malignant hyperthermia
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Malignant Hyperthermia
Dr. Naveen Kumar Gaur
2nd Year Resident
Dept.of Anaesthesiology, Govt. Medical College & Sir T. Hospital,
Bhavnagar(Gujarat)
Definition
• Uncommon, life-threatening, pharmacogenetic, hypermetabolic disorder of the skeletal muscle triggered by inhalation agents and succinylcholine.
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.
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 GA-
1 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)
Definite association: central core disease- autosomal dominant congenital myopathy.
(common gene RyR1 mutation)
Possible association: Duchene, Becker, King-Denborough, 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
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.
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)
- 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.
Identifying Susceptible PatientsMuscle 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.
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.
MH Triggers• Volatile anesthetics
- Ether
- Halothane
- Sevoflurane
- Desflurane- Isoflurane
- Enflurane
• Depolarizing muscle relaxants
- Succinylcholine
Nontriggering drugs for MH
• Barbiturates• Propofol• Benzodiezepins• Opioids• Nitrous oxide• Non depolarizing muscle relaxants• Anticholinergics• Anticholinesterases• Sympathomimetics• Local anaesthetics• Clonidine,dexmedetomidine
Clinical Features
• 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.
• 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.
• Late -
- Clinical signs –
- Generalized skeletal muscle rigidity.
- Prolonged bleeding.
- Dark urine.
- Irregular heart rate.
- Biochemical changes –
- ↑ in s. creatine kinase level.
- Myoglobinuria.
- Hyperkalemia.
• Late complications(if MH untreated)
- DIC(due to release of thromboplastin secondary to cellular destruction)
- Pulmonary edema.
- ARF.
- CNS damage – Blindness
- Seizures
- Coma
- Paralysis
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.
• 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)
- 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.
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)
• 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.
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.
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)
Thank you…
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