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Lactic acidosis: ? An early sign of Propofol Infusion Syndrome in TIVA

 K.J.Turner

Department of anaesthesia, Bradford Royal Infirmary, Bradford U.K.

Introduction

Propofol infusion syndrome is a rare but often fatal syndrome characterized by  brady-arrhythmias, cardiac failure, renal failure, liver failure, rhabdomyolisis and lactic acidosis.  The syndrome was first described in 1992 in children that had been exposed to propofol infusions greater  than 4mg/kg/hr for greater  than 48 hours. Over the last 24 years it has been described in adults (14) and has been associated with a further 20 child deaths.  It is interesting to note that not all of the cases have been associated with prolonged exposure to propofol but all have been exposed to levels of propofol higher than the recommended dose of 4 mg/kg/hr. This concentration is lower than that used in TIVA, which leads to questions about the safety of propofol in this type of anaesthetic.

Methods

Literature review, using Embase, Medline and Google advance search engine, with cross referencing. Search terms included: propofol infusion syndrome, lactic acidosis, TIVA and propofol related deaths.

Results

Propofol is a popular anaesthetic agent used world wide for TIVA It has an enviable safety record when compared to other anaesthetic agents, but of the known side effects Propofol Infusion Syndrome is the most lethal. ( mortality over 85%  once established.)  It appears from the literature that this life threatening condition can occur in TIVA patients but can be averted by awareness of the syndrome and regular lactate level measurements, as this appears to be an early marker of the problem.

To date there have been ten cases reported of Propofol infusion Syndrome associated with TIVA, five in adults and five in children all of them associated with an increase in lactate levels.  All of them survived but required a stay in high dependency due to multi organ impairment.  Propofol doses in anaesthesia vary from 5 to 44.2 mg/kg/hr in different surveys well above the levels required to produce the symptoms.  The shortest time for the lactate to rise in these patients was only 40 minutes, indicating that this syndrome is quite likely to occur in patients undergoing TIVA.

Discussion

The incidence of the syndrome is probably much higher than reported due to lack of awareness and under-reporting. The aetiology of the syndrome is now thought to be associated with propofol inhibiting the metabolism of free fatty acids within mitochondria, producing an energy production/requirement mismatch.  This could lead to the lactic acidosis and subsequent organ failures seen.  This coupled with the fact that fatty acids are pro-arrhythromgenic and the fact that propofol is interacts with calcium and beta receptors within the myocardium may account for the arrhythmogenic changes. It is important to note that the syndrome occurs in TIVA propofol patients and special attention should be given to children, in whom the overall reported incidence is higher.