(940) Phenobarbital Dosing in Critically Ill Patients on Venovenous Extracorporeal Membrane Oxygenation

Introduction: Achieving therapeutic levels of sedatives can be challenging on extracorporeal membrane oxygenation (ECMO) due to altered pharmacokinetics. Phenobarbital (PB), a long-acting barbiturate, can be used as an adjunctive sedative or antiepileptic. The use of PB in ECMO is limited to neonate and pediatric data requiring further exploration on dosing in the adult ECMO population.

Methods: This was an IRB-approved observational study in adult, >18 years, critically ill patients who received PB and concomitant PB serum concentration on venovenous (VV) ECMO. PB levels for analysis were obtained 0.5-4 hours after PB loading dose (LD) and up to 4 hours prior to a maintenance dose (MD); this time frame was adjusted to 0.5-1 hour if on continuous venovenous hemofiltration (CVVH). Volume of distribution (Vd) was calculated using the LD divided by the associated PB level. The primary objective was to describe PB LD requirements and Vd. Secondary objectives included describing PB MD and dose changes if transition off ECMO.

Results: Sixteen patients were included with a median age 40 years (33-48) in which 62.5% were male with a body mass index (BMI) 29.8m2 (25.6-34.2) and actual body weight (ABW) 91.8 kg (71.8-98.9). The time on ECMO to PB LD was 17 days (9-30). The median LD was 1225mg (796.3-1437.8), 15 mg/kg ABW (8.8-16.2) with a post-load PB level of 20.1mg/L (11.2-22.9). 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) ABW. Patients with a BMI >30 m2 Vd was 1.06 L/kg (0.94-1.72) IBW versus 0.74 L/kg (0.7-0.86) ABW. Eight patients received MD, requiring 2.4 mg/kg/day (1.7-2.7) ABW, with a PB level of 21.8 mg/L (17.3-25.4). Two patients on CVVH required a mean dose of 11.7 mg/kg/day ABW with a mean PB level of 10.3 mg/L. The two patients transitioned off ECMO demonstrated no difference in PB levels or dosing required compared to on ECMO.

Conclusions: This is the first study to describe PB LD, Vd and MD in adult patients on VV-ECMO. In patients with BMI >30 m2 Vd using ABW was more reflective of standard adult values suggesting an ABW based LD to achieve a desired concentration. Significantly higher MD were required on CVVH and PB levels should be closely monitored. Lastly, transitioning off ECMO had no impact on PB dose or levels compared to on ECMO.