Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics.
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.
Spies
Claudia
C
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
Eggers
Verena
V
Szabo
Gyongyi
G
Lau
Alexandra
A
von Dossow
Vera
V
Schoenfeld
Helge
H
Althoff
Hilke
H
Hegenscheid
Katrin
K
Bohm
Birgit
B
Schroeder
Torsten
T
Pfeiffer
Sebastian
S
Ziemer
Sabine
S
Paschen
Christian
C
Klein
Martin
M
Marks
Christian
C
Miller
Peter
P
Sander
Michael
M
Wernecke
Klaus-D
KD
Achterberg
Evelin
E
Kaisers
Udo
U
Volk
Hans-Dieter
HD
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
D000935:Antifungal Agents; D016753:Interleukin-10; D000431:Ethanol; D009020:Morphine; D007371:Interferon-gamma; D007654:Ketoconazole; D006854:Hydrocortisone