMPTOMS OF MALIGNANT HYPERTHERMIA CRISIS Masseter muscle rigidity Increasing end-tidal C0 2 Tachycardia Tachypnea Ventricular dysrhythmia Oxygen desaturation Unstable blood pressure Generalized muscular rigidity Mottling and cyanosis Sudden increase in temperature Unexplained acidosis Rhabdomyolysis Elevated serum CK, myoglobin, and potassium
temporary monitoring systems permit the caregiver to identify signs of an MH crisis. These are listed in Box 2. The earliest physiologic signs of a potential crisis in process include masseter muscle rigidity (trismus) during intubation, increased end-tidal C02, tachycardia, ventricular dysrhythmia, and tachypnea (if not paralyzed with muscle relaxants). Of those patients who exhibit trismus after administration of succinylcholine, 20% go on to demonstrate clinical and laboratory signs of full-blown MH. 1• 3, l3, 15, 24 Additional signs include an unexplained generalized somatic muscle rigidity and an increase of core body temperature. As the muscular contractions persist, the patient's body temperature increases because of increased metabolism. Temperature may increase as a late sign. The patient may give the appearance of becoming "light" under general anesthesia by trying to overbreathe the ventilator. The blood in the surgical field becomes darker, and the patient's skin becomes mottled and diaphoretic as the blood level of C02 increases. The blood pressure increases initially because of sympathetic stimulation, hypercarbia, and hyperkalemia but later falls as the syndrome progresses, remaining unstable. Central cyanosis increases to critical levels.• Review of Body Systems During a Malignant Hyperthermia Crisis
Each body system has a collection of signs and symptoms associated with an MH crisis. •References 1, 3, 7, 13, 15, 18, 19, 22, 24, 27, and 29.
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Each affected body system is described below: 1. Cardiac system: tachycardia, ventricular dysrhythmia, ventricular fibrillation, and asystole 2. Peripheral vascular system: vasoconstriction, thready and rapid pulse, and elevated blood pressure followed by unstable hypotension 3. Respiratory system: tachypnea if not paralyzed, hypercarbia, and respiratory acidosis 4. Musculoskeletal system: may have generalized skeletal muscle rigidity that progresses to rhabdomyolysis and the release of free myoglobin into the serum 5. Renal system: decreasing urine production, myoglobinuria progressing to anuria, and metabolic acidosis 6. Integumentary system: erythematous flush, peripheral mottling, central cyanosis, and diaphoresis 7. Thermoregulatory system: palpable warmth of viscera, increase in measurable body temperature, and exhaled gases create heat in the soda lime canister of the anesthesia machine 8. Laboratory studies: increased CK, increased lactate, increased myoglobin, altered coagulation profile, and decreased pH. Electrolyte imbalance of increased magnesium, increased phosphate, increased calcium, and increased potassium. Arterial and venous blood gas samples show severe respiratory and metabolic acidosis. Table 1 describes the results of laboratory studies in an acute MH crisis. Syndromes and Conditions That Mimic Malignant Hyperthermia
The relationship between anesthetic- and nonanesthetic-caused hyperthermia is unclear. Chemically mediated hyperthermia is seen in such conditions as sympathomimetic poisoning, anticholinergic poisoning, serotonin syndrome, sulfasalazine, abuse of Ecstasy (methylenedioxymethamphetamine), and NMS; this type of hyperthermia commonly displays the same signs and symptoms as MH. Nonchemically mediated hyperthermia, such as exercise-induced rhabdomyolysis or myoglobinuria and heatstroke, often mani-
Table 1 LABORATORY FINDINGS IN MALIGNANT HYPERTHERMIA CRISIS ABG {I-pH {l-Po2 {t-Pco2 Electrolytes {t-K {t-Ca {t-Mg {I-Na Serum ft-Lactate {t-Pyruvate {t-CK {t-LDH {t-Aldolase {t-Myoglobin ft-Glucose {t-Creatinine {I-PT
{1-PTI {I-Platelets
Normal Ranges
7.35-745 80-100 mm Hg 35-45 mm Hg 4.0-54 mEq/L 4.5-5.5 mEq/L 1.8-24 mg/dL 138-148 mEq/L 0.7- 2.1 mmol/L 0.03-0.08 mmol/L 40-280 U/L 3.13-6.18 U/L Age specific 6-85 ng/mL 80-120 mg/dL 0.5-1.4 mg/dL
10- 12 22- 27 50,000
Reprinted with oermission from AORN Standards, Recommended Practices, and Guidelines, 1999, p 77. Copyright © AORN. Inc. , 2170 South Parker Road, Suite 300, Denver, 80231 . ABG = arterial blood gases; K = potassium; Ca = calcium, Mg = magnesium; Na = sodium; CPK = creatine phosphokinase; LOH ~~ lactate dehydrogenase; PT = prothrombin time; PTI = partial thromboplastin time.
co
fests in extremely high core temperatures and hypermetabolism. Heatstroke is manifest by elevated temperature and rhabdomyolysis but is not accompanied by skeletal muscle contraction. People who are susceptible to heatstroke during exercise accumulate higher levels of lactate, which stimulate the cell membrane sodium-potassium pump. Intracellular stores of sodium and calcium are affected, causing decreased energy stores. The elevated body temperature cannot dissipate, and the chemical imbalances cause rhabdomyolysis. Studies of armed forces personnel who have experienced exertional\ heatstroke have demonstrated negative caffeine contracture testing but positive halothane testing. The possibility of a relationship between hyperpyrexic states and inherited skeletal muscle defects was demonstrated when family members of the service members underwent the same testing with positive results. Heatstroke is unaffected by dantrolene administration during treatment, suggesting that although
MALIGNANT HYPERTHERMIA
it resembles MH, it is different in pathology. 4, 10, 17, zs
Treatment During a Malignant Hyperthermia Crisis Initial Resuscitation During a Malignant Hyperthermia Crisis
Teamwork during an MH crisis is critical to the outcome of the patient. Intraoperatively, each person in the operating room has a role in the treatment and resuscitative effort. The leader of the team is an anesthesiologist, who should be assisted by a support anesthesia provider. Usually, it is the anesthesiologist or anesthesia provider who detects the impending MH crisis in evolution and starts the cycle of treatment and resuscitative events. Specific protocols are observed. All inhalation anesthetics and depolarizing muscle relaxants are stopped, and the patient is immediately hyperventilated with 100% oxygen. According to recommendations of MHAUS, the breathing circuit, C0 2 absorbant (soda lime canister) , and anesthesia machine do not have to be changed. 19 The sterile team should remain sterile, rapidly end the procedure, and close the surgical site as quickly as possible. If the patient is hyperthermic, the open body cavity should be lavaged with cool saline. Lactated Ringer's solution is avoided both intravenously and intracavitarily because it accelerates metabolic acidosis. 3• 19 The scrub person should remain sterile until the patient's sterile dressing is applied. If the procedure cannot be stopped or if the patient has become stable, surgery may proceed under nontriggering anesthesia agents. 1• 3• 7• 13• 24 • 29 Nontriggering anesthetics are described in Box 3.9. 13, 24 MHAUS has published an emergency treatment poster that outlines immediate treatment of an acute MH episode. The poster is available from the organization. AORN, the Association of Perioperative Registered Nurses, has developed an MH flowchart for patient assessment that is presented in Figure 1. The circulator should summon help to the room and send for the MH supplies. Some facilities use a tackle-style box; others use a cart system. Suggested contents of an MH cart are listed in Box 4. The circulator assists the anesthesia personnel in mixing, preparing,
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Box 3 NONTRIGGERING AGENTS USED IN ANESTHESIA ADMINISTRATION
Inhalation agents: Nitrous oxide Barbiturates : Methohexital sodium Thiopental sodium Benzodiazepines: Diazepam Lorazepam Midazolam hydrochloride Intravenous induction agents: Etomidate Ketamine hydrochloride Propofol Neuromuscular blocking agents nondepolarizing: Atracurium besylate Doxacurium chloride Mivacurium chloride Pancuronium bromide Pipecuronium bromide Rocuronium bromide Vecuronium bromide Narcotic and opioid analgesia: Fentanyl citrate Hydromorphone hydrochloride Meperidine hydrochloride Morphine sulfate Sufentanil citrate Alfentanil hydrochloride Local anesthetic agents: Lidocaine hydrochloride Bupivacaine hydrochloride Chloroprocaine hydrochloride Tetracaine hydrochloride
and administering dantrolene sodium at an initial bolus rate of 2.5 mg/kg. Some patients may require up to 10 mg/kg for stabilization. 20, 25, 29, 30 Dantrolene sodium for injection (Dantrium), introduced in 1979, has proved to be the only drug effective in the treatment of MH. The death rate from MH has dropped to less than 10% since its discovery. It can be given prophylactically or during a crisis. A minimum of 36 vials with adequate sterile water (2500 mL without bacteriostatic agent) for diluant should be kept in close proximity to the operating room. A patient weighing 70 kg requires 9 vials to attain a dosage of 2.5 mg/ kg. If the same size patient requires 10 mg/ kg for stabilization, he or she can rapidly use 35 vials in attainment of this therapeutic dosage. Dantrolene administration is continued
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At increased risk?
Assess
~ Minimal risk
/
Yes / MH susceptible
y/
/ Prevention
Treatme nt of symptoms
!
!
Muscle testing
Monitor physical pa rameters
~ Family involvement
Yes
!
Acute unexpected event
Dantrolene
Lab values, oxygenation/ ventilation, fl uid balance, tempe rature
Cont inue t reatment of symptoms
l Patie nt/fami ly teaching
48-72 hours postoperative
Figure 1. Malignant hyperthermia flow chart. (Reprinted with permission from AORN Standards, Recommended Practices, and Guidelines. 1999, p 79. Copyright © AORN, Inc., 2170 South Parker Road, Suite 300, Denver, co 80231 .)
into the critical care unit postoperatively for 48 to 72 hours after stabilization at a rate of 1 mg/kg as prophylaxis for recurrence. 20 Dantrolene should be protected from direct light after mixing and used within 6 hours. The main ingredients of each vial of Dantrium are dantrolene sodium, 20 mg, and mannitol, 3 g. Dantrolene is supplied in powder form that is mixed with 60 mL sterile water without preservative and shaken until clear before use. The diluted solution may appear yellowish to orange. Normal saline is not used for reconstitution because of the potential for precipitation of free dantrolene caused by ionic effects of the solution. Dextrose, 5% in water (D 5W), is not used because the differences in pH between reconstituted dantrolene sodium (pH 9.5) and D 5W (3.5 to 6.5) also can cause precipitation of the drug. The molecular weight of the dextrose can prevent adequate mixing of the dantrolene in solution because the drug is not highly water soluble.
Shelf-life of dantrolene is 3 years from the date of manufacture. Maintenance of an adequate stock of 36 vials of dantrolene costs an average of $600 per year, according to MHAUS. 20 Dantrolene interferes with the release of calcium from the sarcoplasmic reticulum of skeletal muscle, minimizing contraction and excitation. It does not potentiate or prevent reversal of nondepolarizing relaxants. Dantrolene is not compatible w ith calcium channel blockers, such as verapamil. This combination can cause severe hyperkalemia and myocardial depression. 20• 25, 30 Managing and Monitoring a Malignant Hyperthermia Crisis
Simultaneously with the initial resuscitation steps directed by anesthesia personnel, other personnel in the operating room have specific tasks to perform. The registered nurse (RN) in charge should be available to delegate each
MALIGNANT HYPERTHERMIA
Box 4 SUGGESTED CONTENTS FOR A MALIGNANT HVPERTHERMIA CART
2 breathing circuit adapters 2 pressure bags 2 soda lime canisters
Suggested Medication and Equipment
Miscellaneous
36 ampules dantrolene sodium (i.e. , Dantrium) IV (20-mg vials) 4 500-ml bottles sterile water (preservative free) 6 50-mEq syringes sodium bicarbonate 2 50-ml syringes 50% dextrose 2 4-ml vials furosemide (10 mg/ml) 2 500-ml bottles 20% mannitol 2 prefilled syringes 2% lidocaine 6 20-ml ampules procainamide (1 g) 3 10-ml vials heparin (1000 U) 2 semiautomatic dispensing syringes 2 stopcocks (3-way) 4 60-ml syringes
1 2 1 1
Other Equipment
6 6 6 1 2 2 2 1 1 2 2 2 10 2
10-ml syringes 18-gauge needles alcohol prep pads 4-oz bottle povidone-iodine paint 10-each boxes 4 x 4 sterile gauze tourniquets radial artery catheters arterial line monitoring kit central venous pressure line kit sets cassette tubing for IV pumps sets of IV tubing (pediatric and adult) sets IV extension tubing medication labels wrist splints (1 each , pediatric and adult sizes)
Tubes for Laboratory Tests
6 5-ml heparinized blood gas syringes or ABG kits 2 urine specimen containers 1 bottle urine test strips for myoglobin 6 light blue tubes (pediatric and adult sizes) 6 lavender tubes (pediatric and adult sizes) 1O gold tubes with gel 10 red stopper tubes Cooling Equipment
2 nasogastric tubes (pediatric and adult sizes) 2 30-ml balloon, 3-way Foley catheters (several pediatric and adult sizes) 2 closed-system Foley catheter trays 2 peritoneal lavage trays 2 sets cystoscopy tubing 2 60-ml catheter tip syringes 2 5-in-1 connectors 2 Y connectors 2 plastic buckets to hold ice 10 medium- and large-size plastic bags Anesthesia Equipment
(Have on cart or immediately available) 2 breathing circuits (pediatric and adult sizes)
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sharps container Ambu bags (pediatric and adult sizes) MH cart medications/supplies checklist MHAUS label on front of cart listing hotline telephone number (i.e., [800] 644-9737; ask for Index Zero)
At the Time Cart Is Requested, Add:
Refrigerated IV normal saline solution (1000ml bags) Refrigerated normal saline for irrigation (3000ml bags) Refrigerated regular insulin Ice IV = intravenous; ABG = arterial blood gas. Reprinted with permission from AORN Standards, Recommended Practices, and Guidelines, 1999, p 80. Copyright © AORN, Inc., 2170 South Parker Road, Suite 300, Denver, co 80231 .
support person's role and to facilitate communications throughout the perioperative environment.13· 15 One RN should be assigned to record the drugs and dosages, intake and output, and any treatment given during the MH crisis. Additional RNs should be on hand to assist in mixing the dantrolene and in preparing other drugs as needed by the anesthesiologist. 3· 13• 15· 20• 30 Patient care technicians or other unlicensed assistive personnel should be delegated to obtain supplies and ice, take blood gases to the laboratory, and perform other essential tasks during the stabilization process. A Foley catheter should be placed in the patient's bladder. Physiologic monitoring is essential during an MH crisis. Each body system should be monitored and symptomatically treated until all functions are under control. Arterial blood gas (ABG) analysis will guide the use of bicarbonate. In the absence of ABG testing capabilities, administer 1 to 2 mEq/ kg of bicarbonate to treat acidosis. 19 End-tidal C0 2, oxygen saturation, potassium, calcium, and electrolyte monitoring for baselines and status checks are recommended at frequent intervals during crisis management and physiologic maintenance .19· 24 Hyperkalemia is treated with hyperventilation with 100% oxygen, bicarbonate administration, and intravenous glucose and insulin
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FORTUNATO-PHILLIPS
(0.15 U/kg regular insulin in 1 mL/ kg 50% glucose or 10 U regular insulin in 50 mL 50% glucose titrated to potassium level). Blood glucose levels should be checked every 2 hours if insulin is given. Life-threatening hyperkalemia can be treated with calcium chloride, 2 to 5 mg/kg, according to MHAUS recommendations.19· 24 Hyperthermia is not always an early sign of an MH crisis; however, the patient's temperature can rise suddenly and rapidly. Temperatures as high as 1l4°F have been recorded in the literature.7· 8· 22· 23· 26· 28 Brain damage or death can result from prolonged hyperthermia; therefore, temperature monitoring is vital. Thermal monitoring routes include esophageal, tympanic membrane, nasopharynx, and pulmonary artery for core temperatures. 21 ·24·27 Other routes include mouth, axilla, rectum, and bladder. The least reliable is the skin surface, because the patient usually is diaphoretic and the evaporative process causes surface cooling. 13· 21 Patients in active hyperthermia require rapid cooling. The patient should be undraped and the spotlights should be turned off or directed away from the surgical field. The room temperature can be lowered to facilitate the cooling effort. A hypothermia blanket can be used. Intravenous solutions should be cool. Performing saline lavages of the rectum and abdominal cavity, packing the patient in ice, or both can help to lower body temperature. Continued thermal monitoring is important because vigorous cooling efforts can lead to hypothermia as the patient stabilizes.19 Cardiac dysrhythmias respond to the treatment of hyperkalemia and acidosis. If treatment of a dysrhythmia is necessary, avoid calcium channel blockers as they may cause full cardiovascular collapse from a hyperkalemic state .19, 25 Fluid balance should be closely observed because rapid fluid shifts will occur. The patient is at high risk for pulmonary edema. A central venous or pulmonary artery monitor is recommended because of hemodynamic instability. Adequate fluid hydration and administration of furosemide or mannitol can help promote urinary output. Irrigation of the bladder as a cooling measure could interfere with urinalysis for myoglobinuria and with accurate measurement of urinary output. Pa-
tients in MH crisis are at high risk for renal failure caused by myoglobin accumulation in the renal tubules. Urine output of 2 mL/kg per hour is desired but may be recorded inaccurately if the bladder is irrigated.
Post-Malignant Hyperthermia Crisis Care Post-MH crisis treatment is continued for 24 to 48 hours in an intensive care setting because an acute recurrence is possible. Dantrolene is continued intravenously at a base rate of 1 mg/kg or more as needed during this critical period, and fluid balance is closely observed through strict intake and output measurement. 19 Urinalysis is done to check for myoglobinuria. Continuous measurement of core body temperature is maintained. Serial CK, ABGs, electrolytes, clotting studies, and other blood chemistries are performed to monitor the patient's progress at 6-hour intervals until the patient returns to full baseline.19 Pain assessment is necessary because the patient will have somatic muscle aches associated with the sustained contractions experienced during the crisis period. Obstetric patients should be advised that dantrolene is secreted in breast milk with a half-life of 9.02 hours, and breastfeeding is not advised. 14 The family should have MH risk assessment counseling to determine the extent of the familial inheritance. Medical evaluators will determine the selection of patients and MH testing modalities such as muscle biopsy or genetic marker comparisons. Registration with the No1th American Malignant Hyperthermia Registry is recommended. Prevention of MH Crisis
All efforts are directed to determine MH susceptibility before exposing any patient to potential triggers; however, some patients are not identified clearly before they experience a crisis situation. MH-susceptible patients and the patients at risk for MH are not excluded from surgical intervention under general anesthesia. Surgery can be performed using several nontriggering anesthetics. If general anesthesia is desired, the anesthesia machine should have a fresh soda lime canister and breathing circuit to prevent inadvertent exposure to residual gases that may linger in
MALIGNANT HYPERTHERMIA
the tubing. Regional and local anesthetic techniques are safe for use in the patient at risk. 1•13· 15• 24 •26•29 Postoperative temperature and EKG monitoring for 4 hours before discharge is recommended after ambulatory surgery. Oral forms of dantrolene were given to susceptible patients as preoperative prophylaxis in the past, but it was determined that therapeutic levels were variable and the practice was discontinued. 30 In select situations, the patient who has experienced an MH crisis during previous general anesthesia may be given intravenous dantrolene at 2 to 2.5 mg/ kg 30 minutes before the induction of anesthesia. 20 Intraoperatively, dantrolene can be given as needed. Prophylactic use of dantrolene is highly subjective and may be unnecessary when nontriggering anesthesia is used. 17• 20 Dantrolene can cause muscle weakness in patients with muscular disease and therefore should be used with caution as routine prophylaxis. 30 Every surgical setting wherein a potential trigger may be administered should have a plan of care for the patient in MH crisis. Dantrolene, a minimum of 36 vials with 2500 mL sterile water without bacteriostatic additives,
209
should be immediately available to the operating room and postanesthetic care unit (PACU). A refrigerator with chilled intravenous saline (6L)and1000-ml bottles of saline irrigation (12) should be in readiness and stock rotated periodically to ensure freshness. An ice machine should be easily accessible. A fully stocked MH cart or tackle box system should be assembled and checked for completeness on a routine basis (Box 4). Staff inservice training should be held periodically, and MH crisis management should be included in orientation programs offered to new personnel. Walk-through drills may be beneficial to familiarize the staff with supply location and use. Outdated dantrolene can be mixed as a demonstration of the difficulty associated with preparing the solution in an emergent situation. Familiarity with supplies and equipment can help prevent confusion in the face of a patient in MH crisis. MHAUS offers a full range of literature suitable for staff and patient education. Information about this material is available on their web site. They can be contacted via e-mail (rnhaus@norwich. net) or by calling the information number listed in this article.
SUMMARY
MH is a life-threatening crisis that can be controlled if promptly recognized and appropriately treated. Identification of patients at risk for MH is an ongoing crusade. Preparedness with needed supplies available at hand facilitates optimal treatment. All perioperative personnel should remain current in their knowledge of MH management and treatment to ensure the best possible outcome for their patients.
REFERENCES 1. Abraham RB, et al: Malignant hyperthermia. Postgrad Med J 74:867, 1998 2. Allen GC, Brubaker CL: Human malignant hyperthermia associated with desflurane anesthesia. Anesth Analg 86:6, 1998 3. Association of Operating Room Nurses: Standards, Recommended Practices, and Guidelines. Denver, Association of Operating Room Nurses, 1999 4. Balzan MV: The neuroleptic malignant syndrome: A logical approach to a patient with elevated temperature and rigidity. Postgrad Med] 74:868, 1998 5. Chan TC, Evans SD, Clark RF: Drug-induced hyperthermia. Crit Care Clin 13:4, 1997 6. Curtis S: Update for nurse anesthetists: Genetic testing for malignant hyperthermia. AANAJournal 64:6, 1996
7. Denborough M: Malignant hyperthermia. Lancet 352:9134, 1998 8. Denborough M, Lovell R: Anesthetic deaths in a family. Lancet 2:45, 1960 9. Dunn D: Malignant hyperthermia. AORN] 65:4, 1997 10. Duthie DJR: Heat-related illness. Lancet 352:9137, 1998 11. Fletcher JE, et al: Comparison of European and North American malignant hyperthermia diagnostic protocol outcomes for use in genetic studies. Anesthesiology 90:3, 1999 12. Fletcher JE, Rosenberg H, Aggarwal M: ATX II, a sodium channel toxin, sensitizes skeletal muscle to halothane, caffeine, and ryanodine. Anesthesiology 90:5, 1999 13. Fortunato NH: Berry and Kahn's Operating Room Technique, ed 9. St Louis, Mosby Year Book, 2000
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14. Fricker RM , et al: Secretion of dantrolene into breast milk after acute therapy of a suspected malignant hyperthermia crisis during cesarean section. Anesthesiology 89:4, 1998 15. Golinski M: Malignant hyperthermia: A review. Plastic Surgical Nursing 15:1, 1995 16. Islander G, Twetman ER: Comparison between the European and the North American protocols for diagnosis of malignant hyperthermia susceptibility in humans. Anesth Analg 88:5, 1999 17. Koehntop DE, Beebe DS, Belani KG: Prophylactic use of dantrolene in a patient with central core disease. Anesth Analg 86:4, 1998 18. Lampotang S, et al: Influence of pulse oximetry and capnography on time to diagnosis of critical incidents in anesthesia: A pilot study using full-scale patient simulator.] Clin Monit Comput 14:5, 1998 19. Malignant Hyperthermia Association of the United States: Emergency Therapy for Malignant Hyperthermia. Sherburne, NY, Malignant Hyperthermia Association of the United States, 1999 20. Malignant Hyperthermia Association of the United States: Malignant Hyperthermia Drugs, Equipment, and the Antidote, Dantrolene Sodium. Sherburne, NY, Malignant Hyperthermia Association of the United States, 1996
21. Malignant Hyperthermia Association of the United States: Malignant Hyperthermia Temperature Monitoring in the Perioperative Period: Why, Where, and How. Malignant Hyperthermia Association of the United States, 1997 22. Miranda AD , et al: Malignant hyperthermia. Am] Crit Care 6:5 , 1997 23. Ramirez JA, et al: Suxamethonium, masseter muscle spasm and later malignant hyperthennia. Anaesthesia 53:11 , 1998 24. Rosenberg H: An update on malignant hyperthermia. Ann Acad Med Singapore 23:6, 1994 25. Satoh M, et al: Effect of dantrolene sodium on calcium-overloaded heart. Jpn Circ J 61:10, 1997 26. Sticco SL: Clinical case conference: Malignant hyperthermia. CRNA: The Clinical Forum for Nurse Anesthetists 6: 2. 1995 27. Stolworthy C, Haas RE: Malignant hyperthermia: A potentially fatal complication of anesthesia. Seminars in Perioperative Nursing 7:1, 1998 28. Struebing VL: Differential diagnosis of malignant hyperthermia: A case report. Journal of the American Association of Nurse Anesthetists 63:5, 1995 29. Vermette E: Emergency: Malignant hyperthermia. Am ] Nurs 98:4, 1998 30. Wedel DJ, et al: Clinical effects of intravenously administered dantrolene. Mayo Clin Proc 70, 1995
Address reprint requests to Nancymarie Fortunato-Phillips, MEd, BSN, BA, RN, RNFA, CNOR, CPSN PO Box 422 Wickliffe, OH 44092-0422 e-mail: [email protected]