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Erschienen in: European Journal of Trauma and Emergency Surgery 6/2016

26.10.2015 | Original Article

Persistent lymphopenia is an independent predictor of mortality in critically ill emergency general surgical patients

verfasst von: P. E. Vulliamy, Z. B. Perkins, K. Brohi, J. Manson

Erschienen in: European Journal of Trauma and Emergency Surgery | Ausgabe 6/2016

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Abstract

Introduction

Lymphopenia has been associated with poor outcome following sepsis, burns and trauma. This study was designed to establish whether lymphocyte count was associated with mortality in emergency general surgery (EGS) patients, and whether persistent lymphopenia was an independent predictor of mortality.

Methods

A retrospective review of a prospectively compiled database of adult patients requiring ICU admission between 2002 and 2013 was performed. EGS patients with acute intra-abdominal pathology and organ dysfunction were included. Lymphocyte counts obtained from the day of ICU admission through to day 7 were examined. Multivariate logistic regression models were used to determine the relationship between persistent lymphopenia and outcome. The primary outcome measure was in-hospital mortality.

Results

The study included 173 patients, of whom 135 (78 %) had a low lymphocyte count at admission to ICU and 91 % (158/173) developed lymphopenia on at least one occasion. Lymphocyte counts were lower among non-survivors compared with survivors on each day from day 2 (0.62 vs 0.81, p = 0.03) through to day 7 (0.87 vs 1.15, p < 0.01). Patients with a persistently low lymphocyte count during the study period had significantly higher mortality when compared to patients with other lymphocyte patterns (64 vs 29 %, p < 0.01). On multivariate regression analysis, persistent lymphopenia was independently associated with increased in-hospital mortality [odds ratio 3.5 (95 % CI 1.7–7.3), p < 0.01].

Conclusion

Lymphopenia is commonly observed in critically ill EGS patients. Patients with persistent lymphopenia are 3.5 times more likely to die and lymphopenia is an independent predictor of increased mortality in this patient group.
Literatur
1.
Zurück zum Zitat Cheadle WG, Pemberton RM, Robinson D, Livingston DH, Rodriguez JL, Polk HC Jr. Lymphocyte subset responses to trauma and sepsis. J Trauma. 1993;35(6):844–9.CrossRefPubMed Cheadle WG, Pemberton RM, Robinson D, Livingston DH, Rodriguez JL, Polk HC Jr. Lymphocyte subset responses to trauma and sepsis. J Trauma. 1993;35(6):844–9.CrossRefPubMed
2.
Zurück zum Zitat Unsinger J, Kazama H, McDonough JS, Hotchkiss RS, Ferguson TA. Differential lymphopenia-induced homeostatic proliferation for CD4+ and CD8+ T cells following septic injury. J Leukoc Biol. 2009;85(3):382–90.CrossRefPubMed Unsinger J, Kazama H, McDonough JS, Hotchkiss RS, Ferguson TA. Differential lymphopenia-induced homeostatic proliferation for CD4+ and CD8+ T cells following septic injury. J Leukoc Biol. 2009;85(3):382–90.CrossRefPubMed
3.
Zurück zum Zitat Maldonado MD, Venturoli A, Franco A, Nunez-Roldan A. Specific changes in peripheral blood lymphocyte phenotype from burn patients. Probable origin of the thermal injury-related lymphocytopenia. Burns. 1991;17(3):188–92.CrossRefPubMed Maldonado MD, Venturoli A, Franco A, Nunez-Roldan A. Specific changes in peripheral blood lymphocyte phenotype from burn patients. Probable origin of the thermal injury-related lymphocytopenia. Burns. 1991;17(3):188–92.CrossRefPubMed
4.
Zurück zum Zitat Heffernan DS, Monaghan SF, Thakkar RK, Machan JT, Cioffi WG, Ayala A. Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit Care. 2012;16(1):R12.CrossRefPubMedPubMedCentral Heffernan DS, Monaghan SF, Thakkar RK, Machan JT, Cioffi WG, Ayala A. Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern. Crit Care. 2012;16(1):R12.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock. 2014;42(5):383–91.CrossRefPubMedPubMedCentral Drewry AM, Samra N, Skrupky LP, Fuller BM, Compton SM, Hotchkiss RS. Persistent lymphopenia after diagnosis of sepsis predicts mortality. Shock. 2014;42(5):383–91.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001;166(11):6952–63.CrossRefPubMed Hotchkiss RS, Tinsley KW, Swanson PE, Schmieg RE Jr, Hui JJ, Chang KC, Osborne DF, Freeman BD, Cobb JP, Buchman TG, et al. Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol. 2001;166(11):6952–63.CrossRefPubMed
7.
Zurück zum Zitat Le Tulzo Y, Pangault C, Gacouin A, Guilloux V, Tribut O, Amiot L, Tattevin P, Thomas R, Fauchet R, Drénou B. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock. 2002;18:487–94.CrossRefPubMed Le Tulzo Y, Pangault C, Gacouin A, Guilloux V, Tribut O, Amiot L, Tattevin P, Thomas R, Fauchet R, Drénou B. Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. Shock. 2002;18:487–94.CrossRefPubMed
8.
Zurück zum Zitat Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med. 1997;25(8):1298–307.CrossRefPubMed Hotchkiss RS, Swanson PE, Cobb JP, Jacobson A, Buchman TG, Karl IE. Apoptosis in lymphoid and parenchymal cells during sepsis: findings in normal and T- and B-cell-deficient mice. Crit Care Med. 1997;25(8):1298–307.CrossRefPubMed
9.
Zurück zum Zitat Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohé J, Lepape A, Ayala A, Monneret G. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009;35(4):678–86.CrossRefPubMed Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohé J, Lepape A, Ayala A, Monneret G. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009;35(4):678–86.CrossRefPubMed
10.
Zurück zum Zitat Heidecke CD, Hensler T, Weighardt H, Zantl N, Wagner H, Siewert JR, Holzmann B. Selective defects of T lymphocyte function in patients with lethal intraabdominal infection. Am J Surg. 1999;178(4):288–92.CrossRefPubMed Heidecke CD, Hensler T, Weighardt H, Zantl N, Wagner H, Siewert JR, Holzmann B. Selective defects of T lymphocyte function in patients with lethal intraabdominal infection. Am J Surg. 1999;178(4):288–92.CrossRefPubMed
12.
Zurück zum Zitat Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74.CrossRefPubMedPubMedCentral Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Inoue S, Suzuki-Utsunomiya K, Okada Y, Taira T, Iida Y, Miura N, Tsuji T, Yamagiwa T, Morita S, Chiba T, et al. Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly. Crit Care Med. 2013;41(3):810–9.CrossRefPubMed Inoue S, Suzuki-Utsunomiya K, Okada Y, Taira T, Iida Y, Miura N, Tsuji T, Yamagiwa T, Morita S, Chiba T, et al. Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly. Crit Care Med. 2013;41(3):810–9.CrossRefPubMed
14.
Zurück zum Zitat Pearse RM, Harrison DA, James P, Watson D, Hinds C, Rhodes A, Grounds RM, Bennett ED. Identification and characterisation of the high-risk surgical population in the United Kingdom. Crit Care. 2006;10(3):R81.CrossRefPubMedPubMedCentral Pearse RM, Harrison DA, James P, Watson D, Hinds C, Rhodes A, Grounds RM, Bennett ED. Identification and characterisation of the high-risk surgical population in the United Kingdom. Crit Care. 2006;10(3):R81.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Cullinane M, Gray AJ, Hargraves CM, et al. The 2003 Report of the National confidential enquiry into peri-operative deaths. London: NCEPOD; 2003. Cullinane M, Gray AJ, Hargraves CM, et al. The 2003 Report of the National confidential enquiry into peri-operative deaths. London: NCEPOD; 2003.
16.
Zurück zum Zitat Intensive Care National Audit & Research Centre (ICNARC), London 2010. Data derived from Case Mix Programme Database based on 170,105 admissions to 185 adult, general critical care units in NHS hospitals across England, Wales and Northern Ireland. Intensive Care National Audit & Research Centre (ICNARC), London 2010. Data derived from Case Mix Programme Database based on 170,105 admissions to 185 adult, general critical care units in NHS hospitals across England, Wales and Northern Ireland.
17.
Zurück zum Zitat Wickel DJ, Cheadle WG, Mercer-Jones MA, Garrison RN. Poor outcome from peritonitis is caused by disease acuity and organ failure, not recurrent peritoneal infection. Ann Surg. 1997;225:744–53.CrossRefPubMedPubMedCentral Wickel DJ, Cheadle WG, Mercer-Jones MA, Garrison RN. Poor outcome from peritonitis is caused by disease acuity and organ failure, not recurrent peritoneal infection. Ann Surg. 1997;225:744–53.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care. 2011;17(2):153–9.CrossRefPubMed Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care. 2011;17(2):153–9.CrossRefPubMed
19.
Zurück zum Zitat Lord JM, Midwinter MJ, Chen Y, Belli A, Brohi K, Kovacs EJ, Koenderman L, Kubes P, Lilford RJ. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014;384:1455–65.CrossRefPubMedPubMedCentral Lord JM, Midwinter MJ, Chen Y, Belli A, Brohi K, Kovacs EJ, Koenderman L, Kubes P, Lilford RJ. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014;384:1455–65.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Cheadle WG, Spain DA. The continuing challenge of intra-abdominal infection. Am J Surg. 2003;186(5A):15S–22S.CrossRefPubMed Cheadle WG, Spain DA. The continuing challenge of intra-abdominal infection. Am J Surg. 2003;186(5A):15S–22S.CrossRefPubMed
21.
Zurück zum Zitat Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, STROBE Initiative. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Int Med. 2007;147(8):573–7.CrossRef Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, STROBE Initiative. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Int Med. 2007;147(8):573–7.CrossRef
22.
Zurück zum Zitat Shafi S, Aboutanos MB, Agarwal S Jr, Brown CV, Crandall M, Feliciano DV, Guillamondegui O, Haider A, Inaba K, AAST Committee on Severity Assessment and Patient Outcomes, et al. Emergency general surgery: definition and estimated burden of disease. J Trauma Acute Care Surg. 2013;74(4):1092–7.CrossRefPubMed Shafi S, Aboutanos MB, Agarwal S Jr, Brown CV, Crandall M, Feliciano DV, Guillamondegui O, Haider A, Inaba K, AAST Committee on Severity Assessment and Patient Outcomes, et al. Emergency general surgery: definition and estimated burden of disease. J Trauma Acute Care Surg. 2013;74(4):1092–7.CrossRefPubMed
23.
Zurück zum Zitat Vincent JL, de Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793–800. Vincent JL, de Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793–800.
24.
Zurück zum Zitat Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.CrossRefPubMed Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.CrossRefPubMed
25.
Zurück zum Zitat Arnold CR, Wolf J, Brunner S, Herndler-Brandstetter D, Grubeck-Loebenstein B. Gain and loss of T cell subsets in old age—age-related reshaping of the T cell repertoire. J Clin Immunol. 2011;31(2):137–46.CrossRefPubMed Arnold CR, Wolf J, Brunner S, Herndler-Brandstetter D, Grubeck-Loebenstein B. Gain and loss of T cell subsets in old age—age-related reshaping of the T cell repertoire. J Clin Immunol. 2011;31(2):137–46.CrossRefPubMed
27.
Zurück zum Zitat Bandyopadhyay G, Bankey PE, Miller-Graziano CL. Trauma patients’ elevated tumor necrosis related apoptosis inducing ligand (TRAIL) contributes to increased T cell apoptosis. Clin Immunol. 2012;145(1):44–54.CrossRefPubMedPubMedCentral Bandyopadhyay G, Bankey PE, Miller-Graziano CL. Trauma patients’ elevated tumor necrosis related apoptosis inducing ligand (TRAIL) contributes to increased T cell apoptosis. Clin Immunol. 2012;145(1):44–54.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Crary B, Hauser SL, Borysenko M, Kutz I, Hoban C, Ault KA, Weiner HL, Benson H. Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans. J Immunol. 1983;131(3):1178–81.PubMed Crary B, Hauser SL, Borysenko M, Kutz I, Hoban C, Ault KA, Weiner HL, Benson H. Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans. J Immunol. 1983;131(3):1178–81.PubMed
29.
Zurück zum Zitat Boomer JS, Shuherk-Shaffer J, Hotchkiss RS, Green JM. A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis. Crit Care. 2012;16(3):R112.CrossRefPubMedPubMedCentral Boomer JS, Shuherk-Shaffer J, Hotchkiss RS, Green JM. A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis. Crit Care. 2012;16(3):R112.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Unsinger J, McGlynn M, Kasten KR, Hoekzema AS, Watanabe E, Muenzer JT, McDonough JS, Tshoep J, Ferguson TA, McDunn JE, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis. J Immunol. 2010;184:3768–79.CrossRefPubMedPubMedCentral Unsinger J, McGlynn M, Kasten KR, Hoekzema AS, Watanabe E, Muenzer JT, McDonough JS, Tshoep J, Ferguson TA, McDunn JE, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis. J Immunol. 2010;184:3768–79.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P, Xanthoudakis S, Roy S, Black C, Grimm E, et al. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol. 2000;1(6):496–501.CrossRefPubMed Hotchkiss RS, Chang KC, Swanson PE, Tinsley KW, Hui JJ, Klender P, Xanthoudakis S, Roy S, Black C, Grimm E, et al. Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte. Nat Immunol. 2000;1(6):496–501.CrossRefPubMed
32.
Zurück zum Zitat Hensler T, Hecker H, Heeg K, Heidecke CD, Bartels H, Barthlen W, Wagner H, Siewert JR, Holzmann B. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997;65:2283–91.PubMedPubMedCentral Hensler T, Hecker H, Heeg K, Heidecke CD, Bartels H, Barthlen W, Wagner H, Siewert JR, Holzmann B. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997;65:2283–91.PubMedPubMedCentral
Metadaten
Titel
Persistent lymphopenia is an independent predictor of mortality in critically ill emergency general surgical patients
verfasst von
P. E. Vulliamy
Z. B. Perkins
K. Brohi
J. Manson
Publikationsdatum
26.10.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Trauma and Emergency Surgery / Ausgabe 6/2016
Print ISSN: 1863-9933
Elektronische ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-015-0585-x

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