Propofol infusion syndrome (PRIS)

Link: 200.full.pdf

First defined in Paediatric ICU patients in 1990s, later in adults

Mismatch between energy supply and demand, due to inhibition of mitochondrial oxidative phosphorylation/free fatty acid utilisation

• Propofol increases malonyl co-A, which inhibits enzyme that transports long chain fatty acids into mitochondria
• Also electron transport chain uncoupled from beta-oxidation, so unable to use short or medium chain fatty acids either
• Fatty acids needed under stress conditions to fuel cardiac and skeletal myocytes, so these cells are compromised.

Also direct cardiac depression (beta receptor antagonism and calcium channel antagonism

Risk factors:

Innate:

• Abnormal fatty acid metabolic pathways
• High endogenous catecholamines/glucocorticoids

Acquired:

• Head injury
• Sepsis
• Exogenous catecholamines/glucocorticoids
• Intake ratio low carbohydrate:high lipid

Children at risk as low glycogen stores

Head injuries and SIRS may increase propofol clearance (hyperdynamic) so increasing infusion rates

Detection

Daily CK and triglycerides if >48hr propofol

Lactate monitoring

Prevention

Avoid propofol >4mg/kg/hr

Carbohydrate feeds / glucose infusion to reduce lipolysis

Minimise lipids administered eg Parenteral nutrition

Attention to risk factors - surveillance

Clinical features:

• Metabolic acidosis
• Cardiac dysfunction
• Rhabdomyolysis (cardiac and skeletal)
• Renal failure
• Hypertriglyceridaemia
• Lipaemia
• Hepatomegaly
• Hyperkalaemia

Acidosis aetiology: lactate and renal impairment

ECG changes:

• Coved ST elevation V1-3 (Brugada-like)
• AF
• VT/SVT
• BBB
• Bradycardia - asystole

• Accumulation of fatty acids is arrhythmogenic, so helpful to suppress lipolysis by sufficient carbohydrate/glucose intake
• Cardiac failure often refractory to inotropes

Sympathetic activation - increased cortisol and growth hormone - impaired mitochondrial fatty acid oxidation - LIPAEMIA and HYPERTRIGLYCERIDAEMIA

Direct muscle necrosis - rhabdomyolysis, myoglobinuria - RENAL FAILURE

Management

Stop propofol

Cardiovascular support (inotropes, pacing)

Renal replacement therapy

ECMO