1	Malignant Hyperthermia Syndrome Henry Rosenberg, M.D. President, Malignant Hyperthermia Association of the United States (MHAUS) Director, Department of Medical Education, Saint Barnabas Medical Center, Livingston, NJ
2	Malignant Hyperthermia (MH)- Essential Characteristics An inherited disorder of skeletal muscle triggered in susceptibles (human or animal) in most instances by inhalation agents and/or succinylcholine, resulting in hypermetabolism, skeletal muscle damage, hyperthermia, and death if untreated. Underlying physiologic mechanism – abnormal handling of intracellular calcium levels
3	Trigger Agents for MH Not MH Triggers Intravenous agents Opioids Non-depolarizing agents Ketamine Propofol Anxiolytics MH Trigger Agents Potent Volatile Anesthetics (eg. halothane, sevoflurane, desflurane) Succinylcholine
4	Summary of Clinical Signs
5	Epidemiology of MH Incidence & Prevalence Reported frequency of MH is 1 in 5,000 to 1 in 100,000 anesthetics Reported from every country and ethnic group Based on reports to MHAUS, there are about 600 cases of MH per year in the US. MH “hotspots:” Wisconsin, Michigan, West Virginia
6	"Mortality from MH" Mortality from MH Per data from the North American MH Registry, of 291 events, 8 (2.7%) resulted in cardiac arrests and 4 (1.4%) resulted in death. The median age in cases of cardiac arrest/death was 20 yr (range, 2-31 yr). Factors associated with higher risk of poor outcome were muscular build and disseminated intravascular coagulation (DIC). Increased risk of cardiac arrest/death was related to a longer time period between anesthetic induction and maximum end-tidal carbon dioxide. Larach et al., 2008; Anesthesiology 108(4): 603-611.
7	Epidemiology of MH (continued) Mortality: Hospital vs. Ambulatory Settings During the period January 2006 through May 2008, the MHAUS MH Hotline received: 503 calls from hospitals, 28 determined to be MH, with 2 deaths from MH (7% mortality) 44 calls from ambulatory settings,13 determined to be MH, with 3 deaths (21% mortality) A fulminant MH episode occurring outside of the hospital setting is more likely to lead to a bad outcome as compared with an episode which originates in a hospital setting.
8	Clinical Signs of MH Non-Specific Tachycardia Tachypnea Acidosis (Respiratory/ Metabolic) Hyperkalemia Specific Muscle Rigidity Increased CO₂ Production Rhabdomyolysis Marked Temperature Elevation
9	Spectrum of Clinical Presentations Fulminant MH: muscle rigidity, high fever, increased HR shortly after induction of anesthesia Masseter muscle rigidity (MMR): jaw muscle rigidity after succinylchoine may be an early sign of MH (see next slide) Late onset MH: uncommon, may begin shortly after anesthesia finish time (usually within first hour)
10	Masseter Muscle Rigidity (MMR) and MH Masseter muscle rigidity (MMR) may occur after succinylcholine More common in children Presages MH in 20-30% cases All patients with MMR demonstrate elevated CK and often gross myoglobinuria With muscle breakdown and CK > 20,000IU, the likelihood of MH is very high. Generalized rigidity not always present; if it occurs, MH is almost certain.
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12	"Patients with occult or known..." Patients with occult or known myopathies such as CCD, MmD, DMD, or BMD may have a higher risk for an MH or MH-like episode upon exposure to a triggering anesthetic agent. Such patients should be evaluated by a neurologist prior to providing treatment and/or diagnostic testing recommendations. CCD, MmD associated with MH susceptibility. Patients with Duchenne’s or Becker’s muscular dystrophies are at risk for hyperkalemic cardiac arrest with succinylcholine or other MH triggering agents (but this is NOT MH). Individuals with any form of myotonia should not receive succinylcholine.
13	"Immediate Therapy" Immediate Therapy Discontinue inhalation agents, succinlycholine Hyperventilate with 100% O₂ Bicarbonate 1-2 mg/kg as needed Get additional help Dantrolene 2.5 mg/kg push, repeat PRN Cool patient: gastic lavage, surface, wound Treat arrhythmias – do not use calcium channel blockers Arterial or venous blood gases Electrolytes, coagulation studies
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15	"After Crisis is controlled" After Crisis is controlled Give dantrolene 1 mg/kg every 4-6 hours for 24 – 48 hours Monitor for recrudescence – rate is 25% Follow electrolytes, blood gases, CK, core temperature, urine output and color, coagulation studies Biochemical markers Blood gases – esp pCO₂, pH Myoglobin levels in serum and urine PT, PTT, INR, fibrin split products Liver enzymes, BUN Monitor for signs of myoglobinuria and rhabdomyolysis and institute therapy to prevent renal failure
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