Malignant Hyperthermia: Etiopathology,diagnosis and treatment.

1. Malignant Hyperthermia
Dr. Naveen Kumar Gaur
2nd Year Resident
Dept.of Anaesthesiology, Govt. Medical
College & Sir T. Hospital,
Bhavnagar(Gujarat)

2. Definition
• Uncommon, life-threatening, pharmacogenetic,
hypermetabolic disorder of the skeletal muscle
triggered
by
inhalation
agents
and
succinylcholine.

3. Genetics
• Its an autosomal dominant trait.
• Gene located on19th chromosome (19q11.2-13.2).
• In most cases(>50%) MH is caused by defect in
the ryanodine receptor(RyR1).
(Release of calcium from SR)
• Other chromosomes involved are –
- 17q11.2-q24 – altered Na channel functioning.
7q21.1
–
altered
Dihydropyridine
receptors(DHPR) – voltage sensors for RyR1.

4. Epidemiology
• Usually occurs in children & young adults.
(incidence highest in 1st three decades of life, but
cases reported at extremes of ages)
• Overall incidence rate during GA1 in 3000 – 15,000 children
1 in 50,000 – 100,000 adults
• Geographical variation- more prevalent in certain
areas of North America.
• Male = Female
• Mortality reduced from 70% to <5%(after dantrolene)

5.  Definite association: central core diseaseautosomal dominant congenital myopathy.
(common gene RyR1 mutation)
 Possible association: Duchene, Becker, KingDenborough, other myopathies.
(Pts with Duchene's or Becker’s dystrophy are at
risk for hyperkalemic cardiac arrest with
succinylcholine or other MH triggering agents,
but this is not MH.
 Coincidental association: Neuroleptic Malignant
Syndrome, Heat Stroke, etc

6. Porcine Stress Syndrome
• MH like syndrome in certain breeds of swine.
• Presentation - ↑ metabolism, acidosis, fever, rigidity
& death.
• Triggered by – separation, shipping condition,
weaning, fighting, coitus, preparation for slaughter,
etc.
• This can be induced in stress susceptible swine by
administering halothane & succinylcholine.
• Cause – single mutation in RyR1.

7. Pathophysiology
• MH is an inherited disorder of the skeletal muscle
system in which a defect in the calcium regulation is
expressed by exposure to triggering anesthetic agents
→ intracellular hypercalcemia.
• The ryanodine receptors(RyR1) modulate calcium
release from the channels in the SR.
• ↑ in concentration of calcium in cells (upto 500 folds)

8. - Actomysin cross-bridging
- Sustained muscle contraction
- Rigidity
↓
- ↑ oxygen consumption
- ↑ CO2 and heat production(hyperthermia)
- depletion of ATP stores
- lactic acid(Acidosis)
- marked increase in - myoglobin
- creatine kinase
- potassium.
• Cells damaged due to membrane instability.

9. Identifying Susceptible Patients
Muscle Contracture Test
• Caffeine Halothane Contracture Test(CHCT)
• For patients having H/O MMR.
• Gold Standard.
• Requires 3-4 inch muscle biopsy taken from
thigh(vastus muscle) under GA or LA.
• Protocols –
1. North American MH group – abnormal contracture
to either Halothane or Caffeine labels pt. as MH
susceptible.
2. European MH group – abnormal contracture to both
Halothane & Caffeine labels pt. as MH susceptible.
• 97-99% sensitivity, false negatives are rare.
• 78-94% specificity.

10. Genetic Testing
• Involves isolation of DNA from patient (blood,
muscle cells, or other tissue sample)
• RYRI (ryanodine receptor) found, there are
currently 29 MH causative RYRI mutations.
• Presence of causative mutation in RYRI gene
is diagnostic for MH susceptibility.
• Sensitivity based on population selected and
methodology of testing utilized.

11. MH Triggers
• Volatile anesthetics
- Ether
- Halothane
- Sevoflurane
- Desflurane
- Isoflurane
- Enflurane
• Depolarizing muscle relaxants
- Succinylcholine

12. Nontriggering drugs for MH
•
•
•
•
•
•
•
•
•
•
•
Barbiturates
Propofol
Benzodiezepins
Opioids
Nitrous oxide
Non depolarizing muscle relaxants
Anticholinergics
Anticholinesterases
Sympathomimetics
Local anaesthetics
Clonidine,dexmedetomidine

13. Clinical Features

14. • Early –
- Clinical signs –
- Masseter spasm.
- Tachypnea(in spontaneously ventilating pt).
- Tachycardia.
- Rapid exhaustion of soda lime.
- Irregular pulse.
- Change in monitored variables –
- ↑ in minute ventilation.
- ↑ in EtCO2
- Dysrythmia with peak T wave.
- Biochemical changes –
- ↑ in PaCO2 (100-200 mmHg)
- Acidosis(pH 7.15-6.8)
- Hyperkalemia.

15. • Intermediate –
- Clinical signs –
- Warm skin(temp↑ @ 0.5 C every 15
minutes and reaching levels as high as 46 C.)
- Cyanosis.
- Dark blood on surgical site.
- Dysrythmia.
- Change in monitored variables –
- ↑ in core body temp.
- ↓ Hb saturation.

16. • Late - Clinical signs –
- Generalized skeletal muscle rigidity.
- Prolonged bleeding.
- Dark urine.
- Irregular heart rate.
- Biochemical changes –
- ↑ in s. creatine kinase level.
- Myoglobinuria.
- Hyperkalemia.

17. • Late complications(if MH untreated)
- DIC(due to release of thromboplastin secondary to
cellular destruction)
- Pulmonary edema.
- ARF.
- CNS damage – Blindness
- Seizures
- Coma
- Paralysis

18. Treatment
• Etiologic treatment –
-
Inj. Dantrolene 2-3 mg/kg iv bolus, followed with
repeat dose every 5-10 min to maximum dose upto
10mg/kg.
- To prevent recrudescence – Inj. dantolene 1mg/kg
every 6 hrs for 48-72 hrs.

19. • Symtomatic treatment –
- Immediate termination of inhaled anaesthetic &
conclude surgery.
- Hyperventilation with 100% oxygen.
- Initiate active cooling –
- surface cooling.
- gastric & bladder lavage with iced saline.
- iced saline 15 mg/kg iv every 10 minutes.
(discontinue cooling when temp falls to 38 C)

20. - Correct metabolic acidosis –Inj. Soda bicarb 1-2
mEq/kg iv according to blood pH.
- Maintain UOP – Hydration
- Mannitol(0.25 mg/kg)
- Furosemide(1mg/kg)
- Treat cardiac dysrythmia(Loxicard 1.5mg/kg)
- Monitoring of UOP, ABG, S.electrolytes.

21. Anaesthetic management
• Regional anaesthesia- Acceptable choice(both esters and amides can be
used)
• Dantrolene prophylaxis –
- if past H/O MH – Inj. Dantrolene 2-4mg/kg iv over
10-30 min. just prior to induction.
- Catheterize patient, as drug contains mannitol (to
make drug isotonic).
- Large doses may cause –
nausea, vomiting, diarrhea, blurred vision,
skeletal muscle weakness(post op monitoring is must)

22. • Drug selection –
- Keep preparations to treat MH.
- Good sedation.
- Avoid triggering agents.
- Avoid CCB with dantrolene, may cause hyperkalemia and
myocardial depression.
• Anaesthesia machine –
- “Dedicated” anaesthesia machine preferred(never been used
to deliver volatile anaesthetics).
- Conventional machine with –
- disposable breathing circuits.
- fresh soda lime.
- no vaporizers.
- continues flow of O2 @ 10 L/min for 10-60 minutes
before using for MH susceptible patient.

23. Differential Diagnosis
1. Hyperthyroidism- similar symptoms, but blood gas
abnormality occurs gradually.
2. Pheochromocytoma – marked BP swings.
3. Malignant neuroleptic syndrome – usually associated with
use of neuroleptic/antipsychotic drugs.
4. Cocaine intoxicity – similar to MNS.
5. Heat stroke – outside the OT.
6. Metastatic carcinoid – similar to Pheochromocytoma.
7. Sepsis – usually ABG normal.

24. Dantrolene
• A skeletal muscle relaxant(hydantoin derivative)
• Blocks RyR1 receptors, thus block the calcium
release.
• T1/2 = 4-8 hrs.
• Metabolized in liver.
• Side effects – weakness, dizziness.
• Each vial of dantrolene contains –
- 20 mg dantrolene sodium.
- 3000 mg mannitol(to make solution isotonic.
- Sodium hydroxide(to keep pH near 9.5)

25. Thank you…