ACTIONS OF ACUTE ETHANOL INTOXICATION ON CARDIOPULMONARY FUNCTION AFTER AN ENDOTOXIN CHALLENGE

Background. This study examined whether acute ethanol (EtOH) intoxicat ion could alter the:systemic inflammatory response evoked by endotoxin (lipopolysaccharide, I-PS). Methods. Anesthetized (fentanyl) and mech anically ventilated mongrel pigs were administered 20% EtOH 13 gm/kg) or its vehicle (VEH) by means of gastric lavage. After 60 minutes of e quilibration, blood levels were 110 to 130 mg/dl, and LPS (1 mu g/kg p er 30 minutes) was infused intravenously to mimic the type of sepsis t hat might be encountered after a penetrating abdominal injury. Results . LPS caused initial pulmonary vasoconstriction followed by cardiovasc ular collapse in 7 of 14 pigs with EtOH versus 0 of 14 pigs with VEH ( p = 0.0058); survival time averaged 2.4 +/- 0.5 hours for EtOH versus 4.5 +/- 0.3 hours for VEH (p = 0.002). At 3 to 5 hours after LPS infus ion the survivors were acidotic (base excess, -5.1 +/- 1.5 versus 0.4 +/- 1.1 mEq/L; p = 0.007) and vasodilated (systemic vascular resistanc e, 54% +/- 9% versus 1.1% +/- 9% baseline; p = 0.007). Systemic arteri al pressure and cardiac filling pressures were maintained with fluid r esuscitation, but more was required for EtOH versus VEH (80 +/- 11 ver sus 42 +/- 5 ml/kg/hr; p = 0.0034). A diffuse capillary leak was detec ted with gamma scintigraphy and regional uptake of technetium 99m albu min. With EtOH versus VEH microvascular permeability was higher in abd omen (p = 0.01) and liver (p = 0.06) but not in lung (p = 0.29). These changes were probably mediated in part by leukosequestration: neutrop hil counts were initially reduced more than 80% in both groups, but th ey then rebounded with VEH (p < 0.05) brit not EtOH. The early versus late deaths within the EtOH group were distinguished by higher baselin e levels of cortisol (1.4 +/- 0.3 versus 0.9 +/- 0.2 mu g/dl; P = 0.07 5) and by a 50% decrease evoked by EtOH (p = 0.0042) versus no change in the late death subgroup. After LPS infusion cortisol peaked sooner and then recovered with VEH (p < 0.05), whereas the peak occurred late r and there was no decay with EtOH. In addition, at 60 and 90 minutes after LPS infusion tumor necrosis factor was 119 +/- 27 and 240 +/- 40 pg/ml with VEH versus 62 +/- 15 and 95 +/- 23 pg/ml with EtOH (p = 0. 041 and P = 0.0030). Conclusions. By means of a leukocyte-mediated mec hanism in the splanchnic circulation, acute EtOH impaired host defense , which exacerbated LPS-evoked systemic inflammatory response. In cont ext with our earlier experimental study and two large clinical trials, if appears that acute EtOH can have opposite effects on the vulnerabi lity to posttrauma sepsis, depending on the timing of the septic insul t and on the immune stat rls at the time of septic challenge.