Journal of Hepato-Biliary-Pancreatic Surgery

, Volume 14, Issue 5, pp 484–492 | Cite as

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

  • Sven C. Schmidt
  • Susanne Hamann
  • Jan M. Langrehr
  • Conny Höflich
  • Jens Mittler
  • Dictmar Jacob
  • Peter Neuhaus
Original articles



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.


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.


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.


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.


Liver Resection Hepatic Resection Liver Regeneration Steroid Administration Pringle Maneuver 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Faist, E, Schinkel, C, Zimmer, S 1996Update on the mechanisms of immune suppression of injury and immune modulationWorld J Surg204549PubMedCrossRefGoogle Scholar
  2. 2.
    Menger, MD, Vollmar, B 2004Surgical trauma: hyperinflammation versus immunosuppression?Langenbecks Arch Surg38947584PubMedCrossRefGoogle Scholar
  3. 3.
    Lin, E, Calvano, SE, Lowry, SF 2000Inflammatory cytokines and cell response in surgerySurgery12711726PubMedCrossRefGoogle Scholar
  4. 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;20:864–74Google Scholar
  5. 5.
    Jerin, A, Pozar-Lukanovic, N, Sojar, V, Stanisavljevic, D, Paver-Erzen, V, Osredkar, J 2003Balance of pro- and anti-inflammatory cytokines in liver surgeryClin Chem Lab Med41899903PubMedCrossRefGoogle Scholar
  6. 6.
    Nagelschmidt, M, Fu, ZX, Saad, S, Dimmeler, S, Neugebauer, E 1999Preoperative high dose methylprednisolone improves patients outcome after abdominal surgeryEur J Surg1659718PubMedCrossRefGoogle Scholar
  7. 7.
    Shimada, M, Saitoh, A, Kano, T, Takenaka, K, Sugimachi, K 1996The effect of a perioperative steroid pulse on surgical stress in hepatic resectionInt Surg814951PubMedGoogle Scholar
  8. 8.
    Yamashita, Y, Shimada, M, Hamatsu, T, Rikimaru, T, Tanaka, S, Shirabe, K, Sugimachi, K 2001Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trialArch Surg13632833PubMedCrossRefGoogle Scholar
  9. 9.
    Muratore, A, Ribero, D, Ferrero, A, Bergero, R, Capussotti, L 2003Prospective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clampingBr J Surg901722PubMedCrossRefGoogle Scholar
  10. 10.
    Aldrighetti, L, Pulitano, C, Arru, M, Finazzi, R, Catena, M, Soldini, L,  et al. 2006Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: a prospective randomized studyLiver Transpl129419PubMedCrossRefGoogle Scholar
  11. 11.
    Docke, WD, Hoflich, C, Davis, KA, Rottgers, K, Meisel, C, Kiefer, P,  et al. 2005Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized studyClin Chem5123417PubMedCrossRefGoogle Scholar
  12. 12.
    Kimura, F, Shimizu, H, Yoshidome, H, Ohtsuka, M, Kato, A, Yoshitomi, H,  et al. 2006Circulating cytokines, chemokines, and stress hormones are increased in patients with organ dysfunction following liver resectionJ Surg Res13310212PubMedCrossRefGoogle Scholar
  13. 13.
    Biffl, WL, Moore, EE, Moore, FA, Peterson, VM 1996Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation?Ann Surg22464764PubMedCrossRefGoogle Scholar
  14. 14.
    Pradier, O, Willems, F, Abramowicz, D, Schandene, L, De Boer, M, Thielemans, K,  et al. 1996CD40 engagement induces monocyte procoagulant activity through an interleukin-10 resistant pathwayEur J Immunol26304854PubMedCrossRefGoogle Scholar
  15. 15.
    Hensler, T, Hecker, H, Heeg, K, Heidecke, CD, Bartels, H, Barthlen, W,  et al. 1997Distinct mechanisms of immunosuppression as a consequence of major surgeryInfect Immun65228391PubMedGoogle Scholar
  16. 16.
    Nystrom, PO 1998The systemic inflammatory response syndrome: definitions and aetiologyJ Antimicrob Chemother4117PubMedCrossRefGoogle Scholar
  17. 17.
    Holte, K, Kehlet, H 2002Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implicationsJ Am Coll Surg195694712PubMedCrossRefGoogle Scholar
  18. 18.
    Scheinman, RI, Gualberto, A, Jewell, CM, Cidlowski, JA, Baldwin, AS,Jr 1995Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptorsMol Cell Biol1594353PubMedGoogle Scholar
  19. 19.
    Braughler, JM 1985Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomesJ Neurochem4412828PubMedCrossRefGoogle Scholar
  20. 20.
    Volk, HD, Thieme, M, Heym, S, Docke, WD, Ruppe, U, Tausch, W,  et al. 1991Alterations in function and phenotype of monocytes from patients with septic disease—predictive value and new therapeutic strategiesBehring Inst Mitt8820815PubMedGoogle Scholar
  21. 21.
    Buunen, M, Gholghesaei, M, Veldkamp, R, Meijer, DW, Bonjer, HJ, Bouvy, ND 2004Stress response to laparoscopic surgery: a reviewSurg Endosc1810228PubMedCrossRefGoogle Scholar
  22. 22.
    Carter, JJ, Whelan, RL 2001The immunologic consequences of laparoscopy in oncologySurg Oncol Clin N Am1065577PubMedGoogle Scholar
  23. 23.
    Streetz, KL, Luedde, T, Manns, MP, Trautwein, C 2000Interleukin 6 and liver regenerationGut4730912PubMedCrossRefGoogle Scholar
  24. 24.
    Wustefeld, T, Rakemann, T, Kubicka, S, Manns, MP, Trautwein, C 2000Hyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in miceHepatology3251422PubMedCrossRefGoogle Scholar
  25. 25.
    Glanemann, M, Munchow, S, Schirmeier, A, Al-Abadi, H, Lippek, F, Langrehr, JM,  et al. 2004Steroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regenerationLangenbecks Arch Surg3893806PubMedCrossRefGoogle Scholar
  26. 26.
    Sauerland, S, Nagelschmidt, M, Mallmann, P, Neugebauer, EAM 2000Risk and benefits of preoperative high dose methylprednisolone in surgical patients. A systematic reviewDrug Saf2344961PubMedCrossRefGoogle Scholar
  27. 27.
    Takeda, S, Ogawa, R, Nakanishi, K, Kim, C, Miyashita, M, Sasajima, K,  et al. 1997The effect of preoperative high dose methylprednisolone in attenuating the metabolic response after oesophageal resectionEur J Surg1635117PubMedGoogle Scholar
  28. 28.
    Sato, N, Koeda, K, Ikeda, K, Kimura, Y, Aoki, K, Iwaya, T,  et al. 2002Randomized study of the benefits of preoperative corticosteroid administration on the postoperative morbidity and cytokine response in patients undergoing surgery for esophageal cancerAnn Surg23618490PubMedCrossRefGoogle Scholar
  29. 29.
    Kimura, F, Miyazaki, M, Suwa, T, Itoh, H, Ambiru, S, Shimizu, H, Nakagawa, K 1998Hyperactive cytokine response after partial hepatectomy in patients with biliary obstructionEur Surg Res3025967PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 2007

Authors and Affiliations

  • Sven C. Schmidt
    • 1
  • Susanne Hamann
    • 1
  • Jan M. Langrehr
    • 1
  • Conny Höflich
    • 2
  • Jens Mittler
    • 1
  • Dictmar Jacob
    • 1
  • Peter Neuhaus
    • 1
  1. 1.Department of General-, Visceral- and Transplantation SurgeryUniversity Medicine Berlin, Charité Campus Virchow ClinicBerlinGermany
  2. 2.Institute of Medical ImmunologyUniversity Medicine Berlin, Charité Campus MitteBerlinGermany

Personalised recommendations