Malignant Hyperthermia

Andrew Jones, SRNA

History of MH.
 During the years of 1915 and 1925, one family
experienced three anesthetic-induced deaths featuring
rigidity and hyperthermia. Susceptibility to MH was
eventually confirmed in three descendents.

 In 1924, Ombredanne described the anesthesia-induced

postoperative hyperthermic disease in children, but did not
detect familial relationships. Referred to as Ombredanne’s
syndrome.
History of MH
 Understanding of the disease in 1960 in describing a 21 y/o
Australian man about to undergo anesthesia and surgery
for an open leg wound. He was absolutely terrified of
anesthesia as 10 of his previous relatives had died during
or after anesthesia.
 After induction of anesthesia, he was noted to be
hyperthermic while under Halothane. Technique changed
to spinal anesthetic and surgery proceeded.
 Further research into this young man and families from
Wisconsin (US) and Toronto (CA) demonstrated
recognition of increased muscle metabolism, low-threshold
contracture responses and elevated creatine kinase.
Incidence and Epidemiology
 1:15,000 pediatric anesthetics
 1:50,000 adult anesthetics
 Mortality rate of near 90% untreated.
Pathophysiology of MH
 MH, usually a subclinical myopathy,
features an acute loss of control of
intracellular calcium ions and is an inherited
disorder of skeletal muscle where a defect
in calcium regulation is expressed by
exposure to triggering anesthetic agents;
intracellular hypercalcemia results.
 The ryanodine receptor RYR1 is suspected
to be the culprit in MH.
Pathophysiology of MH.
 Decreased control of intracellular calcium results
in a release of free, unbound ionized calcium from
storage sites that normally maintain muscle
relaxation.
 Aerobic and anaerobic forms of metabolism
increase to provide ATP to drive the calcium
pumps in an attempt to maintain homeostasis.
 Rigidity occurs when unbound calcium
approaches contractile threshold.
 All the above reactions are exothermic in nature.
Clinical Events During MH
 Unexplained and sudden increase in
ETCO2. This is the most sensitive indicator
of MH in the OR setting.
 Tachycardia or tachypnea.
 Temperature elevation (late sign).
 Hypertension
 Acidosis and cardiac dysrhythmias.
 Hypoxemia
Clinical Events During MH..
 Hyperkalemia
 Skeletal muscle rigidity – the most specific sign
 Myoglobinurea

 Masseter Muscle Rigidity (MMR) may be encountered.

Specific Organ and Tissue
Abnormalities in MH
 Loss of control of muscle results in a 3X increase in
aerobic oxygen consumption and a 15-20X increase in
blood lactate levels.
 The heart is affected primarily by the tremendous,
potentially ischemic demands placed on it by exaggerated
whole-body metabolism. Tachcardia and arrhythmias are
followed by hypotension, decreased CO, and eventual
cardiac arrest.
 The central nervous system is affected and results in coma,
areflexia, and fixed, dilated pupils. Severe fever, up to
42.5C may result in a flat EEG and coma.
Specific Organ and Tissue
Abnormalities in MH.
 Circulating levels of epinephrine and norepinephrine
increase markedly (from less than 1 ng to 30ng/mL).

 DIC is caused by the release of tissue thromboplastin

during fever, acidosis, hypoxia, hypoperfusion, and gross
alterations in membrane permeability.

 Renal function during active MH is altered indirectly;

oliguria and anuria result from shock, ischemia, cardiac
failure, myoglobinuria and myoglobinemia.
Laboratory Findings Consistent
with MH.
 ABGs demonstrate a PCO2 > 60 mm Hg,
base excess greater than –8 mEq/L, and a
pH < 7.25.
 Potassium ion > 6 mEq/L.
 CK > 10,000
 Serum myoglobin > 170 mcg/L
 Urine myoblobin > 60 mcg/L
MH Differential Diagnosis
 Hyperthyroidism
 Sepsis
 Pheochromocytoma
 Metastatic Carcinoid
 Cocaine Intoxication similar to NMS
 Heat Stroke
 Malignant Neuroleptic Syndrome
 Serotonin Syndrome
Considering the options..

 Should I call Dr.

Adkins about this?
MH Treatment
 1. Call for help. Management is involved and
difficult for one person.
 Discontinue all anesthetic agents and
hyperventilate with 100% O2. With increased
aerobic metabolism, normal ventilation must
increase. Carbon dioxide production is also
increased because of neutralization of fixed acid
by bicarbonate; hyperventilation removes this
additional CO2.
 Finish or abort procedure.
MH Treatment..
 Administer Dantrolene (2.5 mg/kg bolus). May repeat
2mg/kg bolus q 5 minutes up to a total of 10mg/kg. Higher
doses may be required. Reported doses have been as high
as 29 mg/kg.
 Administer bicarbonate (2-4 mEq/kg). Continued efflux of
lactate from skeletal muscle may result in recurrent
acidosis because lactate, being ionized, slowly crosses the
cell membrane to extracellular fluid.
 Cool patient with iced fluids, surface cooling, cooling of
body cavities with sterile iced fluids, and a cooling blanket.
Halt cooling at 38-39 degrees C to prevent inadvertent
hypothermia.
MH Treatment..
 Change to a clean circuit not exposed to volatile agents.
 Monitor and treat acidosis. Follow serial ABGs.
 Promote and maintain 2 ml/kg/hour urine output with fluid
management, furosemide (0.5-1mg/kg), mannitol (300
mg/kg).
 Treat hyperkalemia with hyperventilation, bicarbonate, and
IV insuline and glucose (10 units regular insulin in 50 ml
50% glucose).
 Treat dysrhythmias with procainamide and calcium
chloride.
 Monitor creatinine kinase, myoglobin, and coagulation for
24-48 hours.
Dantrolene
 Drug of choice for preventing and reversing the
symptoms of MH.
 Dantrolene sodium relaxes but does not totally
paralyze skeletal muscle.
 Dantrolene is effective in an MH crisis
demonstrated by its ability to reduce Ca release
from the SR without altering Ca reuptake.
 Response to dantrolene takes 6-20 minutes.
 ETCO2 begins to decrease in about 6 minutes and
ABGs demonstrate significant restoration within
20 minutes.
Keypoints in History
 A suspicion that testing is needed is based
on the patient’s history, positive family
history, or use of an anesthetic remarkable
for clinical diagnosis of MH.
 Key features in the patient’s history
includes strabismus, myalgias on exercise, a
tendency to fever, myoglobinuria, muscle
disease, and an intolerance of caffeine.
Diagnostic Testing for MH
 The most accurate and accepted test for MH
susceptibility is the caffeine halothane contracture
test (CHCT).
 Sampling involves taking a biopsy of skeletal
muscle from the patient’s thigh and measuring its
contractile response to a 1-3% solution of
halothane and caffeine.
 Normal muscle contracts in exposure to both
agents, but is exaggerated in MH afflicted patients.
 The test is 85% specific and 100% sensitive.
Post-Op Care
 Patients experiencing an acute MH crisis
must be observed in the ICU for 24 hours
post-crisis.
 Recrudescence may occur 10-25%.
 Dantrolene therapy should be continued for
a minimum of 24 hours after the crisis.