Malignant Hyperthermia - rishp.org

Malignant Hy

Matthew
PharmD, M
University of

July,

yperthermia

w Alcusky
MS Student
f Rhode Island
, 2013

Financial D

I have no financial oblig

Disclosure

gations to disclose.

Out

• Introduce malignant hyp
causes and implications

• Describe the underlying
• Detail the clinical presen
• Summarize the necessa

non-pharmacological tre
• Highlight necessary con

dantrolene
• Discuss recrudescence

tline

perthermia including its
s
g pathophysiology
ntation of MH
ary pharmacological and
eatment of MH
nsiderations with the use of

Malignant H

• A life threatening react
triggered by the use of

• Estimated incidence of
100,000 anesthesia ind

• Early recognition and t
reducing morbidity and

• Screening patients for
and family history, as w
testing on at risk individ
reduce MH occurrence

Rosenberg H, Davis M, James
hyperthermia. Orphanet J Rare

Hyperthermia

tion that is most often
f inhalational anesthetics
f 1 in 5,000 to 1 in
ductions
treatment is essential in
d mortality
past anesthesia history
well as conducting
duals is necessary to
e

D, Pollock N, Stowell K. Malignant
e Dis. 2007 Apr 24;2:21. Review.

Drugs Triggering Mal

• Desflurane
• Enflurane
• Halothane
• Isoflurane
• Methoxyflurane
• Sevoflurane

Hopkins PM. Malignant hyperther
Anaesth. 2011 Jul;107(1):48-56. d
May 30. Review.

lignant Hyperthermia

• Succinylcholine-
only non-inhalational
anesthetic that triggers
MH

• Nitrous Oxide- only
inhalational anesthetic
that does not cause
MH

rmia: pharmacology of triggering. Br J
doi: 10.1093/bja/aer132. Epub 2011

Pathoph

• MH partially attributed to
the ryanodine receptror
– Ryanodine receptors
Ca2+ levels, known a
calcium release (SOI
– Mutant receptors are
levels
– Volatile anesthetics fu
threshold

MacLennan DH, Chen SR. Stor
release as a triggering mechan
by in RYR and CASQ genes. J

hysiology

o a dominant mutation in
r 1 (RYR1)
s are activated by elevated
as store overload induced
ICR)
e activated by lower Ca2+

urther lower the SOICR

re overload-induced Ca2mutations +
nism for CPVT and MH episodes caused

Physiol. 2009 Jul 1;587

Pathoph

• In MH, the Ca2+ level re
lowered SOICR thresho
Ca2+ concentrations
– Increased muscle con
hypermetabolism
– ATP hydrolysis by my

• Dantrolene is a RYR1 re
SOICR

MacLennan DH, Chen SR. Sto
release as a triggering mechan
caused by in RYR and CASQ

hysiology

epeatedly exceeds the
old, increasing cytosol

ntracture,

yosin causes hyperthermia
eceptor antagonist, inhibits

ore overload-induced Ca2mutations +
nism for CPVT and MH episodes
genes. J Physiol. 2009 Jul 1;587





Testing

Caffeine Halothane
Contracture Test
• Gold standard
• Requires muscle biopsy,

invasive
• False negatives

extremely rare
• 80% specific, 20% false

positives

MHAUS Guidelines: Testing f
Susceptibility. Malignant Hype
States. Web. <MHAUS.org>.

for MH

RYR Genetic Testing

• At least 29 identified
causative mutations in
RYR

• Presence of any is
diagnostic for MH

• Absence of mutation,
must complete muscle
biopsy

for Malignant Hyperthermia
erthermia Association of the United

Non-Trigger An

• Thiopental sodium
• Pancuronium
• Droperidol
• Benzodiazepines
• Ester-type local

anesthetics
• Nitrous oxide,

ketamine

Rosenberg H, Davis M, Jame
hyperthermia. Orphanet J Ra

nesthetic Agents

• Prophylaxis with IV
dantrolene is not
necessary if these
safe agents are used
in patients with a
history of MH

es D, Pollock N, Stowell K. Malignant
are Dis. 2007 Apr 24;2:21. Review.

Malignant Hy

Clinical Pr

Early Signs

Metabolic
• Tachypnea, elevated CO2

production and increased O2
consumption
• Combination metabolic and
respiratory acidosis
• Profuse sweating and mottling of
skin
Cardiovascular
• Tachycardia
• Arrythmias
Muscle
• Masseter spasm if succinylcholine
has been given
• Generalized muscle rigidity

Glahn KP, Ellis FR, Halsall PJ, Müller
F;European Malignant Hyperthermia G
malignanthyperthermia crisis: guidelin
Hyperthermia Group.Br J Anaesth. 20

yperthermia:
resentation

Later Signs

• Rapid increase in core
temperature (1-2 degrees Celsius
every 5 min)

• Rhabdomyolysis
• Grossly elevated blood CPK and

myoglobin levels
• Darkly colored urine
• Hyperkalemia
• Severe cardiac arrythmias
• Disseminated intravascular

coagulation

r CR, Snoeck MM, Urwyler A, Wappler
Group. Recognizing and managing a
nes from the European Malignant
010 Oct;105(4):417-20.

Differentia

• Insufficient anesthesia
and/or analgesia

• Infection or septicemia
• Insufficient ventilation,

anesthetic machine
malfunction
• Anaphylactic reaction
• Pheochromocytoma
• Thyroid Crisis
• Cerebral Ischemia

Glahn KP, Ellis FR, Halsall PJ, M
Wappler F;European Malignant H
managing a malignanthypertherm
Malignant Hyperthermia Group.B

al Diagnosis

• Neuromuscular
disorders

• Elevated end tidal CO2
due to laparoscopic
surgery

• Use of drugs of abuse
• Malignant neuroleptic

syndrome

Müller CR, Snoeck MM, Urwyler A,
Hyperthermia Group. Recognizing and
mia crisis: guidelines from the European
Br J Anaesth. 2010 Oct;105(4):417-20.

Variable
Malignant H

• The inhalational
anesthetics are
capable of initiating a
MH reaction within
minutes of exposure
to hours after the
initial exposure

Hopkins PM. Malignant hyper
J Anaesth. 2011 Jul;107(1):48
2011 May 30. Review.

e Onset of
Hyperthermia

rthermia: pharmacology of triggering. Br
8-56. doi: 10.1093/bja/aer132. Epub

Post-Operative Mali

• Cases of MH can pres
period, but this is unco

• An analysis of the Nort
Registry detected 10 o
occurring post-operativ

• Of these ten cases the
was 40 minutes from c

• In all 10 cases hyperth
presenting sign

Litman RS, Flood CD, Kaplan R
malignant hyperthermia: an anal
Malignant Hyperthermia Registry

ignant Hyperthermia

sent in the postoperative
ommon
th American MH
of 528 suspected cases
vely
e longest latency time
completion of surgery
hermia was not the initial

RF, Kim YL, Tobin JR. Postoperative
lysis of cases from the North American
y. Anesthesiology. 2008 Nov;109

Treatmen
Malignant H

• Begin treatment as soo
suspected

• Immediately stop admi
agents and change to

• Inform surgeon and ter
surgery

• Hyperventilate with 100
the normal minute volu

• Administer dantrolen

Malignant Hyperthermia Associa
Therapy for Malignant Hyperther
Association of the United States

nt of Acute
Hyperthermia

on as a MH crisis is

inistration of trigger
non-trigger anesthesia
rminate/postpone

0% O2 using 2-3 times
ume
ne

ation of the United States: Emergency
rmia. Malignant Hyperthermia
s. Sherburne, NY. 2008.

Dantrolen

• Dose of 2.5 mg/kg rapi
bore IV, no less than 1

• Higher doses are often
initial dose should be r
MH reversal

• The maximum dose is
larger doses up to 30m

• No dosage adjustment
in active hepatic diseas

Malignant Hyperthermia Assoc
Therapy for Malignant Hyperth
Association of the United State

ne: Dosing

id IV push through large
1 mg/kg should be given
n necessary and the
repeated until signs of

10 mg/kg, although
mg/kg may be needed
t in renal failure, caution
se

ciation of the United States: Emergency
hermia. Malignant Hyperthermia
es. Sherburne, NY. 2008.

Dantrolene:

• 20 mg vials, requiring
dilution with at least 60
mLs of sterile
preservative free water

• Incompatible with NS,
D5W and other acidic
solutions

Revonto [Prescribing Informatio
Pharmaceuticals; 2009.

Preparation

on] Greenville, NC. DSM

Dantrolene: C

• Protect from light
• Vesicant!!!
• Storage is room

temperature
• 6 hours expiration,

prepare immediately
before use

Revonto [Prescribing Informa
Pharmaceuticals; 2009.

Considerations

• Do not prepare
infusion in glass
(precipitates), use
sterile plastic bags

• Prepare using PF
sterile water, may add
multiple vials to bag if
needed for infusion

ation] Greenville, NC. DSM

Treatmen
Malignant H

• Administer bicarbonate fo
mEq/kg if no blood gas va

• If temperature is >39 C, c
to surface, lavage open c
Cease cooling once temp

• Treat dysarrhythmias by
hyperkalemia, use standa
not use calcium channe
with dantrolene (cardiac a
ensue)

Malignant Hyperthermia Associa
Therapy for Malignant Hyperther
Association of the United States

nt of Acute
Hyperthermia

or metabolic acidosis, 1-2
alues are available
cool the patient applying ice
cavities, infuse cold NS IV.
perature is below 38 C
addressing acidosis and
ard drug therapy except do
el blockers in conjunction
arrest, hyperkalemia may

ation of the United States: Emergency
rmia. Malignant Hyperthermia
s. Sherburne, NY. 2008.

Treatmen
Malignant H

• Monitor: ETCO2, elect
CK, core temperature,
coagulation studies

• A rise in CPK and/or K
to less than 0.5 mL/kg/
diuresis at a rate > 1 m

• Bicarbonate should als
the urine and prevent m
renal failure

Malignant Hyperthermia Assoc
Therapy for Malignant Hyperth
Association of the United State

nt of Acute
Hyperthermia

trolytes, blood gases,
urine output and color,

K+ or a fall in urine output
/hr requires induction of
ml/kg/hr
so be given to alkalize
myoglobinuria induced

ciation of the United States: Emergency
hermia. Malignant Hyperthermia
es. Sherburne, NY. 2008.

Management of P
of Malignant H

• Due to risk of recurre
ICU for at least 24 ho

• Give dantrolene 1 mg
0.25 mg/kg/hr by infu
hours. Further doses

• Continue to hydrate,
diuretics to prevent m
in the renal tubules

Malignant Hyperthermia Associ
Emergency Therapy for Maligna
Hyperthermia Association of the
2008.

Post-Acute Phase
Hyperthermia

ence, observe patient in
ours
g/kg q 4-6 hours, or
usion for at least 24

may be indicated.
alkalinize and give
myoglobin precipitation

iation of the United States:
ant Hyperthermia. Malignant
e United States. Sherburne, NY.

Recrudes
Malignant Hy

• The reoccurrence of s
MH after completion o

• One study of 308 rep
of cases recrudesced

• Mean time to recrude
hours, with a range o

• 80% occurred within

Burkman JM, Posner KL, Dom
variables associated with recr
hyperthermia reactions. Anes

scence of
yperthermia

signs and symptoms of
of the initial episode
ports of MH found 20%
d
escence found to be 13
of 2.5-72 hours
16 hours

mino KB. Analysis of the clinical
rudescence after malignant
sthesiology. 2007 May;106(5):901-6

Factors Associated w

with Recrudescence

Malignant Hypertherm
United State

• The goal of MHAUS i
care and scientific un
Malignant Hyperthem
disorders

• Hotline available 24/7
• Office number for non

1-800-986-4287

• www.mhaus.org

"Contact - MHAUS." MHAUS. N

mia Association of the
es (MHAUS)

is to promote optimum
nderstanding of
mia and related

7 : 1 (800) 644-9737
n-emergencies

N.p., n.d. Web. 09 Jan. 2013.

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