Article information
Introducción
Se analizan las definiciones y las teorías fisiopatológicas que se han elaborado para explicar la evolución del síndrome inflamatorio hacia la disfunción multisistémica, analizando el valor predictivo de los diferentes mediadores y de los cambios metabólicos. Tras revisar las características del síndrome inflamatorio se recogen los diferentes intentos terapéuticos para modular el SIRS
MaterialSe ha revisado la bibliografía recogida en Medline, fundamentalmente estudios clínicos realizados en pacientes críticos
ResumenSe describen tres síndromes (SIRS, CARS y MARS) que pueden configurar la respuesta inflamatoria. La evolución hacia la disfunción multisistémica es explicada por diversas teorías, pero queda por estudiar los mecanismos que permiten la modulación y supresión de la respuesta inflamatoria. A pesar de su importancia fisiopatológica, las citocinas de inicio no son buenos marcadores pronósticos. Los marcadores de fase aguda, así como los cambios en el metabolismo lipídico y del hierro, muestran una mejor correlación con la evolución. Tras comentar que la respuesta inflamatoria no es proporcional, estructural ni universal, se revisan los diversos intentos terapéuticos que pretenden antagonizar dicha respuesta. Se comentan las tres líneas que deben regir para las investigaciones futuras
Palabras clave:
SIRS
CARS
síndrome de disfunción multisistémica
marcadores inflamatorios
reactantes de fase aguda
Introduction
The different syndrome definitions that have been developed to explain how the inflammatory syndrome may herald multisystemic dysfunction. Thus, the predictive value of the different mediators and metabolic changes have been analyzed. Once the inflammatory syndrome features were revised, those therapeutic approaches that will likely improve its prognosis are resumed
MethodsSystematic review of Medline’s bibliography, focusing on clinical trials performed in critically ill patients
SummaryThree syndromes (SIRS, CARS, MARS) which can comprise the inflammatory syndome are described. Several hypothesis illustrate its progression to multisystemic dysfunction, but further research is required to explain how inflammation can be regulated or even suppressed. Early relieved cytokines play a major role, but are devoid of prognostic value; on the other hand acute phase markers and changes in lipid and iron metabolism correlate better with final outcome. While the inflammatory reaction is by no means proportional, structural nor universal we turn to assay the different therapeutic approaches intended to antagonize it. The three principles which should underlie further research are reviewed
Key words:
SIRS
CARS
multysystemic dysfunction syndrome
inflammatory markers
acute phase reactants
Full text is only aviable in PDF
Bibliografía
[1.]
American College of Chest Physcians/Society fo Critical Care Medicine Consensus Conference: “Definitions for sepsisorgan failureguidelines for the use of innovative therapies in sepsis”.
Crit Care Med, 20 (1992), pp. 864-874
[2.]
M.S. Rangel-Frausto, D. Pittet, M. Costigan, T. Hwang, C.S. Davis, R.P. Wenzel.
The natural history of the systemic inflammatory response syndrome (SIRS). A pospective study.
JAMA, 273 (1995), pp. 117-123
[3.]
J.L. Vincent.
Dear SIRS, I’m sorry to say that I don’t like you.
Crit Care Med, 25 (1997), pp. 372-374
[4.]
H.H. Simms.
Mechanisms of immune suppression in critically ill patients.
New Horizons, 7 (1999), pp. 147-157
[5.]
G. Bellingan.
Inflammatory cell activation in sepsis.
Br Med Bulletin, 55 (1999), pp. 12-29
[6.]
R.C. Bone.
Sir Isaac Newton, sepsis, SIRS and CARS.
Crit Care Med, 24 (1996), pp. 1.125-1.128
[7.]
R.C. Bone, C.J. Grozdin, R.A. Balk.
Sepsis: A new hypothesis for pathogenesis of the disease process.
Chest, 112 (1997), pp. 235-243
[8.]
F.A. Moore, E.E. Moore.
Evolving concepts in the pathogenesis of postinjury multiple organ failure. Horizons in Trauma Surgery.
Surg Clin North Amer, 75 (1995), pp. 257-277
[9.]
J.C. Marshall, D.J. Cook, N.V. Christou, G.R. Bernand, C.L. Sprung, W.J. Sibbald.
Multiple organ dysfunction score: A reliable descriptor of a complex clinical outcome.
Crit Care Med, 23 (1995), pp. 1.638-1.652
[10.]
P.J. Godin, T.G. Buchman.
Uncoupling of biological oscillators: A complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome.
Crit Care Med, 24 (1996), pp. 1.107-1.116
[11.]
D.C. Henderson, J.J. Ripping.
Stimulus-dependent production of cytokines and pterins by peripheral blood mononuclear cells.
Immunol Lett, 45 (1995), pp. 29-34
[12.]
K.J. Tracery, A. Cerami.
Tumor necrosis factor: An updated review of its biology.
Crit Care Med, 21 (1993), pp. 415-422
[13.]
L.L. Moldawer, S.F. Lowry.
Interactions among proinflammatory cytokines and the classic-endocrine system in sepsis and inflammatori.
Organ Metabolism and Nutrition: Ideas for future Critical Care, pp. 119-136
[14.]
R.M. Strieter, S.L. Kunkel, R.C. Bone.
Role of tumor necrosis factor-alfa in disease states and inflammation.
Crit Care Med, 21 (1993), pp. 447-463
[15.]
P. Kaufman, G.P. Tilz, A. Lueger, U. Demel.
Elevated plasma levels of soluble tumor necrosis factor (sTNFRp60) reflect severity of acute pancreatitis.
Intensive Care Med, 23 (1997), pp. 841-848
[16.]
M. Brockhaus.
Soluble TNF recpetor: What is the significance.
Intensive Care Med, 23 (1997), pp. 808-809
[17.]
C. Silva Mejías, F. Gamboa Antiñolo, L.F. López Cortés, M. Cruz Ruiz, J. Pachón.
Interleukin-1 beta in pleural fluids of different etiologies. Its role as inflammatory mediator in empyema.
Chest, 108 (1995), pp. 942-945
[18.]
L.G. Thijs, C.E. Hack.
Time course of cytokine levels in sepsis.
Intensive Care Med, 21 (1995), pp. 258-263
[19.]
M.R. Pinsky, J.L. Vincent, J. Deviere, M. Alegre, R.J. Kahn, E. Dupont.
Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality.
Chest, 103 (1993), pp. 565-575
[20.]
O.H. Nielsen, T. Ciardelli, Z. Wu, E. Langholz, I. Kirman.
Circulating soluble interleukine-2 receptor alpha and beta chain inflammatory bowel disease.
Am J Gastroenterol, 90: 1301-1306 (1995),
[21.]
J.T. Dipiro, T.R. Howdieshell, J.K. Goddard, D.B. Callaway, R.G. Hamilton, A.R. Jr. Mansberger.
Association of interleukin-4 plasma levels with traumatic injury and clinical course.
Arch Surg, 130 (1995), pp. 1.159-1.162
[22.]
A. Marchand, J. Deviere, B. Byl, D. De Groote, J.L. Vincent, M. Goldman.
Interleukin-10 production during septicaemia.
Lancet, 343 (1994), pp. 707-708
[23.]
L.A. Doughty, S.S. Kaplan, J.A. Carcillo.
Inflammatory and nitric oxide responses in pediatric sepsis and organ failure.
Crit Care Med, 24: 1137-1143 (1996),
[24.]
S.J.H. Van Deventer.
Tolerance and susceptibility to bacterial endotoxins.
Organ Metabolism and Nutrition: Ideas for future Critical Care, pp. 149-169
[25.]
N. Borregaard, L. Kjeldsen, H. Sengelev, M.S. Diamond, T.A. Springer, H.C. Anderson, et al.
Changes in subcellular localization and surface expression of L-selectin, alkaline phosphatase, and Mac-1 in human neutrophils during stimulation with inflammatory mediators.
J Leukoc Biol, 56 (1994), pp. 80-87
[26.]
P.H. Jakobsen, S. Morris-Jones, A. Ronn, L. Hviid, T.G. Theander, I.M. Elhassan, et al.
Increased plasma concentration of sICAM-1, sVCAM-1 and s-ELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity.
Immunology, 83 (1994), pp. 665-669
[27.]
S. Satoh, A.W. Thompson, K. Nakamura, V. Warty, S. Todo.
Circulating ICAM-1, E-selectin, IL-2 receptor, and HLA class I in human small bowel, liver and small bowel-plus-liver transplant recipients.
Transplantation, 60 (1995), pp. 558-562
[28.]
A.J. Rosembloom, M.R. Pinsky, J.L. Bruant, A. Shin, T. Tran, T. Whiteside.
Leukocyte activation in the peripheral blood of patients with cirrhosis of liver and SIRS. Correlation with serum interleukin-6 levels and organ dysfunction.
JAMA, 274 (1995), pp. 58-65
[29.]
F.J. Neumann, I. Ott, M. Gawaz, G. Richardt, H. Holzapfel, M. Jochun, et al.
Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.
Circulation, 92: 748-755 (1995),
[30.]
B. Nohe, H.J. Dieterich, M. Eichner, K. Unertl.
Certain batches of albumin solutions influence the expression of endothelial cell adhesion molecules.
Intensive Care Med, 25 (1999), pp. 1.381-1.385
[31.]
J.P. Christensen, J. Johansen, O. Marker, A.R. Thomsen.
Circulating intercellular adhesion molecule-1 (sICAM-1) as an early and sensitive marker for virus-induced T cell activation.
Clin Exp Immunol, 102 (1995), pp. 268-273
[32.]
P. Kaufmann, G.P. Tilz, K.H. Smolle, U. Demel, G.J. Krejs.
Increased plasma concentrations of circulating intercellular adhesión molecule-1 (cICAM-1) in patients with necrotizing pancreatitis.
Immunolobiology, 195 (1996), pp. 209-219
[33.]
M.A. Boermeester, P.A. Van Leeuwen, S.M. Coyle, G.J. Wolbink, C.E. Hack, S.F. Lowry.
Interleukin-1 blockade attenuates release and dysregulation of the hemostatic mechanism during human sepsis.
Arch Surg, 130 (1995), pp. 739-748
[34.]
K. Saatvedt, H. Lindberg, S. Michelsen, T.E. Mollnes.
Release of interleukin-6 and activation of complement during and after pediatric cardiopulmonary bypass. Effect of autotransfusion of shed mediastinal blood and ultrafiltration.
Citokine, 8 (1996), pp. 417-420
[35.]
J.N. Hoffmann, W.H. Hartl, R. Deppische, E. Faist, M. Jochum, D. Inthorn.
Hemofiltratiion in human sepsis: Evidence for elimination of immunomodulatory substances.
Kidney International, 48 (1995), pp. 1.563-1.570
[36.]
G.P. Chrousos.
The hypothalamic-pituitary-adrenal axis and immune-mediated inflammatorion.
N Engl J Med, 332 (1995), pp. 1.351-1.362
[37.]
A. García de Lorenzo, J. López Martínez, J.M Añón, M. Sánchez Castilla, D. Díaz Díaz, C. Vaquero Collado.
Anterior pituitary and thyroid response after trauma. Modifying factors.
Intensive Care Med, 23 (1997), pp. 188
[38.]
M. Assicot, D. Gendrel, H. Carsin, J. Raymond, J. Guilbaud, C. Bohuon.
High serum procalcitonin concentrations in patients with sepsis and infection.
Lancet, 341 (1993), pp. 515-518
[39.]
B. Al-Nawas, I. Krammer, P.M. Shah.
Procalcitonin in diagnosis of severe infection.
Eur J Med Res, 1 (1996), pp. 331-333
[40.]
J. López Martínez, M. Sánchez Castilla, S. Temprano Vázquez, R. Díaz Abad, J. Rebollo Ferreiro, F. Del Nogal Sáez.
Short half-life proteins and cholesterol in septic patients: Inflammatory or nutritional markers?.
8th European Congress of Intensive Care Medicine. II. Free papers, pp. 259-263
[41.]
W.S. Tillet, T. Jr. Francis.
Serological reactions in pneumonia with mon-protein somatic fraction of Pneumococcus.
J Exp Med, 52 (1930), pp. 561-571
[42.]
H.R. Colten.
Molecular and cellular control of the tissuespecific inflammatory response.
Organ Metabolism and Nutrition: Ideas for future Critical Care, pp. 137-148
[43.]
G.W. Duff.
Cytokines and acute phese proteins in rheumatoid arthritis.
Scand J Rheumatol, 100 (1994), pp. 9-19
[44.]
W.D. Jr. Blackburn.
Validity of acute phase proteins as markers of disease activity.
J Rheumatol, 42 (1994), pp. 9-13
[45.]
S.M. Yentis, N. Soni, J. Sheldon.
C-reactive protein as an indicator of resolution of sepsis in the intensive care unit.
Intensive Care Med, 21 (1995), pp. 602-605
[46.]
M. Kaezmierczak, M. Sobieska, K. Wiktorowicz, H. Wysocki.
Changes of acute phase proteins glycosylation profile as a possible prognostic marker in myocardial infarction.
In J Cardiol, 49 (1995), pp. 201-207
[47.]
J. López Martí, S. Temprano Vánezquez, M. Sánchez Castilla, A. Algora Weber, J. Jiménez Jiménez, F. Del Nogal Sáez.
“Metabolismo del hierro en el paciente crítico.
Med Intensiva, 19 (1995), pp. 285-292
[48.]
M. Sánchez Castilla, J. López Martínez, M. Teulon González, J. Jiménez Jiménez, P. Rodríguez Tato, Lis M.S. Asuero de.
Iron metabolism in elective surgery: The role of anaesthesia.
8th European Congress of Intensive Care Medicine. II. Free papers, pp. 281-284
[49.]
F. Bobbio-Pallavicine, G. Verde, P. Spriano, R. Losi, M.G. Bosatra, A. Braschi, et al.
Estado del hierro corporal en los pacientes en estado crítico: significación de la ferritina sérica. 3Intensive Care Med (ed. eespañola, 15 (1989), pp. 181-188
[50.]
J. López Martínez, M. Sánchez Castilla, M.A. García Salazar, M.J. Jiménez Martín, I. Moreno Porras, F. Del Nogal Sáez.
Acutephase proteins in septic patients. Prognostic related utility and restriction.
Intensive Care Med, 23 (1997), pp. 64
[51.]
J.A. Viedma, M. Pérez Matero, J. Agulló, J.E. Domínguez, F. Carballo.
Inflammatory response in the early prediction of severity in human acute pancreatitis.
Gut, 35 (1994), pp. 822-827
[52.]
R.F. Beezhold, C. Personius.
Fibronectin fragments stimulate tumor necrosis factor secretion by human monocytes.
J Leuk Biol, 51 (1993), pp. 59-64
[53.]
M. Christiansen, C.K. Hogdall, C. Brihmer.
Alpha-fetoprotein and the acute phase response. A study using acute pelvic inflammatory disease as a model system.
Clin Chim Acta, 235 (1995), pp. 71-79
[54.]
C.H. Lang, C. Dobrescu, C.J. Bagby.
Tumor necrosis factor impairs insulin action on perpheral glucose.
Endocrinology, 130 (1992), pp. 43-52
[55.]
A. García de Lorenzo, J.M. Añón, J. López Martínez, J. Pelaez, M. Sisón, Castilla M. Sánchez.
Neuroendocrine and thyroid responses after trauma: Does head injury make and difference?.
Crit Care Med, 25 (1997), pp. 132
[56.]
C. Álvarez, A. Ramos.
Lipids, lipoproteins and apoproteins in serum during infection.
Clin Chem, 32 (1986), pp. 142-145
[57.]
C. Ortiz Leyba, J. Zaldumbide Amézaga, M. Planas Vila.
Soporte nutricional en la sepsis.
Soporte metabólico nutricional del paciente crítico, pp. 96-111
[58.]
F.J. Becares, J. López Martínez, P. De Juana, M. Sánchez Castilla, B. García, et al.
Valor pronóstico de los parámetros bioquímicos en el síndrome de respuesta inflamatoria sistémica.
Nutr Hosp, 12 (1997), pp. 31
[59.]
J. López Martínez, M. Sánchez Castilla, F.J. Ordóñez González, S. Temprano Vázquez, A. García de Lorenzo, F. Del Nogal Sáez.
Utilidad del colesterol como marcador nutrometabólico en el paciente séptico.
Nutr Hosp, 10 (1995), pp. 24-31
[60.]
C.M. Dunham, D. Frankenfield, H. Belzberg, C.E. Wiles III, B. Cushing, Z. Grant.
Inflammatory markers: Superior predictors of adverse outcome in blunt trauma patients?.
Crit Care Med, 22 (1994), pp. 667-672
[61.]
A. Schatzin, P.R. Taylor, C.L. Carter, R.N. Hoover, R.G. Ziegler, D.B. Larson, et al.
Serum cholesterol and cáncer in the NHANES I epidemiologic follow-up study.
Lancet, II (1987), pp. 298-301
[62.]
D. Rudman, D.E. Mattson, H.S. Nagraj, A.G. Feller, D.L. Jackson, N. Caindec, et al.
Prognostic significance of serum cholestrol in nursing home men.
JPEN, 12 (1988), pp. 155-158
[63.]
I. Giovannini, G. Boldrini, C. Ghiarla, F. Giuliante, M. Vellone, G. Nuzzo.
Pathophysiologic correlates of hypocholesterolemia in critically ill surgical patients.
Intensive Care Med, 25 (1999), pp. 748-751
[64.]
C. Meijere, M.G. Statius Muller, P.A.M. van Leeuwen.
The liver in the induction and regulation of the acute stress response.
Acute Catabolic State, pp. 129-140
[65.]
E. Berendes, T. Mollhoff, H. van Aken, M. Erren, M. Deng, H.M. Loick.
Increased plasma concentrations of serum amyloid A: An indicator of the acute-phase response after cardiopulmonary bypass.
Crit Care Med, 25 (1997), pp. 1.527-1.533
[66.]
B. Leithauser, F.R. Matthias, U. Nicolai, R. Voss.
Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis.
Intensive Care Med, 22 (1996), pp. 631-636
[67.]
M. Planas, A. García.
Peroxidación lipídica en enfermos críticos.
Nutr Hosp, 12 (1997), pp. 233-236
[68.]
C. Stein, A.H.S. Hassan, R. Przewlocki, G. Gramsch, K. Peter, A. Herz.
Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation.
Proc Natl Acad Sci USA, 87 (1990), pp. 5935-5939
[69.]
R. Przewlocki.
Opioid systems and stress.
pp. 293-324
[70.]
M. Jiménez Lendínez, A. García de Lorenzo.
Síndrome de respuesta inflamatoria sistémica (SRIS) y disfunción orgánica.
Manual de Medicina Intensiva, pp. 1-6
[71.]
C. Weissman, M. Kemper, J. Harding.
Response of critically ill patients to incresed oxygen demand: Hemodynamic subsets.
Crit Care Med, 22 (1994), pp. 1.809-1.816
[72.]
F. Álvarez Lerma, M. Palomar Martínez.
Decálogo de normas para la utilización de antibióticos en pacientes críticos.
Med Intensiva, 24 (2000), pp. 69-77
[73.]
A. García de Lorenzo, J.M. Culebras.
Nutritional and Metabolic Support: Converging Concepts.
Nutrition, 7 (1991), pp. 163-167
[74.]
A. García de Lorenzo, J. López, M. Planas, J.C. Montejo, J.M. Añón, T. Caparrós.
Síndrome de distrés respiratorio agudo. Soporte nutro-metabólico.
Nutr Hosp, 12 (1997), pp. 237-243
[75.]
R.F. Grimble.
Interaction between nutrients, pro-inflammatory cytokines and inflammation.
Clinical Science, 91 (1996), pp. 121-130
[76.]
M. Senkal, A. Mumme, U. Eickhoff, B. Geier, G. Spath, D. Wulfert, et al.
Early postoperative enteral immunonutrition: Clinical outcome and costcomparison analysis in surgical patients.
Crit Care Med, 25 (1997), pp. 1.489-1.496
[77.]
J.E. Albina, J.S. Reichner.
Nitric oxide in inflammation and immunity.
New Horizons, 3 (1995), pp. 46-64
[78.]
T.G. Buchman, B.A. Zehnbauer.
Molecular biology in the intensive care unit: A fragmework for interpretation.
New Horizons, 3 (1995), pp. 139-145
[79.]
D.L. Roith.
Insulin-like growth factors.
N Engl J Med, 336 (1997), pp. 633-640
[80.]
F.A.M. Gibson, C.J. Hinds.
Growth hormone and insulin-like growth factors in critical illness.
Intensive Care Med, 23 (1997), pp. 369-378
[81.]
A. García de Lorenzo, J.M. Culebras.
Hormonas, factores de crecimiento y fármacos en el metabolismo y la nutrición.
Nutr Hosp, 10 (1995), pp. 297-305
[82.]
J.C. Wherry, J.E. Pennington, R.P. Wenzel.
Tumor necrosis factor and the therapeutic potential of anti-tumor necrosis factor antibodies.
Critical Care Med, 21 (1993), pp. 438-440
[83.]
L.A. Eidelman, R. Pizov, C.L. Sprung.
New therapeutic approaches in sepsis: a critical review.
Intensive Care Med, 21 (1995), pp. 269-272
[84.]
R. Bellomo, P. Tippling, N. Boyce.
Continuous veno-venous hemofiltration with dyalisis removes cytokines from the circulation of septic patients.
Critical Care Med, 21 (1993), pp. 522-526
[85.]
A. Sander, W. Armbruster, B. Sander, A.E. Daul, R. Lange, J. Peters.
Hemofiltration increases IL-6 clearance in early systemic inflammatory response syndrome but does not alter IL-6 and TNF-alfa plasma concentration.
Intensive Care Med, 23 (1997), pp. 878-884
[86.]
J.A. Sánchez-Izquierdo Riera, E. Alted López, M.J. Lozano Quintana, J.L. Pérez Vela, A. Ambrós Checa, M. Sánchez Casado.
Influence of continuous hemofiltration on the hemodynamics of trauma patients.
Surgery, 122 (1997), pp. 902-908
Copyright © 2000. Sociedad Española de Medicina Intensiva, Critica y Unidades Coronarias (SEMICYUC) and Elsevier España, S.L.
