Mechanisms of Action of the Detrimental Effects of Propofol on Survival
Abstract
Due to its favorable pharmacologic features, propofol is the most commonly used hypnotic agent in perioperative and intensive care settings. However, it also has adverse effects like propofol infusion syndrome and an increased risk of infection. Growing evidence suggests that propofol may worsen clinical outcomes by inhibiting the organ-protective properties of other interventions, such as volatile anesthetics or remote ischemic preconditioning. This editorial describes possible mechanisms underlying the detrimental effects of propofol, and provides an overview of the results of clinical trials evaluating the effects of propofol in various settings.
PROPOFOL, 2,6 Di-isopropylphenol, was developed in 1984 from the chemical solvent 1,3 Di-isopropylbenzene by replacing hydrogen with hydroxy groups. Its favorable pharmacokinetic properties (eg, very short onset/offset time and relatively modest hemodynamic impact) have made it the most frequently used hypnotic agent. Currently, it is used in hundreds of millions of major surgeries every year.
Organ-protective techniques, often known as “preconditioning,” have gained popularity over the last decades. These perioperative strategies induce or mimic a transient ischemia event or a transient stressful event, which helps vital organs withstand a subsequent prolonged ischemic event. The most studied preconditioning approaches are remote ischemic preconditioning and volatile preconditioning. Despite experimental studies suggesting the cardioprotective effects of volatile agents, randomized clinical trials evaluating the efficacy of volatile anesthetics reported conflicting results.
A similar pattern was observed for remote ischemic preconditioning, with recent pragmatic randomized trials having contrasting findings.
A similar pattern was observed for remote ischemic preconditioning, with recent pragmatic randomized trials having contrasting findings.
Recent evidence suggests propofol may play a crucial role in these inconsistent results by inhibiting the organ-protective properties produced by other interventions.
A recent meta-analysis of randomized trials documented a statistically significant mortality increase in patients receiving propofol versus any comparator (relative risk = 1.10; 95% CI, 1.01-1.20; number needed to harm = 235).
The evidence came mostly from perioperative studies (relative risk = 1.21; 95% CI, 1.04-1.41).
We hereby describe possible mechanisms of action that may underlie these detrimental effects of propofol.