Background: This study examined whether acute ethanol (EtOH) intoxication could alter the systemic inflammatory response evoked by endotoxin (lipopolysaccharide, LPS).
Methods: Anesthetized (fentanyl) and mechanically ventilated mongrel pigs were administered 20% EtOH (3 gm/kg) or its vehicle (VEH) by means of gastric lavage. After 60 minutes of equilibration, blood levels were 110 to 130 mg/dl, and LPS (1 microgram/kg per 30 minutes) was infused intravenously to mimic the type of sepsis that might be encountered after a penetrating abdominal injury.
Results: LPS caused initial pulmonary vasoconstriction followed by cardiovascular 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 infusion the survivors were acidotic (base excess, -5.1 +/- 1.5 versus 0.4 +/- 1.1 mEq/L; p = 0.007) and vasodilated (systemic vascular resistance, 54% +/- 9% versus 111% +/- 9% baseline; p = 0.005). Systemic arterial pressure and cardiac filling pressures were maintained with fluid resuscitation, but more was required for EtOH versus VEH (80 +/- 11 versus 42 +/- 5 ml/kg/hr; p = 0.0034). A diffuse capillary leak was detected with gamma scintigraphy and regional uptake of technetium 99m albumin. With EtOH versus VEH microvascular permeability was higher in abdomen (p = 0.01) and liver (p = 0.06) but not in lung (p = 0.29). These changes were probably mediated in part by leukosequestration: neutrophil counts were initially reduced more than 80% in both groups, but they then rebounded with VEH (p < 0.05) but not EtOH. The early versus late deaths within the EtOH group were distinguished by higher baseline levels of cortisol (1.4 +/- 0.3 versus 0.9 +/- 0.2 micrograms/dl; p = 0.075) 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 later 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 mechanism in the splanchnic circulation, acute EtOH impaired host defense, which exacerbated LPS-evoked systemic inflammatory response. In context with our earlier experimental study and two large clinical trials, it appears that acute EtOH can have opposite effects on the vulnerability to posttrauma sepsis, depending on the timing of the septic insult and on the immune status at the time of septic challenge.