Understanding Anesthesiology - The Global Regional Anesthesia ...

SECTION 1
Malignant Hyperthermia
In This Section
1. Malignant Hyperthermia
Malignant Hyperthermia (MH) is a potentially
life-threatening pharmacogenetic disorder characterized
by the onset of a hypermetabolic crisis in
response to certain triggers. Since the usual triggers
are succinylcholine and volatile anesthetics,
MH is known as “the anesthesiologist’s disease”.
Although MH is now known to be a genetically
heterogenous disorder, up to 70% of cases involve
a mutation in a gene on chromosome 19
which encodes the ryanodine receptor protein.
The ryanodine receptor is located on the sarcoplasmic
reticulum. This particular mutation
shows autosomal dominant inheritance pattern
with variable penetrance. The other known causative
gene for MH is CACNA1S, which is responsible
for a voltage-gated calcium channel #-
subunit. Several other chromosomal loci have
been linked to MH although the specific genes
have not yet been identified.
The MH-associated mutations cause an abnormality
in skeletal muscle metabolism whereby uncontrolled
intracellular release of calcium leads to
sustained muscular contraction and cellular hypermetabolism.
One very rare neuromuscular disease,
called central core disease, is known to be
associated with MH, while other more common
neuromuscular disorders, such as Duchenne Muscular
Dystrophy, are possibly associated with MH.
Although rare (the incidence is reported to be 1
in 126,000 general anesthetics), MH does occur in
geographical clusters.
The clinical manifestations of an MH crisis reflect
the hypermetabolic state and may occur intraoperatively
or post-operatively. The earliest sign
is tachycardia followed by evidence of increased
carbon dioxide (CO2) production. Increase CO2
production manifests as tachypnea in a
spontaneously-breathing patient or raised endtidal
CO2 levels in a mechanically-ventilated patient.
Skeletal muscle rigidity is prominent. Hyperthermia
is often delayed. Hypoxemia, acidosis,
hyperkalemia, dysrhythmias and hemodynamic
instability may ensue as the reaction progresses.
Without treatment, the mortality rate for
MH reaction is exceedingly high; even with
prompt treatment, mortality may be as high as
10%.
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