Characterization of phenobarbital pharmacokinetics and dosing in adults receiving extracorporeal membrane oxygenation

Achieving adequate sedation on extracorporeal membrane oxygenation (ECMO) is challenging due to altered pharmacokinetics. Limited data exists on phenobarbital in adult ECMO patients. The aim was to characterize the volume of distribution (Vd) and dosing.

This single-center retrospective study examined adult ECMO patients who received intravenous phenobarbital and corresponding serum concentrations between January 1, 2017 and March 1, 2024. Phenobarbital levels for analysis were obtained 0.5-4 h after phenobarbital loading dose (LD) and up to 4 h prior to a maintenance dose; this time frame was adjusted to 0.5-1 h if on continuous venovenous hemofiltration (CVVH).

Sixteen venovenous ECMO patients with 18 LD and 70 phenobarbital concentrations were evaluated. The median LD was 1225 mg (796.3-1437.8); 15 mg/kg (8.8-16.2) total body weight (TBW). The median total Vd was 67.7 L (46.8-80.8), 0.94 L/kg (0.72-1.22) ideal body weight (IBW), and 0.71 L/kg (0.67-0.82) TBW. Weight-based LD and concentration demonstrated a stronger correlation for TBW (r = 0.93, p < 0.001) versus IBW (r = 0.64, p = 0.003). Comparing BMI <30 and BMI ⩾30 kg/m² patients there was a difference in total Vd (p = 0.02) and IBW-normalized Vd (p = 0.006), but no difference in TBW-normalized Vd (p = 0.31). The median maintenance dose was 2.4 mg/kg/day (1.7-2.7) TBW; CVVH patients required 11.7 mg/kg/day TBW. Phenobarbital concentration change was <3% after ECMO decannulation.

In adult ECMO patients, phenobarbital's Vd normalized to TBW, was consistent with critically ill non-ECMO patients. Obesity affected Vd, CVVH influenced maintenance dosing, but ECMO decannulation did not impact phenobarbital concentrations.