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Propofol was launched in the UK in 1986 and granted FDA approval in 1989. Since then it widely became used both as an agent for induction of anaesthesia and as an infusion for TIVA and ICU sedation.

It has many, perhaps relatively unappreciated, features that make it an interesting drug with diverse benefits (1); it has pharmacokinetic properties that render it suitable for continuous infusion, and even in renal and hepatic compromise there is no accumulation; its immediate metabolites have no sedative activity and it appears to have some extra-hepatic elimination, yet to be elucidated. Even after days of ICU sedation, patients wake quickly after cessation. It acts agonistically at GABA receptors and antagonistically at NMDA receptors, ideal for control of status epilepticus. It bronchodilates, is anti-inflammatory (decreasing production of cytokines and lipid peroxidation) and lowers CMRO₂ & intracranial pressure while maintaining cerebral perfusion pressure and CO₂ autoregulation. In sepsis, it inhibits inducible NO production and thus may reduce hypotensive vasodilatation. In short, it should have been an ideal agent for TIVA and the ICU.

However, in 1992, reports of adverse outcomes associated with its use in children appeared (2) and, although this was rebuffed robustly in the USA (3), this was soon followed by an account of 10 further deaths and 3 other survivors that characterised the ‘Propofol infusion syndrome’ (PRIS); disturbance in cardiac rhythm and function, lipaemia, fatty infiltration of the liver, metabolic acidosis and skeletal muscle breakdown (4). Recommendations were made on duration of infusion and dose rates. This syndrome was thought to be restricted to children until the first adult case appeared in 2000 (5) and then a series of 7 deaths in neurosurgical ICU (6). These too were followed by dose/duration limitation recommendations. However, in a good, comprehensive and recent review of this subject (7), these have been challenged with partial emergence of PRIS at one hour in a child and 4.5 hrs in an adult. Complete PRIS has been noted at 5 hours in a child and 36 hrs in an adult. The pathophysiology of this syndrome has been explored further. The ECG resembles Brugada syndrome (8) and the metabolic findings indicate fundamental blocks in mitochondrial respiratory chain functions (9).

Propofol, despite its attributes, brings a rare but significant threat of serious morbidity to the intensive care setting and, quite possibly, this may extend to prolonged TIVA as well. 

1)      Marik PE. Propofol: Therapeutic indications and side effects. Curr Pharm Des 2004; 10: 3639-3649

2)      Parke TJ, Stevens JE, Rice ASC, et al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. Br Med J 1992; 305: 613-616

3)      Reed MD, Blumer JL. Propofol bashing: the time to stop is now! Crit Care Med 1996; 24: 175-177

4)      Bray RJ. Propofol infusion syndrome in children. Paed Anaesth 1998; 8: 491-499

5)      Perrier ND, Baerga-Varela Y, Murray MJ. Death related to propofol use in an adult patient. Crit Care Med 2000; 28: 3071-3074.

6)      Cremer OL, Moons KGM, Bouman EAC, et al. Long-term propofol infusion and cardiac failure in adult head injured patients. Lancet 2001; 357: 117-118.

7)      Fudickar A, Bein B, Tonner P. Propofol infusion syndrome in anaesthesia and intensive care medicine. Curr Opin Anaesthesiol 2006; 19: 404-410.

8)      Vermooy K, Delhaas T, Cremer OL, et al. Electrographic changes predicting sudden death in propofol-related infusion syndrome. Heart Rhythm 2006; 3: 131-137

9)      Wolf A, Weir P, Segar P, et al. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet 2001; 357: 606-607.