FRCA Notes

Propofol Infusion Syndrome

Resources

  • Prolonged and/or high-dose propofol infusion can cause propofol infusion syndrome (PRIS)

Patient factors Propofol factors Pathology factors
Paediatric patient Higher dose (>4mg/kg/hr) Co-administration of catecholamine vasopressors and/or steroids
Inborn error of fatty acid oxidation
e.g. MCAD deficiency		 Longer duration (>48 - 72hrs) Severe head injury ± TBI
Sepsis
Low carbohydrate supply leading to increased lipolysis
e.g. burns, trauma
Pancreatitis


  • It's been suggested a switch from carbohydrate to fat metabolism is responsible for triggering PRIS
  • This is because many of the clinical features are similar to those of mitochondrial myopathies in which there is deranged lipid metabolism

  • Possibly occurs in patients with a genetic susceptibility
  • Paediatric patients are at higher risk according to this model as:
    • They have lower carbohydrate stores than adults
    • They require relatively greater doses of propofol to maintain sedation

  • The mechanism may be inhibition of coenzyme Q (yes, the stuff in face creams) on mitochondrial cytochrome C by propofol itself
    • There is a failure of the electron transport chain and therefore ATP production
    • This leads to anaerobic metabolism and lactate production

  • There is also a failure of mitochondrial free fatty acid metabolism
    • Conversion of FFA to acetyl-CoA is impaired, impairing ATP production via lipolysis
    • The unused FFA enter the plasma, contributing to acidosis

Cardiac

  • ECG changes; sudden onset RBBB + ST-elevation in V1-3
  • Followed by refractory bradycardia ± asystole from depressed myocardial function

  • Other cardiac arrythmias e.g. SVT
  • Progressive myocardial collapse and heart failure

Electrolytes & acid-base

  • Metabolic acidosis (pH <7.35)
    • BE typically -10mmol/L
    • Hyperlactataemia >2mmol/L
    • HAGMA
  • Hyperkalaemia >5.5mmol/L

Renal

  • Elevated CK from myocyte necrosis
  • Myoglobinuria
  • Rhabdomyolysis
  • AKI with elevated serum creatinine

Gastrointestinal

  • Fatty or enlarged liver
  • Hypertriglyceridemia >1.9mmol/L
  • Lipaemic plasma due to hypertriglyceridemia

Other

  • Fatty infiltration of other major organs
  • Raised plasma levels of:
    • Malonyl-carnitine
    • C5-acyl-carnitine

  • Management is supportive
  1. Airway protection as standard (presumably already I&V if you've been lashing them with propofol)
  2. Consider V-A ECMO for combined respiratory/cardiovascular support
  3. Support cardiovascular system with:
    • Inotropic/vasopressor support
    • Cardiac pacing for refractory bradyarrhythmia
  4. Cease propofol infusion and maintain sedation via an alternative means
  5. Haemodialysis to resolve AKI/rhabdomyolysis
    • Maintain ionised calcium >1mmol/L
    • Consider plasma exchange
  6. Adequate carbohydrate administration to suppress lipolysis
    • Involves avoiding further lipid loads i.e. no TPN

Prognosis

  • Mortality as high as 18%