title: The Effect of Concomitant Sirolimus and Propofol Therapy on Triglyceride Concentrations in Critically Ill Patients.
abstract: BACKGROUND
  Sirolimus and propofol are both independently associated with the development of hypertriglyceridemia (HTG) during therapy. To date, there are no published reports describing synergistic or additive drug interaction resulting in HTG with concomitant use of these medications.
  
  
  OBJECTIVE
  To identify the occurrence of HTG in patients receiving concomitant sirolimus and propofol infusion therapy.
  
  
  METHODS
  Adult patients receiving sirolimus and a continuous propofol infusion for at least 12 hours from January 2005 to August 2009 were retrospectively evaluated. Data included Acute Physiology and Chronic Health Evaluation II score, weight, length of propofol therapy, and baseline triglyceride (TG) concentrations. The major outcome was incidence of HTG (TGs ≥500 mg/dL). Minor outcomes included the change in TG concentration from therapy initiation and manifestations of propofol-related infusion syndrome (PRIS).
  
  
  RESULTS
  Sixteen patients were included in the analysis, with 8 (50%) of the patients developing HTG. The patients in this case series had the following mean values: Acute Physiology and Chronic Health Evaluation II score of 20.2 ± 5.3, weight of 76.3 ± 21.2 kg, and baseline TG concentrations of 181.3 ± 89.7 mg/dL. Indications for sirolimus therapy included hematopoietic stem-cell transplantation (n = 15) and heart transplantation (n = 1). Mean length of propofol infusion was 99.8 ± 88.5 hours. The mean TG concentration during infusion was 515.6 ± 468.1 mg/dL. Fourteen (87.5%) patients had an increase of ≥100 mg/dL, 12 (75%) patients had an increase of ≥200 mg/dL, and 6 (37.5%) patients had an increase of ≥300 mg/dL in TG concentrations during therapy. Eleven patients developed one manifestation of PRIS, excluding HTG, and one patient had more than 2 new onset PRIS manifestations during propofol therapy.
  
  
  CONCLUSIONS
  Coadministration of propofol and sirolimus can potentially result in HTG, which may warrant more frequent monitoring. Further analysis is needed to examine the mechanism and clinical impact of this interaction.
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Dube
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Szumita
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
authors.forename: Megan A
authors.initials: MA
authors.lastname: Rocchio
authors.affiliation: Executive Vice President, Chief Medical Officer, Proteostasis Therapeutics, Inc., Cambridge, MA.
authors.forename: Po-Shun
authors.initials: PS
authors.lastname: Lee
authors.affiliation: Investigation Drug Services, Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Anger
mesh_terms: D000328:Adult; D000368:Aged; D016638:Critical Illness / Q000628:therapy*; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D015994:Incidence; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000009:adverse effects*; D000072736:Propofol Infusion Syndrome / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects*; D014280:Triglycerides / Q000097:blood*
chemical_list: D014280:Triglycerides; D020123:Sirolimus; D015742:Propofol