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Detailed information of MALIGNANT HYPERTHERMIA
DEFINITION:
An acute
potentially fatal metabolic disorder characterized by
acute hypercatabolic reactions in muscles in response
to specific triggering factors.
EPIDEMIOLOGY:
- incidence:
1/12-15,000 children (greater than in adults)
- age of
onset:
- risk
factors:
- familial
- autosomal dominant, autosomal recessive, and
multigenic inheritence pattern
- chrom. #:
19q13.1
- gene:
ryanodine receptor (RYR1)
- M > F
-
associations:
- Central
Core Disease
- DMD
- King
Syndrome
- SIDS
- Evan
Syndrome
-
osteogenesis imperfecta
PATHOGENESIS:
-
triggering agent -> exaggerated release of calcium
from the SR -> sudden rise of intracellular
calcium -> hypermetabolic state characterized by:
-
increased conversion of phosphorylase b -> a
-
stimulation of glycolysis
-
hydrolysis of ATP
-
uncoupling of oxidative phosphorylation
- the
exaggerated release of calcium seems to be the
primary defect and may be related to a mutation in
the ryanodine receptor (RYR) gene (Ca-release
channel of the sarcoplamic reticulum) resulting in
an unusually high sensitivity to calcium augmented
by caffeine
NOTES:
- clinical
features of patients with succinylcholine-induced
muscle rigidity:
-
succinylcholine used for intubation
- halothane
used for induction
- age
range: 4 - 15 years (mean 10 years)
-
temperature increases not marked
-
significant arrhythmias not noted
- muscle
rigidity lasts for only 2-3 minutes
- family
history of MH generally not found
- if
perioperative CK conc. > 20,000 -> usually +
muscle biopsy
- dd:
dystrophia myotonica, myotonia contenita
CLINICAL
FEATURES:
- sinus
tachycardia
- fever (>
41 C) - variable (minutes -> usually hours)
- rigidity
- masseter jaw spasm -> generalized
- unstable
BP - with upward trend
- tachypnea
- skin
changes - sweating/flushing/mottled cyanosis
-
ventricular arrhythmias - extrasystole -> bigeminy
-> VT
2. Late
-
encephalopathy with cerebral edema
- pulmonary
edema
- renal
failure
-
consumption coagulopathy (DIC)
- skeletal
muscle edema and pain
- increased
danger of relapse for 3 days post crisis even
without exposure to triggering agents
INVESTIGATIONS:
- in
vitro contraction test
-
caffeine-halothane contracture
-
caffeine - increased resting tension with
incremental doses
-
halothane - contraction of several minutes
duration
2.
Polymerase Chain Reaction
2.
Respiratory
- rising
PECO2 - earliest observable sign
-
oxygenation - normal PaO2 but decreased PvO2
3.
Metabolic
- acidosis
- both respiratory and metabolic (lactic)
- potassium
- initally increased then prolonged decrease
- rebound
hyperkalemia 6-12 hours
-
electrolytes
- calcium
- initally increased -> prolonged decrease for
days
- PO4, Mg
- persistent increase
- glucose -
persistent increase
4. Muscle
- CPK -
persistent elevation (peak at 12-24 hours)
- myoglobin
- myoglobinemia -> -uria -> increased BUN
MANAGEMENT:
- stop
trigger - halothane, succinylcholine
-
hyperventilate - to correct respiratory acidosis
- dantrolene
- acts directly on the SR to increase contraction
activation threshold -> prevents depolarization
- initally
2.5 mg/kg IV
- if symptoms
persist after 45 min -> 7.5 mg/kg
-
continuously until crisis resolves - 2.5 mg/kg q6H
- supportive
- correct metabolic acidosis - HCO3
- treat
arrhythmias
- control
temperature - cooling
- moniter -
lytes, Ca, Mg, PO4, glucose, lactate, BUN
- muscle
enzymes: CPK, LDH, AST, aldolase
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Pediatric Database - MALIGNANT HYPERTHERMIA
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