17. Malignant hyperpyrexia Flashcards
Intro
It is safe to say that the majority of us are unlikely to ever experience a case of malignant hyperpyrexia (MH) during
our careers. However, malignant hyperpyrexia remains a life-threatening anaesthetic emergency with a mortality rate
of approximately 10%.
Describe the pathophysiology of MH.
> Malignant hyperpyrexia
or malignant hyperthermia)
is an autosomal dominant disorder
of skeletal muscle.
Its genetics are complex,
with over 15 causative mutations;
chromosome 19 is most commonly involved.
The incidence of genetic susceptibility is now thought to be between 1:5000 and 1:10 000.
> The various gene mutations affect the calcium release channels in the sarcoplasmic reticulum (SR).
The ryanodine receptor
(a calcium release channel)
fails and
intracellular calcium levels
increase up to 500-fold,
leading to sustained muscle contraction.
> MH is an anaesthetic-related disorder.
All inhalational agents and
depolarising muscle relaxants
can trigger the abnormal handling of
calcium within skeletal muscles.
How would you recognise MH?
The successful management of
MH begins with its
prompt recognition.
MH presents in two main ways,
either with excessive muscle rigidity
or with signs of hypermetabolism.
> Excessive muscle rigidity:
This often presents at induction as
masseter spasm following suxamethonium,
although generalised muscle rigidity may also occur.
With ongoing muscle rigidity
rhabdomyolysis occurs,
serum potassium (K+) increases (potentially causing arrhythmias),
creatinine kinase (CK) increases and acute renal failure can ensue.
> Hypermetabolism:
This occurs due to the increased AT P demand
required to fuel the abnormal contractions and membrane calcium pumps.
The earliest signs include:
- Unexplained tachycardia
- Tachypnoea (in a spontaneously breathing patient)
- Rising end-tidal CO2 (ETCO2)
- Falling arterial O2 tensions (PaO2).
With time,
the patient’s temperature rises,
sometimes by as much as 1 °C every 10 minutes.
As more oxygen is consumed,
hypoxaemia and cyanosis occur,
giving rise to a metabolic acidosis.
As CO2 levels continue to rise, a respiratory acidosis develops.
Describe your management of MH.
1
State that this is an anaesthetic emergency.
2
Call for senior help urgently and
inform the theatre team that you have
an emergency.
Also, call for help from any
free operating department
practitioners (ODPs).
> Disconnect patient from the
anaesthetic machine immediately and begin
hand hyperventilation
with 100% oxygen (to reduce PaCO2).
Use O2 drawn from an alternative source to the anaesthetic machine so that it is
free of inhalational agents.
With a new circuit,
use high flows to wash out
the inhalational agents and CO2.
> Maintain anaesthesia using intravenous agents (e.g. propofol).
> Ask an ODP to bring and prepare the ‘vapour-free’ anaesthetic machine for use (every department should have one and you must know where it is kept). Ventilate with this when ready.
> Send assistants to prepare
dantrolene sodium urgently. Each vial contains
20 mg dantrolene and 3 g mannitol and this crystalline mixture must be mixed with 60 mL water.
When it is ready, give 1 mg/kg IV.
Repeat dose every 5–10 min until the tachycardia, hypercapnia and temperature start to subside.
On average 3 mg/kg is needed
but up to 10 mg/kg may be required.
Doses may need to be repeated in the
subsequent 48 hours if the reaction recurs,
although this is rare.
Dantrolene works within skeletal
muscles by preventing the release of
calcium from the sarcoplasmic reticulum.
> Ask the surgeons to conclude surgery as fast as possible.
> Instigate active cooling measures. The surgeons are well placed to do this. Use cold intravenous fluids, cold body cavity lavages, ice packs to groin and axillae, and cooling blankets.
> Appoint someone to record observations,
drug doses, times, etc.
> Gain sufficient intravenous access,
site an arterial cannula, temperature
probe and urinary catheter.
> Manage hyperkalaemia and acidosis expectantly,
guided by regular arterial blood gas analysis and electrolyte measurements.
Use insulin/ dextrose and
bicarbonate infusions as appropriate.
> Send regular clotting profiles to check for disseminated intravascular coagulopathy (DIC)
and treat appropriately (e.g. with fresh frozen plasma).
> Manage rhabdomyolysis expectantly guided by renal function, CK levels and urinary myoglobin concentrations.
Maintain urine output at 2 mL/kg/h with fluid and diuretics to limit renal tubular damage.
> Finally, when stable, transfer patient to ITU.
Help Oxygen Stop inhalational agents/Stop surgery Propofol infusion Intravenous dantrolene Temperature regulation Address metabolic derangement Liaise with ITU
Describe your subsequent
management.
> Counsel the patient and their relatives about events and the implications of a potential diagnosis of MH.
> Document events in clinical notes and inform the GP.
> Suggest a MedicAlert bracelet.
> Patients must be referred to St James’s University Hospital MH investigation unit in Leeds, where a muscle biopsy will be taken for ‘in vitro muscle contracture testing’ (muscle tissue is exposed to caffeine and halothane, which reduce the threshold for muscle contraction).
This is the gold standard diagnostic test for MH.
