3. Introduction
• Malignant hyperthermia(MH) manifests
manifests clinically as a hypermetabolic crises
when an MH susceptible individual – exposed
to volatile anesthetic or succinyl choline
• Incidence – estimated to be 1:100000
anesthetics administered
– Males > Females
– Children less than 19 contribute to ~ 50%
4. Pathophysiology
• MH susceptible patients have genetic skeletal muscle
receptor abnormalities allowing excessive calcium
accumulation in presence of certain anesthetic
triggering agents
• Mechanism how anesthetic triggers MH by interacting
with the receptors – Unknown
• Due to an episode of MH Clinical manifestations are
due to cellular hypermetabolism sustained muscle
contraction and breakdown( rhabdomyolysis)
anaerobic metabolism acidosis sequelae
5. • Normal Muscle Physiology:
– Depolarization spreads throughout the muscle cell via t-tubule system
Activates Dihydropyridine(DHP) receptors located in t-tubule
membrane
These receptors are coupled to ryanodine receptors which are
calcium channels embedded In the wall of Sarcoplasmic reticulum
Calcium release through DHP receptor trigger RYR1 receptors to
release calcium from SR into intracellular space
Calcium combines with troponin to cross link actin and myosin
resulting in muscle cell contraction
Reuptake of calcium by Sarcoplasmic reticulum ATPase leads
to muscle cell relaxation
6. • Malignant Hyperthermia:
– MH susceptible patients have mutations for abnormal RYR1 or DHP
receptors
unregulated passage of calcium from sarcoplasmic reticulum into
intracellular space
ACUTE MH CRISIS
Accelerated levels of aerobic metabolism sustain muscle for a time,
but produce CO2 and cellular acidosis and deplete oxygen and ATP
Early signs: Hypercarbia + Respiratory/
Metabolic acidosis
A change to anaerobic metabolism worsens acidosis with
production of lactate
7. – Once energy stores are depleted , rhabdomyolysis
occurs and results in hyperkalemia and myoglobinuria
Hyperkalemia occurs early in Muscular patients
– Overtime sustained contractions generates more heat
than the body is able to dissipate
Marked hyperthermia occurs minutes to hours
following onset of symptoms
Core body temperature may increase rise 1 C
every few minutes
Severe hyperthermia leads to increase in CO2
production and increased Oxygen consumption with
widespread organ dysfunction DIC
8.
9. Triggering Agents
• Vast majority of patients developed MH while
patient was receiving volatile anesthetic agent
with or without succinylcholine
11. • Clinical signs present perioperatively in
several possible patterns
– Intraoperatively during any phase of anesthetic
manifested by gradually worsening hypercarbia,
tachycardia, metabolic acidosis and generalised
rigidity
– Perioperatively with isolated rhabdomyolysis in
otherwise asymptomatic patients
16. Clinical Diagnosis
• During an acute event, diagnosis of MH is
presumptive, based on 1 or more clinical findings
a/w MH
• Diagnosis must be considered in all patients
receiving triggering agents as 90% have negative
family history for MH
• Treatment is initiated emergently as soon as
diagnosis of MH is considered
18. Differential Diagnosis
• Anesthesia/Surgery related:
– Insufficient anesthesia/ analgesia
– Insufficient ventilation/ fresh gas flow
– Overheating
– Increased CO2 absorption during laparoscopy
• Drug related:
– Anaphylaxis – low BP ; high PCO2; no muscle signs
– Transfusion reactions- fever; brown urine; hyperkalemia
– Drugs of abuse: Cocaine, Ecstasy,Metamphetamine- sudden cardiovascular collapse ;
tachypnea
• Alcoholic withdrawal syndrome – delirium, high HR, BP
• NMS- slow onset ; fever, rigidity, autonomic instability
• Serotonin syndrome – fever, high BP, muscle rigidity
• EPS sideeffects of antipsychotics – Rigidity
• Pheochromocytoma
• Thyroid storm
19. Management
• Approach to management of suspected MH crisis:
– Evaluate and manage hypercarbia
• Increase minute ventilation
• Eliminate obstruction of ventilation
• Seek sources of increased CO2
– Confirm other signs of MH:
• Generalised rigidity
• PVC (or other signs of hyperkalemia)
• Tachycardia
• Unstable hemodynamic stability (high or low)
• Masseter spasm
• Unexplained metabolic acidosis
20. • Initiate MH protocol:
– Optimize oxygenation and ventilation:
• Increase FiO2 to 100%
• Increase RR and TV to maximise ventilation and reduce
etCO2
• If not intubated ETT done and NDMR given
– Discontinue triggering agents
• Inform surgeon of the diagnosis
• Surgical procedure should be terminated if not
possible to be finished under intravenous anesthesia
• Charcoal filter to be placed at expiratory and inspiratory
limbs of circuit not necessary to change machine
21.
22. • Administer Dantrolene:
– Skeletal muscle relaxant –directly acting at cellular level
– Chemical strucutre – consists of Hydantoin group
– Only known antidote for MH
– Dose :2.5mg/kg- continuous repeat dose of 1mg/kg until
symptoms subside or cumulative dose of 10mg/kg reached in
large iv line
– No renal/hepatic dose adjustments
– Paediatric and Geriatric dosing – similar to adult dose
– Brand –Ryanodex (newer) supplied as 250mg vial reconstituted
with 5ml sterile water
as it is hyperconcentrated it will achieve higher
concentrations faster
23. • Older brands- Dantrium and Revonto
– Present as 20mg vial to be reconstituted with 0.9%
NS or 5%D to 60 ml
– After given iv – has to be flushed with saline
24. – Mechanism of action:
• Acts directly on skeletal muscle by interfering with release of
calcium ion from sarcoplasmic reticulum
Prevents or reduces increases in myoplasmic calcium ion
concentration that activates the acute catabolic process
associated with malignant hyperthermia
– Pharmacokinetics:
• Time to peak concentration : 1 min post iv
• Metabolism: Hepatic; metabolites – 5-hydroxydantrolene
• Half life elimination: 4-11 hours
• Excretion: Feces (50%) and Urine(25% as unchanged drug)
26. – Monitor and treat hyperkalemia:
Based on ECG changes to prevent life threatening
arrhythmias and cardiac arrest
USE OF CCBS – CONTRAINDICATED IN MH AS IT
CAN WORSEN HYPERKALEMIA AND
HYPOTENSION
– Check labs:
• Electrolytes, Blood gases, CK , serum myoglobin,
coagulation parameters and fibrin split products
27. • Initiate supportive care:
– Monitor and treat acidosis:
• Bicarbonate
– Treat cardiac arrhythmias as per ACLS protocol
– Treat hyperthermia can precipitate DIC
• >39 C should be cooled infuse cold saline intravenously, lavage
open body cavity, apply ice to surfaces till temp <38.5 C
– Insert bladder catheter to monitor urine color and volume.
• Urine dipstick test + for heme myoglobinuria
• Urine output >1ml/kg/hr
– Monitor muscle compartment for compartment syndrome
– Institute measures to prevent rhabdomyolysis induced renal
failure
• Hydration + Soda Bicarbonate + Diuretics
28. • Ongoing care:
– When surgery over, patient should be transferred to
ICU for ventilatory support and hemodynamic
monitoring for 24 hours
– Dantrolene can be stopped or interval between dosing
increased to every 8-12 hours if the following criteria
met:
• Metabolic stability for 24 hours
• Core temperature less than 38 C
• CK is decreasing
• No evidence of myoglobinura
• Muscle no longer rigid
29. • Counselling after acute MH:
– Not have anesthesia with triggering agents
– Avoid exercises in excessive heat or humidity as
they can trigger event
– Inform family members of possible MH episode
MH- genetic