Gamma-scintigraphy and early hepatocellular dysfunction during posttraumatic sepsis.
BACKGROUND
To determine whether the hepatic conjugation-detoxification function was altered during sepsis, the metabolism of bilirubin was measured with gamma-scintigraphy.


METHODS
Time-activity curves were generated after a radiolabeled bilirubin analog (technetium 99m-mebrofenin, hepatoiminodiacetic acid [HIDA]) was administered to anesthetized (fentanyl) mongrel pigs in the following conditions: control (n = 16); 30 minutes after 5 micrograms/kg intravenous Escherichia coli endotoxin (LPS; n = 6); 30 minutes after trauma (40% arterial hemorrhage plus soft tissue injury, n = 9); 72 hours after sham trauma (n = 6); 72 hours after fluid resuscitated trauma either before (n = 9) or 30 minutes after (n = 10) LPS administration. All were ventilated with 65% O2 and instrumented with pulmonary artery oximetric catheters.


RESULTS
After trauma plus LPS, the rate of HIDA uptake was depressed 20% to 30% (p < 0.05), whereas its elimination half-time was increased almost threefold (p < 0.05) relative to before LPS administration. At the corresponding time after trauma alone or LPS alone, uptake was not altered and elimination was prolonged less than twofold (p < 0.05) relative to control. Perfusion differences could not explain these data because cardiac index (CI, ml/min/kg) was reduced to the same extent after trauma alone (62 +/- 10), LPS alone (79 +/- 6), or trauma plus LPS (71 +/- 6) compared with control (102 +/- 5), sham (112 +/- 11), or pre-LPS (120 +/- 10) (p < 0.05, respectively). Levels of serum alanine aminotransferase and creatine kinase were both elevated (p < 0.05) 72 hours after resuscitation, but there were no added increments caused by LPS administration. Levels of other enzymes and plasma bilirubin were not increased by trauma or LPS alone or in combination. Changes in HIDA uptake-excretion within 30 minutes of LPS after resuscitated trauma coincided with neutropenia and pulmonary hypertension and preceded a hyperdynamic inflammatory state characterized by increased CI (194 +/- 19 ml/min/kg, p < 0.05) at 90 +/- 13 minutes, decreased systemic vascular resistance (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 O2 consumption (6.96 +/- 0.93 vs 4.16 +/- 0.23 ml O2/min/kg, p < 0.05 relative to pre-LPS) at 96 +/- 12 minutes.


CONCLUSIONS
(1) A prior episode of resuscitated traumatic shock exhausts hepatic reserve and this occult dysfunction in the conjugation-detoxification system or bilirubin metabolism is unmasked by LPS; (2) hepatic dysfunction could have a role in the pathogenesis of the hyperdynamic circulatory response evoked by LPS because HIDA clearance was reduced before 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 septic trauma or others with occult liver dysfunction.
McGinty
M P
MP
Department of Pediatrics (Critical Care Division, Emergency Medicine), LeBonheur Children's Medical Center, Memphis, Tenn.
Stewart
R M
RM
Fabian
M J
MJ
Fabian
T C
TC
Proctor
K G
KG
D000814:Aniline Compounds; D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D001772:Blood Cell Count; D004798:Enzymes / Q000097:blood; D004926:Escherichia coli; D005260:Female; D005998:Glycine; D006439:Hemodynamics; D007098:Imino Acids / Q000493:pharmacokinetics*; D007239:Infections / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism; D013552:Swine; D014947:Wounds and Injuries / Q000150:complications / Q000378:metabolism
D000814:Aniline Compounds; D004798:Enzymes; D007098:Imino Acids; D008070:Lipopolysaccharides; D015609:Organotechnetium Compounds; C034837:technetium Tc 99m mebrofenin; D001663:Bilirubin; D005998:Glycine