Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!

ResumenLa sepsis ocupa el primer lugar entre las causas de mortalidad en las unidades de cuidado intensivo, razón por el cual su comprensión ha sido objetivo de múltiples estudios. Esta patologÍa representa un reto para el médico ya que sus criterios diagnósticos nunca han podido llegar a un consens...

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Autores:: Torres Dueñas, Diego
Espinosa Peña, Andrés Eduardo
Alarcón Forero, Laura Carolina
Niño Mantilla, María Eugenia
Cárdenas Angelone, María Eugenia

Tipo de recurso:: Article of journal

Fecha de publicación:: 2010

Institución:: Universidad Autónoma de Bucaramanga - UNAB

Repositorio:: Repositorio UNAB

Idioma:: spa

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repository_id_str
dc.title.none.fl_str_mv	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
title	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
spellingShingle	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío! Ciencias de la salud Medicina Ciencias médicas Ciencias biomédicas Ciencias de la vida Innovaciones en salud Investigaciones Health Sciences Medicine Medical Sciences Biomedical Sciences Life Sciences Innovations in health Research Medicina Investigación Ciencias biomédicas Innovaciones en salud Medidores de inflamación Térapeutica Síndrome de respuesta inflamatoria sistémica Sepsis
title_short	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
title_full	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
title_fullStr	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
title_full_unstemmed	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
title_sort	Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!
dc.creator.fl_str_mv	Torres Dueñas, Diego Espinosa Peña, Andrés Eduardo Alarcón Forero, Laura Carolina Niño Mantilla, María Eugenia Cárdenas Angelone, María Eugenia
dc.contributor.author.spa.fl_str_mv	Torres Dueñas, Diego Espinosa Peña, Andrés Eduardo Alarcón Forero, Laura Carolina Niño Mantilla, María Eugenia Cárdenas Angelone, María Eugenia
dc.contributor.cvlac.spa.fl_str_mv	Torres Dueñas, Diego [0000066885] Espinosa Peña, Andrés Eduardo [0001356787] Niño Mantilla, María Eugenia [0000535885] Cárdenas Angelone, María Eugenia [0000066761]
dc.contributor.googlescholar.spa.fl_str_mv	Niño Mantilla, María Eugenia [1R_FcOoAAAAJ]
dc.contributor.orcid.spa.fl_str_mv	Torres Dueñas, Diego [0000-0002-8006-7461] Espinosa Peña, Andrés Eduardo [0000-0002-1584-7218] Alarcón Forero, Laura Carolina [0000-0002-0610-1174] Niño Mantilla, María Eugenia [0000-0003-2945-5175]
dc.contributor.researchgate.spa.fl_str_mv	Alarcón Forero, Laura Carolina [Laura-Alarcon-Forero] Niño Mantilla, María Eugenia [Maria-Nino-3]
dc.contributor.researchgroup.spa.fl_str_mv	Grupo de Investigación en Ciencias y Educación en Salud Grupo de Investigaciones Clínicas
dc.subject.none.fl_str_mv	Ciencias de la salud Medicina Ciencias médicas Ciencias biomédicas Ciencias de la vida Innovaciones en salud Investigaciones
topic	Ciencias de la salud Medicina Ciencias médicas Ciencias biomédicas Ciencias de la vida Innovaciones en salud Investigaciones Health Sciences Medicine Medical Sciences Biomedical Sciences Life Sciences Innovations in health Research Medicina Investigación Ciencias biomédicas Innovaciones en salud Medidores de inflamación Térapeutica Síndrome de respuesta inflamatoria sistémica Sepsis
dc.subject.keywords.eng.fl_str_mv	Health Sciences Medicine Medical Sciences Biomedical Sciences Life Sciences Innovations in health Research
dc.subject.lemb.spa.fl_str_mv	Medicina Investigación Ciencias biomédicas Innovaciones en salud
dc.subject.proposal.spa.fl_str_mv	Medidores de inflamación Térapeutica Síndrome de respuesta inflamatoria sistémica Sepsis
description	ResumenLa sepsis ocupa el primer lugar entre las causas de mortalidad en las unidades de cuidado intensivo, razón por el cual su comprensión ha sido objetivo de múltiples estudios. Esta patologÍa representa un reto para el médico ya que sus criterios diagnósticos nunca han podido llegar a un consenso, dificultando asÍ su enfoque terapéutico.[Torres-Dueñas D, Espinosa AE, Alarcón LC, Niño ME, Cárdenas ME. Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafÍo!.Palabras clave: Sepsis, SÍndrome de respuesta inflamatoria sistémica, Mediadores de inflamación, Terapéutica.
publishDate	2010
dc.date.issued.none.fl_str_mv	2010-04-11
dc.date.accessioned.none.fl_str_mv	2020-10-27T14:20:38Z
dc.date.available.none.fl_str_mv	2020-10-27T14:20:38Z
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dc.type.local.spa.fl_str_mv	Artículo
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url	http://hdl.handle.net/20.500.12749/10258
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language	spa
dc.relation.none.fl_str_mv	https://revistas.unab.edu.co/index.php/medunab/article/view/440/422
dc.relation.uri.none.fl_str_mv	https://revistas.unab.edu.co/index.php/medunab/article/view/440
dc.relation.references.none.fl_str_mv	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; 29:1303-10 Bone RC, Fisher CJ, Clemmer TP, Slotman GJ, Metz CA, Balk RA. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med 1989; 17:389–93. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions of sepsis and organ failure and guidelines for the use of innovative therapies in sepsis The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101:1644-55. Poeze M, Ramsay G, Gerlach H, Rubulotta F, Levy M. An international sepsis survey: a study of doctors' knowledge and perception about sepsis. Crit Care 2004; 8:R409–13. Vincent JL. Dear Sirs, I'm sorry to say that I don't like you. Crit Care Med 1997; 25:372–4. Jaimes F, Garcés J, Cuervo J, Ramírez F, Ramírez J, Vargas A, et al. The systemic inflammatory response syndrome (SIRS) to identify infected patients in the emergency room. Intensive Care Med 2003; 29:1368–71. Carlet J, Cohen J, Calandra T, Opal SM, Masur H. Sepsis: time to reconsider the concept. Crit Care Med 2008; 36:964-6. Calandra T, Cohen J. The International Sepsis ForumConsensus Conference on definitions of infection in the intensive care unit. Crit Care Med 2005; 33:1538–48. Marshall JC. Sepsis research: Where have we gone wrong? Crit Care Resusc 2006; 8:241-3. Jaimes F. A literature review of the epidemiology of sepsis in Latin America. Rev Panam Salud Publica 2005; 18:163 71. Michalek SM, Moore RN, McGhee JR, Rosenstreich DL, Mergenhagen SE. The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. J Infect Dis 1980; 141:55-63. Ziegler EJ, McCutchan JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, et al. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 1982; 307:1225–30. Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/ tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229:869–71. Remick DG. Cytokine therapeutics for the treatment of sepsis: why has nothing worked? Curr Pharm Des 2003; 9:75–82. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in the Tir4 gene. Science 1998; 282:2085–88. Sansonetti PJ. The innate signaling of dangers and the dangers of innate signaling. Nat Immunol 2006; 7:1237-42. Liu SF, Malik AB. NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 2006; 290:L622–L645. Casey LC, Balk RA, Bone RC. Plasma cytokines and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 1993: 119:771–8. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, et al. A network-based analysis of systemic inflammation in humans. Nature 2005;437:1032–37. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008; 34:17–60. Hauser B, Bracht H, Matejovic M, Radermacher P, Venkatesh B. Nitric Oxide Synthase Inhibition in Sepsis? Lessons Learned from Large-Animal Studies. Anesth Analg 2005; 101:488–98. Torres-Dueñas D, Benjamim CF, Ferreira SH, Cunha FQ. Failure of neutrophil migration to infectious focus and cardiovascular changes on sepsis in rats: effects of the inhibition of nitric oxide production, removal of infectious focus, and antimicrobial treatment. Shock 2006; 25:267 (Suppl 1):107–19. 25. Alves-Filho JC, de Freitas A, Russo M, Cunha FQ. Toll-like receptor 4 signaling leads to neutrophil migration impairment in polymicrobial sepsis. Crit Care Med 2006; 34:461–70. Abraham E, Anzueto A, Gutierrez G, Tessler S, San Pedro G, Wunderink R, et al. Double-blind randomized controlled trial of monoclonal antibody to human tumor necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 1998: 351:929–33. Lopez A. Lorente JA, Steingrub J. Bakker J. McLuckie A. Willatts S, et al. Multiple-center, randomized, placebo controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 2004;32:21–30. Hoesel LM, Neff TA, Neff SB, Younger JG, Olle EW, Gao H, et al. A. harmful and protective roles of neutrophils in sepsis. Shock 2005; 24:40–7. Fierro IM, Nascimento-DaSilva V, Arruda MA, Freitas MS, Plotkowski MC, Cunha FQ, et al. Induction of NOS in rat blood PMM in vivo and in vitro: modulation by tyrosine kinase and involvement in bactericidal activity. J Leukoc Biol 1999; 65:508-14. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109-42. McGown CC, Brookes ZL. Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br JAnaesth. 2007; 98:163-75. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709. Eichacker PQ, Natanson C. Recombinant human activated protein C in sepsis: inconsistent trial results, an unclear mechanism of action, and safety concerns resulted in labeling restrictions and the need for phase IV trials. Crit Care Med 2003; 31(Suppl 1):S94-6. Gentry CA, Gross KB, Sud B, Drevets DA. Adverse outcomes associated with the use of drotrecogin alfa (activated) in patients with severe sepsis and baseline bleeding precautions. Crit Care Med 2009;37:19–25.
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dc.publisher.none.fl_str_mv	Universidad Autónoma de Bucaramanga UNAB
dc.publisher.faculty.spa.fl_str_mv	Facultad Ciencias de la Salud
publisher.none.fl_str_mv	Universidad Autónoma de Bucaramanga UNAB
dc.source.none.fl_str_mv	MedUNAB; Vol. 13 Núm. 1 (2010): Sepsis, Sedentarismo, Estado epiléptico; 13-16
institution	Universidad Autónoma de Bucaramanga - UNAB
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spelling	Torres Dueñas, Diego6c1aa657-9370-4eb6-aa42-14e1b27c6d67Espinosa Peña, Andrés Eduardo82a0f566-4b30-42d6-808b-09637d29f2e7Alarcón Forero, Laura Carolinae92b6746-9ba9-44b3-805f-c59a886c579bNiño Mantilla, María Eugeniaf0c9eb6a-9beb-4cdf-acbd-317451b44772Cárdenas Angelone, María Eugenia39db2a52-eeb3-4719-8dff-8460661358e4Torres Dueñas, Diego [0000066885]Espinosa Peña, Andrés Eduardo [0001356787]Niño Mantilla, María Eugenia [0000535885]Cárdenas Angelone, María Eugenia [0000066761]Niño Mantilla, María Eugenia [1R_FcOoAAAAJ]Torres Dueñas, Diego [0000-0002-8006-7461]Espinosa Peña, Andrés Eduardo [0000-0002-1584-7218]Alarcón Forero, Laura Carolina [0000-0002-0610-1174]Niño Mantilla, María Eugenia [0000-0003-2945-5175]Alarcón Forero, Laura Carolina [Laura-Alarcon-Forero]Niño Mantilla, María Eugenia [Maria-Nino-3]Grupo de Investigación en Ciencias y Educación en SaludGrupo de Investigaciones Clínicas2020-10-27T14:20:38Z2020-10-27T14:20:38Z2010-04-112382-46030123-7047http://hdl.handle.net/20.500.12749/10258instname:Universidad Autónoma de Bucaramanga UNABrepourl:https://repository.unab.edu.coResumenLa sepsis ocupa el primer lugar entre las causas de mortalidad en las unidades de cuidado intensivo, razón por el cual su comprensión ha sido objetivo de múltiples estudios. Esta patologÍa representa un reto para el médico ya que sus criterios diagnósticos nunca han podido llegar a un consenso, dificultando asÍ su enfoque terapéutico.[Torres-Dueñas D, Espinosa AE, Alarcón LC, Niño ME, Cárdenas ME. Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafÍo!.Palabras clave: Sepsis, SÍndrome de respuesta inflamatoria sistémica, Mediadores de inflamación, Terapéutica.application/pdfspaUniversidad Autónoma de Bucaramanga UNABFacultad Ciencias de la Saludhttps://revistas.unab.edu.co/index.php/medunab/article/view/440/422https://revistas.unab.edu.co/index.php/medunab/article/view/440Angus 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; 29:1303-10Bone RC, Fisher CJ, Clemmer TP, Slotman GJ, Metz CA, Balk RA. Sepsis syndrome: a valid clinical entity. Methylprednisolone Severe Sepsis Study Group. Crit Care Med 1989; 17:389–93.Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions of sepsis and organ failure and guidelines for the use of innovative therapies in sepsis The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101:1644-55.Poeze M, Ramsay G, Gerlach H, Rubulotta F, Levy M. An international sepsis survey: a study of doctors' knowledge and perception about sepsis. Crit Care 2004; 8:R409–13.Vincent JL. Dear Sirs, I'm sorry to say that I don't like you. Crit Care Med 1997; 25:372–4.Jaimes F, Garcés J, Cuervo J, Ramírez F, Ramírez J, Vargas A, et al. The systemic inflammatory response syndrome (SIRS) to identify infected patients in the emergency room. Intensive Care Med 2003; 29:1368–71.Carlet J, Cohen J, Calandra T, Opal SM, Masur H. Sepsis: time to reconsider the concept. Crit Care Med 2008; 36:964-6.Calandra T, Cohen J. The International Sepsis ForumConsensus Conference on definitions of infection in the intensive care unit. Crit Care Med 2005; 33:1538–48.Marshall JC. Sepsis research: Where have we gone wrong? Crit Care Resusc 2006; 8:241-3.Jaimes F. A literature review of the epidemiology of sepsis in Latin America. Rev Panam Salud Publica 2005; 18:163 71.Michalek SM, Moore RN, McGhee JR, Rosenstreich DL, Mergenhagen SE. The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. J Infect Dis 1980; 141:55-63.Ziegler EJ, McCutchan JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, et al. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 1982; 307:1225–30.Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/ tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229:869–71.Remick DG. Cytokine therapeutics for the treatment of sepsis: why has nothing worked? Curr Pharm Des 2003; 9:75–82.Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in the Tir4 gene. Science 1998; 282:2085–88.Sansonetti PJ. The innate signaling of dangers and the dangers of innate signaling. Nat Immunol 2006; 7:1237-42.Liu SF, Malik AB. NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 2006; 290:L622–L645.Casey LC, Balk RA, Bone RC. Plasma cytokines and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 1993: 119:771–8.Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, et al. A network-based analysis of systemic inflammation in humans. Nature 2005;437:1032–37.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 2008; 34:17–60.Hauser B, Bracht H, Matejovic M, Radermacher P, Venkatesh B. Nitric Oxide Synthase Inhibition in Sepsis? Lessons Learned from Large-Animal Studies. Anesth Analg 2005; 101:488–98.Torres-Dueñas D, Benjamim CF, Ferreira SH, Cunha FQ. Failure of neutrophil migration to infectious focus and cardiovascular changes on sepsis in rats: effects of the inhibition of nitric oxide production, removal of infectious focus, and antimicrobial treatment. Shock 2006; 25:267(Suppl 1):107–19. 25. Alves-Filho JC, de Freitas A, Russo M, Cunha FQ. Toll-like receptor 4 signaling leads to neutrophil migration impairment in polymicrobial sepsis. Crit Care Med 2006; 34:461–70.Abraham E, Anzueto A, Gutierrez G, Tessler S, San Pedro G, Wunderink R, et al. Double-blind randomized controlled trial of monoclonal antibody to human tumor necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 1998: 351:929–33.Lopez A. Lorente JA, Steingrub J. Bakker J. McLuckie A. Willatts S, et al. Multiple-center, randomized, placebo controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 2004;32:21–30.Hoesel LM, Neff TA, Neff SB, Younger JG, Olle EW, Gao H, et al. A. harmful and protective roles of neutrophils in sepsis. Shock 2005; 24:40–7.Fierro IM, Nascimento-DaSilva V, Arruda MA, Freitas MS, Plotkowski MC, Cunha FQ, et al. Induction of NOS in rat blood PMM in vivo and in vitro: modulation by tyrosine kinase and involvement in bactericidal activity. J Leukoc Biol 1999; 65:508-14.Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:109-42.McGown CC, Brookes ZL. Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br JAnaesth. 2007; 98:163-75.Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709.Eichacker PQ, Natanson C. Recombinant human activated protein C in sepsis: inconsistent trial results, an unclear mechanism of action, and safety concerns resulted in labeling restrictions and the need for phase IV trials. Crit Care Med 2003; 31(Suppl 1):S94-6.Gentry CA, Gross KB, Sud B, Drevets DA. Adverse outcomes associated with the use of drotrecogin alfa (activated) in patients with severe sepsis and baseline bleeding precautions. Crit Care Med 2009;37:19–25.http://creativecommons.org/licenses/by-nc-nd/2.5/co/Atribución-NoComercial-SinDerivadas 2.5 Colombiahttp://purl.org/coar/access_right/c_abf2MedUNAB; Vol. 13 Núm. 1 (2010): Sepsis, Sedentarismo, Estado epiléptico; 13-16Ciencias de la saludMedicinaCiencias médicasCiencias biomédicasCiencias de la vidaInnovaciones en saludInvestigacionesHealth SciencesMedicineMedical SciencesBiomedical SciencesLife SciencesInnovations in healthResearchMedicinaInvestigaciónCiencias biomédicasInnovaciones en saludMedidores de inflamaciónTérapeuticaSíndrome de respuesta inflamatoria sistémicaSepsisFármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!info:eu-repo/semantics/articleArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/redcol/resource_type/ARTORIGINAL440-Texto del artículo (sin nombre de autor)-1271-1-10-20100621 (2).pdf440-Texto del artículo (sin nombre de autor)-1271-1-10-20100621 (2).pdfArtículoapplication/pdf7544585https://repository.unab.edu.co/bitstream/20.500.12749/10258/1/440-Texto%20del%20art%c3%adculo%20%28sin%20nombre%20de%20autor%29-1271-1-10-20100621%20%282%29.pdf479fe54b3b474b3c5237875255eb8c09MD51open accessTHUMBNAIL440-Texto del artículo (sin nombre de autor)-1271-1-10-20100621 (2).pdf.jpg440-Texto del artículo (sin nombre de autor)-1271-1-10-20100621 (2).pdf.jpgIM Thumbnailimage/jpeg12875https://repository.unab.edu.co/bitstream/20.500.12749/10258/2/440-Texto%20del%20art%c3%adculo%20%28sin%20nombre%20de%20autor%29-1271-1-10-20100621%20%282%29.pdf.jpgb8f43f074630466efc5d043f7e0ce1d8MD52open access20.500.12749/10258oai:repository.unab.edu.co:20.500.12749/102582024-01-19 15:00:20.995open accessRepositorio Institucional \| Universidad Autónoma de Bucaramanga - UNABrepositorio@unab.edu.co

Fármaco-terapéutica de la sepsis: ¡un proceso frustrante y un gran desafío!

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