Association of preservative-free propofol use and outcome in critically ill patients Samir Haddad, MD, CES, a Hani Tamim, MPH, PhD, b Ziad A. Memish, MD, FRCPC, FACP, c and Yaseen Arabi, MD, FCCP, FCCM a,b Riyadh, Saudi Arabia Background: Propofol is widely used to provide sedation to patients in the intensive care unit (ICU). This study examined whether preservative-free propofol infusion independently influences outcome in critically ill patients. Methods: This was a nested cohort study within a randomized controlled trial. ICU patients who received preservative-free pro- pofol and those who did not were compared. The following datawere collected: demographic information, APACHE II score, ad- mission category, chronic severe illnesses, nutritional data, and blood glucose level and insulin dose. The main exposurewas the use of preservative-free propofol infusion. The main outcomes were the occurrence of ICU-acquired infections, ICU-acquired sep- sis, and ICU and hospital mortality. Results: A total of 523 patients were included (no propofol group, n 5 399; propofol group, n 5 124). After adjustment for differ- ences in baseline characteristics, preservative-free propofol use was associated with increased risk of ICU-acquired infections (adjusted odds ratio [aOR], 1.89, 95% confidence interval [CI], 1.17-3.06; P 5 .009) and ICU-acquired severe sepsis and septic shock (aOR, 1.91; 95% CI, 1.12-3.28; P 5 .02), but not with ICU or hospital mortality. Conclusion: Preservative-free propofol infusion in critically ill patients may be associated with increased risk of ICU-acquired in- fections and ICU-acquired sepsis, with no significantdifference in ICU or hospital mortality. This association might have been re- lated to the use of preservative-free preparations. Key Words: Infection; sepsis; intensive care unit; mortality. Copyright ª 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. (Am J Infect Control 2011;39:141-7.) Propofol (2, 6-diisopropylphenol) is a versatile, po- tent, short-acting intravenous sedative-hypnotic agent widely used to provide continuous sedation for intu- bated, mechanically ventilated patients in the intensive care unit (ICU). 1 Proposed benefits of propofol sedation include rapid onset of action, rapid rate of dis- tribution, dose-related hypnotic effect, rapid clearance, improved patient comfort, 2 safe pharmacologic profile, immunomodulatory activity, and anti-inflammatory properties. 3-6 Propofol use has been associated with adverse reactions and drug-related events, however. 7 Prolonged administration of propofol in ICU patients has been implicated in major complications such as fa- tal multiorgan dysfunction syndrome 8 and propofol in- fusion syndrome (PRIS). 9-11 Associated with high and prolonged propofol administration, 12-15 PRIS is characterized by severe lactic acidosis, rhabdomyoly- sis, renal failure, cardiovascular collapse, and cardiac arrest. 16 Propofol administration also has been implicated in outbreaks of bloodstream and surgical site infections, sepsis, and acute febrile episodes after surgical proce- dures. 17-24 Some epidemiologic and laboratory investi- gations have pointed to extrinsic contamination of propofol as the cause of some of these infection out- breaks. 17,19,22 Other studies have reported an ex- tremely low risk of nosocomial infection secondary to extrinsic contamination of propofol in the ICU setting. 25 The purpose of the present study was to examine whether preservative-free propofol infusion indepen- dently influences outcomes (infections and mortality) in critically ill patients. From the Intensive Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia a ; Department of Medical Education, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia b ; and Preventive Medicine Directorate, Ministry of Health, Riyadh, Saudi Arabia. c Address correspondence to Yaseen Arabi, MD, FCCP, FCCM, Intensive Care Department, MC 1425, PO Box 22490, Riyadh 11426, KSA. E-mail: yaseenarabi@yahoo.com or arabi@ngha.med.sa. This work was presented at the American Society of Anesthesiology’s 2008 Annual Meeting, Orlando, FL, October 18-22, 2008. Conflicts of interest: None to report. 0196-6553/$36.00 Copyright ª 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.ajic.2010.05.027 141