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April 1997
Volume 61 |
Number 4
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| Malignant Hyperthermia
- Prevention and Treatment |
Denise J. Wedel, M.D.
Prevention of a malignant hyperthermia (MH) crisis is straightforward
in those patients with a family or clinical history of MH. Nontriggering
anesthetics have been shown to be safe for MH-affected individuals,
and dantrolene pretreatment is no longer recommended for routine
prophylaxis. The list of "safe" anesthetics includes
all of the newer induction agents and neuromuscular blockers as
well as all local anesthetics, allowing tremendous flexibility
in the anesthetic approach.
MH-prevention in the undiagnosed surgical population, however,
is less certain and requires familiarity with the epidemiology
of this condition, carefully directed preoperative questioning
and a high index of suspicion for unusual anesthetic events that
might represent early or atypical MH reactions.
Epidemiology and Environmental Factors
Although the incidence of the MH trait in the general population
is quite low, reportedly ranging from 1:4,500 (when succinylcholine
is used) to 1:60,000 anesthetics, the incidence varies depending
on the prevalence of the gene(s) for MH in any given geographic
area, the type of anesthetic given and a multitude of patient
factors. MH is reported worldwide and affects all racial groups;
however, it is rare in infants [1,2,3]
and the incidence decreases after 50 years of age. Most cases
occur in children and young adults. Males are more frequently
affected than females, although this may be related to other demographic
factors such as the incidence of emergency surgery in this group.
Complicating the ability to predict accurately even further,
approximately 50 percent of MH-susceptible individuals have had
a previous triggering anesthetic without developing a clinically
diagnosed episode. [4] Possible explanations
for this phenomena include cool, ambient temperatures in the operating
room, [5] use of nontriggering agents
that delay onset of MH such as sodium Pentothal, narcotics or
nondepolarizing muscle relaxants, variable responses to different
potent gas anesthetics [6] and short
anesthetic exposure, all of which have been shown to prevent or
delay MH triggering in the animal model. In the past, less sophisticated
intraoperative physiologic monitoring may have resulted in mild
clinical MH episodes that were not diagnosed. There also may be
variable gene penetrance affecting individual responses [7]
and other undetermined factors.
The infrequent occurrence of acute MH in neonates is an interesting
observation that also has been reported in the swine model. MH
susceptible neonatal piglets were shown to have a lower frequency
of halothane-triggered MH compared to 4 week and older piglets
in both in vivo and in vitro (muscle strips) studies. [8]
The mechanism for this age-related difference in sensitivity is
not understood.
A family history of anesthetic problems deserves close scrutiny.
Hospital and anesthetic records should be obtained for review
if possible. If the patient or a family member has undergone muscle
biopsy for contracture testing, several avenues of information
are available. The family may have records with them, contracture
results can be obtained from the biopsy center, the biopsy center
director can be called directly, or the North American MH Registry
may have the results on file. With the permission of the patient,
these sources can be contacted by telephone or fax for an immediate
response.
Evidence of muscle disease on physical examination or a family
history of muscle problems may be a red flag. MH-like symptoms
have been reported in association with certain myopathic disorders
such as central core disease, Duchenne's muscular dystrophy and
King Denborough Syndrome. Association with other muscular defects,
sudden infant death syndrome, neuroleptic malignant syndrome and
sudden death in adults is controversial. [9]
Management of the MH Susceptible Patient
Machine preparation can be accomplished by removing or completely
draining all vaporizers, replacing rubber hoses and soda lime
and flushing with high flow oxygen or air (10 L/min) for 10 minutes.
If vaporizers are drained and left in place, the dials should
be taped securely with a warning label as a reminder that inhalation
agents should not be delivered.
The standard intraoperative monitors are recommended, including
end-tidal CO2 and core temperature in all patients.
[10] Early diagnosis and treatment,
two elements associated with better outcome, have been greatly
aided by the routine addition of end-tidal CO2 monitoring
to anesthetic management. Arterial and central venous monitoring
are added as indicated by the surgical procedure or medical condition.
Exposure to trace gas contamination in the recovery room is unlikely
to be a problem. Most experts do not recommend special procedures,
although this theoretical concern can be managed by isolating
the patient or by recovering from anesthesia in the operating
room and sending the patient directly to the ward. However, these
solutions are expensive and probably unnecessary.
MH susceptible patients can be managed as outpatients as long
as the usual precautions are observed. Ambulatory centers should
have dantrolene available in dosages sufficient to treat a fulminant
episode in an adult. Postoperative observation can be managed
according to the hospital protocol.
Treatment Plan for MH
A treatment plan for MH should be available wherever general
anesthesia is delivered. It is helpful to have an MH cart in a
central, readily accessible area (e.g., the recovery room) that
contains dantrolene, sterile water for mixing, blood gas kits,
resuscitation drugs and other items such as laboratory order forms
and an MH protocol. Discontinue triggers and hyperventilate with
100 percent oxygen while instituting symptomatic treatment.
Table 1
|
Symptomatic Treatment of MH
|
| Cooling |
|
Surface (ice, cooling blanket) |
|
Central |
|
|
Intravenous iced saline |
|
|
Nasogastric and rectal lavage |
|
|
Intra-abdominal lavage |
|
|
Cardiac bypass |
| Sodium Bicarbonate for metabolic
acidosis |
| Antiarrhythmics |
| Management of hyperkalemia - insulin/glucose |
| Diuretics - mannitol, lasix |
| (dantrolene contains 3 grams mannitol
per bottle) |
Dantrolene should be given early and aggressively when MH is
suspected. A multicenter study examining the effects of early-versus-late
dantrolene treatment showed clear improvement in patient outcome
in the early treatment group. [11] The
initial dosage is 2.5 mg/kg, which can be repeated as needed until
signs of MH abate. A total dose of 10 mg/kg is recommended, although
this dose can be exceeded safely. [12]
However, if the patient does not respond after receiving this
dose, alternative diagnoses should be considered. Caution should
be taken to avoid overcooling the patient. Administration of dantrolene
will usually decrease the core temperature promptly, so external
cooling efforts must be monitored closely.
Dantrolene is a hydantoin derivative that is very safe when administered
intravenously in the recommended dosages. Side effects include
nausea, malaise, light-headedness, muscle weakness and irritation
at the site of administration due to the high pH (9.5) of the
drug. [13] Muscle weakness is usually
peripheral and does not significantly affect respiration, although
it may be a problem in newborns. If possible, dantrolene should
be avoided during labor and delivery. Dantrolene contains a large
amount of mannitol, a fact that should be considered when treating
the patient with diuretics.
Dantrolene formulations that dissolve more rapidly, cause fewer
side effects or are less cumbersome to store and mix would be
welcome improvements. A promising formulation involves lecithin-coated
microcrystals of dantrolene, which were effective in treating
and preventing MH episodes when tested in animals. [14]
Following successful treatment, intravenous dantrolene 1 mg/kg
every six hours for 24 hours is recommended. The patient should
be observed and appropriate laboratory testing performed for at
least 24 to 48 hours following an MH episode. A subacute episode
may regress with discontinuation of the anesthetic; however, treatment
with dantrolene is advised since recrudescence can theoretically
occur. Some resuscitative medications may be contraindicated in
MH treatment. Potassium salts have been reported to retrigger
MH, and calcium channel blockers should not be given in the presence
of dantrolene due to the risk of life-threatening hyperkalemia.
Catecholamines, once considered possible triggers of MH, have
been shown to be safe and can be administered if necessary.
[15]
Once the patient is stable, genetic counseling should be offered
to the family. Materials describing MH, contracture testing, safe
anesthetic management in the operating room and the dental office,
and patient support information are available from the Malignant
Hyperthermia Association of the United States (MHAUS). The patient's
medical records should be clearly marked to avoid future exposures
to triggering anesthetics, and the patient should be instructed
to wear a medic alert bracelet or tag indicating susceptibility
to MH. It is especially important to clarify the familial nature
of this problem to the patient and immediate family so that the
information regarding the reaction can be disseminated to other
family members.
An MH episode cannot always be avoided, but with appropriate
monitoring and prompt diagnosis and treatment, the outcome of
this once devastating anesthetic "nightmare" can be
successful.
References:
- Bailey AG, Bloch EC. Malignant hyperthermia
in a
3-month-old American Indian infant. Anesth Analg. 1987;
66:1043-1045.
- Faust DK, Gergis SD, Sokoll MD. Management of
suspected malignant hyperpyrexia in an infant. Anesth Analg.
1979; 58:33-35.
- Sewell K, Flowerdew RM, Bromberger P. Severe muscular rigidity
at birth: Malignant hyperthermia syndrome? Can Anaesth Soc
J. 1980; 27:279-282.
- Halsall PJ, Caine PA, Ellis FR. Retrospective
analysis of anaesthetics received by patients before susceptibility
to malignant hyperpyrexia was recognized. Br J Anaesth.
1979; 51: 949-954.
- Nelson TE. Porcine malignant hyperthermia:
Critical temperatures for in vivo and in vitro responses. Anesthesiology.
1990;73: 449-454.
- Wedel DJ, Gammel SA, Milde JH, et al. Delayed
onset of malignant hyperthermia induced by isoflurane and desflurane
compared with halothane in susceptible swine. Anesthesiology.
1993; 78:1138-1144.
- Levitt RC, Nouri N, Jedlicka AE, et al.
Evidence for genetic heterogeneity in malignant hyperthermia
susceptibility. Genomics. 1991; 11:543-547.
- Wedel DJ. The effect of age on the development
of MH in susceptible piglets. Anesthesiology. 1994; 81:A426.
- Wedel DJ. Malignant hyperthermia and neuromuscular
disease. Neuromuscul Disord. 1992; 2:157-164.
- Baumgarten RK, Reynolds WJ. Early detection
of malignant hyperthermia. Anesthesiology. 1985; 63:123.
- Kolb ME, Horne ML, Martz R. Dantrolene
in human malignant hyperthermia. Anesthesiology. 1982;
56:254-262.
- DeRuyter ML, Wedel DJ, Berge KH. Delayed
malignant hyperthermia requiring prolonged administration of
high dose dantrolene in the postoperative period. Anesth
Analg. 1995; 80:834-836.
- Wedel DJ, Quinlan JG, Iaizzo PA. Clinical
effects of intravenous dantrolene. Mayo Clin Proc. 1995;
70:241-246.
- Karan SM, Lojeski EW, Haynes DH, et al.
Intravenous lecithin-coated microcrystals of dantrolene are
effective in the treatment of malignant hyperthermia: An investigation
in rats, dogs and swine. Anesth Analg. 1996; 82:796-802.
- Maccani RM, Wedel DJ, Hofer RE. Norepinephrine
does not potentiate porcine malignant hyperthermia. Anesth
Analg. 1996; 82:790-795.
Denise J. Wedel, M.D., is Professor of
Anesthesiology at the Mayo Medical School, Rochester, Minnesota.
E-mail the author.
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