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

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.

Immune reactivity is more suppressed in patients with alcoholic liver disease than in patients with virus-induced cirrhosis after CRH stimulation.

BACKGROUND: The most frequent diagnoses for liver transplantation are virus-induced cirrhosis (VIC) and alcoholic liver disease (ALD), after an abstinence period of at least 6 months. Chronic ethanol consumption has been linked to an abnormal neuroendocrine-immune axis and to an altered surgical stress response inducing an increased infection rate. Preoperative stress testing might be relevant to detect stress-induced immune alteration. The aim of this study was to investigate the preoperative stress-like response to corticotrophin-releasing-hormone challenge (CRH) of patients with ALD compared with patients with VIC and their immune sequelae. METHODS: Nine patients with ALD and 8 patients with VIC were included in this clinical study prior to transplantation. All patients received CRH in the morning. Blood samples were drawn before and after stress testing. RESULTS: In response to CRH, the ALD patients showed a significant decrease in the plasma interleukin (IL)-6/IL-10 ratio. After lipopolysaccharide stimulation of whole blood from CRH-challenged ALD patients, IL-10 increased significantly. The cytotoxic T1-(Tc1) to cytotoxic T2 (Tc2) ratio was significantly decreased in ALD patients after the stress test. Infections occurred significantly more often in ALD patients within the past year before study inclusion. CONCLUSIONS: ALD patients showed a stronger anti-inflammatory immune status and response than VIC patients. This difference was associated with a higher infection rate despite a median alcohol abstinence time of 3.5 years. Although an altered immune response is well known among patients with actual alcohol-use disorders, to the best of our knowledge, it is not described in patients after such a long abstinence time.