Free On-line Access

SPCI - Sociedade Portuguesa de Cuidados Intensivos

Revista Brasileira de Terapia Intensiva

AMIB - Associação de Medicina Intensiva Brasileira


ISSN: 0103-507X
Online ISSN: 1982-4335

Ícone Fechar

How to Cite


Westphal GA, Feijó J, Andrade PS, Trindade L, Suchard C, Monteiro MAG, et al. Estratégia de detecção precoce e redução de mortalidade na sepse grave. Rev Bras Ter Intensiva. 2009;21(2):113-123



Original Article

Early detection strategy and mortality reduction in severe sepsis

Estratégia de detecção precoce e redução de mortalidade na sepse grave

Glauco Adrieno WestphalI, Janaína FeijóII, Patrícia Silva de AndradeIII, Louise TrindadeII, Cezar SuchardIV, Márcio Andrei Gil MonteiroIV, Sheila Fonseca MartinsV, Fernanda NunesV, Milton Caldeira FilhoVI

IPhD, Preceptor of Intensive Care Medicine Residency, Hospital Municipal São José - HMSJ - Joinville (SC), Brazil
IIResident of Intensive Care Medicine, Hospital Municipal São José - HMSJ - Joinville (SC), Brazil
IIIPhysician of General Intensive Care Unit, Imperial Hospital de Caridade, Florianópolis (SC), Brazil
IVMedical Student of Universidade da Região de Joinville, Joinville (SC), Brazil
VNurse from the Hospital Infection Control Center, Hospital Municipal São José - HMSJ - Joinville (SC), Brazil
VIPhysician, General Intensive Care Unit and General Coordinator of Intensive Medical Residency, Hospital Municipal São José - HMSJ - Joinville (SC), Brazil.Received from Hospital Municipal São José - HMSJ - Joinville (SC), Brazil

Submitted on March 30, 2009
Accepted on May 12, 2009

Corresponding author:

Janaina Feijó
Rua Profª Ana Maria Harger, 62 - apt. 201
Bairro Anita Garibaldi
CEP: 89202-020 - Joinville (SC), Brasil
Phone: (47) 9193-3374
Email: [email protected]



OBJECTIVE: To evaluate the impact of implementing an institutional policy for detection of severe sepsis and septic shock.
METHODS: Study before (stage I), after (stage II) with prospective data collection in a 195 bed public hospital.. Stage I: Patients with severe sepsis or septic shock were included consecutively over 15 months and treated according to the Surviving Sepsis Campaign guidelines. Stage II: In the 10 subsequent months, patients with severe sepsis or septic shock were enrolled based on an active search for signs suggesting infection (SSI) in hospitalized patients. The two stages were compared for demographic variables, time needed for recognition of at least two signs suggesting infection (SSI-Δt), compliance to the bundles of 6 and 24 hours and mortality.
RESULTS: We identified 124 patients with severe sepsis or septic shock, 68 in stage I and 56 in stage II. The demographic variables were similar in both stages. The Δt-SSI was 34 ± 54 hours in stage I and 7 ± 8.4 hours in stage II (p <0.001). There was no difference in compliance to the bundles. In parallel there was significant reduction of mortality rates at 28 days (54.4% versus 30%, p <0.02) and hospital (67.6% versus 41%, p <0.003).
CONCLUSION: The strategy used helped to identify early risk of sepsis and resulted in decreased mortality associated with severe sepsis and septic shock.

Keywords: Shock, septic /diagnosis; Shock, septic/therapy; Shock, septic/mortality; Sepsis/diagnosis; Sepsis/therapy; Sepsis/mortality




Sepsis is a set of sometimes dramatic and catastrophic reactions of human beings in response to invasion by pathogenic microorganisms. It is a clinical syndrome that presents with different degrees of severity. If not diagnosed and adequately treated it may worsen over time. Usually, the clinical condition begins with nonspecific and subtle changes of the vital signs such as tachycardia and tachypnea.(1-4)

Generally speaking, sepsis often goes unnoticed until advanced stages even in hospital settings(4) because its manifestations are not marked by an ictus as in acute myocardium infraction (AMI) or stroke (S).

Diagnosis of the septic syndrome is clinical, based on changes that comprise the systemic inflammatory response syndrome SIRS. It was defined in 1991 by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee as a set of at least two of the following manifestations: a) fever or hypothermia; b) tachycardia c|) tachypnea, d) leukocytosis or leukopenia. It is an acute condition caused by systemic release of inflammatory mediators and generalized activation of the endothelium, generating break of the endothelial homeostasis with impairment and dysfunction of organs distant from the primary focus. It reflects the level of organic stress associated to different clinical conditions such as: trauma, burns, acute severe pancreatitis, surgery, transfusion therapy and infection. When SIRS is secondary to infection, the diagnosis is sepsis. Sepsis is considered severe when there is at least one associated organ dysfunction and, if hypotension persists regardless of vigorous administration of water, it is septic shock.(1)

It was proven that adopting the therapeutic strategy proposed by the Serving Sepsis Campaign (SSC) that includes early tissue reperfusion and control of the infection focus,(2,5,6) bring about decreased mortality.(7-14) In our hospital, as well as in other Brazilian institutions, notwithstanding adhesion to SSC, mortality rates continue to be unacceptably high.(15-17) Perhaps this was related to delay in diagnosis of sepsis. Failure to identify sepsis delays onset of adequate treatment, causes progress of multiple organ dysfunction and severely jeopardizes prognosis of patients.(16) Therefore, ongoing search for detection of signs of SIRS and organ dysfunction during routine control of vital signs, might involve identification of patients at risk of sepsis. In this context we proposed a simple institutional procedure to facilitate identification of severe sepsis or septic shock in our hospital.

This study intended to verify if institutional emphasis to identify risk of sepsis may help early recognition of severe sepsis or septic shock and influence its prognosis.



This is a before/after study (stage 1/stage II) conducted from August 2005 to September 2007, in the wards of the emergency department and intensive care unit (ICU) of the Hospital Municipal São José (HMSJ), Joinville, Santa Catarina, Brazil. HMS is a general and public hospital with 195 beds for general admission and 2 ICU with 14 beds. Written consent was not given, as it is an institutional program to attend patients. Patients detected in any sector of the hospital with a diagnosis of severe sepsis or septic shock was included. Terminal disease or shock by other etiologies were considered exclusion criteria.

The study encompasses two distinct periods (stage I and stage II) that differ according to the screening strategy of patients with risk of sepsis. In stage I (15 months) were consecutively included patients with severe sepsis or septic shock, managed according to the SSC recommendations. Diagnosis and treatment strategy was divided into three parts, shown in chart 1.(17)

At stage II, (10 months) patients with sepsis or septic shock were identified as from an active search strategy for signs suggesting infection (SSI) in all patients admitted to the hospital. A new form was devised for a record of SSI (Appendix 1), grouping vital signs and eventual clinical signs of organ dysfunction of all patients in each ward. Register of at least two SSI in this form were promptly informed to the responsible nurse by the sector that completed the screening form (Appendix 2). A single nursing technician in each ward was in charge of the task. After initial assessment by the responsible nurse and by the sector, the nursing staff of the Hospital Infection Control Committee (HICC) was advised to evaluate and follow-up the case. The on duty physician (internal medicine resident) was immediately called when suspicion of sepsis was confirmed (Appendix 2). When diagnosis was defined, therapeutic bundles were started from 6 and 24 hours (Appendix 3 and 4) according to SSC guidelines (Figure 1).

Nurses and resident physicians of intensive care and internal medicine of HMS were trained and supervised by intensivists to ascertain that patients were adequately treated in any ward. In our hospital, as well as many others in Brazil, often a bed is not available in the ICU. That is why many training sessions were carried out so that all understood severe sepsis/septic shock, stressing the importance of changes in the vital signs.

The groups of patients of stage I and stage II were compared for: age, gender, provenance (ward, ICU, emergency room), time elapsed since first record (medical chart) of at least two SSI, moment of diagnosis of severe sepsis (Δt-SSI), APACHE, Acute Physiology and Chronic Health Evaluation II score, complete compliance to the bundles of 6 and of 24 hours, ICU and hospital stay, mortality at 28th day and intra-hospital.

For statistical analysis of data, the programs NCSS: Statistical Software 2000 & PASS 2000: Power Analysisande Sample Size and GraphPad Prism 4 were used. Continuous variables were presented as mean ± standard deviations and compared using the Student's t test. Categorical variables were expressed in absolute and relative values and compared by the Chi-Square test. A p=0.05 value was considered statistically significant.



Three hundred seventy eight patients were consecutively assessed. During stage I, 76 patients were identified with severe sepsis or septic shock, of which 8 were excluded for lack of a therapeutic perspective related to the baseline disease. At stage II, 240 patients had two or more signs suggesting infection. Sixty two patients presented severe sepsis criteria (n=26) or septic shock (n=30) and 6 were excluded. That is to say, in the second stage of the study for each 2.7 patients with at least two signs suggesting infection, one patient presented severe sepsis or septic shock (Figure 2).

The groups of patients of stage I and of stage II were similar regarding age, gender and APACHE II at the time of diagnosis. Compliance to the therapeutic bundles of 6 and 24 hours was similar at the two stages, while Δt-SSI was lower at stage II (p < 0.001). At this stage, the number of severe sepsis or septic shock detected was significantly higher in the wards (p < 0.02).Together with earlier detection, there was a significant drop of mortality at the 28th day (p < 0.02) and in hospital (p < 0.003). It was further observed that length of stay in the ICU and hospital was not significantly different between stages (Table 1).

It was noted that dosage of lactate (p < 0.001) and creatinine (p < 0.001), oliguria (p < 0.001) and hypotension (p < 0.008) were significantly more present in stage I patients.

Table 2 shows comparisons among survivors and not survivors in the 2 stages of this study. When comparing the total of survivors to the total of not survivors it was found that age, APACHE II, number of patients in septic shock, number of patients of male gender and time of detection of severe sepsis were significantly higher among not survivors. Length of hospital stay was significantly shorter among not survivors.

APACHE II score was evidently higher among not survivors when compared to survivors in both stages. At stage II, the Δt-SSI was lower among survivors as well as not survivors. Time of detection of survivors was similar in both stages (Table 2).



Findings of this study disclosed that the organized search for signs suggesting infection leads to an earlier diagnosis of sepsis and implies decreased mortality related with this disease.

A series of evidences presented in the last decades clearly point that quick and systematic assistance in clinical situations like AMI, stroke and trauma results in an impressive decrease of associated deaths. However, severe sepsis and septic shock related mortality has undergone changes in the last 25 years.(2,18-23) In Brazil it is higher than in other countries, 56% of mortality versus 30% in the developed countries and 45% in other developing countries.(2,24) Possibly these high rates are due to delay in starting therapy which greatly contributes to spreading of the inflammatory response and development of multiple organ dysfunction (MOD). Patients under treatment, even when appropriate, after multiple organ dysfunction have a worse prognosis.(13,14,25-28)

There is evidence that therapeutic intervention with hemodynamic resuscitation and antibiotic therapy are associated to lower mortality rates.(7-12,15) As such, agile and adequate treatment is the "mainstay" for a successful approach to severe sepsis.(18-20)

Goal directed early therapy proposed by Rivers et al.(13), an early hemodynamic resuscitation protocol, provided an evident decrease of mortality in patients with severe sepsis and septic shock. The basis of this strategy is to treat overall tissue hypoxia as fast as possible to revert the unbalance between offer and consumption of oxygen to avoid development of MOD.(13,26-28) Furthermore, control of the infection focus, with broad spectrum antibiotics and/or surgical drainage in the first hours after diagnosis, also has a major impact on prognosis.(9,10)

All patients cared in the first stage of this study were treated according to SSC guidelines. They set forth that management of the patient be grouped in two "bundles" of procedures which should be accomplished until the sixth and 24th hours. Respectively, "6 hours bundle" and 24 hours bundle".( 5,6) At the first stage, compliance to these bundles (6 hours = 17%; 24 hours = 30%) was even higher that that observed by SSC worldwide (6 hours= 13%; 24 hours = 15%).(17) Notwithstanding the good performance regarding management of severe sepsis., mortality remained unacceptably high (67,6%). This rate was higher than Brazilian mortality observed in the PROGRESS study (56%), years before implementation of the SSC.(24)

Probably, the high mortality rate of patients was associated to delayed identification of the septic condition. The long time period needed to detect sepsis at stage I, if compared to stage II, was remarkable. It is possible that organizational shortcomings associated to the low specificity of the systemic signs of infection are the main causes of delay in reaching diagnosis of sepsis, as noted in the first stage.

APACHE II score was similar in both stages, regardless of the diagnostic forecast and lower mortality occurred in stage II. Probably, early detection permitted identification of patients prior to worsening of lactic acidosis and organ dysfunction such as renal failure, and volume-nonresponsive hypotension. Subsequent early intervention brings about more effective reperfusion and interruption of the sepsis "cascade" effect blocking evolution of this dysfunction. Furthermore, am immeasurable aspect must be considered, the motivational factor that resulted in greater collective involvement surrounding the septic patients and better quality of assistance (Hawthorne effect).

It was possible to reproduce findings from other studies showing a decrease in mortality after adoption of the SSC guidelines.(7,8,11-16) At the second stage, even if there had not been a greater compliance to the bundles, mortality decreased considerably, showing that prognosis does not rely on compliance to the therapeutic bundles, but also on the earlier diagnosis.

Unquestionably, subjectivity and subtlety of signs of inflammation delay diagnosis of sepsis in some patients, with no evident focus of infection at the syndrome's early stages.(1,5,6,29-31) At the same time, international consensus that reviewed SIRS criteria, concluded that: "... these criteria are excessively sensitive and not specific".(29,30) This makes identification and dealing with such a common and lethal syndrome even more difficult. In this context, we added to the screening of sepsis protocols besides the most recent leukometry analysis, manifestations that show organ dysfunction and that might be clinically detected. Probably, increase of sensitivity generated by these screening models has facilitated early identification of physiological changes associated to infectious activity.

Although lack of specificity of the discrete diagnostic signs make earlier recognition of sepsis more difficult, implementation of systematic search for signs of SIRS and/or organic dysfunction in all sectors of the hospital redressed operational shortcomings. This correction was based on retrieval of the importance of care with the patient, the role of each professional involved and importance of vital signs as marker for alert.(31) Changes of the vital signs must be promptly reported by the nursing staff and duly registered by the physician. To investigate the cause of these changes and assess the need for an aggressive treatment is crucial.



To adopt a multidisciplinary institutional strategy focused on early identification of patients at risk of sepsis, thwarts evolution of the syndrome towards more severe stages and brings about a decreased risk of death associated to severe sepsis and septic shock.



1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. 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. 1992;101(6):1644-55.

2. Teles JM, Silva E, Westphal G, Filho RC, Machado FR. Surviving sepsis campaign in Brazil. Shock. 2008;30 Suppl 1:47-52.

3. Instituto Latino Americano Para Estudos da Sepse. Sepse manual. 2a ed. Rio de Janeiro: Atheneu; 2006.

4. Knobel E, Beer I. Objetivos hemodinâmicos na sepse. Prat Hosp [Internet]. 2005;7(38). [citado 2009 Jan 12]. Disponível em:

5. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32(3):858-73. Review. .

6. 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; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296-327.

7. Kortgen A, Niederprüm P, Bauer M. Implementation of an evidence-based "standard operating procedure" and outcome in septic shock. Crit Care Med. 2006;34(4):943-9.

8. Micek ST, Roubinian N, Heuring T, Bode M, Williams J, Harrison C, et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med. 2006;34(11):2707-13.

9. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma A, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589-96.

10. Kumar A, Kazmi M, Ronald J, Seleman M, Roberts D, Gurka D, et al. Rapidity of source control implementation following onset of hypotension is a major determinant of survival in human septic shock: 564. Crit Care Med. 2004;32(12 Suppl):A158.

11. Marshall JC, Maier RV, Jimenez M, Dellinger EP. Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med. 2004;32(11 Suppl):S513-26.

12. Otero RM, Nguyen HB, Huang DT, Gaieski DF, Goyal M, Gunnerson KJ, et al. Early goal-directed therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings. Chest. 2006;130(5):1579-95.

13. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77.

14. Gao F, Melody T, Daniels DF, Giles S, Fox S. 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. 2005;9(6):R764-70.

15. Fernandes Júnior CJ, Souza AG, Santos GPD, Silva E, Akamine N, Lisboa LF. Mortality rate reduction associated with a severe sepsis management protocol implementation. Crit Care 2007; 11(Suppl 3):30.

16. Freitas FG, Salomão R, Tereran N, Mazza BF, Assunção M, Jackiu M, et al. The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock. Clinics (Sao Paulo). 2008;63(4):483-8.

17. Latin American Sepsis Institute. Campanha sobrevivendo a sepse [Internet].[cited 2009 Jan 12]. Available frim: Available at:

18. Hollenberg SM. Top ten list in myocardial infarction. Chest. 2000;118(5):1477-9.

19. Mullins RJ, Mann NC. Population-based research assessing the effectiveness of trauma systems. J Trauma. 1999;47(3 Suppl):S59-66.

20. Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, Friedman JM. Improvement in stroke mortality in Canada and the United States, 1999 to 2002. Circulation. 2006;113(10):1335-43.

21. Friedman G, Silva E, Vincent JL. Has the mortality of septic shock changed with time. Crit Care Med. 1998;26(12):2078-86.

22. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med. 2001;29(7 Suppl):S109-16.

23. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546-54.

24. Beale R, Reinhart K, Brunkhorst FM, Dobb G, Levy M, Martin G, Martin C, Ramsey G, Silva E, Vallet B, Vincent JL, Janes JM, Sarwat S, Williams MD; for the PROGRESS Advisory Board. Promoting Global Research Excellence in Severe Sepsis (PROGRESS): Lessons from an International Sepsis Registry. Infection. 2009 Apr 28. [Epub ahead of print]

25. Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, Childs EW. The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med. 2007;35(9):2016-24.

26. Kern JW, Shoemaker WC. Meta-analysis of hemodynamic optimization in high-risk patients. Crit Care Med. 2002;30(8):1686-92.

27. Vincent JL, Gerlach H. Fluid resuscitation in severe sepsis and septic shock: an evidence based review. Crit Care Med. 2004;32(11 Suppl):S451-4.

28. Rhodes A, Bennett ED. Early goal-directed therapy: an evidence-based review. Crit Care Med. 2004;32(11 Suppl):S448-50.

29. Giuliano KK. Continuous physiologic monitoring and the identification of sepsis: what is the evidence supporting current clinical practice? AACN Adv Crit Care. 2006;17(2):215-23.

30. Gropper MA. Evidence-based management of critically ill patients: analysis and implementation. Anesth Analg. 2004;99(2):566-72

31. Tulli G. Critical points for sepsis management at the patient bedside. Minerva Anestesiol. 2003;69(1-2):35-56, 56-65.



Received from Hospital Municipal São José - HMSJ - Joinville (SC), Brazil.



Submission On-line

Indexed in




Associação de Medicina Intensiva Brasileira - AMIB

Rua Arminda nº 93 - 7º andar - Vila Olímpia - São Paulo, SP, Brasil - Tel./Fax: (55 11) 5089-2642 | e-mail: [email protected]

Cookie Policy

GN1 - Systems and Publications