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Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study

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Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

Background/Purpose

Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping.

Methods

Twenty patients who underwent hepatic resection were randomized into two groups: a steroid group (n = 10), in which patients were given 30 mg/kg per body weight (BW) methylprednisolone intravenously, and a control group (n = 10), in which patients received a placebo (sodium chloride) infusion. The main outcome parameter to assess systemic stress was the serum plasma level of interleukin-6 (IL-6). To evaluate cell-mediated immune function, human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes and lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) release by peripheral monocytes was measured. Other investigated serum parameters included C-reactive protein (CRP), total bilirubin, alanine aminotransferase (ALT), prothrombin time (PT)-INR, and cytokines such as IL-8 and IL-10 and TNF-α. Postoperative convalescence, complication rate, and length of hospital stay were compared between the groups.

Results

Postoperative plasma concentrations of IL-6 (days 1 and 2), IL-8 (days 2 and 3), and CRP (days 1–4) were significantly lower in the steroid than in the control group. The total bilirubin concentration was significantly lower on day 6 in the steroid than in the control group. Four hours after surgery, LPS-induced TNF-α secretion was significantly reduced in the steroid group, but it increased rapidly during the following days. HLA-DR, ALT, and PT-INR levels were not different between the two groups. The postoperative hospital stay in the steroid group was significantly lower compared to that in the control group (mean, 10.5 days versus 14.8 days; P < 0.05). No differences were found in the convalescence score or postoperative complication rate.

Conclusions

Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release. No adverse effect on immunity was noted due to the methylprednisolone. We found no significant difference in the convalescence score, but a significantly shorter hospital stay in the steroid group. Further studies with more patients are needed to elucidate the clinical impact of preoperative steroid bolus therapy in liver surgery.

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References

  1. E Faist C Schinkel S Zimmer (1996) ArticleTitleUpdate on the mechanisms of immune suppression of injury and immune modulation World J Surg 20 454–9 Occurrence Handle8662134 Occurrence Handle10.1007/s002689900071 Occurrence Handle1:STN:280:BymB2s%2FisFM%3D

    Article  PubMed  CAS  Google Scholar 

  2. MD Menger B Vollmar (2004) ArticleTitleSurgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch Surg 389 475–84 Occurrence Handle15173946 Occurrence Handle10.1007/s00423-004-0472-0

    Article  PubMed  Google Scholar 

  3. E Lin SE Calvano SF Lowry (2000) ArticleTitleInflammatory cytokines and cell response in surgery Surgery 127 117–26 Occurrence Handle10686974 Occurrence Handle10.1067/msy.2000.101584 Occurrence Handle1:STN:280:DC%2BD3c7ltFGqsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864–74

    Google Scholar 

  5. A Jerin N Pozar-Lukanovic V Sojar D Stanisavljevic V Paver-Erzen J Osredkar (2003) ArticleTitleBalance of pro- and anti-inflammatory cytokines in liver surgery Clin Chem Lab Med 41 899–903 Occurrence Handle12940515 Occurrence Handle10.1515/CCLM.2003.136 Occurrence Handle1:CAS:528:DC%2BD3sXmtlymu7k%3D

    Article  PubMed  CAS  Google Scholar 

  6. M Nagelschmidt ZX Fu S Saad S Dimmeler E Neugebauer (1999) ArticleTitlePreoperative high dose methylprednisolone improves patients outcome after abdominal surgery Eur J Surg 165 971–8 Occurrence Handle10574107 Occurrence Handle10.1080/110241599750008107 Occurrence Handle1:STN:280:DC%2BD3c%2FjvFaltg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  7. M Shimada A Saitoh T Kano K Takenaka K Sugimachi (1996) ArticleTitleThe effect of a perioperative steroid pulse on surgical stress in hepatic resection Int Surg 81 49–51 Occurrence Handle8803706 Occurrence Handle1:STN:280:BymA1MnlvVI%3D

    PubMed  CAS  Google Scholar 

  8. Y Yamashita M Shimada T Hamatsu T Rikimaru S Tanaka K Shirabe K Sugimachi (2001) ArticleTitleEffects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial Arch Surg 136 328–33 Occurrence Handle11231856 Occurrence Handle10.1001/archsurg.136.3.328 Occurrence Handle1:CAS:528:DC%2BD3MXitF2is7c%3D

    Article  PubMed  CAS  Google Scholar 

  9. A Muratore D Ribero A Ferrero R Bergero L Capussotti (2003) ArticleTitleProspective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clamping Br J Surg 90 17–22 Occurrence Handle12520569 Occurrence Handle10.1002/bjs.4055 Occurrence Handle1:STN:280:DC%2BD3s%2FhtlWltQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  10. L Aldrighetti C Pulitano M Arru R Finazzi M Catena L Soldini et al. (2006) ArticleTitleImpact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized study Liver Transpl 12 941–9 Occurrence Handle16710858 Occurrence Handle10.1002/lt.20745

    Article  PubMed  Google Scholar 

  11. WD Docke C Hoflich KA Davis K Rottgers C Meisel P Kiefer et al. (2005) ArticleTitleMonitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study Clin Chem 51 2341–7 Occurrence Handle16214828 Occurrence Handle10.1373/clinchem.2005.052639

    Article  PubMed  Google Scholar 

  12. F Kimura H Shimizu H Yoshidome M Ohtsuka A Kato H Yoshitomi et al. (2006) ArticleTitleCirculating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resection J Surg Res 133 102–12 Occurrence Handle16386757 Occurrence Handle10.1016/j.jss.2005.10.025 Occurrence Handle1:CAS:528:DC%2BD28XkvVGjtbk%3D

    Article  PubMed  CAS  Google Scholar 

  13. WL Biffl EE Moore FA Moore VM Peterson (1996) ArticleTitleInterleukin-6 in the injured patient. Marker of injury or mediator of inflammation? Ann Surg 224 647–64 Occurrence Handle8916880 Occurrence Handle10.1097/00000658-199611000-00009 Occurrence Handle1:STN:280:ByiD2svksFc%3D

    Article  PubMed  CAS  Google Scholar 

  14. O Pradier F Willems D Abramowicz L Schandene M De Boer K Thielemans et al. (1996) ArticleTitleCD40 engagement induces monocyte procoagulant activity through an interleukin-10 resistant pathway Eur J Immunol 26 3048–54 Occurrence Handle8977303 Occurrence Handle10.1002/eji.1830261234 Occurrence Handle1:CAS:528:DyaK28XnsVGqtLk%3D

    Article  PubMed  CAS  Google Scholar 

  15. T Hensler H Hecker K Heeg CD Heidecke H Bartels W Barthlen et al. (1997) ArticleTitleDistinct mechanisms of immunosuppression as a consequence of major surgery Infect Immun 65 2283–91 Occurrence Handle9169765 Occurrence Handle1:CAS:528:DyaK2sXjsFWns7w%3D

    PubMed  CAS  Google Scholar 

  16. PO Nystrom (1998) ArticleTitleThe systemic inflammatory response syndrome: definitions and aetiology J Antimicrob Chemother 41 IssueIDSuppl A 1–7 Occurrence Handle9511080 Occurrence Handle10.1093/jac/41.suppl_1.1 Occurrence Handle1:CAS:528:DyaK1cXhtlWjt74%3D

    Article  PubMed  CAS  Google Scholar 

  17. K Holte H Kehlet (2002) ArticleTitlePerioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications J Am Coll Surg 195 694–712 Occurrence Handle12437261 Occurrence Handle10.1016/S1072-7515(02)01491-6

    Article  PubMed  Google Scholar 

  18. RI Scheinman A Gualberto CM Jewell JA Cidlowski AS Baldwin SuffixJr (1995) ArticleTitleCharacterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors Mol Cell Biol 15 943–53 Occurrence Handle7823959 Occurrence Handle1:CAS:528:DyaK2MXjtlant70%3D

    PubMed  CAS  Google Scholar 

  19. JM Braughler (1985) ArticleTitleLipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes J Neurochem 44 1282–8 Occurrence Handle3882888 Occurrence Handle10.1111/j.1471-4159.1985.tb08755.x Occurrence Handle1:CAS:528:DyaL2MXhsl2gtrk%3D

    Article  PubMed  CAS  Google Scholar 

  20. HD Volk M Thieme S Heym WD Docke U Ruppe W Tausch et al. (1991) ArticleTitleAlterations in function and phenotype of monocytes from patients with septic disease—predictive value and new therapeutic strategies Behring Inst Mitt 88 208–15 Occurrence Handle2049040

    PubMed  Google Scholar 

  21. M Buunen M Gholghesaei R Veldkamp DW Meijer HJ Bonjer ND Bouvy (2004) ArticleTitleStress response to laparoscopic surgery: a review Surg Endosc 18 1022–8 Occurrence Handle15136930 Occurrence Handle10.1007/s00464-003-9169-7 Occurrence Handle1:STN:280:DC%2BD2cznvFChtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  22. JJ Carter RL Whelan (2001) ArticleTitleThe immunologic consequences of laparoscopy in oncology Surg Oncol Clin N Am 10 655–77 Occurrence Handle11685934 Occurrence Handle1:STN:280:DC%2BD3MnhtFWrtw%3D%3D

    PubMed  CAS  Google Scholar 

  23. KL Streetz T Luedde MP Manns C Trautwein (2000) ArticleTitleInterleukin 6 and liver regeneration Gut 47 309–12 Occurrence Handle10896929 Occurrence Handle10.1136/gut.47.2.309 Occurrence Handle1:CAS:528:DC%2BD3cXlvVygu7k%3D

    Article  PubMed  CAS  Google Scholar 

  24. T Wustefeld T Rakemann S Kubicka MP Manns C Trautwein (2000) ArticleTitleHyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in mice Hepatology 32 514–22 Occurrence Handle10960443 Occurrence Handle10.1053/jhep.2000.16604 Occurrence Handle1:CAS:528:DC%2BD3cXmsF2mur8%3D

    Article  PubMed  CAS  Google Scholar 

  25. M Glanemann S Munchow A Schirmeier H Al-Abadi F Lippek JM Langrehr et al. (2004) ArticleTitleSteroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regeneration Langenbecks Arch Surg 389 380–6 Occurrence Handle15605169 Occurrence Handle10.1007/s00423-004-0507-6

    Article  PubMed  Google Scholar 

  26. S Sauerland M Nagelschmidt P Mallmann EAM Neugebauer (2000) ArticleTitleRisk and benefits of preoperative high dose methylprednisolone in surgical patients. A systematic review Drug Saf 23 449–61 Occurrence Handle11085349 Occurrence Handle10.2165/00002018-200023050-00007 Occurrence Handle1:CAS:528:DC%2BD3cXosFOksr4%3D

    Article  PubMed  CAS  Google Scholar 

  27. S Takeda R Ogawa K Nakanishi C Kim M Miyashita K Sasajima et al. (1997) ArticleTitleThe effect of preoperative high dose methylprednisolone in attenuating the metabolic response after oesophageal resection Eur J Surg 163 511–7 Occurrence Handle9248985 Occurrence Handle1:STN:280:ByiA1M%2FgsVI%3D

    PubMed  CAS  Google Scholar 

  28. N Sato K Koeda K Ikeda Y Kimura K Aoki T Iwaya et al. (2002) ArticleTitleRandomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancer Ann Surg 236 184–90 Occurrence Handle12170023 Occurrence Handle10.1097/00000658-200208000-00006

    Article  PubMed  Google Scholar 

  29. F Kimura M Miyazaki T Suwa H Itoh S Ambiru H Shimizu K Nakagawa (1998) ArticleTitleHyperactive cytokine response after partial hepatectomy in patients with biliary obstruction Eur Surg Res 30 259–67 Occurrence Handle9704752 Occurrence Handle10.1159/000008585 Occurrence Handle1:CAS:528:DyaK1cXkvVGltr0%3D

    Article  PubMed  CAS  Google Scholar 

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Schmidt, S., Hamann, S., Langrehr, J. et al. Preoperative high-dose steroid administration attenuates the surgical stress response following liver resection: results of a prospective randomized study. J Hepatobiliary Pancreat Surg 14, 484–492 (2007). https://doi.org/10.1007/s00534-006-1200-7

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  • DOI: https://doi.org/10.1007/s00534-006-1200-7

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