department of o utcomes r esearch. malignant hyperthermia daniel i. sessler, m.d. professor and...
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Department of OUTCOMES RESEARCH
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Malignant Hyperthermia
www.or.org
Daniel I. Sessler, M.D.
Professor and ChairDepartment of OUTCOMES RESEARCH
The Cleveland Clinic
No conflicts related to this presentation
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History
Described in humans by Denborough, 1961
Porcine model recognized by Nelson in 1966•“Porcine stress syndrome” reported in 1953
Caffeine/halothane contracture test•Developed by Kalow and Britt in 1970
Prevention and treatment by dantrolene•Recognized by Harrison in 1975
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Ryanodine Receptor Pathology
C a+2
C a+2
C a+ 2
C a+ 2
S a r c o p l a s m i c R e t i c u l u m
S a r c o l e m a
V o l t a g e - g a t e dD i h y d r o p y r i d i n e
C h a n n e l
C a l c i u m - g a t e dR y a n o d i n eR e c e p t o r
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Epidemiology
Incidence•≈1 in 100,000 adults•Apparently more common in children•More common in men•Rare at extremes of age
Susceptibility•Mutation of the ryanodine receptor (RYR1) on chromosome 19•Autosomal dominant: variable penetrance & expressivity•Susceptible patients often fail to trigger
Associated with minor myopathies•Central core disease•Duchenne’s, King-Denborough, myotonia congenita
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Triggers in Humans
Succinylcholine
Volatile anesthetics•Halothane > isoflurane or enflurane•Desflurane and sevoflurane
Stress?•Alpha (but not beta) agonists trigger swine•Causes rare crises in patients not exposed to triggers?
Psychotropics?•Neuroleptic malignant syndrome, but not MH
° C
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Clinical Presentation of Crisis
50% had ≥2 previous uneventful anesthetics•<10% have family history of MH•Often occurs an hour or more into anesthesia
Most important signs•Tachycardia (all)•Hypercarbia (all)•Rapid temperature increase / hyperthermia (≈70%)•Generalized muscular rigidity (≈40%)•Lactic acidosis (≈25%)
Larach, et al. A&A, in press
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Respiratory Acidosis in Swine
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Expected Consequences
Pulmonary•Tachypnea (from increased PCO2 and VO2)•Arterial oxygenation remains normal
Myocardium normal•Norepinephrine increases 20-fold•Hypertension, tachycardia, ventricular arrhythmias
Renal: oliguria from myoglobinuria
Hepatic: hyperkalemia from glycogen use
Disseminated intravascular coagulation
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Treatment
1) Discontinue triggering drugs•≈Rare mortality if anesthesia stopped within 10 min•≈100% mortality after 2 hours rigid crisis
2) Hyperventilate with 100% oxygen
3) Dantrolene 2.5 mg/kg iv•Repeat every 30 min until symptoms resolve (≤ 10 mg/kg)•Continue 1 mg/kg iv every 6 h for 24 h (20% recrudescence)•Mortality was 60% before dantrolene•Mortality rare with rapid dantrolene treatment
Do not change anesthesia machine, soda lime
For Help: call 800-MH-HYPER
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Dantrolene
A diphenylhydantoin•Half-life 4-8 hours•Metabolized to 5-hydroxydantrolene which also is active•Must be dissolved in sterile water•Takes 1.5 minutes to disolve
Mechanism of action•Decreases calcium-induced calcium release from SR
Primary antiarrhythmic
Toxicity•Occasional profound muscle weakness•Synergistic toxicity with diltiazem
Rx
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Active Cooling Generally a Low Priority
3 2
3 3
3 4
3 5
3 6
3 7
C o r e
T e m p
( ° C )
0 1 0 2 0 3 0 4 0
E l a p s e d T i m e ( m i n )
W a t e r I m m e r s i o n
F o r c e d - A i r
C i r c u l a t i n g - W a t e r
B l a d d e r L a v a g e
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Caffeine/Halothane Test
Available in ≈8 North American centers
Requires ≈4 g fresh muscle•Femoral and lateral femoral cutaneous nerve block•Children >2 yrs, unless other myopathies suspected
North American protocol•> ≈0.5 g contracture after 3% halothane•≥ 0.2 g contracture with 2 mM caffeine•≥ 1 g contracture with 1 mM caffeine and 1% halothane
Only widely-accepted test•Sensitive, not specific
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Monitoring During Crisis
Arterial blood gases•Ventilate to reduce respiratory acidosis (i.e., 15 L/min)•Bicarbonate if respiratory acidosis controlled
Urine for myoglobin•Give fluids and diuretics to maintain renal function
Serum potassium•Initially high, then low•Treatment usually not required
Plasma [CK] correlates with severity of crisis•Sample every 6 h for 24 h
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Safe Elective Anesthesia
Premedication to decrease stress
Any regional technique•All local anesthetics are safe
Balanced general anesthesia•Propofol•Opioids•Nitrous oxide•Non-depolarizing muscle relaxants•Barbiturates•Benzodiazepines, hypnotics•Ketamine, etomidate
Allow mild hypothermia
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Preparation of Anesth Machine
Washout (min)
[Halothane](PPM)
0 1 10 100 1,0000
1
10
100
1,000
10,000
100,000
Everything intactNew absorber
New absorber, circle, hose
New absorber, circle,hose, bellows
1.0
0.01
0.1
%
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Masseter Muscle Rigidity
Teeth clenched: mouth cannot be opened
“Stiffness” ≠ spasm•≈1% of children given halothane/succinylcholine•2.8% during strabismus repair with halothane/sux•Rare in children not given succinylcholine•Rare in adults (even with succinylcholine)
Etiology unknown•Extreme fasiculation?•50% of patients with spasm susceptible to MH
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Management of Masseter Spasm
Don't give more succinylcholine!•Ventilate using mask
Discontinue triggering drugs
Monitoring•Arterial blood gas, end-tidal CO2
•Core temperature•Urine for myoglobin•CK: immediately and next morning
CK > 20,000 = MH or myopathy
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Conundrum
Cancel case?•Rosenberg: cancel•Gronert: OK to proceed if labs normal•Littleford: OK to proceed with triggering drugs. Not!
Keep patient in hospital?•Usually, but not absolutely required•Monitor for several hours in PACU
Refer for Biopsy?•Yes•Explain risks/benefits of biopsy
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Neuroleptic Malignant Syndrome
Symptoms similar to malignant hyperthermia•Gradual onset, sub-acute course•Central etiology, whereas MH is of peripheral origin
Triggered by•Phenothiazines•Tricyclic antidepressants•Monoamine oxidase inhibitors
May have positive caffeine/halothane tests
Bromocriptine is primary treatment•Dantrolene may also be helpful
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Summary
Triggers•Volatile anesthetics•Succinylcholine
Presentation•Tachycardia (all)•Respiratory acidosis (all)•Rapid increase in Temperature or hyperthermia (≈70%)•Generalized muscular rigidity (40%)•Lactic acidosis (25%)
Treatment•1) Discontinue triggering drugs•2) Hyperventilate•3) Dantrolene 2.5 mg/kg iv PRN
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Department of OUTCOMES RESEARCH
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Dantrolene Prophylaxis
IV dantrolene unavailable before 1979•No effective treatment during crisis
Probably no longer necessary•Crises rare during non-triggering anesthesia•Crises easily treated with iv dantrolene•Dantrolene decreases muscle strength
Administration routes•IV: 1-2.5 mg/kg 30 min before anesthesia•PO: 1.25 mg/kg every 6 h for 24 h