Malignant Hyperthermia

1. Malignant Hyperthermia
Gary Oh

2. Introduction
• Hypermetabolic crisis when an MH-susceptible (MHS) individual is
exposed to a volatile anesthetic (eg, halothane, isoflurane, enflurane,
sevoflurane, desflurane) or succinylcholine

3. Incidence
• 1:100,000 administered anesthetics.
• Approximately half of patients who develop acute MH have one or
two uneventful exposures to triggering agents.
• All ethnic groups.
• All parts of the world.
• Males > Females (2:1).
• Children <19 years (45-52% of reported events).

4. Pathophysiology
• Genetic skeletal muscle receptor abnormality
• Excessive Ca accumulation in the presence of certain anesthetic
triggering agents.
• Clinical manifestations due to cellular hypermetabolism, leading to
sustained muscular contraction and breakdown (rhabdomyolysis),
anaerobic metabolism, acidosis, and their sequelae.

5. Normal muscle physiology
• Depolarization spreads throughout the muscle cell via the transverse
tubule system, which activates dihydropyridine (DHP) receptors
located within the t-tubule membrane.
• DHP R are coupled to ryanodine receptors (RYR1), which are Ca
channels embedded in the wall of the SR.
• Ca release through the DHP R triggers the RYR1 R to release Ca from
the SR into the intracellular space.
• Ca combines with troponin to cross-link actin and myosin, resulting in
muscle cell contraction.
• Reuptake of Ca by the SR Ca ATPase (SERCA) leads to relaxation.

6. Malignant hyperthermia
• Mutations encoding for abnormal RYR1 or DHP R.
• Triggering agents (volatile anesthetics) lead to unregulated passage of
Ca from the SR into the intracellular space causing sustained muscle
contraction.
• Hyperthermia occurs minutes to hours following the initial onset of
symptoms. (1ºC every few minutes).
• Increase in CO2 production, and increased O2 consumption can cause
widespread vital organ dysfunction and disseminated intravascular
coagulation (DIC).

8. Trigger
• Volatile anesthetic agent (eg, halothane, isoflurane, sevoflurane,
desflurane) +/- succinylcholine.
• MH has been reported following administration of succinylcholine in
the absence of an inhalational agent (eg, to facilitate endotracheal
intubation)
• MH crisis may develop at first exposure to a triggering agent, however
the average patient has had previous exposures prior to having a
documented reaction.

9. Clinical Signs - Early
• Perioperative:
• Hypercarbia
• Sinus tachycardia
• Masseter muscle rigidity (MMR)
• Generalized muscle rigidity

10. • Most common initial sign of an MH crisis is an unexpected rise in end-
tidal carbon dioxide (ETCO >60 mmHg ), which is difficult to decrease
as minute ventilation is increased.
• Masseter muscle rigidity (MMR) (in the presence of succinylcholine
and/or volatile agents).
• Generalized muscle rigidity in the presence of neuromuscular
blockade is virtually pathognomonic for MH when other signs are
present.

11. Clinical Signs - Later
• Electrocardiogram changes (Hyperkalemia):
• Ventricular ectopy/bigeminy
• Ventricular tachycardia/fibrillation
• Hyperthermia
• Myoglobinuria
• Excessive bleeding (DIC)

12. • Hyperthermia
• Widespread misconception that acute MH begins with hyperthermia as the
presenting sign.
• Hyperthermia generally a later sign of MH and is typically absent when the
diagnosis is initially suspected.
• Myoglobinuria
• Brownish, cola or tea-colored urine indicates the presence of myoglobinuria.

13. Labs
• Excess CO2 and cellular H+ deplete O2 and ATP.
• Early Sx: hypercarbia and mixed respiratory/metabolic acidosis.
• Shift to anaerobic metabolism worsens acidosis with the production
of lactate.
• Once energy stores are depleted, rhabdomyolysis occurs
(hyperkalemia and myoglobinuria).
• Elevated creatine kinase and myoglobinuria — Plasma CK and urine
myoglobin levels peak (14 h) after an acute MH episode.

14. Treatment
• Discontinue triggering agents and inform the operating surgeon of the
diagnosis.
• Initiate MH protocol - Additional personnel should be mobilized
• Dantrolene - Only known antidote which binds to the RYR1 R to
inhibit the release of Ca from the SR; this reverses the negative
cascade of effects. ETCO will normalize as the dantrolene takes effect
(within minutes).
• Optimize O2 and ventilation – 100% oxygen. Increase RR and/or Vt to
maximize ventilation and reduce the ETCO .
• Consider ET tube (using only non-depolarizing muscle relaxants)

15. • Hyperkalemia treatment based upon the presence of abnormal
electrocardiogram waveforms (eg, peaked T waves) to prevent the development
of life-threatening arrhythmias or cardiac arrest.
• ACLS to treat cardiac arrhythmias. Dysrhythmias usually respond to the treatment
of acidosis and hyperkalemia.
• Contraindicated - Use of Ca channel blockers during an acute MH crisis because of
the possibility that it can worsen hyperkalemia and hypotension.
• Check labs - electrolytes, blood gasses for acid/base status, CK, serum myoglobin,
coagulation parameters, and fibrin split products
• Arterial or venous blood gases should be collected initially and as needed until pH
and K levels trend toward normal values.
• Initiate supportive care
• Monitor and treat acidosis; consider bicarbonate

16. • Monitor core temperature continuously.
• Bladder catheter (urine color and volume) - Urine output should be kept
above 1 mL/kg/hour until the urine color returns to normal and the CK
begins to decrease.
• Monitor for myoglobinuria-induced renal failure (ie, hydration, diuretics,
bicarbonate).
• Monitor muscle compartments for acute compartment syndrome -
rhabdomyolysis can result in compartment syndrome, especially in patients
who have developed DIC. Consider muscle compartment release (ie, four
compartment fasciotomy).
• Monitor for DIC.

17. Mortality
• Declined significantly and is estimated to be between 1 and 17
percent

18. References
• Brady JE, Sun LS, Rosenberg H, Li G. Prevalence of malignant
hyperthermia due to anesthesia in New York State, 2001-2005.
Anesth Analg 2009; 109:1162.
• Harrison GG. Control of the malignant hyperpyrexic syndrome in MHS
swine by dantrolene sodium. Br J Anaesth 1975; 47:62.
• Larach MG, Gronert GA, Allen GC, et al. Clinical presentation,
treatment, and complications of malignant hyperthermia in North
America from 1987 to 2006. Anesth Analg 2010; 110:498.
• O'Sullivan GH, McIntosh JM, Heffron JJ. Abnormal uptake and release
of Ca2+ ions from human malignant hyperthermia-susceptible
sarcoplasmic reticulum. Biochem Pharmacol 2001; 61:1479.