MALIGNANT HYPERTHERMIA

PRESENTATION BY :
DR RAMANESH MAGESWARAN
HOSPITAL KUALA LUMPUR
MALIGNANT HYPERTHERMIA
PREVIEW:
1) Introduction
2) Why is it important?
3) History & Incidence
4) Pathophysiology
5) Clinical Presentation
6) Management – initial crisis & MH Kit
- after controlling initial reaction
- after crisis
7) Confirmation of diagnosis
8) Anaesthesia for susceptible patients
9) Conditions associated with MH
MH Introduction
MH  pharmacogenetic disorder of muscle induced by exposure to
suxamethonium and all volatile anaesthetic agents.

hypermetabolism
Characterised by muscle rigidity
muscle injury

in vitro contracture test

Confirmation of clinically suspected histological tests of muscle
DNA diagnosis
MH – Why is it important?
- potentially fatal disorder
- anaesthetic nightmare
- crucial for early diagnosis & appropriate intervention
MH – History
- 1962 : Dr J.D. Villers & Denborough
- Young man – looking anxious - surgery for fracture of leg
- History of 10 relatives died without explanation – GA
- Dr Villers proceeded using halothane, patient developed
tachycardia & tachypoea & severe hyperthermia
- Patient survived event by aggressive cooling
- Denborough noted autosomal dominant pattern  concluded
susceptibility to disorder was inherited
- Later, syndrome named MH because
of fatal nature & high body temp
 MH – Incidence

->Described in all racial groups

->Majority MH reactions children and young adult
->2:1 male preponderance of clinical reactions
->In UK approx 1:40,000 to 1:100,000 MH reactions
(? Lack info concerning GA & uninformed cases MH)
->Leeds MH Invest unit- 100-200 cases annually
->Mortality MH reaction 2-3 %(past 10 years)
MH – Pathophysiology
 MH –PATHOPHYSIOLOGY
->Triggering agent- direct effect DHPR-RyR complex to cause
release SR Calcium
->MH reaction can develop irrespective if NM blockade because
AP not required for reaction to proceed
->supraphysiological levels SR Ca release-> increase of
intracellular Calcium conc
->Increase utilization of ATP to sequestrate Calcium back to SR
produces positive feedback effect on glycolysis & oxidative
metabolism
->causes increase oxygen consumption and CO2 production
MH – Pathophysiology
MH – Clinical Presentation
- loss of skeletal muscle cell calcium homeostasis

increase in intracellular Ca2+ concentration

- onset C/F reflects cellular changes

CO2 production
- initial changes O2 consumption
sympathetic response
 MH – Clinical Presentation
- CO2 production - spont breath  RR + depth
 compensatory mech
- mechanical  CO2 rapid w constant MV
- Reaction progress  CO2 prod will > capacity to compensate
Soda lime exhausted – very warm (touch)
 MH – Clinical Presentation
- O2 consumption  O2 delivery incapable of meeting
metabolic demands
 difference insp + exp fractions
 SaO2
ABG - pCO2 , pH
- mixed respiratory & metabolic acidosis
- lactate

Sympathetic response to hypermetabolism

- heart rate
 MH – Clinical Presentation
TEMPERATURE
- Later feature of MH
- Caused by – excessive heat – excessive muscle contraction &
metabolic stimulation
- Heat production > heat losing capabilities
- Rate of rise of temp > 1o C per 10 mins
 MH – Clinical Presentation
MUSCLE RIGIDITY
- Shows 1st indication pt susceptible to MH following sux
- Masseter muscle spasm (MMS)
* increase jaw tension – intensed & prolonged
* inability to open mouth 2 mins after sux / easily demonstratable
resistance 4 mins after sux
* 25% of pt – susceptible to MH
* muscle spasm + muscle rigidity / evidence of rhabdo, ie.
likelihood of MH 75 – 90%
 MH – Clinical Presentation
RHABDOMYOLYSIS
- 1st indication  “cola” colored urine – due to myglobinuria
- Surgeon might ask to increase dose of muscle relaxant –
because of increased tension in muscles

- Rhabdo leakage K+ ===> Hyper K===> arrythymia

myoglobin in blood ===> ARF

- Necrotising muscle ===> release tissue clotting activators

DIVC
MH – Differential Diagnosis
MH – Clinical Presentation
MH Kit
MH – Clinical Presentation
MH – Clinical Presentation
MH – Clinical Presentation
MH – Clinical Presentation
 MH – Management
DANTROLENE SODIUM 20mg
- MOA: binds to RyR protein within the skeletal muscle cells to
reduce SR Ca2+ release
: depresses EC coupling in skeletal muscle
: dramatic effect in reversing MH
- Presentation : powder for solution
: 20mg dantrolene sodium, 3g mannitol (solublising
agent), mixed with 60ml of water
- Dose : 2.5mg / kg (further 1mg /kg can be given every 5 mins)
 MH – Management
DANTROLENE SODUIM (continued)
no response
not reaching site of action
Up to 10mg / kg (assuming diagnosis is correct)
possible mitochondria incapacity not
treatable

CNS – blurring of vision, headache

Side effect GI – nausea, vomiting, diarrhoea
Prolongation of NDMR
Injection site – erythema & swelling
MH – Clinical Presentation
MH – Clinical Presentation
MH – Clinical Presentation
MH – Clinical Presentation
 MH – Management
AFTER CONTROLLING THE INITIAL REACTION
- transfer ICU (24 hrs monitor after MH settled)
- CK – peaks 12 – 24 hrs after event
- regular assessment for compartment syndrome
- recurrence – dantrolene 1mg / kg
- isolated pyrexia - ? SIRS / infection

AFTER CRISIS
- Referral – MH investigation unit
- family counseling – written info to be
distributed to all blood relatives
 MH – Confirmation of Diagnosis
INVITRO CONTRACTURE TESTING
- living tissue required – pt must attend centre
- muscle biopsy from vastus muscle (under RA)
- test – measurement of tension generated in muscle in response
to exposure of halothane & caffeine
- tension in muscle from MH susceptible patient increases @
lower concentration of halothane & caffeine
 MH – DNA Testing
->DNA sample – buccal cells , WBC, muscle cells
->MH- complex disorder at DNA level
->Current knowledge , -- gene RYR1
coding the skeletal muscle ryanodine receptor implicated
in majority of families
-- However minority of families (10-20%) no defect in
RYR1 gene
-- Likelihood defect on other gene contributing is high
-- DNA analysis designed to reduce risk of false -ve
MH – Screening
Anaesthesia for susceptible pts
MANAGING PATIENT WHO IS SUSCEPTIBLE - MH
 Anaesthesia for susceptible pts
MANAGING PATIENT WHO IS SUSCEPTIBLE – MH
- MH pts should not be denied anaesthesia
- Avoid trigger drugs
- Use regional anaesthesia techniques
- Preparation of anaesthetic machine
*remove vaporiser, replace sodalime with fresh sodalime
*replace hoses & rebreathing bags with new
*flush with 10 L/min oxygen for @ least 20 mins
*use new mask & new LMA
*continue use high flows through out to avoid accum of
small quantities of volatile agent
- Preferably place MH patients first on operating list
Anaesthesia for susceptible pts
DRUGS THAT MUST BE AVOIDED IN MH PTS
 MH - Conditions Associated MHS
DISEASE CLEARLY LINKED TO MHS
(genetic linkage or overwhelming clinical evidence)
1.Central Core Disease (CCD)
2.Multiminicore Disease
3.King – Denborough Syndrome

DISEASE WITH ANAESTHESIA INDUCED MH-LIKE SYN

1.Muscular dystrophies eg, Duchenne`s Muscular Dystrophy
(Similar signs & sympt when exposed to trigger agents)
2.McArdle`s disease
3.Heat & exercise –induced rhabdomyolysis(reports of assoc)- avoid
trigger
MH- Conditions Associated MHS
DISEASE LINKED TO MHS WITHOUT EVIDENCE
(may continue trigger agents)
1.Noonan`s Syndrome
2.Osteogenesis imperfecta
3.Mitochondrialmyopathies
4.Neuroleptic Malignant Syndrome
 MH – REFLECTING BACK
Good History important
Early Diagnosis- vigilant anaesthetist
Early intervention – life saving
Use MH Kit – “ dantrolene”
IVCT-Gold Standard
DNA diagnosis complements IVCT cannot be used in isolation
MH – Reference
KEY REFERENCES:
1. Hatsall Malignant Hyperthermia – Cont Educ Anaesth Crit Care & Pain
2003volume3;5-9
2. Philip M Hopkins Malignant Hyperthermia Current Anaesth & Critical Care
2008 19;22-33
3. Philip M Hopkins Malignant Hyperthermia Anaesth Intensive Care Med
2008 ;9;244-46
4. Ronald S Litman MH associated disease. Seminars in
Anaesthesia,Perioperative medicine and Pain 2007 , 26,113-119
5. www.malignanthyperthermia.com.au
6. http://www.aagbi.org/publications/guidelines/docs/malignanthyp07.pdf
7. http://medical.mhaus.org/pubdata/podcast/1/index.xml
THANK YOU