Malignant Hyperthermia
OVERVIEW
- Malignant Hyperthermia = pharmacogenetic disease of skeletal muscle induced by exposure to certain anaesthetic agents
- incidence 1:5,000 -> 1:65,000 anaesthetics (suspected)
- mutation in the gene coding for the ryanodine receptor
- autosomal dominant
- gene on chromosome 19
- thymidine instead of cytosine
- produces a cysteine for arginine substitution at position 615 of the receptor.
PATHOPHYSIOLOGY
- excess Ca2+ release during muscle contraction -> increased musle metabolism + heat production.
- prolonged and intensified interation between actin and myosin.
- enhanced aerobic metabolism -> lactic acidosis -> accumulation of intra-mitochondrial calicum -> deconjugation of oxidative phosphorylation -> cytolysis.
TRIGGERS
- stress (in pigs)
- all volatile agents (except N2O)
- suxamethonium
-> these all either enhance Ca2+ influx or slowing its efflux
- some may have tolerated the same agents previously
- rare in barbiturate-N2O-opiate-tranquiliser-non-depolarising muscle relaxant anaesthesia
- sux potent trigger (first exposure)
- volatiles (median exposure till fulminant -> 3)
CLINICAL
- in lower North Island of NZ trigger names = Harvey, Harwere & Cook
- history of Central Core Disease
(1) increased ETCO2
(2) tachycardia
(3) tachypnoea
(4) masseter spasm (if develops this convert to a MH safe anaesthetic)
(5) muscle rigidity
(6) temp increase (late) – 1 C\15min
- intra-op & 4\24 post op
- tachyarrhythmia
- difficulty ventilation
- hypertension
- sweating
- DIC
- hyperkalaemia
- cardiac arrest
INVESTIGATIONS
- PaCO2 >60mmHg
- PvCO2 >90mmHg and increasing
- BE -5 and falling
- metabolic acidosis
- CK >50,000 IU/L
- K+ increases
- Na+ increases
- myoglobinuria
ACUTE MANAGEMENT
- call for help
- discontinue all anesthetic agents
- maintain anaesthesia with hypnotics and opioids.
- muscle relaxation with NDNMBD
- terminate surgery
- hyperventilate
- 100% O2
- cool (N/S stomach lavage)
- maintain urine output
- inotropes as needed
- HCO3 2-4mEq/kg
- Dantrolene 2.5mg/kg every 5min (total dose 10mg/kg/day – continuous infusion or treat recurrence (25%))
- cardiac arrhythmias -> beta blockers & lignocaine.
- high K+ -> glucose-insulin & frusemide
- watch for DICCK Q6hrly
PROGNOSIS
- mortality without dantrolene = 70%
- mortality with dantrolene = 5%
LONG-TERM MANAGEMENT
- referral to an MH centre
- warn patient and family of impending consequences
- if uncertain about diagnosis -> must screen
- IVCT
- subsequent gene mutations studies if positive + family screening
- if blood test negative -> must have a muscle biopsy
- medic alert and appropriate documentation
PROPHYLACTIC MANAGEMENT
- take history
- decrease anxiety with midazolam
- machine -> remove vapourisers, flush with O2 @ 10 L\min for 20min
- new circuit and airway devices
- ETCO2 monitoring
- nasal temp probe
- dantrolene available
OBSTETRIC PATIENTS
- baby = 50% chance of having MH
- planned delivery with early anaesthetic advice
- anticipate airway problems -> AFOI
- RA safe and preferred
- MH safe drugs
- sux doesn’t cross the placenta
References and Links
CCC Toxicology Series
General
Approach to acute poisoning, ECGs in Tox, Evidenced-based Tox, Toxicology literature summaries, Does anti-venom work?
Toxins / Overdose
Amphetamines, Barbituates, Benzylpiperazine, Beta Blockers, Calcium Channel Blocker, Carbamazepine, Carbon Monoxide, Ciguatera, Citrate, Clenbuterol, Cocaine, Corrosive ingestion, Cyanide, Digoxin, Ethanol, Ethylene Glycol, Iron, Isoniazid, Lithium, Local anaesthetic, Methanol, Monoamine oxidase inhibitor (MAOI), Mushrooms (non-hallucinogenic), Opioids, Organophosphate, Paracetamol, Paraquat, Plants, Polonium, Salicylate, Scombroid, Sodium channel blockers, Sodium valproate, Theophylline, Toxic alcohols, Tricyclic antidepressants (TCA)
Envenomation
Marine, Snakebite, Spider, Tick paralysis
Syndromes
Alcohol withdrawal, Anticholinergic syndrome, Cholinergic syndrome, Drug withdrawals in ICU, Hyperthermia associated toxidromes, Malignant hyperthermia (MH), Neuroleptic malignant syndrome (NMS), Opioid withdrawal, Propofol Infusion Syndrome (PrIS) Sedative toxidrome, Serotonin syndrome, Sympatholytic toxidrome, Sympathomimetic toxidrome
Decontamination
Activated Charcoal, Gastric lavage, GI Decontamination
Enhanced Elimination
Enhanced elimination, Hyperbaric therapy for CO
Antidotes
Antidote summary, Digibind, Glucagon, Flumazenil, HIET – High dose euglycaemic therapy, Intralipid, Methylene Blue, N-Acetylcysteine (NAC), Naloxone
Miscellaneous
Cocaine chest pain, Digoxin and stone heart theory, Hyperbaric oxygen, Hypoxaemia in tox, Liver failure in tox, Liver transplant for paracetamol, Methaemoglobinaemia, Urine drug screen
- Cadogan M. Michael Denborough (1929-2014). Eponymictionary
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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