Published ahead of print on May 25, 2006, doi:10.1164/rccm.200506-907OC Am. J. Respir. Crit. Care Med., Volume 174, Number 4, August 2006, 408-414 A more recent version of this article appeared on August 15, 2006
Submitted on June 13, 2005 Intervention of Neuroendocrine-Immune Axis and Postoperative Pneumonia Rate in Long-term AlcoholicsClaudia Spies1*,1 CCM and CVK, Department of Anesthesiology and Intensive Care Medicine, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 2 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA, 3 CCM and CVK, Doctorial Thesis Group: Katrin Hegenscheid, Birgit Bohm, Department of Anesthesiology and Intensive Care Medicine, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 4 Institute of Medical Immunology, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 5 CCM and CVK, Institute of Laboratory Medicine and Pathobiochemistry, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 6 CCM, CVK, CBF, Department of Otorhinolaryngology and Head and Neck Surgery, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 7 CVK, Clinic and Policlinic for Oral and Maxillofacial Surgery and Plastic Surgery, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 8 CBF, Department of Maxillofacial and Plastic Surgery, Charite - University Medicine Berlin, Berlin, Berlin, Germany, 9 Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, South Carolina, USA, 10 CCM and CVK, Institute of Medical Biometry, Charite - University Medicine Berlin, Berlin, Berlin, Germany * To whom correspondence should be addressed. E-mail: claudia.spies{at}charite.de.
Rationale: Postoperative pneumonia is 3-to 4-times more frequent in patients with alcohol use disorders followed by prolonged ICU stay. Long-term alcohol use leads to an altered perioperative 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-blinded controlled study, 122 consecutive patients undergoing elective surgery of aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60g ethanol daily and fulfilling the DSM-IV criteria for either alcohol abuse or dependence. Non-alcoholic patients were included but considered only descriptive. Perioperative intervention with low-dose ethanol (0.5g per kg bodyweight per day), morphine (15µg per kg bodyweight per hour), ketoconazole (200mg four times daily) and placebo, was started on the morning before surgery and continued for 3 days 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 the postoperative hypercortisolism and prevented the impaired cytotoxic lymphocyte ratio (Tc1/Tc2). All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened ICU stay in median by 9 days compared to the placebo-treated long-term alcoholic patients. Conclusions: Intervention of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened ICU stay in long-term alcoholic patients. Key words: alcohol use disorder, cortisol, T-cell mediated immunity, pneumonia aerodigestive tract cancer
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