Safety of Target-Controlled Infusion in Patients with Obesity: A Narrative Review

Background/Objectives: Obesity alters propofol pharmacokinetics, creating bidirectional safety concerns during Target-Controlled Infusion (TCI). The 5th National Audit Project reported that patients with obesity were over-represented among cases of accidental awareness, and that awareness was more frequent when neuromuscular blockade was used. Methods: We examined the literature on the mechanisms and clinical evidence underlying relative overdosing, underdosing, awareness, and postoperative respiratory risk in patients with obesity receiving propofol anesthesia. Results: Total body-weight dosing may produce an excessive initial concentration, because the central compartment expands less than body weight, contributing to hemodynamic instability at induction. Conversely, inappropriate dose reduction based on lean or ideal body weight may result in inadequate anesthetic depth. Risk reduction requires the best-validated pharmacokinetic model or weight-adjustment method available, stepwise titration of the target concentration, processed electroencephalographic monitoring when total intravenous anesthesia is combined with neuromuscular blockade, quantitative neuromuscular monitoring, delivery-system checks, and vigilant postoperative respiratory monitoring. Closed-loop delivery may improve control of anesthetic depth, but a reduction in serious adverse events has not been demonstrated. Conclusions: Evidence remains limited at the upper extremes of body mass index; model predictions and fixed weight scalars should be interpreted cautiously, and dosing should be individualized using measured pharmacodynamic endpoints.