1. Malignant Hyperthermia

2. Malignant Hyperthermia
History
Pathophysiology
Diagnosis
Signs and Symptoms
Treatment

3. Malignant Hyperthermia
History
Initially identified in Australia 1961
Initially very high mortality
Diagnostic testing 1971
Association with Masseter muscle rigidity 1970
Dantrolene 1975
Genetic component identified 1990”s
DNA testing ?

4. Malignant Hyperthermia
Caused by mutation of the sarcolamma ryanodine receptor RyR1 which is coded on chromosome 19
Responsible for intracellular calcium metabolism
RyR1 receptor

5. Malignant Hyperthermia
Incidence
1/ with Succinylcholine 1/65000
Mortality with treatment 10 %
Poor outcome related to delay in administering Dantrolene and peak temperature

6. Malignant Hyperthermia
Triggers
Succinylcholine
Volatile “….ane” anaesthetics
Not N2O
All other anaesthetic drugs safe

7. Malignant Hyperthermia
MH occurs because of an increase in metabolism due to rapid and uncontrolled increase in calcium within the sarcolema (muscle cells).

8. Malignant Hyperthermia
2. The increase in calcium level overwhelms the capacity of the muscle cell for active calcium reuptake.
3. This results in muscle contraction and increased breakdown of ATP, enhanced glycolysis, uncoupling of oxidative phosphorylation, & activation of actin-myosin filaments yielding significant heat production causing cell damage, and membrane leak.

9. Malignant Hyperthermia
Familial Dominant trait but with incomplete penetrance
Males more common than females
May not trigger with first exposure to volatiles
Succinylcholine greatly increases risk

10. Diseases Associated with MH
King Denborough syndrome
Caution in children with delayed motor function
Ion channel mutations
Myopathic syndromes
Duchenne muscular dystrophy
Brody’s Disease -deficient calcium, ATP (rhabdomyolysis, not MH)
McArdles Diseas -glycogen storage (rhabdomyolysis, not MH)
Myotonia congenita
Central Core disease

11. Malignant Hyperthermia
Early Signs
Hypercarbia 40% - respiratory acidosis
Innappropriate for case setting after considering opioids, ventilator settings, laparoscopic surgery etc
If in doubt obtain blood gas
Tachycardia 30%
Masseter Spasm 20%
Hypertension ?

12. Malignant Hyperthermia
Late Signs
Tachypnea
Arterial hypoxemia
Metabolic / Respiratory acidosis
Hyperkalemia
Cardiac arrhythmias
Hypotension
Hyperthermia
Rhabdomyolysis
Increased CPK –20,000 I.U

13. Malignant Hyperthermia Differential Diagnosis
Neuroleptic Malignant Syndrome
•Severe muscle rigidity and elevated temperature associated with the use of antipsychotic medication
•Thyrotoxic crisis –Thyroid Storm
•Cocaine toxicity
•Heat stroke
•Serotonin syndrome -excessive serotonin usually r/t combining meds
•Status Epilepticus
•Pheochromocytoma
•Lymphoma

14. Malignant Hyperthermia

15. Malignant Hyperthermia Treatment
Call for assistance
Immediately terminate trigger drugs & conclude surgery as soon as possible
•Hyperventilate with 100% oxygen
•Initiate active cooling
•Iced saline
•Gastric lavage with iced saline
Surface cooling

16. Malignant Hyperthermia Treatment
Dantrium®IV-2 mg/kg IV q4-8hrs repeated 24-48hrs or until symptoms resolve ( max 10 mg/Kg )
Dantrium®IV each vial contains
1. 20 mg dantrolene sodium
mg mannitol
3. Sodium Hydroxide to yield a pH
of approximately 9.5 when
reconstituted with 60 mL sterile water

17. Malignant Hyperthermia Treatment
Correct metabolic acidosis
(NaHCO3 1-2mEq/kg IV based on arterial ph)
Maintain urine output
Hydration
Furosemide ( 1mg/ kg )
Treat hyperkalemia – glucose + insulin
Treatment of arrythmias
Avoid Ca channel blockers – myocardial depression

18. Malignant Hyperthermia Key Patient Stability Indicators
ETCO2 is declining or normal
HR is stable or decreasing
No ominous dysrhythmias
Temperature is declining
Generalized muscular rigidity is resolving (if present)
IV dantrolene administration has begun

19. Malignant Hyperthermia What is Dantrolene ?
Dantium ( Dantrolene )
Skeletal muscle relaxant by inhibiting sarcoplasmic release of calcium
Half life 4-8 hrs metabolized by liver
Causes generalized muscle weaknes
No cardiac effects
No effect on train of four

20. Management of MH Susceptible Patients
Preparation of anaesthesia machine
Fresh circuit, absorber flushed at 10 lpm x 10 min
Triggers disconnected from circuit and out of room
Non triggering anaesthetic
Propofol, ketamine, N2O,narcotics
Regional techniques
PACU
Extended stay
Observe 2-4 hours prior to discharge

21. For More MH Information