الفهرس 
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Abstract
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SUM MAR Y
Since its recognition (Denborough and Lovell,
1960), malignant hyperthermia (Mil) has aroused great
interest among anaesthetists. It can occur in genetically
predisposed human patients on administration of
inhalational general anaesthetics; either alone or in
combination with muscle relaxants~
The report in 1966 by Hall et al. of MH indued by
halothane and succinylcholine in a stress-susceptible
strain of swine, provided an animal model of the human
disease .
The incidence of MH ia one in 15,000 anesthetic
children and one in 50,000 anesthetic adults (Hritt,
1972). Males and females are af~ected equally in children
but there is a preponderance of males in adulthood (Gritt
et al., 1977; Ellis and Halsall, 1980). Susceptibility
to MH appears to be inherited in an autosoma~. dominant
fashion, with .incomplete penetrance and variable expressivity
(Britt et al.,1969).
Occasionally, these patients will have mild subclinical
weakness, mild creatine phosphokinase (CPK) elevation,
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and nonspecific changes on muscle biopsy (lsaace and
Larlow, 1970; Harriman et al., 1973). In general,Mti
has not been associated with well-defined neuromuscular
disorders (Engel, 1977). However, Watters et
al • (1977) reported three children with Duchenne
musclar dystrophy in whom muscle breakdown waa enhanced
by general anesthesia with halothane and succinylcholine.
There have also been a number of reports
of t1H assoc ia ted wit h my otonia dys trophi ca myotonia congenita
and central core disease (Kaufman, 1960; Saidman et
al. 1)64; Cody, 1968; Ravin et al. 1975; Engel, 1977,
Mitchell et al. 1978).
The syndrome of MH developing during anathesia
is marked by tachycardia, arrhythmia, tachypnea, unstable
blood pressure, cyanosis, skin mottling and rigidity
(Gronert, 1980). Elevated temperature, a result
of the underlying biochemical deragnement, occurs as the
syndrome evolves (Britt, 1979a). The temperature may soar,
rising at a rate of 1 degree every five minutes, to as
high as 43°C. There is hypercarbia, acidemia, hyperkalemia
and massive elevation of CPK. Early hy~ercalcemia
may be followed by late hypocalcemia (Britt, 1979a).
Myoglobinuria and resulting renal failure are serious
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complications of Mli. The mortality rate is 64 percent
(urIt t and Kalow, 1970a).
The disorder can be triggered by any potent volatile
agent, ketamine and depolarizing relaxants. Uee of
succinylcholine is often associated with an abrupt
onset of MH (i3ritt, 1979a; Gronert, 1980 ).
Excessively elevated myoplamsic calcium can
centration causes the acute catabolic liH crisis (Btitt,
1979a). Heat-generating mechanisms initiated by hypercalcemia
include breakdown of glycogen, uncoupling
of oxidative phosphorylation , and accelerated hydrolysis
of ATP by myosin ATPase (Britt, 1979a). High myoplamic
calcium also produces muscle contracture.
The defect that underlies the abnormal regulation
of intracellular calcium is not known. A fragile sercolemmal
membrane, allowing calcium influx, defective mitochondria,
or sarcoplasmic reticulum that is unable to
pump calcium may all be involved (Engel, 1977; Britt,
1979a; Gronert, 1980 )
As soon as the diagnosis is suspected, all anesthesia
should be discontinued.Patients with the fulil -til own ”syndromerequire
prompt treatmentwith hyperventillationwith 100 percent oxygen,
biocarbonate, cooling, and
known specific therapeutic
diuretics. Dantrolene is the only
agent. lt should be given as soon 8~
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the diognosis is made.The recommended dose is 1 to 2
mg per Kilogram 1VJ which may be repeated every 5 to
10 minutes, to a total dose of 10 mg per kilogram. The
drug should be continued orall¥ for 24 hours following
control .Vigilance over the patient’s clinical state
and laboratory values is required for several days after
the attack , as later renal and hematologic complications
may occur (critt and Kalow, 1970a; Faust et aI, 1979~
Gronert, 1980 and Waterman, 1981).
•
Screening of relatives of affected patients for
susceptibility to MH is important. Seventy percent of the
cases at risk have increased serum CPK activities (Britt
et al. 1976). Without this finding, in vitro testing of
muscle strips for an abnormal contracture response to halothane,
caffeine or a combination of both agents can be
done (~alow et al. ,1977; Ellis et al., 1978c; ~rding
)
E 11is et a!’ (1978b) have indicated that
et a L, , 1984 •
the fluoride-resistant gene for plasma cholinesterase
has an increased frequency in relatives of patients who
had experienced MH. The findings of Willner et al.(1980)
that the phosphorylase ratio in muscle from susceptible
patients was elevated held promise of such a test , in
part because needle biopsy could supply the specimen.
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A relatively non-invasive screening technique using
venous blood analyzed by high performance liquid chromatography
(1IPLC) was developed to assess the effects of
halothane on platelet nucleotide metabolism. The platelet-
halothane bioassay (PHS) is highly reproducible and
specific for detecting MH with a significant degree of
expression at the time of the venipuncture (Solomons and
Masson, 1984)
Pretreatment with Dantrolene p.o.the day before
surgery (4 to 7mq per kg., individed doses), avoidaDce of
premedication with phenothiazines or atropine, use of
safe anesthetic agents such as nitrous oXide, thiopental
and opiates, and csreful perioperative monitoring will
prevent the MH syndrome (Gronert, 1980).