title: Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics.
abstract: BACKGROUND
  Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity.
  
  
  OBJECTIVE
  The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients.
  
  
  METHODS
  In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 mug/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery.
  
  
  RESULTS
  In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients.
  
  
  CONCLUSIONS
  Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité-University Medicine Berlin, Campus Charité Virchow Klinikum and Campus Charité Mitte, Augustenburger Platz 1, 13353 Berlin, Germany. claudia.spies@charite.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Spies
authors.forename: Verena
authors.initials: V
authors.lastname: Eggers
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lau
authors.forename: Vera
authors.initials: V
authors.lastname: von Dossow
authors.forename: Helge
authors.initials: H
authors.lastname: Schoenfeld
authors.forename: Hilke
authors.initials: H
authors.lastname: Althoff
authors.forename: Katrin
authors.initials: K
authors.lastname: Hegenscheid
authors.forename: Birgit
authors.initials: B
authors.lastname: Bohm
authors.forename: Torsten
authors.initials: T
authors.lastname: Schroeder
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pfeiffer
authors.forename: Sabine
authors.initials: S
authors.lastname: Ziemer
authors.forename: Christian
authors.initials: C
authors.lastname: Paschen
authors.forename: Martin
authors.initials: M
authors.lastname: Klein
authors.forename: Christian
authors.initials: C
authors.lastname: Marks
authors.forename: Peter
authors.initials: P
authors.lastname: Miller
authors.forename: Michael
authors.initials: M
authors.lastname: Sander
authors.forename: Klaus-D
authors.initials: KD
authors.lastname: Wernecke
authors.forename: Evelin
authors.initials: E
authors.lastname: Achterberg
authors.forename: Udo
authors.initials: U
authors.lastname: Kaisers
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
mesh_terms: D018806:APACHE; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology*; D000935:Antifungal Agents / Q000008:administration & dosage*; D015897:Comorbidity; D003480:Cushing Syndrome / Q000276:immunology / Q000517:prevention & control*; D004067:Digestive System Neoplasms / Q000453:epidemiology / Q000601:surgery; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007654:Ketoconazole / Q000008:administration & dosage*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000517:prevention & control; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D012372:ROC Curve; D013312:Stress, Physiological / Q000276:immunology* / Q000517:prevention & control; D018417:Th1 Cells; D018418:Th2 Cells
chemical_list: D000935:Antifungal Agents; D016753:Interleukin-10; D000431:Ethanol; D009020:Morphine; D007371:Interferon-gamma; D007654:Ketoconazole; D006854:Hydrocortisone