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Terminal complement complex in septic shock with capillary leakage: marker of complement activation?

Published online by Cambridge University Press:  29 June 2005

T. Schuerholz ,
M. Leuwer ,
M. Cobas-Meyer ,
B. Vangerow ,
F. Kube ,
M. Kirschfink  and
G. Marx
T. Schuerholz
Affiliation:
Friedrich Schiller University, Department of Anaesthesiology and Intensive Care, Jena, Germany
M. Leuwer
Affiliation:
University of Liverpool, University Department of Anaesthesia, Liverpool, UK
M. Cobas-Meyer
Affiliation:
Eli Lilly and Company, Critical Care Division, Heidelberg, Germany
B. Vangerow
Affiliation:
Eli Lilly and Company, Critical Care Division, Heidelberg, Germany
F. Kube
Affiliation:
Hannover Medical School, Department of Anaesthesia, Hannover, Germany
M. Kirschfink
Affiliation:
University of Heidelberg, Institute of Immunology, Heidelberg, Germany
G. Marx
Affiliation:
Friedrich Schiller University, Department of Anaesthesiology and Intensive Care, Jena, Germany
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Summary

Background and objective: The aim of this study was to evaluate the value of terminal complement complex (C5b-9) plasma levels as a marker for complement activation in septic shock with concomitant capillary leak syndrome. Methods: In a prospective animal study 10 fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.6 ± 1.3 kg) were investigated over a period of 8 h. Sepsis was induced by faecal peritonitis (1 g kg−1 body weight faeces, n = 5) and compared to controls (n = 5). The animals received 6% hydroxyethyl starch 200/0.5 to maintain a central venous pressure of 12 mmHg. To quantify capillary leak syndrome, albumin escape rate was measured using 99mTc-labelled human serum albumin. Plasma levels of terminal complement complex were measured in a double antibody immunoassay (neoepitope-specific MoAb aE11 as catching antibody). Immunohistological studies of renal specimens were performed to detect terminal complement complex deposition. Results: Albumen escape rate increased in septic animals (+52%) compared to controls (+3%, P < 0.05). Plasma levels of terminal complement complex decreased during the study period in both groups. In septic animals this finding was accompanied by a significant deposition of terminal complement complex in renal specimens (P < 0.05). Conclusion: We found an activation of the complement system proven by marked deposition of terminal complement complex in renal specimen, while its plasma levels decreased during the study period in septic and control animals. These results suggest that in septic shock with capillary leak syndrome plasma level of terminal complement complex may not be a reliable marker of complement activation.

Keywords

SEPSISSEPSIS SYNDROMECOMPLEMENTCOMPLEMENT MEMBRANE ATTACK COMPLEXIMMUNOHISTOCHEMISTRYCAPILLARY LEAK SYNDROME
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 7 , July 2005 , pp. 541 - 547
Copyright
© 2005 European Society of Anaesthesiology

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References

Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. New Engl J Med 2003; 348: 1546–1554.Google Scholar
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29: 1303–1310.Google Scholar
de Boer JP, Wolbink GJ, Thijs LG, Baars JW, Wagstaff J, Hack CE. Interplay of complement and cytokines in the pathogenesis of septic shock. Immunopharmacology 1992; 24: 135–148.Google Scholar
Robin M, Intrator L, Rapin M. Complement activation in septic shock. New Engl J Med 1975; 293: 304.Google Scholar
Hack CE, Nuijens JH, Felt-Bersma RJ et al. Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis. Am J Med 1989; 86: 20–26.Google Scholar
Hack C, Voerman H, Eisele B et al. C1-esterase inhibitor substitution in sepsis. Lancet 1992; 339: 378.Google Scholar
Marx G, Nashan B, Cobas Meyer M et al. Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor. Intens Care Med 1999; 25: 1017–1020.Google Scholar
Morgan BP. Regulation of the complement membrane attack pathway. Crit Rev Immunol 1999; 19: 173–198.Google Scholar
Heideman M, Norder-Hansson B, Bengtson A, Mollnes TE. Terminal complement complexes and anaphylatoxins in septic and ischemic patients. Arch Surg 1988; 123: 188–192.Google Scholar
Lin R, Astiz M, Saxon J, Saha D, Rackow E. Alterations in C3, C4, factor B, and related metabolites in septic shock. Clin Immunol Immunopathol 1993; 69: 136–142.Google Scholar
George C, Regnier B, Le Gall JR, Gastinne H, Carlet J, Rapin M. Hypovolaemic shock with oedema due to increased capillary permeability. Intens Care Med 1978; 4: 159–163.Google Scholar
Fleck A, Raines G, Hawker F et al. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet 1985; 1: 781–784.Google Scholar
Nuijens JH, Huijbregts CC, Eerenberg Belmer AJ et al. Quantification of plasma factor XIIa-Cl(−)-inhibitor and kallikrein-Cl(−)-inhibitor complexes in sepsis. Blood 1988; 72: 1841–1848.Google Scholar
Marx G, Cobas Meyer M, Schuerholz T et al. Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage. Intens Care Med 2002; 28: 629–635.Google Scholar
Radke A, Mottaghy K, Goldmann C et al. C1 inhibitor prevents capillary leakage after thermal trauma. Crit Care Med 2000; 28: 3224–3232.Google Scholar
Loss M, Vangerow B, Schmidtko J et al. Acute vascular rejection is associated with systemic complement activation in a pig-to-primate kidney xenograft model. Xenotransplantation 2000; 7: 186–196.Google Scholar
Pearson ES, Please N. Relation between the shape of population distribution and the robustness of four simple test statistics. Biometrika 1975; 62: 223–241.Google Scholar
Traber DL. Microvascular leakage in sepsis. Crit Care Med 2000; 28: 882–883.Google Scholar
Filep JG. Endogenous endothelin modulates blood pressure, plasma volume, and albumin escape after systemic nitric oxide blockade. Hypertension 1997; 30: 22–28.Google Scholar
Marx G, Vangerow B, Burczyk C et al. Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients. Intens Care Med 2000; 26: 1252–1258.Google Scholar
Sumpelmann R, Schurholz T, Marx G, Thorns E, Hausdorfer J. Haemodynamic, acid–base and electrolyte changes during plasma replacement with hydroxyethyl starch or crystalloid solution in young pigs. Paediatr Anaesth 2000; 10: 173–179.Google Scholar
Obertacke U, Neudeck F, Majetschak M et al. Local and systemic reactions after lung contusion: an experimental study in the pig. Shock 1998; 10: 7–12.Google Scholar
Kerr MA, Wilton E, Naama JK, Whaley K. Circulating immune complexes associated with decreased complement-mediated inhibition of immune precipitation in sera from patients with bacterial endocarditis. Clin Exp Immunol 1986; 63: 359–366.Google Scholar
Boulton-Jones JM, Sissons JG, Evans DJ, Peters DK. Renal lesions of subacute infective endocarditis. BMJ 1974; 6: 11–14.Google Scholar
Vakeva A, Meri S, Lehto T, Laurila P. Activation of the terminal complement cascade in renal infarction. Kidney Int 1995; 47: 918–926.Google Scholar
Morita Y, Ikeguchi H, Nakamura J, Hotta N, Yuzawa Y, Matsuo S. Complement activation products in the urine from proteinuric patients. J Am Soc Nephrol 2000; 11: 700–707.Google Scholar
Busund R, Balteskard L, Ronning G, Hogasen K, Revhaug A. Fatal myocardial depression and circulatory collapse associated with complement activation induced by plasma infusion in severe porcine sepsis. Acta Anaesthesiol Scand 1995; 39: 100–108.Google Scholar