Hemorrhage-Induced Hepatic Injury and Hypoperfusion can be Prevented by Direct Peritoneal Resuscitation

Hurt, Ryan T.; Zakaria, El Rasheid; Matheson, Paul J.; Cobb, Mahoney; Parker, John R.; Garrison, R. Neal

doi:10.1007/s11605-008-0796-0

Cited by 26 publications

(18 citation statements)

References 34 publications

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“…Once TLR-4s are activated, Kupffer cells produce large amounts of cytokines and chemokines including TNF-␣, INF-␥, IL-6, IL-8, MCP-1, IL-17, and CXCL-10. Our previous data demonstrated elevated liver enzymes following HS, and we found elevated serum HMGB1 in this study (8,21,30). Adjunct DPR prevented hepatocyte cell death (HMB1) and improved liver histopathology scores and serum liver enzymes compared with HSϩCR alone.…”

Section: Discussionsupporting

confidence: 69%

“…Patients who developed high serum levels of bilirubin, a serum marker of liver injury, had longer stays in the intensive care unit and higher mortality (16.2% vs. 2.5%) compared with patients with normal or slightly elevated bilirubin. While these observational studies suggest an association between HS and significant liver dysfunction, necrosis, and mortality, the mechanisms of this liver injury have not been well defined.Experimental evidence suggests that despite return of central hemodynamic performance by aggressive intravenous fluid resuscitation, the gut and liver experience a progressive vasoconstriction and hypoperfusion after HS (5,14,21,42). End organ tissue hypoperfusion has been linked to several mechanisms of postresuscitation (post-RES) injury: endothelial cell dysfunction, tissue hypoxia, compromised capillary filling and fluid exchange, deranged electrolyte handling, and altered release of cytokine mediators that exaggerate the systemic inflammatory response (40).…”

mentioning

confidence: 99%

“…These mechanisms of cellular and end organ tissue injury translate clinically into organ dysfunction, which can progress to MOF and death. While the role of the gut as a potential motor for MOF has been extensively studied and promoted, the role of the liver in post-RES tissue injury has not been well defined (5,21). This paper will examine hepatic perfusion, function, and histopathology following resuscitated HS and will analyze the potential for a new resuscitation regimen termed direct peritoneal resuscitation (DPR) to ameliorate the HS/resuscitation-induced liver injury.…”

mentioning

confidence: 99%

“…Experimental evidence suggests that despite return of central hemodynamic performance by aggressive intravenous fluid resuscitation, the gut and liver experience a progressive vasoconstriction and hypoperfusion after HS (5,14,21,42). End organ tissue hypoperfusion has been linked to several mechanisms of postresuscitation (post-RES) injury: endothelial cell dysfunction, tissue hypoxia, compromised capillary filling and fluid exchange, deranged electrolyte handling, and altered release of cytokine mediators that exaggerate the systemic inflammatory response (40).…”

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confidence: 99%

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Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Hurt

Matheson²,

Smith

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hurt RT, Matheson PJ, Smith JW, Zakaria ER, Shaheen SP, McClain CJ, Garrison RN. Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 303: G1144 -G1152, 2012. First published September 17, 2012 doi:10.1152/ajpgi.00278.2011.-Conventional resuscitation (CR) from hemorrhagic shock (HS) results in gut and liver hypoperfusion, organ and cellular edema, and vital organ injury. Adjunct direct peritoneal resuscitation (DPR) with dialysate prevents gut vasoconstriction, hypoperfusion, and injury. We hypothesized that DPR might also improve hepatocellular edema, inflammation, and injury. Anesthetized male SD rats were assigned to groups (n ϭ 8/group): 1) sham (no HS); 2) HS (40% MAP/60 min) ϩ intravenous fluid conventional resuscitation [CR; shed blood ϩ 2 vol saline (SAL)/30 min]; 3) HSϩCRϩDPR (30 ml ip 2.5% glucose dialysate); or 4) HSϩCRϩSAL (30 ml ip saline). Histopathology showed lung and liver injury in HSϩCR and HSϩCRϩSAL up to 24-h postresuscitation (post-RES) that was not in shams and which was prevented by adjunct DPR. Wet-to-dry weight ratios in HSϩCR revealed organ edema formation that was prevented by adjunct DPR. HSϩCR and HSϩCRϩSAL had 34% mortality by 24-h post-RES, which was absent with DPR (0%). Liver IFN-␥ and IL-6 levels were elevated in CR compared with DPR or shams. TNF-␣ mRNA was upregulated in CR/sham and DPR/sham. IL-17 was downregulated in DPR/sham. CXCL10 mRNA was upregulated in CR/sham but downregulated in DPR/sham. Despite restored central hemodynamic performance after CR of HS, liver blood flow was compromised up to 24 h post-RES, and the addition of DPR restores and maintains liver perfusion at 24-h post-RES. DPR prevented liver injury, histological damage, and edema formation compared with CR alone. DPR provided a mitigating anti-inflammatory dampening of the systemic inflammatory response. In all, these effects likely account for improved survivorship in the DPR-treated group. hemorrhagic shock; liver blood flow; liver injury DESPITE ADVANCES IN TREATMENT and therapies, hemorrhagic shock (HS) remains a major cause of morbidity and mortality following trauma in the United States (18). The clinical role the liver plays during HS and in subsequent multiple organ failure (MOF) is unclear. The largest and most recent clinical study followed 1,962 trauma patients with injury severity score Ͼ 14 (ISS Ͼ14) during a 3-year period (17). Of the patients who met the study's inclusion criteria, 154 (7.9%) exhibited signs of liver dysfunction during their hospital course. In general, these patients with liver dysfunction were older and had higher injury severity scores and lower prehospital blood pressure (17). Patients who developed high serum levels of bilirubin, a serum marker of liver injury, had longer stays in the intensive care unit and higher mortality (16.2% vs. 2.5%) compared with patients with normal or slightly elevated bilirubin. While these observational...

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Section: Discussionsupporting

confidence: 69%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Preservation of hepatic blood flow by direct peritoneal resuscitation improves survival and prevents hepatic inflammation following hemorrhagic shock

Hurt

Matheson²,

Smith

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In mehreren Studien sowie im Tiermodell haben sich posttraumatische Leberschäden, insbesondere Schäden an den intrahepatischen Gallenwegen, bei einer schweren Hypotonie mit einem systolischen Blutdruck von <100 mmHg und Hypovolamie eingestellt [6,9,13]. Ursache der Schäden an den intrahepatischen Gallenwegen ist die besondere arterielle Versorgung der Gallengangsepithelzellen.…”

Section: Hypotonie Im Splanchnikusgebietunclassified

Spätfolgen von Lebertraumen

Winter

Oestmann

Lenz

2009

Chirurg

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Severe trauma has a major influence on the visceral organs, especially on the liver. Splanchnic hypotension leads to necrosis of the bile duct cells as well as to damage to hepatocytes. Furthermore, the liver is a very immunologically active organ so that damage to the liver can increase the amount of proinflammatory cytokines. The major complication of post-traumatic damage to the liver is secondary sclerosing cholangitis (SCC) a highly progressive disease for which there is no sufficient therapy except liver transplantation. Therefore it is very important to put all efforts into avoiding posttraumatic liver damage from the very beginning. A sophisticated resuscitation therapy is the most important aspect. Direct peritoneal volume resuscitation is a promising possibility to improve perfusion of the visceral organs. Other possibilities are substitution with 17beta-estradiol as a strongly vasoactive hormone with a positive effect on liver perfusion and interleukin-10 as modulator of the immune reaction caused by the liver.

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