title: Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus.
abstract: OBJECTIVE
  Deep sedation with barbiturates or propofol is a standard therapy for patients with critically elevated intracranial pressure. Such patients are prone to infectious complications, especially to pneumonias, which are most commonly caused by Staphylococcus aureus. Although various immunomodulatory effects of barbiturates have been described in vitro, their influence on the phagocytosis of viable S. aureus has yet to be investigated. Therefore, we examined the effects of thiopentone, methohexitone, and propofol on the phagocytosis of viable S. aureus.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Ten healthy volunteers aged 32.5 +/- 7 yrs.
  
  
  METHODS
  Blood sampling.
  
  
  RESULTS
  Whole blood samples were preincubated with different concentrations of thiopentone, methohexitone, and propofol, which is an isopropylphenol derivate. After viable S. aureus was added, phagocytosis was stopped at different time points. Leukocytes were then stained with monoclonal antibodies for flow cytometric analysis of granulocyte recruitment (ratio of ingesting granulocytes) and phagocytosis activity (fluorescence intensity of ingested bacteria). Both barbiturates inhibited granulocyte recruitment and phagocytosis activity in a dose-dependent manner, whereas propofol did not affect any of the investigated variables. At concentrations higher than 7.6 x 10(-3) M (for thiopentone, p < .008) and 1.1 x 10(-3) M (for methohexitone, p < .04), granulocyte recruitment and phagocytosis activity were significantly inhibited. The calculated inhibitory concentrations (IC50) of thiopentone for granulocyte recruitment and for phagocytosis activity were 1.3 x 10(-2) M and 1.1 x 10(-2) M, respectively. The corresponding values for methohexitone were 3.6 x 10(-3) M and 1.1 x 10(-3) M.
  
  
  CONCLUSIONS
  Our in vitro model points at substantially different effects of barbiturates and propofol on phagocytosis of S. aureus, which is one of the most important pathogens in patients who need neuroprotective therapy. The inhibitory effects of both barbiturates demonstrate a strong dose-dependency, with more pronounced effects for methohexitone. Impairment of phagocytosis activity was more pronounced than granulocyte recruitment.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Ploppa
authors.forename: Ralph-Thomas
authors.initials: RT
authors.lastname: Kiefer
authors.forename: Boris
authors.initials: B
authors.lastname: Nohé
authors.forename: Helene A
authors.initials: HA
authors.lastname: Haeberle
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Dieterich
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Unertl
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Krueger
mesh_terms: D000328:Adult; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008723:Methohexital / Q000008:administration & dosage / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D013874:Thiopental / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D008723:Methohexital; D013874:Thiopental; D015742:Propofol