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April 1997
Volume 61 |
Number 4
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| North American
Malignant Hyperthermia Registry Clinical and Research Mission |
Marilyn G. Larach, M.D.
Sheila M. Muldoon, M.D.
The North American Malignant Hyperthermia Registry (Registry)
of the Malignant Hyperthermia Association of the United States
(MHAUS) gathers, analyzes
and disseminates patient-specific clinical and laboratory information
on malignant hyperthermia (MH) to anesthesiologists and other
health professionals caring for MH-susceptible patients and to
scientific investigators.
Data are submitted to the Registry on standardized report forms
from health care providers managing patients at the time of an
adverse anesthetic event and MH biopsy center directors at the
time a patient undergoes biopsy. These report forms are entered
into the Registry's computerized database which now contains nearly
1,000 reports representing the world's largest collection of clinical
and laboratory data on MH-susceptible individuals.
This unique database permits the Registry to pursue its research
mission: 1) to standardize the clinical and laboratory diagnosis
of MH; 2) to identify the genetic defects causing MH susceptibility
in patients who have been clinically diagnosed as MH-susceptible;
3) to investigate the epidemiology of MH and other adverse musculoskeletal
anesthetic reactions; and 4) to improve treatment of MH crises
[Figure 1].
Individual MH Hotline Reports
To date, 926 patients with abnormal reactions to anesthetics
have been entered into the Registry. More than 1,250 relatives
of individuals who have had abnormal reactions to anesthetics
and who may be susceptible to MH are registered as well [Figure
2]. Prior to anesthetizing an MH-susceptible individual, the
anesthesiologist may contact the Registry to obtain a one-page
MH Hotline Report, which summarizes the patient's database entry,
including: adverse anesthetic event, MH family history, muscle
biopsy result and subsequent anesthetic course. The Registry has
prepared more than 1,334 MH Hotline Reports; these may be accessed
by calling the Registry database manager at (717) 531-6936. Prior
to calling, the anesthesiologist should have at hand the patient's
full name, birth date and the patient's mother's maiden name.
Standardization of MH Diagnosis
Under the auspices of the Registry, an international MH clinical
grading scale has been developed to rank the likelihood that an
abnormal reaction to an anesthetic is a true MH event. The rank
may underestimate (but will rarely overestimate) the likelihood
of MH, making the clinical grading scale useful in scientific
research. The clinical grading scale depends upon the anesthesiologist's
judgment of whether specific clinical signs are appropriate for
the patient's medical condition, anesthetic technique being used
and the surgical procedure. [1]
In one recent study, the Registry analyzed the validity of MH
muscle biopsy by studying reports from 32 individuals who experienced
"almost certain" MH events, as ranked by the clinical
grading scale. Those data were compared with biopsy results from
a population of "control" individuals who had no personal
or family history of MH. Preliminary data indicate that the MH
diagnostic muscle biopsy (halothane caffeine contracture test)
has a sensitivity of 97 percent and a specificity of 78 percent.
[1] These results compare favorably with
those of an elevated creatine kinase-MB value to diagnose an acute
myocardial infarction.
While safe nontriggering anesthetic techniques exist, accurate
diagnosis of MH-susceptibility remains important for the practicing
anesthesiologist. Individuals labeled MH-susceptible can suffer
a number of sequelae such as being unable to enlist in the U.S.
military forces; experiencing problems obtaining life or health
insurance; and being placed at risk while traveling to third-world
countries. These potential socioeconomic problems extend to first-degree
relatives of those labeled MH-susceptible. Further, the accurate
phenotyping of individuals is a necessary prerequisite for determining
the molecular genetic basis of MH susceptibility in our large
and genetically heterogeneous North American population.
MH Genotyping - Future Goals
This year, the Registry will begin a study to determine whether
the previously identified mutations linked to MH susceptibility
are present in the clinically well-characterized individuals entered
in the Registry database. For MH families without known mutations,
the Registry will work with genetic researchers to determine the
gene abnormalities associated with their MH susceptibility. We
hope that the Registry database will soon contain linked clinical,
laboratory (including MH muscle biopsy) and molecular genetic
data on many MH-susceptible individuals in North America.
MH Epidemiology
Using the international MH clinical grading scale, the Registry
has been able to analyze more than 250 full-blown MH episodes.
We find that those experiencing MH events are disproportionately
young men and boys. This is surprising since MH is thought to
be inherited in an autosomal dominant fashion and should be present
for the lifetime of the individual. Additionally, MH events appear
to be triggered most often during ear, nose and throat surgery
or orthopedic procedures. Thus, additional factors besides genetic
susceptibility and exposure to "triggering" anesthetic
agents appear to play important roles in the development of MH
events. The nature of these factors is unknown and requires investigation.
[2]
Pediatric Hyperkalemic Cardiac Arrest
Over the last few years, the Registry and MH Hotline consultants
have received more than 25 reports of cardiac arrests in apparently
healthy children receiving general anesthetics. More than 10 of
these patients have died. The majority of these arrests were associated
with very high potassium levels and may be due to massive muscle
breakdown triggered by commonly used potent inhalation anesthetics
and/or succinylcholine. Many of these children were found to have
a previously unsuspected skeletal myopathy that was not MH.
It should be emphasized that in eight cases reported to the Registry,
potent inhalation anesthetics triggered massive muscle breakdown
and cardiac arrest even though succinylcholine had not been given.
For many of these children, the first sign or symptom of myopathy
may be a perioperative hyperkalemic cardiac arrest; therefore,
we recommend that pediatricians and anesthesiologists screen children
for underlying muscle problems prior to their anesthetics. The
best time to screen children with a simple serum creatine kinase
measurement may actually be when they are infants. If Duchenne
or Becker muscular dystrophy is suspected, both potent inhalation
anesthetics and succinylcholine should be avoided.
Anesthesiologists, emergency personnel and intensive care professionals
should suspect high serum potassium levels when pediatric patients
arrest shortly after receiving potent anesthetic agents or succinylcholine.
Potassium should be measured. Early, aggressive treatment with
calcium salts, sodium bicarbonate, hyperventilation, glucose plus
insulin, epinephrine and/or cardiopulmonary bypass may improve
survival. Even after prolonged resuscitation efforts, Registry
reports indicate that good neurologic outcomes may be achievable
in some survivors. [3]
MH Treatment
A Registry study of MH treatment reveals that dantrolene has
markedly reduced MH death rates to less than 4 percent. However,
6 percent of treated patients experienced respiratory failure
and nearly 25 percent relapsed at some point after the currently
recommended dose of dantrolene had been given. The relapse rate
suggests that dantrolene treatment recommendations need to be
changed. [4]
The Registry encourages anesthesiologists to continue to report
adverse perianesthetic metabolic and/or musculoskeletal events
so that expanded studies of MH treatment and epidemiology may
be conducted. Registry report forms may be obtained from MHAUS
(607) 674-7901 or the Registry database manager at (717) 531-6936.
The Registry acknowledges its many benefactors, including ASA,
the Foundation for Anesthesia Education and Research, and the
Pennsylvania State University Department of Anesthesia. The Registry
also thanks the thousands of anesthesiologists who have contributed
reports of their patients' experiences to the Registry.
Summary
In the 10 years since it was established, the North American
Malignant Hyperthermia Registry has collected patient specific
information on more than 1,000 patients with abnormal reactions
suspected to be malignant hyperthermia, has standardized the clinical
and laboratory diagnosis of MH, has performed epidemiologic studies
on MH and other adverse reactions to anesthesia and has published
the results of these studies in peer-reviewed journals. The Registry,
thus, provides a vital database for the clinician and investigator
alike.
References:
- Larach MG, Localio AR, Allen GC, et al.
A clinical grading scale to predict malignant hyperthermia susceptibility.
Anesthesiology. 1994; 80:771-779.
- Larach MG, Fuhrmann LJ, Allen GC. The
epidemiology of malignant hyperthermia events in North America.
In: Morio M, Kikuchi H, Yuge O. eds. Malignant Hyperthermia:
Proceedings of the 3rd International Symposium on Malignant
Hyperthermia, 1994. Tokyo, New York: Springer; 1996;39-41.
- Larach MG, Rosenberg H, Gronert GA, Allen
GC. Hyperkalemic cardiac arrest during anesthesia in infants
and children with occult myopathies. Clinical Pediatrics.
1997; 36:9-16.
- Larach MG, Simon LJ, Allen GC, et al.
Safety and efficacy of dantrolene sodium for the treatment of
malignant hyperthermia events. Anesthesiology. 1993;
79:A1079.
Marilyn G. Larach, M.D., is Associate
Professor of Anesthesiology and Critical Care Medicine, Johns
Hopkins University School of Medicine, Baltimore, Maryland. She
is a member of the Board of Directors of the Malignant Hyperthermia
Association of the United States.
E-mail the author.
Sheila M. Muldoon, M.D., is Professor
and Chair of the Department of Anesthesiology at the Uniformed
Services University of the Health Sciences, Bethesda, Maryland.
She is Chair of the Advisory Board for the North American Malignant
Hyperthermia Registry and a member of the Board of Directors of
the Malignant Hyperthermia Association of the United States.
E-mail the author.
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