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Vol. 35. Issue 4.
Pages 236-245 (January 2011)
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Vol. 35. Issue 4.
Pages 236-245 (January 2011)
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New therapeutic alternatives for severe sepsis in the critical patient. A review
Nuevas alternativas terapéuticas para la sepsis grave en el paciente crítico. Revisión
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A. Loza Vázqueza,
Corresponding author
aloza@telefonica.net

Corresponding author.
, C. León Gila, A. León Regidorb
a Servicio de Medicina Intensiva, Hospital Universitario de Valme, Sevilla, Spain
b Servicio de Medicina Intensiva, Hospital General de Catalunya, Barcelona, Spain
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Article information
Abstract
Background

Despite efforts to establish uniform protocols for the management of severe sepsis, this condition continues to have high morbidity and mortality. This is due, among other factors, to the many barriers for the development of the protocols and the application time. That is why new therapeutic measures are continuing to be investigated and developed.

Objective

To review the literature on the new and future therapeutic alternatives available in the management of sepsis in critically ill patients.

Data source and search method

A search was made for articles consistent with evidence-based medicine guidelines published between 2004 and 2009 in different databases (Cochrane Plus Library, National Guideline Clearinghouse, Clinical Evidence, REMI and PubMed) and the NIH Clinical Trails database (ClinicalTrials.gov) using the TRIP meta-search engine.

Study selection

A total of 357 documents were retrieved, selecting 48 of which included systematic reviews, meta-analyses, clinical practice guidelines, structured abstracts of original articles, and clinical trials. The selection criteria followed the peer review process.

Data extraction

Data were extracted by two independent reviewers.

Conclusions

Based on the 2004–2009 study period, sufficient evidence was not obtained to make further recommendations on the treatment of sepsis. Although the abundant evidence needed to suggest the utility of these therapeutic measures, inhaled nitric oxide, statins, and immunoglobulins are probably good options for the adjuvant treatment of sepsis. However, we must wait for the results of different ongoing clinical trials on new treatment modalities. Stem cells and gene therapy will probably emerge as novel therapies in the future.

Keywords:
New therapies
Sepsis
Critically ill patient
Resumen
Introducción

La sepsis grave sigue teniendo elevadas morbilidad y mortalidad, a pesar de los esfuerzos realizados en la instauración de protocolos uniformes de actuación, debido, entre otros muchos factores, a la existencia de múltiples barreras para la implantación, así como su tiempo de aplicación. Es por ello que se sigue desarrollando e investigando sobre nuevas medidas terapéuticas.

Objetivo

Realizar una revisión de la literatura sobre las nuevas y futuras alternativas terapéuticas de que disponemos para el tratamiento de la sepsis en los pacientes críticos.

Fuentes de datos y método de búsqueda

Se llevo a cabo una búsqueda limitada por tiempo desde 2004 hasta 2009, a través del metabuscador Trip Database en las páginas de medicina basada en la evidencia (Cochrane Plus, National Guideline Clearinghouse, Clinical Evidence, REMI y PubMed) y base de datos de ensayos clínicos (ClinicalTrials.gov).

Selección de los estudios

Se obtuvieron de la búsqueda 357 documentos, de los cuales se seleccionaron 48 que incluyen revisiones sistemáticas, metaanálisis, guías de práctica clínica, resúmenes estructurados de un artículo original y ensayos clínicos. El método empleado para aplicar estos criterios se hizo mediante una revisión por pares.

Extracción de datos

Un posterior análisis por dos revisores independientes.

Conclusiones

En el periodo de estudio 2004–2009 no ha habido aportaciones con evidencia suficiente como para realizar nuevas recomendaciones en el tratamiento de la sepsis. Aunque no se aporta la abundante evidencia que señale la utilidad de estas medidas terapéuticas, probablemente el óxido nítrico inhalado, las estatinas y las inmunoglobulinas sean buenas alternativas en el tratamiento adyuvante de la sepsis. Tendremos que esperar, de todas maneras, los resultados de los diferentes ensayos clínicos que se encuentran en marcha sobre las nuevas terapias. El futuro posiblemente podría estar en las células madre y la genoterapia.

Palabras clave:
Nuevas terapias
Sepsis
Paciente crítico
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References
[1.]
R.P. Dellinger, J.M. Carlet, H. Masur, H. Gerlach, T. Calandra, J. Cohen, et al.
Surviving Sepsis Campaign. Guidelines for management of severe sepsis and septic shock.
Crit Care Med, 32 (2004), pp. 858-873
[2.]
R.P. Dellinger, M.M. Levy, J.M. Carlet, J. Bion, M.M. Parker, R. Jaeschke, et al.
International guidelines for management of severe sepsis and septic shock.
Crit Care Med, 36 (2008), pp. 1394-1396
[3.]
C. León, L. García-Castrillo, M. Moya, A. Artigas, M. Borges, F.J. Candel, et al.
Documento de consenso (Semes-Semicyuc). Recomendaciones del manejo diagnóstico-terapéutico inicial y multidisciplinario de la sepsis grave en los servicios de urgencias hospitalarios.
Med Intensiva, 31 (2007), pp. 375-387
[4.]
A. Kumar, R. Daniel, W. Kenneth, L. Bruce, J.E. Parrillo, S. Satendra, et al.
Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.
Crit Care Med, 34 (2006), pp. 1589-1596
[5.]
E. Rivers, B. Nguyen, S. Havstad, J. Ressler, A. Muzzin, B. Knoblich, et al.
Early goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med, 345 (2001), pp. 1368-1377
[6.]
R. Ferrer, A. Artigas, M.M. Levy, J. Blanco, G. González, J. Garnacho-Montero, et al.
Improvement in Process of Care and Outcome after a Multicenter Severe Sepsis Educational Program in Spain.
JAMA, 299 (2008), pp. 2294-2303
[7.]
J. Iñigo, J.M. Sendra, R. Díaz, C. Bouza, A. Sarría- Santamera.
Epidemiología y costes de la sepsis grave en Madrid. Estudio de altas hospitalarias.
Med Intensiva, 30 (2006), pp. 197-203
[8.]
A. Esteban, F. Frutos-Vivar, N.D. Ferguson, O. Peñuelas, J.A. Lorente, F. Gordo, et al.
Sepsis incidence and outcome: Contrasting the intensive care unit with the hospital ward.
Crit Care Med, 35 (2007), pp. 1284-1289
[9.]
J.M. De Miguel-Yanes, J.A. Andueza-Lillo, V.J. González-Ramallo, L. Pastor, J. Muñoz.
Failure tu implement evidence-based clinical guidelines for sepsis at the ED.
Am J Emerg Med, 24 (2006), pp. 553-559
[10.]
D.J. Carlbom, G.D. Rubenfeld.
Barriers to implementing protocolbased sepsis resuscitation in the emergency department. Results of a national survey.
Crit Care Med, 35 (2007), pp. 2525-2532
[11.]
A.F. Shorr, S.T. Micek, W.L. Jackson, M.H. Kollef.
Economic implications of an evidence-based sepsis protocol: Can we improve outcomes and lower costs?.
Crit Care Med, 35 (2007), pp. 1257-1262
[12.]
R. Ferrer, A. Artigas, D. Suarez, E. Palencia, M.M. Levy, A. Arenzana, et al.
Effectiveness of treatments for severe sepsis: a prospective multicenter observational study.
Am J Respir Crit Care Med, 180 (2009), pp. 861-866
[13.]
D. Annane, P. Vignon, A. Renault, P.E. Bollard, C. Charpentier, C. Martin, CATS Study Group, et al.
Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial.
[14.]
D. De Backer, P. Biston, J. Devriendt, C. Madl, D. Chochrad, C. Aldecoa, et al.
Comparison of dopamine and norepinephrine in the treatment of shock.
N Engl J Med, 362 (2010), pp. 779-789
[15.]
McLean AS. Levosimendan versus dobutamine in shock patients. ClinicalTrials.gov Identifier: NCT00093301.
[16.]
Latour-Pérez J, García MA. Dosis óptima de diálisis en pacientes con daño renal agudo. Una revisión crítica de la literatura. Revista Electrónica de Medicina Intensiva. Artículo especial n.°104 REMI 2009; 9(6):A104. Available from: http://remi.uninet.edu/2009/06/REMIA104.html.
[17.]
D.N. Cruz, M. Antonelli, R. Fumagalli, F. Foltran, N. Brienza, A. Donati, et al.
Early use of polymyxin B hemoperfusionin abdominal septic shock. The EUPHAS Randomized Controlled Trial.
JAMA, 301 (2009), pp. 2445-2452
[18.]
R. Busund, V. Koukline, U. Utrobin, E. Nedashkovsky.
Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial.
Intensive Care Med, 28 (2002), pp. 1434-1439
[19.]
Livigni S. COMPACT - Combining Plasma-filtration and Adsorption Clinical Trial. ClinicalTrials.gov Identifier: NCT00332371.
[20.]
D. Griesdale, R.J. De Souza, R.M. Van Dam, D.K. Heyland, D.J. Cook, A. Malhotra, et al.
Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data.
CMAJ, 180 (2009), pp. 821-827
[21.]
R.S. Wiener, D.C. Wiener, R.J. Larson.
Benefits and risks of tight glucose control in critically ill adults a meta-analysis.
JAMA, 300 (2008), pp. 933-944
[22.]
Anticoagulant therapy in severe sepsis.
American Thoracic Society CAT, (2005),
[23.]
A. Eid, C.J. Wiedermann, G.T. Kinasewitz.
Early administration of high-dose antithrombin in severe sepsis: single center results from the KyberSept-Trial.
Anesth Analg, 107 (2008), pp. 1633-1638
[24.]
A. Abraham, K. Reinhart, S. Opal, I. Demeyer, C. Doig, A. López, et al.
Efficacy and Safety of Tifacogin (Recombinant Tissue Factor Pathway Inhibitor) in Severe Sepsis: A Randomized Controlled Trial.
JAMA, 290 (2003), pp. 238-247
[25.]
Martí-Carvajal AJ, Salanti G, Cardona AF-Zorrilla. Proteína C activada recombinante para la sepsis grave en humanos Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD004388. DOI: 10.1002/14651858.CD004388.
[26.]
Efficacy and Safety of Drotrecogin Alfa (Activated) in Adult Patients With Septic Shock. ClinicalTrials.gov Identifier: NCT00604214.
[27.]
Misset B, Martin C, Cariou A, Carlet J, Brun Buisson C, Annane D. Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHS). ClinicalTrials.gov: NCT00625209.
[28.]
C.L. Sprung, D. Annane, D. Keh, R. Moreno, M. Singer, K. Freivogel, et al.
Hydrocortisone therapy for patients with septic shock.
N Engl J Med, 358 (2008), pp. 111-124
[29.]
D. Annane, E. Bellissant, P.E. Bollaert, J. Briegel, M. Confalonieri, R. De Gaudio, et al.
Corticosteroids in the treatment of severe sepsis and septic shock in adults. A systematic review.
JAMA, 301 (2009), pp. 2362-2375
[30.]
The use of nitric oxide in acute respiratory distress syndrome. Accession number: 32007000487. Centre for Reviews and Diseminación. DARE 07.
[31.]
Trzeciak S. Randomized Trial of Inhaled Nitric Oxide to Augment Tissue Perfusion in Sepsis. ClinicalTrials.gov: NCT00608322.
[32.]
P. Kopterides, M.E. Falagas.
Statins for sepsis: a critical and updated review.
Clin Microbiol Infect, 15 (2009), pp. 325-334
[33.]
Schenk P. Simvastatin in Patients With Septic Shock. ClinicalTrials.gov: NCT00450840.
[34.]
Truwit J. Statins for Acutely Injured Lungs From Sepsis (SAILS). ClinicalTrials.gov: NCT00979121.
[35.]
K.B. Laupland, A.W. Kirkpatrick, A. Delaney.
Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: A systematic Review and metaanalysis.
Crit Care Med, 35 (2007), pp. 2686-2692
[36.]
V. Gómez-Tello.
Inmunoglobulinas en el tratamiento de la sepsis.
REMI, 8 (2008), pp. 1186
[37.]
Massey E, Paulus U, Doree C, Stanworth S. Transfusiones de granulocitos para la prevención de infecciones en pacientes con neutropenia o disfunción de los neutrófilos. La Biblioteca Cochrane Plus 2009, Número 3.
[38.]
Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, et al. Update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. National Guideline Clearinghouse.
[39.]
H. Wang, M.F. Ward, E. Andrew, E. Sama.
Novel HMGB1-inhibiting therapeutic agents for experimental sepsis.
[40.]
M. Angstwurm, L. Engelmann, T. Zimmerman, C. Lehmann, C.H. Spes, P. Abel, et al.
Selenium in Intensive Care (SIC): Results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.
Crit Care Med, 35 (2007), pp. 118-126
[41.]
Schiller F. Placebo Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT). ClinicalTrials.gov: NCT00832039.
[42.]
Pontes-Arruda A. The Effects of Eicosapentaenoic Acid (EPA), Gamma-Linolenic Acid (GLA) and Antioxidants in the Treatment. ClinicalTrials.gov: NCT00329680.
[43.]
B.R. Weil, T.A. Markel, J.L. Herrmann, A.M. Abarbanell, M.L. Kelly, D.R. Meldrum.
Stem cells in sepsis.
[44.]
M.M. Würfel.
Genetic insights into sepsis: what have we learned and how will it help?.
Curr Pharm Des, 14 (2008), pp. 1900-1911
[45.]
Wong HC. Anti-TF Antibody (ALT-836) to Treat Septic Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome. ClinicalTrials.gov: NCT00879606.
[46.]
Guntupalli KK. Safety and Efficacy Study of Recombinant Human Lactoferrin to Treat Severe Sepsis. ClinicalTrials.gov: NCT00630656.
[47.]
Said S. Phase I Study of Vasoactive Intestinal Peptide in Patients With Acute Respiratory Distress Syndrome and Sepsis. ClinicalTrials.gov: NCT00004494.
[48.]
Takeda Global Research & Development. Efficacy & Safety of Resatorvid in Adults With Severe Sepsis. ClinicalTrials.gov: NCT00143611.

These data were presented in part at the XXXI Congress of the Sociedad Andaluza de Medicina Intensiva, Urgencias y Coronarias (SAMIUC). Málaga, 12-14 November 2009.

Copyright © 2011. Elsevier y Sociedad Española de Medicina Intensiva, Critica y Unidades Coronarias
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