GAMMA-SCINTIGRAPHY AND EARLY HEPATOCELLULAR DYSFUNCTION DURING POSTTRAUMATIC SEPSIS

Background. To determine whether the hepatic conjugation-detoxificatio n function was altered during sepsis, the metabolism of bilirubin was measured with gamma-scintigraphy. Methods. Time-activity curves were g enerated after a radiolabeled bilirubin analog (technetium 99m-mebrofe nin, hepatoiminodiacetic acid [HIDA]) was administered to anesthetized (fentanyl) mongrel pigs in the following conditions: control (n = 16) ; 30 minutes after 5 mu g/kg intravenous Escherichia coli endotoxin (L PS; n = 6); 30 minutes after trauma (40% arterial hemorrhage plus soft tissue injury, n = 9); 72 hours after sham trauma (n = 6); 72 hours a fter fluid resuscitated trauma either before (n = 9) or 30 minutes aft er (n = 10) LPS administration. All were ventilated with 65% O-2 and i nstrumented with pulmonary artery oximetric catheters. Results. After trauma plus PLS, the rate of HIDA uptake was depressed 20% to 30% (p < 0.05), whereas its elimination half-time was increased almost threefo ld (p < 0.05) relative to before LPS administration. At the correspond ing time after trauma alone or LPS alone, uptake was not altered and e limination was prolonged less than twofold (p < 0.05) relative to cont rol. Perfusion differences could not explain these data because cardia c index (CI, ml/min/kg) was reduced to the same extent after trauma al one (62 +/- 10), LPS alone (79 +/- 6), or trauma plus LPS (71 +/- 6) c ompared with control (102 +/- 5), sham (112 +/- 11), or pre-LPS (120 /- 10) (p < 0.05, respectively). Levels of serum alanine aminotransfer ase and creatine kinase were both elevated (p < 0.05) 72 hours after r esuscitation, but there were no added increments caused by LPS adminis tration. Levels of other enzymes and plasma bilirubin were not increas ed by trauma or LPS alone or in combination. Changes in HIDA uptake-ex cretion within 30 minutes of LPS after resuscitated trauma coincided w ith neutropenia and pulmonary hypertension and preceded a hyperdynamic inflammatory state characterized by increased CI (194 +/- 19 ml/min/k g, p < 0.05) at 90 +/- 13 minutes, decreased systemic vascular resista nce (0.48 +/- 0.04 mm Hg per ml/min/kg, p < 0.05 relative to 1.08 +/- 0.07 for control or 0.88 +/- 0.08 for pre-LPS) at 81 +/- 8 minutes and increased systemic O-2 consumption (6.96 +/- 0.93 vs 4.16 +/- 0.23 ml O-2/min/kg, p < 0.05 relative to pre-LPS) at 96 +/- 12 minutes. Concl usion. (1) A prior episode of resuscitated traumatic shock exhausts he patic reserve and this occult dysfunction in the conjugation-detoxific ation system or bilirubin metabolism is unmasked by LPS; (2) hepatic d ysfunction could have a role in the pathogenesis of the hyperdynamic c irculatory response evoked by LPS because HIDA clearance was reduced b efore CI increased or systemic vascular resistance decreased; (3) HIDA clearance is a rapid, reliable, and inexpensive estimate of bilirubin metabolism that may have a practical application in patients with sep tic trauma or others with occult liver dysfunction.