TRIGGERING OF MALIGNANT HYPERTHERMIA
Acute episodes of MH depend on three variables: a genetic (perhaps
rarely acquired) predisposition, the absence of inhibiting factors, and the presence
of a sufficiently potent anesthetic or nonanesthetic trigger.
Anesthetic Triggering
Anesthetic drugs that trigger MH include halothane, enflurane,
isoflurane, desflurane, sevoflurane, and succinylcholine. Desflurane and sevoflurane
are less potent triggers, producing a more gradual onset of MH.[95]
[96]
The onset may be explosive if succinylcholine
is used.[46]
Inbred, susceptible swine are identified
during an inhalation induction with a potent volatile anesthetic; they develop pronounced
hind limb rigidity within 5 minutes.[46]
Prior
exercise even an hour before induction of anesthesia increases the severity and hastens
the onset of these attacks in swine.[46]
Mild hypothermia,
depressants such as barbiturates and tranquilizers, and nondepolarizing relaxants
delay the onset of MH.[15]
[97]
[98]
Susceptible humans respond less predictably than swine to these
triggers. Many affected humans have previously tolerated potent triggers without
visible difficulty.[14]
This unpredictability may
in part be related to the delaying effects described earlier, as well as to a brief
anesthetic. Some patients have experienced MH episodes during anesthesia that did
not involve recognized triggering agents; fortunately, all have responded appropriately
to dantrolene. The mechanism of anesthetic triggering in humans is unsolved.
Succinylcholine has several variant responses that can occur singly
or in combination. The first is a muscle contracture, also observed in muscle that
is myotonic or denervated.[89]
The second is a
change in muscle membrane permeability without contracture, resulting in the release
of CK and myoglobin from muscle. Even in normal patients, succinylcholine releases
CK and myoglobin from muscle in small amounts. This action is exaggerated in the
presence of halothane and attenuated by curare[46]
;
myoglobin release can be fairly marked even in the absence of obviously discolored
urine.[94]
The third response is an increase in
metabolism, as in MH, which is usually associated with muscle contracture and increased
membrane permeability.[46]
Nitrous oxide has been proposed as a weak trigger of human MH.
[46]
This is most unlikely because it has been
used
repeatedly and safely as the basic anesthetic in MH-susceptible humans and swine.
Hyperbaric nitrous oxide does not produce MH in susceptible swine, even in concentrations
causing apnea.[99]
Nondepolarizing muscle relaxants block the effects of succinylcholine
in triggering MH. They attenuate the effects of volatile anesthetics.[15]
[97]
D-Tubocurarine
has been incriminated as an MH trigger because it produced fever in two susceptible
children.[46]
D-Tubocurarine
results in greater lactate production in susceptible pigs exposed to environmental
stress,[46]
but it has not been shown to be a trigger;
it does produce a contracture in denervated muscle, suggesting that it may have a
mild depolarizing action that is not generally apparent.[100]
Reversal of a nondepolarizing neuromuscular blockade does not trigger MH.
Episodes of MH have been reported during various operative procedures,
with general or regional anesthesia, and in extremes of ages. Prior fever or succinylcholine-induced
trismus should not be ignored, even if the patient survived without obvious mishap.
[101]
The youngest probable case of MH involved
succinylcholine-related muscle rigidity in utero just before birth.[102]
Presumably, the fetus inherited the paternal susceptibility that was triggered by
maternal anesthesia.
Prolonged propofol infusions in pediatric intensive care are associated
with complications that may mimic MH reactions.[103]
[104]
Propofol is not an MH trigger, and its effects
on membranes of MH-affected skeletal muscle are stabilizing and opposite to those
of volatile triggers.[105]
