title: Immunosuppressive aspects of analgesics and sedatives used in mechanically ventilated patients: an underappreciated risk factor for the development of ventilator-associated pneumonia in critically ill patients.
abstract: OBJECTIVE
  To evaluate the evidence describing the immunosuppressive and pharmacokinetic properties of commonly used analgesic and sedation agents in critically ill patients.
  
  
  METHODS
  MEDLINE (January 1980-September 2013) was searched.
  
  
  METHODS
  All in vitro and in vivo studies that evaluated the immune-modulating properties of analgesic and sedation agents commonly used in the critically ill were included. Full-text and abstract-only articles (noted) were included in this review. Inclusion criteria were met by 46 studies and were evaluated.
  
  
  RESULTS
  Analgesic and sedation agents have been shown to be immunosuppressive in a variety of models. In vitro models use a variety of immune cells to demonstrate the immunosuppressive properties of opioids, benzodiazepines, and to a lesser extent, propofol. In each case, animal studies provide more robust data supporting the concept that opioids, benzodiazepines, and propofol exhibit immunosuppressive activities ranging from innate to adaptive immune alterations. Human studies, though more limited, provide further support that these agents inhibit the immune response. In contrast, data have shown that dexmedetomidine may attenuate the immune system. Clinical trial data evaluating the immunosuppressive properties of these agents is limited.
  
  
  CONCLUSIONS
  Analgesic and sedation agents have clearly been shown to alter cellular function and other mediators of the immune system; yet the clinical impact remains to be fully elucidated. The mechanism by which sedation interruption reduces ventilator-associated pneumonia may in fact be a reduction in immunosuppressive effects. Studies linking the immune-modulating effects of analgesic and sedation agents in critically ill patients are needed.
authors.affiliation: University of the Sciences, Philadelphia, PA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Smith
authors.forename: Maho
authors.initials: M
authors.lastname: Hibino
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Falcione
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Eichinger
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Empey
mesh_terms: D000700:Analgesics / Q000009:adverse effects*; D000818:Animals; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D053717:Pneumonia, Ventilator-Associated / Q000453:epidemiology* / Q000209:etiology; D012121:Respiration, Artificial / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives; D007166:Immunosuppressive Agents
keywords: analgesia; immune system; sedation; ventilator-associated pneumonia