Malignant : Turn COM . THEISPOT / USTIN A ICHAEL M

Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. down the heat By Fay Mitchell-Brown, MSN, BSN, RN

AN INHERITED DISORDER, malignant hyperthermia (MH) is a life- threatening reaction to certain common inhalational agents or 2.1 the depolarizing relaxant succinylcholine in susceptible ANCC people. Characterized by a hypermetabolic state, it causes , sus- CONTACT HOURS tained generalized muscle contractions, and high body temperature that may exceed 110º F (43.3º C).1,2 MH usually occurs during surgery or with- in an hour after exposure to the triggering agent, but it can develop up to 36 hours later.1-3 When MH was first identified, mortality from the disorder was 80%. With greater awareness of the risk and the discovery of sodium, the only drug that effectively treats MH, mortality has dropped to about 5%.3 Death from MH is usually secondary to cardiovascular collapse.2 Nurses who care for patients during or after surgery must be knowledge- able about signs, symptoms, and treatments so they can identify MH imme- diately and respond appropriately. In addition, nurses assessing patients preoperatively must be able to identify patients at risk so the provider can administer drugs that don’t trigger MH. Finally, because sus- ceptibility to MH is inherited, nurses must educate patients and their fami- lies about the risk. This article discusses how to identify patients at risk, respond to a crisis, and educate patients and their families.

Genetic basis Over 80 genetic defects have been linked to MH. Because MH susceptibility is an autosomal dominant inherited disorder, a child or sibling of a suscep- tible patient has a 50% chance of inheriting a defective gene.2 Two dramatic experiences from my career illustrate the risks faced by families susceptible to MH. As a nursing instructor in a rural hospital, I met RB, a 15-year-old male scheduled for an orthopedic procedure. Admitted via the outpatient surgi- cal center, RB was taken to the OR where he underwent induction of gen- eral anesthesia with and succinylcholine. Thirty minutes into the procedure, RB developed tachycardia: HR 102/

minute from a baseline of 72/minute. His end-tidal carbon dioxide (ETCO2) level was slightly elevated and his temperature increased to 101.5º F (38.6º C) from a baseline of 99.3º F (37.4º C). Arterial blood gas (ABG) values showed respiratory with pH of 7.3 (normal, 7.35 to 7.45) and a

PaCO2 of 48 mm Hg (normal, 35 to 45 mm Hg). The surgeon suspected that RB was experiencing MH and aborted the procedure.

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Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. RB was hyperventilated with choline. Shortly after induction, TJ MH occurs most commonly in

100% oxygen and the surgical team developed a rapid rise in ETCO2, children and young adults. It’s more initiated the MH protocol developed with frequent pre- common in men than in women, by the Malignant Hyperthermia mature ventricular contractions, and and found equally among various Association of the United States generalized muscular rigidity. ABG ethnicities.3 (MHAUS), which includes I.V. ad- values indicated severe respiratory MH occurs worldwide but is ministration of dantrolene. RB was acidosis. TJ was cyanotic and his more common in areas that have transferred to the ICU for observation. core body temperature was 103.6º F MH-susceptible families. In the Fortunately, he responded quickly (39.8º C). The MH protocol was ini- United States, the incidence of MH to treatment and was transferred tiated immediately and TJ was trans- is especially high in Wisconsin, West out of the ICU in 24 hours. ferred to an acute care hospital for Virginia, Nebraska, and Michigan due Several months later, I assisted a higher level of care. But despite to concentrations of MH-susceptible with the care of RB’s uncle, who was prompt and appropriate treatment, families.1,2 Patients with certain pre- admitted to the ICU with an acute TJ died. existing muscle disorders associated MH crisis. TJ, 43, had been sched- with genetic abnormalities, such as uled for abdominal surgery in an Who’s at risk? central core myopathy, are also at outpatient surgical center. He too In susceptible patients, MH is trig- risk.3 However, most muscular and was given sevoflurane and succinyl- gered by certain specific drugs: the neuromuscular disorders aren’t as- depolarizing muscle relaxant succinyl- sociated with MH.2 choline and the inhalational anes- Safe or unsafe?1,2 thetic agents , , What goes wrong? These drugs are MH triggers sevoflurane, , , MH is a hypermetabolic crisis set in ether, and .2 (See Safe motion by excess release Inhalation anesthetic agents: • desflurane or unsafe?) Patients may develop an from muscle. After a susceptible per- • enflurane acute MH crisis at initial exposure to son is exposed to a triggering agent, • halothane a triggering drug, or after several ap- genetic muscle receptor abnormali- 3 • isoflurane parently uneventful exposures. Some ties lead the • methoxyflurane evidence indicates that strenuous ex- in skeletal muscle to release exces- • sevoflurane ercise or heat exposure can also trig- sive calcium. (See Making a muscle.) • ether ger MH in susceptible people.4 This leads to sustained muscle con- Depolarizing muscle relaxant: Patients at risk for MH can safely traction and rigidity, increasing me- • succinylcholine undergo surgery as long as they’re tabolism and generating heat.2,3 induced with nontriggering agents, Eventually the overworked cells are These drugs are safe to use as anesthetic agents in MH-susceptible such as . Local depleted of oxygen and adenosine 2 patients: are also safe. triphosphate (ATP), their energy • /I.V. anesthetics such as Not all patients susceptible to MH source. These changes produce car- and propofol are diagnosed because they may never bon dioxide and cellular acidosis. • the inhaled nonvolatile general an- be exposed to triggering agents—or, An eventual switch to anaerobic esthetic if their exposure time is brief, their metabolism accelerates acidosis.2,5 • local anesthetics such as may escape no- As stores of ATP in muscle cells and tice because they’re nonspecific and are depleted, cells die and release • opioids such as and mor- mild. Uncomplicated cases can be into the bloodstream. The phine difficult to diagnose.1 resulting can trigger • muscle relaxants such as doxacu- For these reasons, the exact inci- fatal cardiac dysrhythmias. rium and vecuronium • antianxiety agents such as dence of MH is unknown. The inci- Dying cells also release the pigment and diazepam. dence of MH episodes may range , causing myoglobinemia. Note: Visit the Malignant Hyperthermia Association from 1 in 5,000 to 1 in 65,000 ad- Myoglobin forms precipitate in the of the United States website for a more complete ministrations of general anesthesia renal tubules, resulting in acute kid- list of safe drugs: www.mhaus.org. with triggering agents.2 ney injury.1

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Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. If the acute MH crisis continues, Making a muscle the patient will experience multiple potentially fatal complications, such Bone Skeletal muscle surrounded as , left ventricu- by epimysium lar dysfunction secondary to hyper- tension, pulmonary edema, and dis- seminated intravascular coagulation Fascicle surrounded by perimysium (DIC).1 Tendon An MH crisis must be differenti- Muscle fiber (cell) A surrounded by ated from disorders causing similar Blood vessel endomysium signs and symptoms, such as trau- Sarcomere matic brain injury; hypoxic encepha- M line Myofibrils lopathy; neuroleptic malignant syn- contained drome; heat stroke; thyroid storm; in muscle fiber pheochromocytoma; ; cocaine, T tubules H zone I band amphetamine, and salicylate toxicity; Z line or alcohol withdrawal.3,6 B A band Relaxation Recognizing the danger Actin Signs and symptoms of MH include Myosin the following. Note that hyperthermia is a later sign of MH and is usually C Contraction D Sarcoplasmic reticulum not present early in the crisis.3 • . A progressive, unex- (A) Connective tissue components of a skeletal muscle. pected increase in ETCO2 is the ear- (B) Striations of the myofibril showing the overlap of contractile proteins and the liest and most sensitive sign that a A and I bands, the H zone, and the Z and M lines. (C) The relaxed and contracted patient might be experiencing MH.3,5 states of the myofibril showing the position of actin filaments (blue) between the 7 myosin filaments (pink) in the relaxed muscle (top) and pulling of the Z membranes Normal ETCO2 is 35 to 45 mm Hg. toward each other (bottom) as the muscle contracts. (D) The sarcoplasmic reticulum In MH, the ETCO2 value may dou- ble or even triple on . with T tubules. Be suspicious if you find an unex- Source: Porth CM. Essentials of Pathophysiology. 3rd ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2011:26. plained increase in ETCO2 that doesn’t respond to increased ventila- tion or additional administration of succinylcholine and doesn’t necessar- urine myoglobin, which peak about anesthetic.8 ily indicate MH unless it persists 14 hours after the acute MH episode, • Tachycardia. Although an early sign after potential triggering agents are vary depending on the patient’s of MH, tachycardia is nonspecific. discontinued.3 muscle mass and the severity of the • Generalized muscle rigidity, espe- • ECG changes. Hyperkalemia may patient’s condition.3 cially of the jaw, trunk, and extremi- cause premature ventricular contrac- • Hyperthermia. An increase in ties. According to Noble (2007), tions, which may progress to life- body temperature, usually a later muscle rigidity, especially masseter threatening sign, confirms the suspicion of MH. muscle rigidity, is seen in 75% of or .3 The patient’s temperature may rise patients experiencing an MH epi- • . Destruction of 1º C every 5 minutes and might sode.9 When masseter muscle rigid- skeletal muscle releases large even exceed 105º F (40.6º C). ity is present, the patient’s mouth amounts of the enzyme Severe hyperthermia is associated can’t be opened after exposure to the kinase (CK) and myoglobin, which with DIC.3 triggering drug. However, transient accumulates in the kidneys. Red or • Electrolyte imbalances. Besides masseter muscle rigidity is normally tea-colored urine is a sign of myo- hyperkalemia, monitor for hyper- associated with the administration of globinuria. Levels of serum CK and phosphatemia and hypocalcemia. www.Nursing2012.com May l Nursing2012 l 41

Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. • Other signs and symptoms. Pro- for insertion of an and Because MH signs and symptoms re- gression of an MH crisis results in central venous access if not already cur in up to 25% of patients after ini- mottling and of the skin, in place. Assign a nurse to the MH tial treatment, maintenance doses of and a mixed respiratory and meta- cart, which should be standard dantrolene should continue for 48 bolic acidosis. The patient is at in- equipment in any facility where sur- hours after the last observed sign of creased risk for sudden cardiac gical procedures are performed, and acute MH. If signs continue despite death. The clinical signs indicate have the MH protocol and treatment ongoing treatment, additional dan- that the body can’t keep up with the sheet available. Staff roles, such as trolene doses or a dantrolene infusion increased metabolic demand, result- team leader, medication nurse, re- may be required. ing in multisystem organ failure. corder, lab liaison, I.V. access nurse, Monitor the venous access site lavage nurse, and ice liaison, should closely for signs of dantrolene ex- Respond quickly be defined ahead of time. travasation, including pain, erythe- If you suspect your patient is experi- • Administer dantrolene. Consid- ma, and edema, which can lead to encing an MH crisis, take action im- ered the gold standard, dantrolene tissue necrosis due to its high pH. mediately.6 DeJohn (2008) believes sodium is the only known effective Administer fluid resuscitation as pre- there is a strong correlation between treatment for MH. Dantrolene is scribed to prevent dantrolene-related the timing of interventions and posi- classified as a direct-acting skeletal crystalluria. tive patient outcomes.10 muscle relaxant. It may stop skeletal • Provide adequate oxygenation. During surgery, the first priority muscle contraction by interfering Administer oxygen at 100% to meet is to discontinue the use of any in- with calcium release from the sarco- the patient’s high metabolic demands. halational anesthetics and succinyl- plasmic reticulum, reversing skeletal The patient will most likely be endo- choline, optimize oxygenation and muscle hypermetabolism.3,11 tracheally intubated if arriving from ventilation, and administer dan- Dantrolene is supplied in vials and the OR. If not, prepare to assist with trolene immediately. Postoperatively, must be reconstituted before admin- intubation as indicated. Hyperventi- priorities for treating an MH crisis istration. MHAUS recommends hav- late the patient as prescribed, increas- are identified by MHAUS as follows. ing 36 vials of dantrolene available at ing the rate and tidal volume to com-

(The MH treatment protocol and all times. Each 65-mL vial contains pensate for increased PaCO2. treatment sheet are available on the 20 mg of dantrolene sodium and 3 g Collaborate with the respiratory

MHAUS website; see Resources for mannitol, plus sodium hydroxide to therapist to monitor ETCO2 by healthcare providers and patients.) maintain a pH of 9 to 10.11 continuous capnography. Assess the • Team initiation. Collaboration At least two qualified team mem- patient for signs and symptoms of among all members of the health bers should be available to reconsti- fluid volume overload, such as team is crucial. The team leader as- tute and administer the drug. The pulmonary crackles, because the signs roles as would be done to man- powder can be reconstituted only patient will be receiving large amounts age any crisis. Notify the anesthesia with 60 mL of sterile preservative-free of I.V. fluids. Closely monitor con- provider, the surgeon, and the critical water for injection. It’s incompatible tinuous pulse oximetry and ABG care intensivist immediately. Prepare with 5% dextrose, 0.9% sodium values. chloride, bacteriostatic water for in- • Maintain hemodynamic stability. Resources for healthcare jection, and other acidic solutions, Place the patient on a continuous providers and patients and precipitates if added to a glass cardiac monitor and frequently assess container for infusion. Shake the vial BP, heart rate, core body temperature, Malignant Hyperthermia Association for about 20 seconds until the solution and central venous pressure. An of the United States (MHAUS) 607-674-7901 is clear. The reconstituted solution arterial line is beneficial not only http://www.mhaus.org should be used within 6 hours and for continuous BP but protected from direct light.11 also for frequent arterial blood sam- MH hotline for emergencies only: Administer dantrolene as pre- pling. 800-644-9737 (in US and Canada) scribed by rapid I.V. bolus until Ventricular dysrhythmias can oc- 001-1-315-464-7079 (from outside signs subside or the maximum cumu- cur approximately 20 minutes after the United States) lative dose (10 mg/kg) is reached.11 the patient becomes hyperthermic.1

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Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Dysrhythmias may resolve once aci- ensure that expired supplies are re- dosis and hyperkalemia are corrected. moved and replaced. MHAUS recommends treating persis- • Staff should have access to an ice tent life-threatening dysrhythmias machine, cooled I.V. fluids, and a with standard drug therapy, but cooling blanket. warns against using • An MH treatment protocol should blockers with dantrolene. This com- be developed or adapted and made bination can cause hyperkalemia or readily available to all staff. Posters cardiac arrest.2 and wallet cards with the recom- • Correct metabolic abnormalities. mended MH protocol are available The hypermetabolism of MH causes from MHAUS. both respiratory and metabolic aci- • Post the MHAUS 24-hour emer- dosis. This is treated by hyperventi- gency hotline—800-644-9737—in a lation to two to three times the pre- prominent place on the unit. dicted minute volume with 100% • Fill out an adverse medical reaction oxygen.1 MHAUS recommends treat- to anesthesia (AMRA) form when a ing hyperkalemia with hyperventila- patient is diagnosed with MH and tion, I.V. calcium, I.V. sodium bicar- An increase in body send it to MHAUS. bonate, and I.V. insulin-glucose. temperature, usually Check blood glucose levels hourly if a later sign, confirms Testing confirms the diagnosis the patient is receiving I.V. insulin. the suspicion of MH. The gold standard for identifying • Initiate cooling measures. Monitor patients susceptible to MH is the core body temperature continuously -halothane contracture test via esophageal, rectal, or bladder (CHCT), which involves an excisional probes. Several team members are cellular hypoxia and prevent worsen- muscle . According to MHAUS, needed to cool the patient externally ing of acidosis if ongoing volume it’s performed only in specialized cen- with cooling blankets and ice bags, loss and diuresis is a concern. ters; there are 30 centers worldwide and internally by administering cool MHAUS recommends that for treat- and only 6 in North America. Because I.V. fluids and lavaging the nasogas- ing acute rhabdomyolysis and myo- the CHCT test must be performed on tric tube and urinary catheter with globinuria, urine output should be a fresh muscle specimen, the patient cool fluids. Cooling by convection maintained above 2 mL/kg/hour. must travel to one of these centers with wet towels and a fan can be This can be achieved by hydration for testing. Contractile responses to very effective as well. Once the pa- and diuretics. A sodium bicarbonate caffeine and halothane are measured tient’s temperature reaches 38º C, infusion is also recommended for relative to baseline muscle tension. cooling efforts are minimized; how- alkalinization of urine, with close lab Genetic testing can also be done to ever, continue to closely monitor the monitoring of urine and serum pH look for genetic commonly patient’s temperature.2 values.2 associated with MH. Genetic testing is • Provide fluid resuscitation. Ideally, less costly but has a significant false- central venous pressure should be Staff education negative rate for MH susceptibility.1 monitored to assess fluid volume All staff members caring for patients status. Insert an indwelling urinary recovering from general anesthesia Prevention and teaching catheter for accurate hourly output should receive education about MH, A thorough preoperative assessment measurements. A three-way urinary with periodic reviews and updates. can help minimize the risk of MH. catheter can also be used to promote In addition: When obtaining a patient’s health active cooling through continuous • an MH cart stocked with dan- history, establish if the patient has bladder irrigation. A urine output of trolene and other emergency sup- experienced any adverse reactions to 1 to 2 mL/kg/hour is necessary to plies needed during an MH crisis anesthesia. Also ask if the patient prevent acute kidney injury. Ade- should be readily available. The MH knows of any blood relatives who quate fluid resuscitation helps treat cart should be checked frequently to experienced an adverse reaction www.Nursing2012.com May l Nursing2012 l 43

Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. (such as muscle rigidity) or unex- risks and complications by seeking 5. Litman RS. Susceptibility to malignant hyperther- mia. UpToDate. 2012. http://www.uptodate.com. plained death during anesthesia. information from MHAUS, which 6. Hernandez JF, Secrest JA, Hill L, McClarty SJ. After recovering from an acute MH offers resources for both healthcare Scientific advances in the genetic understanding and crisis, patients should be informed professionals and patients and fami- diagnosis of malignant hyperthermia. J Perianesth Nurs. 2009;24(1):19-31. about the disorder and genetic coun- lies affected by MH. Recommend 7. Tautz TJ, Urwyler A, Antognini JF, Riou B. Case seling should be offered. Family mem- that anyone susceptible to MH wear a scenario: increased end-tidal carbon dioxide: a diagnostic dilemma. . 2010;112(2): bers should also be tested. Only one medical alert bracelet or tag. 440-446. parent needs to carry a defective gene Awareness of risk factors, detec- 8. Hsu SC, Huang WT, Yeh HM, Hseieh AY. Sus- for the child to inherit the disease. tion of early signs, and prompt ap- pected malignant hyperthermia during sevoflurane Tell patients who are or may be propriate treatment are the keys to anesthesia. J Chin Med Assoc. 2007;70(11):507-510. 9. Noble KA. Malignant hyperthermia: hot stuff! susceptible to MH that while they prevent complications and death J Perianesth Nurs. 2007;22(5):341-345. must avoid surgery involving trigger- from this anesthetic emergency. ■ 10. DeJohn P. Be prepared: malignant hyperthermia. ing drugs, the anesthesia provider OR Manager. 2008;24(6):26-27, 30. 11. Revonto (dantrolene sodium for injection). REFERENCES can administer alternative drugs that Product insert. http://www.revonto.com. 1. Stratman RC, Flynn JD, Hatton KW. Malignant won’t trigger a crisis. Encourage 12. Haslego SS. Malignant hyperthermia: how to hyperthermia: a pharmacogenetic disorder. Ortho- spot it early. RN. 2002;65(7):31-35. them to spread the word among fam- pedics. 2009;32(11):835. ily members, who could also be at 2. Malignant Hyperthermia Association of the Fay Mitchell-Brown is a lecturer in the School of risk. Warn patients to avoid exces- United States; 2011. http://www.mhaus.org. Nursing at California State University, Chico and a per sive heat, stress, vigorous exercise, 3. Litman RS. Malignant hyperthermia: clinical diem critical care staff nurse at Enloe Medical Center diagnosis and management of acute crisis. UpTo in Chico, Calif. alcohol, and cocaine in addition to Date. 2012. http://www.uptodate.com. MH-triggering anesthetics.2,12 4. Capacchione JF, Muldoon SM. The relationship The author and planners have disclosed that they between exertional heat illness, exertional rhabdo- have no financial relationships related to this article. Empower patients and their fami- myolysis, and malignant hyperthermia. Anesth lies to learn more about reducing Analg. 2009;109(4):1065-1069. DOI-10.1097/01.NURSE.0000413609.98565.96

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