ACUTE ETHANOL INTOXICATION AND ENDOTOXEMIA AFTER TRAUMA

To determine actions of acute intoxication on pathophysiologic respons es to trauma, anesthetized and ventilated mongrel pigs received a 20% solution of ethanol (EtOH) by an intravenous (IV group; 2 g/kg, n = 8) or an oral (PO group; 3 g/kg, n = 12 x 60 minutes) route of administr ation, or the lactated Ringer's vehicle (LR group; n = 12), After 60 m inutes, all were subjected to soft tissue injury and 30 to 35% hemorrh age, 60-minute shock, and then resuscitation, with shed blood plus sup plemental LR, After 3 days, host defense was challenged with Escherich ia coli lipopolysaccharide (LPS); (1 mu g/kg x 30-minutes IV), The sup plemental resuscitation was identical (50-53 ml/kg/hours), but posttra umatic acidosis was observed in the IV group and the PO group (base de ficit = 4.4 +/- 1.3 and 5.5 +/- 0.9 mEq/L) and not in the LR group, Af ter 3 days, the acid-base equilibrium was restored, but a difference i n host defense was unmasked by LPS, In the LR group, LPS-evoked pulmon ary vasoconstriction was followed by decreased compliance and ventilat ion-perfusion mismatch, which was associated at 3 to 5 hours with a ba se deficit, reduced Svo(2), and reduced Po-2 (-0.5 +/- 0.2 mEq/L, 46 /- 1%, 127 +/- 1 mm Hg). These changes were blunted in the PO group (2 .0 +/- 0.1 mEq/L, 56 +/- 1%, 183 +/- 4 mm Hg) and potentiated in the I V group (-4.3 +/- 0.5 mEq/L, 40 +/- 2%, 60 +/- 2 mm Hg), even though m ore fluid was required to maintain systemic arterial and cardiac filli ng pressures following LPS administration in the IV (40 +/- 6 mL/kg/ho urs) versus the LR or PO groups (31 +/- 5 or 23 +/- 3). The PO versus LR differences could not be attributed to enteral nutrition because an isocaloric solution of 50% dextrose had no effect versus LR solution, EtOH caused neutropenia following trauma, relative to LR solution, bu t the IV versus PO differences could not be discriminated on the basis of neutrophil or lymphocytes counts, nor CD18 receptor expression, no r renal or hepatic dysfunction. However, T4 lymphocytes and cortisol, a nonspecific index of inflammation, were higher for at least 24 hours after trauma with IV, relative to PO or LR. Blood EtOH was similar wi th IV or PO during resuscitation (100-120 mg/dL), but the kinetics wer e different prior to trauma, With PO, blood EtOH slowly accumulated to a steady state plateau, the level of which was higher with no anesthe sia or no trauma, With IV, blood EtOH peaked at 275 mg/dL and then exp onentially declined with a rate that was not influenced to a major ext ent by trauma or by anesthesia, Therefore: 1) EtOH absorption is impai red during trauma (in part because of reduced gut blood flow); 2) acut e EtOH intoxication at the time of trauma altered neutrophils, plasma cortisol, and T4 lymphocytes during recovery and host defense to a sup erimposed LPS challenge, The apparently favorable effect of PO versus IV EtOH on the response to endotoxemia after trauma probably reflects differences in the kinetics of blood EtOH in the interval before reper fusion, but a ''first pass'' effect (metabolism in the gut or liver) m ight also explain the data.