title: Influence of Granulocyte-Macrophage Colony-Stimulating Factor or Influenza Vaccination on HLA-DR, Infection and Delirium Days in Immunosuppressed Surgical Patients: Double Blind, Randomised Controlled Trial.
abstract: OBJECTIVE
  Surgical patients are at high risk for developing infectious complications and postoperative delirium. Prolonged infections and delirium result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and influenza vaccination are known to increase HLA-DR on monocytes and improve immune reactivity. This study aimed to investigate whether GM-CSF or vaccination reverses monocyte deactivation. Secondary aims were whether it decreases infection and delirium days after esophageal or pancreatic resection over time.
  
  
  METHODS
  In this prospective, randomized, placebo-controlled, double-blind, double dummy trial setting on an interdisciplinary ICU of a university hospital 61 patients with immunosuppression (monocytic HLA-DR [mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after esophageal or pancreatic resection were treated with either GM-CSF (250 μg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on monocytes was measured daily until day 5 after surgery. Infections and delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR on monocytes, and secondary outcomes were duration of infection and delirium.
  
  
  RESULTS
  mHLA-DR was significantly increased compared to placebo (p < 0.001) and influenza vaccination (p < 0.001) on the second postoperative day. Compared with placebo, GM-CSF-treated patients revealed shorter duration of infection (p < 0.001); the duration of delirium was increased after vaccination (p = 0.003).
  
  
  CONCLUSIONS
  Treatment with GM-CSF in patients with postoperative immune suppression was safe and effective in restoring monocytic immune competence. Furthermore, therapy with GM-CSF reduced duration of infection in immune compromised patients. However, influenza vaccination increased duration of delirium after major surgery.
  
  
  BACKGROUND
  www.controlled-trials.com ISRCTN27114642.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Spies
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Alawi
authors.initials: A
authors.lastname: Luetz
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Lachmann
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Renius
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Clarissa
authors.initials: C
authors.lastname: von Haefen
authors.affiliation: Sostana GmbH, Berlin, Germany.
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Wernecke
authors.affiliation: Department of General, Abdominal and Transplantation Surgery, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bahra
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schiemann
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Paupers
authors.affiliation: Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
mesh_terms: D000368:Aged; D003693:Delirium / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D004947:Esophagus / Q000601:surgery; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010179:Pancreas / Q000601:surgery; D014611:Vaccination
chemical_list: D006684:HLA-DR Antigens; D007252:Influenza Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor