Intensive Care Medicine

, Volume 40, Issue 2, pp 182–191 | Cite as

Implementation of a multifaceted sepsis education program in an emerging country setting: clinical outcomes and cost-effectiveness in a long-term follow-up study

  • Danilo Teixeira Noritomi
  • Otavio T. RanzaniEmail author
  • Mariana Barbosa Monteiro
  • Elaine Maria Ferreira
  • Sergio Ricardo Santos
  • Fernando Leibel
  • Flavia Ribeiro Machado



To evaluate whether a multifaceted, centrally coordinated quality improvement program in a network of hospitals can increase compliance with the resuscitation bundle and improve clinical and economic outcomes in an emerging country setting.


This was a pre- and post-intervention study in ten private hospitals (1,650 beds) in Brazil (from May 2010 to January 2012), enrolling 2,120 patients with severe sepsis or septic shock. The program used a multifaceted approach: screening strategies, multidisciplinary educational sessions, case management, and continuous performance assessment. The network administration and an external consultant provided performance feedback and benchmarking within the network. The primary outcome was compliance with the resuscitation bundle. The secondary outcomes were hospital mortality, hospital and ICU length of stay, quality-adjusted life year (QALY) gain, and cost-effectiveness.


The proportion of patients who received all the required items for the resuscitation bundle improved from 13 % [95 % confidence interval (CI) 8–18 %] at baseline to 62 % (95 % CI 54–69 %) in the last trimester (p < 0.001). Hospital mortality decreased from 55 % (95 % CI 48–62 %) to 26 % (95 % CI 19–32 %, p < 0.001). Full compliance with the resuscitation bundle was associated with lower risk of hospital mortality (propensity weighted corrected risk ratio 0.74; 95 % CI 0.56–0.94, p = 0.02). There was a reduction in the total cost per patient from 29.3 (95 % CI 23.9–35.4) to 17.5 (95 % CI 14.3–21.1) thousand US dollars from baseline to the last 3 months (mean difference −11,815; 95 % CI −18,604 to −5,338). The mean QALY increased from 2.63 (95 % CI 2.15–3.14) to 4.06 (95 % CI 3.58–4.57). For each QALY, the full compliance saves US$5,383.


A multifaceted approach to severe sepsis and septic shock patients in an emerging country setting led to high compliance with the resuscitation bundle. The intervention was cost-effective and associated with a reduction in mortality.


Infection Sepsis Sepsis bundles Sepsis syndrome Septic shock Severe sepsis Surviving Sepsis Campaign Cost-effectiveness 



We thank all study coordinators and case managers from the participating hospitals: Hospital ABC Cirúrgico, Santo André (Alessandra Rosa Tavares; Claudia Benevides; Luciane Marques Bertoldo Viñas; and Ricardo Seiler); Hospital Alvorada Moema, São Paulo (Alfonso Migliore Neto; Bruno F Mazza; Ceu Cordeiro G. Moura; Gisele da Silva Oliveira; and Heloisa Moreira); Hospital da Luz Santo Amaro, São Paulo (Alexandra Silva; Bruno Toldo; Helenice Maida; and Tomi Uchida Lovet); Hospital e Maternidade Ipiranga, Mogi das Cruzes (Manuel Leitão Neto; Marjorie Tamaki Mori; Tania Aparecida Machado; and Vinicius Ferreira Rocha); Hospital da Luz Vila Mariana, São Paulo (Heraldo Jesus; Jose Luiz Cunha Carneiro Junior; Roseane Fernandes Romualdo; and Sylas Bezerra Cappi); Hospital Metropolitano Butantã, São Paulo (Antonio Claudomiro A. Beneventti; Masao Murata; Oswaldo Americo C. de Oliveira; and Silza Tamar dos Santos de Andrade); Hospital Metropolitano Lapa, São Paulo (Ana Maria Cristina B. Sogayar; Darcy Lisbão Moreira de Carvalho; Janaína Silva; and Maria Claudia Dalaneze Gomes); Hospital Paulistano, São Paulo (Danilo Teixeira Noritomi; Marcio J. C. Arruda; Marco Antonio G. Baroni; and Mariana Barbosa Monteiro); Hospital TotalCor, São Paulo (Antonio Claudio do Amaral Baruzzi; Damiana Vieira dos Santos Rinaldi; and Valter Furlan); Hospital Vitória, São Paulo (Luiz Cervone; Paulo Sergio de Andrade Rehder; Pedro Fausto; Priscila Salvador Baptista; and Ricardo Goulart Rodrigues). We thank Pierre Schippers (Latin America Sepsis Institute) for the development of the software used to collect data and Ilusca Cardoso de Paula (Latin America Sepsis Institute) for her help with the hospital performance reports. We would like thank Lucas Fahham and Vanessa Teich for their help with the statistics. We would like to thank the Research and Education Institute, Rede Amil, São Paulo, Brazil. Finally, we would like to thank Nelson Akamine for his fundamental contribution in the beginning of the initiative.

Conflicts of interest

The authors have no conflict of interest.

Supplementary material

134_2013_3131_MOESM1_ESM.docx (570 kb)
Supplementary material 1 (DOCX 570 kb)


  1. 1.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRefGoogle Scholar
  2. 2.
    Silva E, Pedro MA, Sogayar AC, Mohovic T, Silva CL, Janiszewski M, Cal RG, de Sousa EF, Abe TP, de Andrade J, de Matos JD, Rezende E, Assuncao M, Avezum A, Rocha PC, de Matos GF, Bento AM, Correa AD, Vieira PC, Knobel E (2004) Brazilian sepsis epidemiological study (BASES study). Crit Care 8:R251–R260PubMedCrossRefGoogle Scholar
  3. 3.
    Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, Gomersall CD, Faruq MO, Shrestha BR, Gia BN, Arabi YM, Salahuddin N, Wahyuprajitno B, Tu ML, Wahab AY, Hameed AA, Nishimura M, Procyshyn M, Chan YH (2011) Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ 342:d3245PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC (2010) The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med 36:222–231PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Quartin AA, Schein RM, Kett DH, Peduzzi PN (1997) Magnitude and duration of the effect of sepsis on survival. Department of Veterans Affairs Systemic Sepsis Cooperative Studies Group. JAMA 277:1058–1063PubMedCrossRefGoogle Scholar
  6. 6.
    Drabinski A, Williams G, Formica C (2001) Observational evaluation of health state utilities among a cohort of sepsis patients. Value Health 4:128–129Google Scholar
  7. 7.
    Jones AE, Troyer JL, Kline JA (2011) Cost-effectiveness of an emergency department-based early sepsis resuscitation protocol. Crit Care Med 39:1306–1312PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Suarez D, Ferrer R, Artigas A, Azkarate I, Garnacho-Montero J, Goma G, Levy MM, Ruiz JC (2011) Cost-effectiveness of the Surviving Sepsis Campaign protocol for severe sepsis: a prospective nation-wide study in Spain. Intensive Care Med 37:444–452PubMedCrossRefGoogle Scholar
  9. 9.
    Sogayar AM, Machado FR, Rea-Neto A, Dornas A, Grion CM, Lobo SM, Tura BR, Silva CL, Cal RG, Beer I, Michels V, Safi J, Kayath M, Silva E (2008) A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. Pharmacoeconomics 26:425–434PubMedCrossRefGoogle Scholar
  10. 10.
    Shorr AF, Micek ST, Jackson WL Jr, Kollef MH (2007) Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs? Crit Care Med 35:1257–1262PubMedCrossRefGoogle Scholar
  11. 11.
    Huang DT, Clermont G, Dremsizov TT, Angus DC (2007) Implementation of early goal-directed therapy for severe sepsis and septic shock: a decision analysis. Crit Care Med 35:2090–2100PubMedCrossRefGoogle Scholar
  12. 12.
    Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R, Subgroup SSCGCiTP (2013) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228PubMedCrossRefGoogle Scholar
  14. 14.
    Cardoso T, Carneiro AH, Ribeiro O, Teixeira-Pinto A, Costa-Pereira A (2010) Reducing mortality in severe sepsis with the implementation of a core 6-hour bundle: results from the Portuguese community-acquired sepsis study (SACiUCI study). Crit Care 14:R83PubMedCrossRefGoogle Scholar
  15. 15.
    Ferrer R, Artigas A, Suarez D, Palencia E, Levy MM, Arenzana A, Perez XL, Sirvent JM (2009) Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med 180:861–866PubMedCrossRefGoogle Scholar
  16. 16.
    Stoneking L, Denninghoff K, Deluca L, Keim SM, Munger B (2011) Sepsis bundles and compliance with clinical guidelines. J Intensive Care Med 26:172–182PubMedCrossRefGoogle Scholar
  17. 17.
    Black MD, Schorr C, Levy MM (2012) Knowledge translation and the multifaceted intervention in the intensive care unit. Crit Care Med 40:1324–1328PubMedCrossRefGoogle Scholar
  18. 18.
    Gao F, Melody T, Daniels DF, Giles S, Fox S (2005) The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: a prospective observational study. Crit Care 9:R764–R770PubMedCrossRefGoogle Scholar
  19. 19.
    Barochia AV, Cui X, Vitberg D, Suffredini AF, O’Grady NP, Banks SM, Minneci P, Kern SJ, Danner RL, Natanson C, Eichacker PQ (2010) Bundled care for septic shock: an analysis of clinical trials. Crit Care Med 38:668–678PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Levy MM, Artigas A, Phillips GS, Rhodes A, Beale R, Osborn T, Vincent JL, Townsend S, Lemeshow S, Dellinger RP (2012) Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 12:919–924PubMedCrossRefGoogle Scholar
  21. 21.
    Mahavanakul W, Nickerson EK, Srisomang P, Teparrukkul P, Lorvinitnun P, Wongyingsinn M, Chierakul W, Hongsuwan M, West TE, Day NP, Limmathurotsakul D, Peacock SJ (2012) Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected]. PLoS ONE 7:e29858PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Kuan WS, Mahadevan M, Tan JH, Guo J, Ibrahim I (2013) Feasibility of introduction and implementation of the Surviving Sepsis Campaign bundle in a Singapore emergency department. Eur J Emerg Med 20:344–349PubMedCrossRefGoogle Scholar
  23. 23.
    Li ZQ, Xi XM, Luo X, Li J, Jiang L (2013) Implementing Surviving Sepsis Campaign bundles in China: a prospective cohort study. Chin Med J (Engl) 126:1819–1825Google Scholar
  24. 24.
    Na S, Kuan WS, Mahadevan M, Li CH, Shrikhande P, Ray S, Batech M, Nguyen HB, Investigators A (2012) Implementation of early goal-directed therapy and the Surviving Sepsis Campaign resuscitation bundle in Asia. Int J Qual Health Care 24:452–462PubMedCrossRefGoogle Scholar
  25. 25.
    Antonelli M, Bonten M, Cecconi M, Chastre J, Citerio G, Conti G, Curtis JR, Hedenstierna G, Joannidis M, Macrae D, Maggiore SM, Mancebo J, Mebazaa A, Preiser JC, Rocco P, Timsit JF, Wernerman J, Zhang H (2013) Year in review in Intensive Care Medicine 2012. II: pneumonia and infection, sepsis, coagulation, hemodynamics, cardiovascular and microcirculation, critical care organization, imaging, ethics and legal issues. Intensive Care Med 39:345–364PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Baelani I, Jochberger S, Laimer T, Otieno D, Kabutu J, Wilson I, Baker T, Dünser MW (2011) Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: a self-reported, continent-wide survey of anaesthesia providers. Crit Care 15:R10PubMedCrossRefGoogle Scholar
  27. 27.
    Dünser MW, Festic E, Dondorp A, Kissoon N, Ganbat T, Kwizera A, Haniffa R, Baker T, Schultz MJ, Medicine GICWGoESoIC (2012) Recommendations for sepsis management in resource-limited settings. Intensive Care Med 38:557–574PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Freitas FG, Salomão R, Tereran N, Mazza BF, Assunção M, Jackiu M, Fernandes H, Machado FR (2008) The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock. Clinics (Sao Paulo) 63:483–488CrossRefGoogle Scholar
  29. 29.
    Conde KA, Silva E, Silva CO, Ferreira E, Freitas FG, Castro I, Rea-Neto A, Grion CM, Moura AD, Lobo SM, Azevedo LC, Machado FR (2013) Differences in sepsis treatment and outcomes between public and private hospitals in Brazil: a multicenter observational study. PLoS ONE 8:e64790PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Assunção M, Akamine N, Cardoso GS, Mello PV, Teles JM, Nunes AL, Maia MO, Rea-Neto A, Machado FR, SEPSES Study Group (2010) Survey on physicians’ knowledge of sepsis: do they recognize it promptly? J Crit Care 25:545–552PubMedCrossRefGoogle Scholar
  31. 31.
    Phua J, Lim HF, Tay CK, Aung NW (2013) Public awareness of sepsis and stroke in singapore: a population-based survey. Ann Acad Med Singapore 42:269–277PubMedGoogle Scholar
  32. 32.
    Talmor D, Greenberg D, Howell MD, Lisbon A, Novack V, Shapiro N (2008) The costs and cost-effectiveness of an integrated sepsis treatment protocol. Crit Care Med 36:1168–1174PubMedCrossRefGoogle Scholar
  33. 33.
    Latin American Sepsis Institute (2012) Accessed 13 Feb 2012
  34. 34.
    Surviving Sepsis Campaign (2012) Accessed 13 Feb 2012
  35. 35.
    Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RMH, Sibbald WJ (1992) Definitions for 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 101:1644–1655PubMedCrossRefGoogle Scholar
  36. 36.
    Brazilian Institute of Geography and Statistics (2012) Brazilian life expectancy tables. Accessed 24 Jul 2012
  37. 37.
    Zhang J, Yu KF (1998) What’s the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. JAMA 280:1690–1691PubMedCrossRefGoogle Scholar
  38. 38.
    Bozza FA, Salluh JI (2010) An urban perspective on sepsis in developing countries. Lancet Infect Dis 10:290–291PubMedCrossRefGoogle Scholar
  39. 39.
    Whippy A, Skeath M, Crawford B, Adams C, Marelich G, Alamshahi M, Borbon J (2011) Kaiser Permanente’s performance improvement system, part 3: multisite improvements in care for patients with sepsis. Jt Comm J Qual Patient Saf 37:483–493PubMedGoogle Scholar
  40. 40.
    Miller RR, Dong L, Nelson NC, Brown SM, Kuttler KG, Probst DR, Allen TL, Clemmer TP, Program ftIHIMC (2013) Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med 188:77–82PubMedCrossRefGoogle Scholar
  41. 41.
    Multz AS, Chalfin DB, Samson IM, Dantzker DR, Fein AM, Steinberg HN, Niederman MS, Scharf SM (1998) A “closed” medical intensive care unit (MICU) improves resource utilization when compared with an “open” MICU. Am J Respir Crit Care Med 157:1468–1473PubMedCrossRefGoogle Scholar
  42. 42.
    Kiefe CI, Allison JJ, Williams OD, Person SD, Weaver MT, Weissman NW (2001) Improving quality improvement using achievable benchmarks for physician feedback: a randomized controlled trial. JAMA 285:2871–2879PubMedCrossRefGoogle Scholar
  43. 43.
    Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, Rubin HR (1999) Why don’t physicians follow clinical practice guidelines? A framework for improvement. JAMA 282:1458–1465PubMedCrossRefGoogle Scholar
  44. 44.
    Blomkalns AL, Roe MT, Peterson ED, Ohman EM, Fraulo ES, Gibler WB (2007) Guideline implementation research: exploring the gap between evidence and practice in the CRUSADE Quality Improvement Initiative. Acad Emerg Med 14:949–954PubMedGoogle Scholar
  45. 45.
    Bouza E, Granda MJ, Hortal J, Barrio JM, Cercenado E, Muñoz P (2013) Pre-emptive broad-spectrum treatment for ventilator-associated pneumonia in high-risk patients. Intensive Care Med 39:1547–1555PubMedCrossRefGoogle Scholar
  46. 46.
  47. 47.
    Garg AX, Adhikari NK, McDonald H, Rosas-Arellano MP, Devereaux PJ, Beyene J, Sam J, Haynes RB (2005) Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: a systematic review. JAMA 293:1223–1238PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • Danilo Teixeira Noritomi
    • 1
  • Otavio T. Ranzani
    • 1
    • 2
    Email author
  • Mariana Barbosa Monteiro
    • 1
  • Elaine Maria Ferreira
    • 3
  • Sergio Ricardo Santos
    • 1
  • Fernando Leibel
    • 1
  • Flavia Ribeiro Machado
    • 3
    • 4
  1. 1.Unidade de Terapia IntensivaHospital PaulistanoSão PauloBrazil
  2. 2.Unidade de Terapia Intensiva, Disciplina de Emergências Clínicas, Hospital das ClínicasUniversidade de São PauloSão PauloBrazil
  3. 3.Latin America Sepsis InstituteSão PauloBrazil
  4. 4.Disciplina de Anestesiologia, Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil

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