Effect of obesity on propofol dosing requirements in mechanically ventilated patients in a medical intensive care unit

Abstract

Background: Propofol is a lipophilic medicationshown in pharmacokinetic studies to accumulate over time and potentially causeover sedation in obese patients when dosing is based on total body weight. Thereis a lack of intensive care unit (ICU) studies assessing the accumulation ofpropofol in obese patients that are mechanically ventilated receiving long-termsedation. The purpose of this study is to describe the difference in dosingrequirements of propofol in obese vs. non-obese patients that are mechanicallyventilated in a medical ICU (MICU). Methods: Retrospective, IRB approved,sequential chart review conducted in a MICU in a large academic teachinghospital. Patient population included intubated, mechanically ventilated(>24 hours) adults receiving a propofol infusion based on actual body weightwith a goal RASS score of 0 to −3. Data was collected through sequential chartreview from January 2013 to March 2015 using electronic records. Results: In total, 424 charts were reviewed and100 patients met inclusion criteria: 36 in the obese and 64 in the non-obesegroup. Obese patients required lower dosages of propofol to achieve initialgoal RASS score (20 vs. 30 µg/kg/min, P=0.037). In obese patients, theinfusion rate of propofol decreased progressively over time to maintain goalRASS score (days 2–5). Daily median requirements were day 1: 25 µg/kg/min ineach group (P=0.618); day 2: 20 µg/kg/min in the obese vs. 25 µg/kg/min(P=0.006) in the non-obese group; day 3: 18 vs. 25 µg/kg/min (P=0.032);day 4: 17 vs. 30 µg/kg/min (P=0.008); day 5: 15 vs. 25 µg/kg/min(P=0.025). Hospital mortality was higher in obese patients (56% vs. 31%,P=0.017). Other predetermined secondary outcomes were not statisticallysignificant. Adverse events were similar in both groups. Morbidly obesepatients with body mass index (BMI) >40 kg/m 2 had a similar trendin dosing requirement on day 4. Conclusions: Compared tonon-obese patients, obese patients required lower propofol infusion doses (perkilogram) to achieve goal RASS scores and progressively decreasing infusionrates over days 1–5 to maintain target sedation levels.