15.8 PRIS Flashcards
a) What is Propofol-Related Infusion Syndrome (PRIS) and what are its clinical effects? (7 marks)
What is PRIS? >> Life-threatening syndrome associated with propofol use, usually at high doses for prolonged duration, in susceptible individuals.
> > Propofol uncouples intracellular
oxidative phosphorylation and inhibits
electron flow through electron transport chain.
>> Therefore, free fatty acids (which are an essential fuel for cardiac and skeletal myocytes) cannot be used for metabolism and reach elevated levels in the blood, risking arrhythmia and cardiac dysfunction.
> > Cardiac and skeletal myocytes
deprived of nutrition start to necrose.
Clinical effects PRIS?
>> Cardiac dysfunction and arrhythmias: coved ST elevation in V1–V3 is characteristic, atrial or ventricular fibrillation, supraventricular tachycardia, bundle branch blocks, bradycardia, asystole.
> > Rhabdomyolysis.
> > Acute kidney injury.
> > Lactic acidosis.
> > Hypertryglyceridaemia.
> > Hepatomegaly.
> > Hyperkalaemia.
> > Lipaemia.
c) What specific laboratory findings might be expected in a case of PRIS? (3 marks)
> > Raised triglycerides.
> > Raised creatinine kinase (CK).
> > Raised lactate with accompanying acidosis.
> > Evidence of acute kidney injury:
elevated potassium, urea, creatinine.
d) How may PRIS be prevented (3 marks)
Prevention:
> > Aim to keep infusion rates less than 4 mg/kg/h.
> > If infusion rates are high,
limit duration to less than 48 hours.
> > Use alternative drugs for sedation.
> > Ensure adequate carbohydrate supply
(glucose infusion, ensuring parenteral nutrition offers adequate carbohydrate:lipid balance).
> > Monitor markers of onset of syndrome:
CK, lactate, triglycerides.
How may PRIS be managed? (2 marks)
Management:
> > Retain high index of suspicion for
possibility of syndrome to facilitate
timely management.
> > Stop propofol, use alternative sedation.
> > Pacing, inotropes, consideration of ECMO.
> > Renal replacement therapy
to manage lactic acidosis, acute kidney injury
and to clear propofol and its metabolites.
b) List the risk factors for PRIS. (5 marks)
> > High infusion rates
(greater than 4 mg/kg/h) for
long duration (greater than 48 hours).
> > Young age.
> > Severe head injuries.
> > Sepsis.
> > High exogenous or endogenous catecholamines.
> > High exogenous or endogenous glucocorticoids.
> > Inborn errors of fatty acid oxidation.
> > High ratio of lipid to carbohydrate intake.
Explanation of the RF
They have asked for a list, which makes life easier, but here is a bit of an explanation of why certain situations increase the risk as understanding the underlying reasons may help cement the list into your brain better:
> > Lipid overload from propofol or
parenteral nutrition exacerbates
accumulation of free fatty acids,
which are proarrythmogenic.
Adequate carbohydrate intake is
required to suppress endogenous lipolysis in ill
patients to reduce further increases in free fatty acid levels.
>> Propofol antagonises β receptor and calcium channel binding, thus further depressing cardiac function whilst also reducing the effectiveness of inotropes to improve the situation.
> > PRIS was first reported in
children but is also seen in adults.
Children may be more susceptible due to low glycogen stores causing increased
endogenous lipolysis
> > Hyperdynamic circulation of sepsis or raised catecholamine levels of
intracerebral lesions result in more rapid plasma clearance, insufficient
sedation and, therefore, increased dose.
