Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics

UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Publication Date


Document Type



APACHE; Aged; Alcoholism; Antifungal Agents; Comorbidity; Cushing Syndrome; Digestive System Neoplasms; Double-Blind Method; Ethanol; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Interferon-gamma; Interleukin-10; Ketoconazole; Length of Stay; Male; Middle Aged; Morphine; Pituitary-Adrenal System; Pneumonia; Postoperative Complications; ROC Curve; Stress, Physiological; Th1 Cells; Th2 Cells


Circulatory and Respiratory Physiology | Gastroenterology


RATIONALE: 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.

OBJECTIVES: 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.

MEASUREMENTS AND MAIN 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.

DOI of Published Version



Am J Respir Crit Care Med. 2006 Aug 15;174(4):408-14. Epub 2006 May 25. Link to article on publisher's site

Journal/Book/Conference Title

American journal of respiratory and critical care medicine

Related Resources

Link to Article in PubMed

PubMed ID