PubMed1996
To determine actions of acute intoxication on pathophysiologic responses 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 administration, or the lactated Ringer's vehicle (LR group; n = 12). After 60 minutes, all were subjected to soft tissue injury and 30 to 35% hemorrhage, 60-minute shock, and then resuscitation, with shed blood plus supplemental LR. After 3 days, host defense was challenged with Escherichia coli lipopolysaccharide (LPS); (1 microgram/kg x 30-minutes IV). The supplemental resuscitation was identical (50-53 mL/kg/hours), but posttraumatic acidosis was observed in the IV group and the PO group (base deficit = 4.4 +/- 1.3 and 5.5 +/- 0.9 mEq/L) and not in the LR group. After 3 days, the acid-base equilibrium was restored, but a difference in host defense was unmasked by LPS. In the LR group, LPS-evoked pulmonary vasoconstriction was followed by decreased compliance and ventilation-perfusion mismatch, which was associated at 3 to 5 hours with a base deficit, reduced SVO2, and reduced PO2 (-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 IV group (-4.3 +/- 0.5 mEq/L, 40 +/- 2%, 60 +/- 2 mm Hg), even though more fluid was required to maintain systemic arterial and cardiac filling pressures following LPS administration in the IV (40 +/- 6 mL/kg/ hours) 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, but the IV versus PO differences could not be discriminated on the basis of neutrophil or lymphocytes counts, nor CD18 receptor expression, nor 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 with IV or PO during resuscitation (100-120 mg/dL), but the kinetics were different prior to trauma. With PO, blood EtOH slowly accumulated to a steady state plateau, the level of which was higher with no anesthesia or no trauma. With IV, blood EtOH peaked at 275 mg/dL and then exponentially declined with a rate that was not influenced to a major extent by trauma or by anesthesia. Therefore: 1) EtOH absorption is impaired during trauma (in part because of reduced gut blood flow); 2) acute EtOH intoxication at the time of trauma altered neutrophils, plasma cortisol, and T4 lymphocytes during recovery and host defense to a superimposed 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 reperfusion but a "first pass" effect (metabolism in the gut or liver) might also explain the data.