Chapter 29
- Malignant Hyperthermia
- Gerald A. Gronert
- Isaac N. Pessah
- Sheila M. Muldoon
- Timothy J. Tautz
Malignant hyperthermia (MH), an eerie and erratic metabolic mayhem,
is a clinical syndrome that in its classic form occurs during anesthesia with a potent
volatile agent such as halothane and the depolarizing muscle relaxant succinylcholine,
producing rapidly increasing temperature (by as much as 1° C/5 min) and extreme
acidosis. The effects result from loss of control of intracellular calcium levels
and compensatory acute, uncontrolled increases in skeletal muscle metabolism that
may proceed to severe rhabdomyolysis. Initially, the mortality rate was 70%; earlier
diagnosis and use of dantrolene have reduced it to less than 5%. MH now occurs in
muted forms because of diminished use of succinylcholine, diagnostic awareness, early
detection through end-expired carbon dioxide, use of less potent triggers, and use
of drugs that attenuate its onset. Wilson and colleagues[1]
first used the term malignant hyperthermia in print
in 1966. A Danish survey[2]
indicates an incidence
of fulminant MH of one case per 250,000 anesthetics. However, considering only potent
anesthetics and succinylcholine, one case of fulminant MH occurred per 62,000 anesthetics.
The incidence of suspected MH was one case per 16,000 anesthetics or one case per
4,200 anesthetics involving potent volatile agents in combination with succinylcholine.
Public education and communication are provided by a layman's
organization, Malignant Hyperthermia Association of the United States (MHAUS, 11
E. State Street, P.O. Box 1069, Sherburne, New York 13460-1069; telephone: 1-607-674-7901;
fax: 1-607-674-7910; email: mhaus@norwich.net; web site: www.mhaus.org) and by
a
medical professional's 24-hour, 7-day telephone service for emergency consultation,
the MH Hotline (1-800-MHHYPER, or 1-800-644-9737). The professional subsidiary of
MHAUS, the North American MH Registry, collates findings from biopsy centers in Canada
and the United States and provides access to specific patient data through the Hotline
or its Director, Dr. Barbara Brandom (North American MH Registry of MHAUS, Room 7449,
Department of Anesthesiology, Children's Hospital, University of Pittsburgh, 3705
Fifth Avenue at DeSoto St., Pittsburgh, Pennsylvania, 15213-2583; telephone: 1-888-274-7899;
fax: 1-412-692-8658; email: bwb@pitt.edu).
Of the three forms of the ryanodine receptor, RYR1, RYR2, and
RYR3, only mutations in RYR1 have been linked to MH. The genetics of MH and the
related abnormal function of RYR1 are being investigated at the molecular biologic
level, with the porcine model providing intricate detail. Equivalent parallels in
humans are limited by scarcer material for scientific study and the difficulty in
identifying underlying sources of abnormal responses, complicated by the fact that
phenotypes vary within a genotype (i.e., discordance between genetic results and
MH testing by contracture studies). Dantrolene remains essential in therapy, although
its mechanism of action is elusive. Standardization of in vitro MH muscle contracture
testing with two slightly different protocols, the European (contracture test [IVCT])
and the North American (caffeine-halothane contracture test [CHCT]), has resulted
in sufficiently large databases to confirm sensitivity and specificity. Diagnostic
challenges occur with intra-anesthetic changes that mimic MH, particularly in its
earlier manifestations.
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