HISTORY
Between 1915 and 1925, one family experienced three anesthetic-induced
MH deaths featuring rigidity and hyperthermia and was puzzled for decades regarding
the cause of these deaths. Susceptibility was eventually confirmed in three descendants.
[3]
In 1929, Ombrédanne[4]
described anesthesia-induced postoperative hyperthermia and pallor in children with
significant mortality (i.e., Ombrédanne's syndrome) but did not detect familial
relationships. Critical worldwide insight into MH began in 1960, when Denborough
and Lovell[5]
described a 21-year-old Australian
with an open leg fracture who was more anxious about anesthesia than about surgery
because 10 of his relatives had died during or after anesthesia. Lovell initially
anesthetized him with the then-new agent halothane, halted it when signs of MH appeared,
and subsequently used spinal anesthesia. Further evaluations of affected families
came from George Locher in Wausau, Wisconsin, in conjunction with Beverly Britt in
Toronto, Canada. Direct skeletal muscle involvement rather than central loss of
temperature control was established by recognition of increased muscle metabolism
or muscle rigidity early in the syndrome, low-threshold contracture responses,[6]
and elevated values for creatine kinase (CK).
Swine inbred for muscle development (e.g., Landrace, Pietrain,
Poland China) provide an excellent animal model. The single-point mutation producing
porcine MH is probably caused by the random occurrence of the altered RYR1
allele, followed by deliberate inbreeding for desirable traits. International sharing
of breeding stock accounts for its worldwide spread. Affected swine are detected
by testing for the ubiquitous Arg615Cys mutation. The experimental model evolved
from earlier reports describing unsuitable pork[7]
;
the stresses of the abattoir result in accelerated metabolism and rapid deterioration
of the muscle, resulting in pale, soft, exudative pork.[8]
Its incidence increased with breeding patterns designed to produce rapid growth
rate, superior muscling, and hybrid vigor, although the drawback is a link with stress
susceptibility. This increased incidence led to the term porcine
stress syndrome.[9]
Any stresses, such
as separation, shipping, weaning, fighting, coitus, or preparation for slaughter,
can lead to increased metabolism, acidosis, rigidity, fever, and death.
In 1966, Hall and coworkers[10]
reported MH induced by halothane and succinylcholine in stress-susceptible swine.
The human and porcine forms are virtually identical in comparisons of the clinical
and laboratory changes of anesthesia-induced MH.[11]
In 1975, Harrison[12]
described the efficacy of
dantrolene in preventing and treating porcine MH, which was confirmed in humans by
a multihospital evaluation of dantrolene used to treat unanticipated anesthetic-induced
episodes.[13]
MH in swine is a manifestation of
a generalized susceptibility to stress. Stress-induced awake triggering is common
in MH-susceptible swine but uncommon in MH-susceptible humans.
MH presents several paradoxes. Anesthetics are inconsistent in
their ability to trigger MH and are frequently ineffective in triggering episodes
in affected humans[14]
; this may be related to delay
of the response by various depressants and nondepolarizing muscle relaxants.[15]
Conversely, "safe" anesthetics, which are more appropriately described as those
less likely to trigger MH, can still be associated with apparent MH episodes; these
have always responded appropriately to dantrolene.[16]
Susceptible individuals appear normal in regard to structure and function until
they are stressed, complicating detection of the condition. Detection requires an
anesthetic challenge, an invasive and destructive muscle biopsy with contracture
responses to caffeine or halothane, or genetic investigation for causative mutations.
