Malignant hyperthermia: Difference between revisions
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==Background==
==Background==
*Inherited disorder of skeletal muscles triggered most often by anesthesia inhalation agents and/or succinylcholine
*Life-threatening hypermetabolic reaction to volatile anesthetic agents or succinylcholine
*Results in hypermetabolism, skeletal muscle damage, hyperthermia, and death if not treated quickly
*Caused by uncontrolled skeletal muscle calcium release via ryanodine receptor (RyR1) mutations
*GENERALIZED rigidity NOT always present; if it occurs, MH is almost certain
*Autosomal dominant inheritance with variable penetrance<ref name="rosenberg">Rosenberg H, et al. Malignant hyperthermia: a review. ''Orphanet J Rare Dis''. 2015;10:93. PMID 26238698.</ref>
*Incidence: ~1:5,000 to 1:50,000 anesthetics
*Mortality: <5% with early recognition and dantrolene; historically >70% without treatment
*Can also be triggered by extreme heat and exertion in susceptible individuals (exertional heat stroke variant)


===Likelihood of Complications===
==Triggering Agents==
*Increased time from 1st sign to 1st dantrolene
*Volatile inhalational anesthetics: sevoflurane, desflurane, isoflurane, halothane
**For every 30 minute increase in the interval, complication likelihood increases x 1.6
*[[Succinylcholine]]
* Increased maximal temperature
*Safe agents: propofol, etomidate, ketamine, nitrous oxide, all non-depolarizing paralytics, opioids, benzodiazepines, local anesthetics
**For every 2°C increase in max temp, complication likelihood increases x 2.9


==Work-Up==
==Clinical Features==
*Core temperature
*Often occurs intraoperatively but can present in the PACU or ED
*CBC
*Earliest sign: unexplained rise in end-tidal CO2 and tachycardia
*Chem 7
*'''Masseter muscle rigidity''' (particularly after succinylcholine) — early warning sign
*Total CK
*Generalized skeletal muscle rigidity
*PT/PTT
*Rapidly rising temperature (may exceed 40°C; >1°C rise every 5 min)
*ABG
*Tachycardia, dysrhythmias, unstable blood pressure
*Dark urine ([[Rhabdomyolysis|myoglobinuria]])
*Metabolic and respiratory acidosis
*[[Hyperkalemia]], elevated CK, myoglobinuria
*Late: [[DIC]], [[Acute kidney injury|renal failure]], cardiac arrest


==Diagnosis==
==Differential Diagnosis==
*Muscle contraction
*[[Neuroleptic malignant syndrome]] (NMS) — antipsychotics, slower onset (days)
*Fever
*[[Serotonin syndrome]] — serotonergic drugs, clonus prominent
 
*[[Heat stroke]] — environmental exposure
*First signs
*Thyroid storm
**Hypercarbia
*Pheochromocytoma crisis
**Sinus tachycardia
*Sepsis
**Masseter spasm
*Drug-induced hyperthermia (cocaine, amphetamines, MDMA)
**Temperature abnormalities (may be early)
*Most common pattern
**Respiratory acidosis and muscular abnormalities


===Presentations===
==Evaluation==
*99% Respiratory Acidosis
*Elevated and rapidly rising end-tidal CO2
*26% Metabolic Acidosis
*ABG: combined respiratory and metabolic acidosis
*80% Muscular Abnormalities
*BMP: [[Hyperkalemia|hyperkalemia]], hypercalcemia
Watch for it with succinylcholine use.
*CK: markedly elevated (often >10,000 U/L)
*Coagulation studies: may show DIC
*Urinalysis: myoglobinuria
*Core temperature monitoring
*Definitive diagnosis: caffeine-halothane contracture test (done later, not acutely)


===Types===
==Management==
*Fulminant MH
===Immediate===
**muscle rigidity, high fever, increased HR shortly after induction of anesthesia
*'''STOP all triggering agents immediately'''
*Masseter muscle rigidity
*Call for Malignant Hyperthermia Hotline: 1-800-644-9737 (MHAUS)
**jaw muscle rigidity after succinylchoine
*Hyperventilate with 100% O2 at high fresh gas flows
**More common in children
*Change anesthesia circuit and CO2 absorber if possible
**Presages MH in 20-30% cases
**All patients demonstrate elevated CK and often gross myoglobinuria
**CK >20,000IU = high likelihood of MH
* Late onset MH
**Uncommon, may begin shortly after anesthesia termination (usually within first hour)


==Differential Diagnosis==
===Dantrolene===
{{AMS and fever DDX}}
*[[Dantrolene]] 2.5 mg/kg IV bolus, repeat every 5-10 minutes until symptoms resolve<ref name="glahn">Glahn KP, et al. Recognizing and managing a malignant hyperthermia crisis. ''Br J Anaesth''. 2010;105(4):417-420. PMID 20837722.</ref>
*Maximum total dose: up to 10 mg/kg (no absolute ceiling if still symptomatic)
*Reconstitute with sterile water (each 20 mg vial in 60 mL) — time-consuming; assign dedicated team
*Newer formulation (Ryanodex): 2.5 mg/kg in single vial, faster to prepare
*Continue dantrolene 1 mg/kg IV q4-6h for 24-48 hours to prevent recrudescence


==Treatment==
===Cooling===
*Initial
*Aggressive active cooling: ice packs to axillae/groin, cooling blankets, cold IV saline
**Declare MH Emergency: (call OR for anesthesia to bring MH cart)
*Target temperature <38.5°C
** Discontinue Triggering Agents
*Avoid overcooling
** 100% Oxygen at High Flow
** Give Dantrolene
***Designate 2 or 3 people to mix sterile water into Dantrolene \
****60ml sterile water into each vial of dantrolene; may need up to 36 vials
****If using Dantrium® (20 mg/vial), each vial contains 3 g of mannitol (renal vasodilation); newer nanocrystalline dantrolene (250 mg/vial) has 250 mg mannitol per vial and requires mannitol supplementation
*** '''2.5 mg/kg IV push'''
*** Titrate to effect; may need more than 10 mg/kg
**Bicarb for metabolic acidosis
*** 1-2 mEQ/kg if blood gas values not yet available
** Cool the patient if core temp >39 deg C (102.2 deg F)
*** Stop cooling when temp reaches 100.4
** Dysrhythmias usually respond to treatment of acidosis and hyperkalemia
*** Standard therapy EXCEPT NO CA CHANNEL BLOCKERS:
****may cause hyperkalemia or cardiac arrest in presence of dantrolene
** Treat hyperkalemia: standard treatment, remember to check glucose levels q1h after treatment with insulin/glucose
** Call MHAUS Hotline if needed: 1-800-644-0737
*Continued Care
**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


==Prognosis==
===Supportive===
===Stable to Transfer Criteria===
*Treat [[Hyperkalemia]]: calcium gluconate, insulin + glucose, sodium bicarbonate
*ETCO2 is declining or normal
*IV fluids to maintain urine output >2 mL/kg/hr (prevent myoglobin-induced AKI)
*HR is stable or decreasing
*Treat dysrhythmias (avoid calcium channel blockers with dantrolene — risk of hyperkalemia)
*No ominous dysrhythmias
*Monitor for [[DIC]], [[Rhabdomyolysis|rhabdomyolysis]], [[Compartment syndrome]]
*Temperature is declining
*Generalized muscular rigidity is resolving (if present)
*IV dantrolene administration has begun


===Complications===
==Disposition==
*Consciousness Level Change/Coma
*ICU admission for all MH episodes
*Cardiac Dysfunction
*Monitor for recrudescence (recurrence in 25% within 24 hours)
*Pulmonary Edema
*Genetic counseling and testing for patient and family
*Renal Dysfunction
*Disseminated Intravascular Coagulation
*Hepatic Dysfunction
*Relapse
*Death


==See Also==
==See Also==
*[[Succinylcholine]]
*[[Neuroleptic malignant syndrome]]
*[[Acute Fever (DDX)]]
*[[Serotonin syndrome]]
*[[Toxidromes]]
*[[Heat stroke]]
*[[Rhabdomyolysis]]
 
==References==
<references/>


[[Category:Tox]]
[[Category:Critical Care]]
[[Category:Pharmacology]]

Latest revision as of 09:12, 22 March 2026

Background

  • Life-threatening hypermetabolic reaction to volatile anesthetic agents or succinylcholine
  • Caused by uncontrolled skeletal muscle calcium release via ryanodine receptor (RyR1) mutations
  • Autosomal dominant inheritance with variable penetrance[1]
  • Incidence: ~1:5,000 to 1:50,000 anesthetics
  • Mortality: <5% with early recognition and dantrolene; historically >70% without treatment
  • Can also be triggered by extreme heat and exertion in susceptible individuals (exertional heat stroke variant)

Triggering Agents

  • Volatile inhalational anesthetics: sevoflurane, desflurane, isoflurane, halothane
  • Succinylcholine
  • Safe agents: propofol, etomidate, ketamine, nitrous oxide, all non-depolarizing paralytics, opioids, benzodiazepines, local anesthetics

Clinical Features

  • Often occurs intraoperatively but can present in the PACU or ED
  • Earliest sign: unexplained rise in end-tidal CO2 and tachycardia
  • Masseter muscle rigidity (particularly after succinylcholine) — early warning sign
  • Generalized skeletal muscle rigidity
  • Rapidly rising temperature (may exceed 40°C; >1°C rise every 5 min)
  • Tachycardia, dysrhythmias, unstable blood pressure
  • Dark urine (myoglobinuria)
  • Metabolic and respiratory acidosis
  • Hyperkalemia, elevated CK, myoglobinuria
  • Late: DIC, renal failure, cardiac arrest

Differential Diagnosis

Evaluation

  • Elevated and rapidly rising end-tidal CO2
  • ABG: combined respiratory and metabolic acidosis
  • BMP: hyperkalemia, hypercalcemia
  • CK: markedly elevated (often >10,000 U/L)
  • Coagulation studies: may show DIC
  • Urinalysis: myoglobinuria
  • Core temperature monitoring
  • Definitive diagnosis: caffeine-halothane contracture test (done later, not acutely)

Management

Immediate

  • STOP all triggering agents immediately
  • Call for Malignant Hyperthermia Hotline: 1-800-644-9737 (MHAUS)
  • Hyperventilate with 100% O2 at high fresh gas flows
  • Change anesthesia circuit and CO2 absorber if possible

Dantrolene

  • Dantrolene 2.5 mg/kg IV bolus, repeat every 5-10 minutes until symptoms resolve[2]
  • Maximum total dose: up to 10 mg/kg (no absolute ceiling if still symptomatic)
  • Reconstitute with sterile water (each 20 mg vial in 60 mL) — time-consuming; assign dedicated team
  • Newer formulation (Ryanodex): 2.5 mg/kg in single vial, faster to prepare
  • Continue dantrolene 1 mg/kg IV q4-6h for 24-48 hours to prevent recrudescence

Cooling

  • Aggressive active cooling: ice packs to axillae/groin, cooling blankets, cold IV saline
  • Target temperature <38.5°C
  • Avoid overcooling

Supportive

  • Treat Hyperkalemia: calcium gluconate, insulin + glucose, sodium bicarbonate
  • IV fluids to maintain urine output >2 mL/kg/hr (prevent myoglobin-induced AKI)
  • Treat dysrhythmias (avoid calcium channel blockers with dantrolene — risk of hyperkalemia)
  • Monitor for DIC, rhabdomyolysis, Compartment syndrome

Disposition

  • ICU admission for all MH episodes
  • Monitor for recrudescence (recurrence in 25% within 24 hours)
  • Genetic counseling and testing for patient and family

See Also

References

  1. ↑ Rosenberg H, et al. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015;10:93. PMID 26238698.
  2. ↑ Glahn KP, et al. Recognizing and managing a malignant hyperthermia crisis. Br J Anaesth. 2010;105(4):417-420. PMID 20837722.
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