Malignant Hyperthermia

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Malignant Hyperthermia

• Franklin L. Scamman, MD

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References

• Litman and Rosenberg JAMA 2932918, 2005, the
  June 15 issue
• Torpy, Lynm and Glass JAMA 2932958, 2005, the
  patient page
• http//www.mhaus.org the web site of the
  Malignant Hyperthermia Association of the US.

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History of MH

• 1961 Proband family identified in Australia
• 1971 First international symposium on MH
  caffeine-halothane contracture test developed
• 1970s Relation of masseter muscle rigidity to MH
  realized
• 1975 Dantrolene treatment of MH

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History of MH

• 1979 FDA approves dantrolene
• 1982 National society formed establishing the MH
  hotline
• 1980s End tidal CO2 identified as an early sign
• 1990s Ryanodine receptor identified
• 2000 Genetic testing

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Characteristics of MH

• Sustained, significant hypermetabolism
• Inherited component autosomal dominant
• Abnormal handling of intracellular calcium levels
• Triggered by pharmacologic agents, possibly by
  heat/exercise

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Triggering Agents for MH

• Trigger agents
• Halothane
• Sevoflurane
• Isoflurane
• Desflurane
• Succinylcholine

• Non-trigger agents
• Opioids
• Non-depolarizing muscle relaxants
• Ketamine
• Propofol
• Anxiolytics
• Nitrous oxide

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Current Concepts of MH

• Muscle rigidity may not be present
• Temperature increase is a late sign
• Increased end-tidal CO2 is an early sign
• MH may occur at any point during an anesthetic
  even on emergence and in PACU
• May reoccur despite treatment

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Signs of MH

• Specific
• Muscle rigidity
• Increased CO2 production
• Rhabdomyolysis
• Marked temperature elevation

• Non-specific
• Tachycardia
• Tachypnea
• Acidosis
• Hyperkalemia

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Masseter Rigidity

• May occur after succinylcholine
• More common in children
• Presages MH in 20-50
• Generalized rigidity not always present
• When present, generally associated with MH
  susceptibility

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Masseter Rigidity

• Incidence in children
• Halothane/succinylcholine 0.5-1
• Halothane/STP/succinylcholine 0.5
• Overall 0.008
• Males 3X over females

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Masseter Rigidity Treatment

• Stop inhalation agents/succinylcholine
• Continue with non-trigger agents
• Follow end-tidal CO2
• Observe in ICU for 24 hours
• Monitor potassium, myoglobin, CPK
• Dantrolene as needed
• Recommend Bx or genetic studies

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Masseter Rigidity Treatment

• OR awaken patient
• Observe in ICU for 24 hours
• Monitor potassium, myoglobin, CPK
• Dantrolene as needed
• Recommend Bx or genetic studies

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Muscular Dystrophies

• Duchennes
• Beckers
• Evans
• Central core disease
• Exercise-induced rhabdomyolysis
• Hypokalemic periodic paralysis
• NOT neuroleptic malignant syndrome

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Diagnosis of MH

• Halothane/caffeine contracture test using muscle
  biopsy the gold standard
• 6,000 not covered by insurance
• Must go to the center
• Genetics looking for mutation of RYR-1 receptor
  hits only 30 of MH positive so far

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Muscle Biopsy Centers

• Bethesda
• Chicago
• Los Angeles
• Minneapolis
• Philadelphia
• Rochester
• Sacramento
• Winston-Salem

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Incidence of MH

• One in 20,000 50,000 anesthetics, depending on
  drugs and location
• One in 2,000 3,000 based on genetic testing
• Low penetration

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Immediate Therapy of MH

• Discontinue triggering agents
• Hyperventilate with oxygen
• Get help
• Dantrolene 2.5 mg/kg push. Must dilute 20 mg
  bottle with 60 ml DW. Continue for 24-48 hours
• Cool patient PRN
• Do not give calcium channel blockers
• Labs as necessary for K, myoglobin

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Prevention of MH

• Get Hx of MH susceptibility, muscle diseases,
  family anesthesia problems
• CO2 and temperature monitoring during anesthesia
• Recognition of masseter rigidity
• Investigation of unexplained tachycardia,
  hypercarbia and hyperthermia

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Prevention of MH

• Use succinylcholine only when indicated
• Avoid triggering agents in MH susceptible
  patients
• Have dantrolene available in any location using
  general anesthesia

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Preparation for MH Susceptible

• Disable vaporizers
• Flush system for 20 min with 10 l/min oxygen
  change CO2 absorber
• Hide succinylcholine
• Use non-triggering anesthesia agents
• Have dantrolene available

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Anesthesia for MH Proven

• Anxiolytic
• Propofol-narcotic induction
• Non-depolarizing muscle relaxant
• Maintenance with nitrous-narcotic-propofol-relaxan
  t technique
• Reversal of muscle relaxant
• Observe for 4 hours

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North American MH Hotline

• Emergency 1-800-MH-HYPER 24/7
• Routine 1-800-98-MHAUS
• Registry 1-888-274-7899
• http//www.mhaus.org
• http//www.mhreg.org

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Future Developments

• Additional work on genetics and genetic testing
• Better dantrolene (the current formulation is
  hard to dissolve)
• Better understanding of pathophysiology