Hemorrhage-induced hepatic injury and hypoperfusion can be prevented by direct peritoneal resuscitation

Abstract

Background: Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes).

Methods: Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet-dry ratio).

Results: Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 +/- 28 microg/mL and aspartate aminotransferase (AST), 234 +/- 24 microg/mL; p < 0.05) compared to group 1 (73 +/- 9 and 119 +/- 10 microg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 +/- 9 microg/mL and AST 150 +/- 17 microg/mL), and tissue edema was similar to sham.

Conclusions: CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.

Figure 1

Heart rate and mean arterial pressure. BL baseline; groups: Sham surgical cannulations but no hemorrhage shock or resuscitation; HS + CR hemorrhagic shock plus conventional intravenous fluid resuscitation; HS + CR + DPR hemorrhagic shock and resuscitation plus 30 mL of clinical peritoneal dialysis solution (Delflex™) intraperitoneally at the time of resuscitation; HS + CR + IPS hemorrhagic shock and resuscitation plus 30 mL of normal saline intraperitoneally at the time of resuscitation. *p<0.01 versus corresponding baseline by repeated measures ANOVA and Dunnett's post-test.

Figure 2

Effective hepatic blood flow. Groups: Sham surgical cannulations but no hemorrhage shock or resuscitation; HS + CR hemorrhagic shock plus conventional intravenous fluid resuscitation; HS + CR + DPR hemorrhagic shock and resuscitation plus 30 mL of clinical peritoneal dialysis solution (Delflex™) intraperitoneally at the time of resuscitation; HS + CR +IPS hemorrhagic shock and resuscitation plus 30 mL of normal saline intraperitoneally at the time of resuscitation. Baseline values in mL/min/100 g body weight were: Sham, 5.6±0.3; HS + CR, 6.3±0.5; HS + CR + IPS, 5.9±0.4; and HS + CR + DPR, 6.1±0.4. *p<0.01 versus corresponding baseline by repeated-measures ANOVA and Dunnett's post-test. Section sign p<0.01 versus the HS + CR group by two-way ANOVA and Bonferroni post-test.

Figure 3

Liver histopathology (blinded scoring). a Sham; b HS + CR; c HS + CR + IPS; d HS + CR + DPR. HS hemorrhagic shock, CR conventional intravascular fluid resuscitation, IPS intraperitoneal saline (30 mL) at time of the fluid resuscitation, DPR adjunct direct peritoneal resuscitation (30 mL Delflex™ with 2.5% glucose) at the time of the fluid resuscitation.

Figure 4

Liver function test. Groups: Sham surgical cannulations but no hemorrhage shock or resuscitation; HS + CR hemorrhagic shock plus conventional intravenous fluid resuscitation; HS + CR + DPR hemorrhagic shock and resuscitation plus 30 mL of clinical peritoneal dialysis solution (Delflex™) intraperitoneally at the time of resuscitation; HS + CR + IPS hemorrhagic shock and resuscitation plus 30 mL of normal saline intraperitoneally at the time of resuscitation. *p<0.01 versus Sham control by one-way ANOVA and Bonferroni post-test. Section sign p<0.01 versus the HS + CR group by two-way ANOVA and Bonferroni post-test.

Figure 5

Total tissue water. AAM anterior abdominal muscle; Groups: Sham surgical cannulations but no hemorrhage shock or resuscitation; HS + CR hemorrhagic shock plus conventional intravenous fluid resuscitation; HS + CR + DPR hemorrhagic shock and resuscitation plus 30 mL of clinical peritoneal dialysis solution (Delflex™) intraperitoneally at the time of resuscitation; HS + CR + IPS hemorrhagic shock and resuscitation plus 30 mL of normal saline intraperitoneally at the time of resuscitation. *p<0.01 versus Sham control by one-way ANOVA and Bonferroni post-test. Section sign p<0.01 versus the HS + CR group by two-way ANOVA and Bonferroni post-test.