Malignant hyperthermia

Introduction.

• Inherited disorder in skeletal muscle cells
• Autosomal dominant
• Variable penetrance
• Incidence:-   1:15 000 – paediatrics         1: 40 000 – adult
• Can be lethal

Aetiology.

• A genetic mutation in Rynodine receptor, an intracellular calcium channel in sarcoplasmic reticulum.
• When triggered, there is an exaggerated release of calcium ions causing hypermetabolism.
• Triggering agents:- Halogenated inhalational anaesthetic agents Suxamethonium
• They can be otherwise healthy individuals.
• More susceptible in :-
• Duchenne muscular dystrophy
• Central core disease
• Osteogenesis imperfecta
• Strabismus surgery
• Repeated anaesthetics
• Positive family history.

 Clinical signs

Can appear intra-operatively or post-operatively even up to 24 hours.

Exaggerated calcium release causes increased ADP/ATP activity and hypermetabolism in skeletal muscles.

(a)    Due to hypermetabolism:

                  Hypercarbia > 70 mmHg  (If not paralysed, inc.RR)

                  Tachycardia >140 / min

                  Hypertension ( later hypotension due to myocardial depression)

                  Arrhythmias, usu VF (due to acidosis, hyperkalaemia , symp stimulation)

                  Cyanosis
                  Mottling
                  Ix: ABG – Mixed acidosis, base deficit
                  Reduced mixed venous Oxygen

(b)   Muscular effects
                     Masseter muscle spasm

Generalised muscle rigidity

Compartment syndrome

Dark urine and ARF 

Ix: Hyperkalaemia

     Inc.CK > 20 000 u/l  ( follow up to 24 hrs)

     Inc. LDH

     Inc. plasma myoglobin

     Myoglobinuria

     S.Ca – initially inc. later dec.

 (c)     Due to Hyperthermia

2° C rise over 10 min – 1 hr

DIC

Cerebral oedema, seizures

Hepatic failure

Management

Early

1. Call for help.
2. Withdraw all trigger agents. (all anaesthetic vapours)
3. Install clean anaesthetic breathing system and hyperventilate for 2 – 3 times MV with 100% Oxygen. Airway pressure may be high!
4. Abandon surgery if possible. If not, ct with TIVA. (proofol, midazolam, opioids)
5. Give specific therapy – Dantrolene 1 mg/kg initially up to 10 mg/kg
6. Measure ABG, K and CK
7. Measure core temperature
8. Active cooling – ice packs, cold iv fluids, NG lavage – until 38° C

Intermediate

1. Control serious arrhythmias. βblockers preferred. Avoid Ca channel blockers, which increase K⁺ release.
2. Control hyperkalaemia, metabolic acidosis.

Later

1. Clotting screen to detect DIC
2. Urine for myoglobin
3. Chart UOP.
4. Promote diuresis with fluids, mannitol, frusemide.
5. Once stabilized, admit to ICU.
6. Monitor at least 24 hrs.

Subsequent

1. Exclude myopathy, other DDs
2. Councel patient & family
3. Investigate for confirmation. (Caffeine test, Halothane test )

Dantrolen Ca receptor antagonist. Bolus 1 mg/kg , rept every 10 min until symptoms regress, up to 10 mg/kg Ct 0.25 – 0.5 mg/kg, 4-6 hourly as t1/2 is 4 hrs. Vials – orange colour powder, contains 20 mg dantrolene with mannitol 3 g. Dissolve in 60 ml sterile water. Difficult to reconstitute. Risks – generalised muscle weakness causing resp. failure, phlebitis

Differential Diagnosis of MH

• Neuroleptic malignant syndrome
• Thyrotoxic crisis
• Pheochromocytoma
• Iatrogenic
• Sepsis

Anaesthesia for a patient with known MH

• Try local / regional techniques
• TIVA + NDB. Can also use N₂O, opioids, ketamine, BDZ.
• Use disposable clean circuits and a fresh CO₂ canister
• Disconnect vapourizer
• Flush machine & ventilator with O₂ 10 l/min for 10 minutes.

Premedication with dantrolene is not recommended.

Post op monitoring: Minor surgeries – 4 hrs, major surgeries – 24 hrs.