Malignant Hyperthermia - A Short Review

 

MALIGNANT HYPERTHERMIA (MH)

This is a life-threatening Autosomal Dominant Clinical Syndrome of HYPEMETABOLISM in Skeletal Muscle triggered by volatiles and certain drugs to genetically predisposed individuals.

PATHOPHYSIOLOGY

It is the RYANODINE receptor that becomes dysfunctional.

ABOUT RYANODINE

1. It is located in Sarcoplasmic Reticulum

2. Ryanodine is the gatekeeper that controls calcium release from the sarcoplasmic reticulum

3. It becomes dysfunctional when exposed to volatile agents in patients who develop malignant hyperthermia

4. This causes a continuos leak of Calcium from the Sarcoplasm

5. ↑Calcium In the Cytosol.

The CONSEQUENCES of Malignant Hyperthermia if not treated are

1.↑O2 consumption

2.↑CO2 production

3.↑Heat

4.↑Sympathetic Activity

5.↑Heart rate

6.↑Respiratory rate

7.↑Potassium

8. Myoglobinuria

9. DIC - Disseminated intravascular coagulation 10. Multi-organ dysfunction and failure

->Death

DIAGNOSIS INTRAOPERATIVE

1. Early Signs

2. Late Signs

EARLY

↑CO2 (even with increasing minute ventilation),

Tachycardia,

Tachypnea,

Muscle rigidity

Masseter spasm

LATE

Fever,

Myoglobinuria,

DIC

Multiorgan failure.

GENETICS

1. Autosomal dominant myopathy in humans

2. Male ＞ female

3. There are more than 30 mutations

4. 1/15,000–20,000 anesthetics in children;

5. 1/50,000–100,000 in adults depending on use of trigger agents, gene pool

The WORRY

1. NOT easy to pick up those at risk.

There are no phenotypic signs to predict MH other than

Previous Hx of MH or family Hx

Unexplained elevated CK

3. MORBIDITY & MORTALITY

is a Perioperative Risk as

Mortality with MH in North America

Less than 10%, when the event occurs in a hospital;

20% when the patient is transferred into a hospital;

More than 80% if ununtreated,

2. UNPREDICTABILITY

Anesthetic agents are inconsistent in triggering MH.

A susceptible individual may undergo anesthesia with MH-Triggering agents on multiple occasions WITHOUT incident but still react to such agents on a subsequent occasion.

TESTING

1. The Caffeine halothane contracture test (CHCT) remains the criterion standard

2. Genetic testing is available to establish a diagnosis,

ASSOCIATED CONDITIONS

1. Masseter muscle rigidity (MMR)

10–20% of pts experiencing MMR develop clinical MH

Generalised rigidity

Predicts clinical MH in ＞60% Of Cases

2. Central core myopathy

-> Very high risk for MH

3. Multiminicore is also associated with MH susceptibilty

4. Certain forms of muscle disorders also lead to risk for MH and/or hyperkalemia with succinylcholine

From European Malignant Hyperthermia Group

#EMHG Guidelines:

Managing an MH Crisis

TREATMENT is as soon as an MH crisis is suspected.

The clinical presentation of MH varies and treatment should be modified accordingly.

Immediately Stop all trigger agents.

Hyperventilate (use a minute volume 2–3 times normal) with 100% O2 at high flow.

Declare an emergency and call for help.

Change to non-trigger anaesthesia (TIVA).

Inform the surgeon and ask for termination/postponement of surgery.

Disconnect the vaporizer—do not waste time changing the circuit/anaesthetic machine.

A. DANTROLENE

Give dantrolene 2 mg kg−1 i.v.

(ampoules of 20 mg are mixed with 60 ml sterile water).

Obtain dantrolene from other sources, for example, pharmacy/nearby hospitals.

(at least 36–50 ampoules may be needed for an adult patient)

Dantrolene infusions should be repeated until the cardiac and respiratory systems stabilize.

The maximum dose (10 mg kg−1) may need to be exceeded.

B. SYMPTOMATIC treatment

Treat hyperthermia

- 2000–3000 ml of chilled (4°C) 0.9% saline at i.v.

- Surface cooling: wet, cold sheets, fans, and ice packs placed in the axillae and groin.

- Other cooling devices if available.

Stop cooling once temperature <38.5°C

Treat hyperkalaemia

C. MONITORING

Monitor the patient for a minimum of 24 h (ICU, HDU, or in a recovery unit).

Continue routine anaesthetic monitoring

(SaO2, ECG, NIAP, E′CO2).

Measure core temperature.

Establish good i.v. lines with wide-bore cannulas.

Consider inserting A- line, CVP, and a urinary catheter.

Check electrolytes, arterial blood gases, myoglobin, and glucose.

Check renal and hepatic function and coagulation.

Check for signs of compartment syndrome.

About DANTROLENE

1. The antidote, that works on thE RYANODINE receptor.

2. It decreases the loss of calcium from the sarcoplasmic reticulum in the skeletal muscle

3. Restores normal metabolism and early detection and treatment improves outcome.