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Revista Brasileira de Terapia Intensiva

AMIB - Associação de Medicina Intensiva Brasileira

OFFICIAL JOURNAL OF THE ASSOCIAÇÃO BRASILEIRA DE MEDICINA INTENSIVA AND THE SOCIEDADE PORTUGUESA DE CUIDADOS INTENSIVOS

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

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Zanon F, Caovilla JJ, Michel RS, Cabeda EV, Ceretta DF, Luckemeyer GD, et al. Sepse na unidade de terapia intensiva: etiologias, fatores prognósticos e mortalidade. Rev Bras Ter Intensiva. 2008;20(2):128-134

 

 

2008;20(2):128-134
Original Article

http://dx.doi.org/10.1590/S0103-507X2008000200003

Sepsis in the intensive care unit: etiologies, prognostic factors and mortality

Sepse na unidade de terapia intensiva: etiologias, fatores prognósticos e mortalidade

Fernando ZanonI, Jairo José CaovillaII, Regina Schwerz MichelIII, Estevan Vieira CabedaIII, Diego Francisco CerettaIII, Graziela Denardin LuckemeyerIV, Cássia BeltrameIV, Naiana PosenattoIV

ISpecialist in Intensive Care, Associação de Medicina Intensiva Brasileira
IIProfessor, Medical Clinics, Universidade de Passo Fundo
IIIResident, Department of Medical Clinics, Hospital da Cidade de Passo Fundo
IVResident, Department of Medical Clinics, Hospital São Vicente de Paulo, Passo Fundo

Presented in February 19, 2008
Accepted for publication in April 13, 2008

Corresponding author:

Fernando Zanon, M.D.
Rua Paissandu, 488/402 - Centro
99010-101 Passo Fundo, RS, Brazil
Phone: +55-54-30457217
E-mail: [email protected]

 

Abstract

BACKGROUND AND OBJECTIVES: Sepsis is the main cause of death in patients treated in intensive care units (ICU). The aim of this study was to evaluate etiology, prognostic factors and mortality of septic patients treated in ICU of Passo Fundo, Brazil.
METHODS: Out of 971 consecutive patients prospectively evaluated from August 2005 to February 2006, 560 were selected due to presence of systemic inflammatory response syndrome (SIRS) and followed for 28 days or until discharge or death. Patients were categorized according with the etiology of SIRS and further classified as having SIRS, sepsis, severe sepsis and septic shock. Prognosis was assessed by means of Apache II and SOFA. Mortality was compared in different etiologies of sepsis, APACHE II and SOFA scores, parameters.
RESULTS: Of the 971 patients admitted to the ICU, 560 developed SIRS (58%). The most frequent cause of internation was neurological disease (28.9%), the most frequent site of infection was the respiratory tract (71.6%), and the most prevalent pathogens were gram-negative bacilli (53.2%). Mean APACHE II score was 18 - 9, and mean SOFA score was 5 - 4. Median ICU stay was 6 (3-11) days and overall mortality rate was 31.1%: 6.1% for non-infectious SIRS, 10.1% for sepsis, 22.6% for severe sepsis, and 64.8% for septic shock.
CONCLUSIONS: Sepsis is an important health problem that leads to an extremely high mortality rate in the ICU of Passo Fundo, Brazil.

Keywords: epidemiology, sepsis, septic shock, severe sepsis, systemic inflammatory response syndrome.

 

 

INTRODUCTION

Sepsis is an important cause of hospitalization and the main cause of death in intensive care unit (ICU)1-3. In 1990, the Center for Disease Control and Prevention (CDC) estimated an incidence of 450 thousand cases of sepsis per year and over 100 thousand deaths in the United States4. In 2001, Angus et al.5 studied over six million records of hospital discharges in seven states in the US and found an estimate of 751 thousand cases of severe sepsis per year, with a mortality rate of 28.6%. Martin et al.6 reviewed data on hospital discharges for 750 million admissions in the US in 22 years, and found more than 10 million cases of sepsis and an increase in frequency to 82.7/100000 inhabitants in 2000. Studies conducted in Europe, Australia and New Zealand reported that the prevalence rate of sepsis in ICU ranged from 5.1% to 30%7-11. The Brazilian Sepsis Epidemiological Study (Bases Study), conducted in five ICU, found mortality rates of 11%, 33.9%, 46.9% and 52.2% in patients with SIRS, sepsis, severe sepsis and septic shock12. Another study conducted in Brazil analyzed data from 75 ICU in different regions, and found mortality rates of 16.7% for sepsis, 34% for severe sepsis, and 65.3% for septic shock13. Overall mortality rates for sepsis have decreased, but, at 20% to 80%, are still unacceptably high14. The incidence of sepsis has increase because of population ageing, more invasive procedures, the use of immunosuppressive drugs and increased prevalence of HIV infection, and this trend is expected to accelerate in the future5,6. Few studies investigated the epidemiology of sepsis in ICU in the state of Rio Grande do Sul, where Passo Fundo is located. This study evaluated epidemiologic data and mortality rates of patients with sepsis in the ICU of three hospitals in Passo Fundo, Brazil.

 

METHODS

This prospective multicenter observational cohort study included patients at the time of diagnosis of SIRS (time zero). It was conducted form August 2005 to February 2006, in Passo Fundo (population, 180,000), a city in the State of Rio Grande do Sul, Brazil, whose hospitals provide care to the population living in the northern area of this state and in the western region of the neighboring state of Santa Catarina. The general ICU studied are located in three hospitals: Hospital da Cidade de Passo Fundo (HCPF), Hospital Prontoclínica (HP) and Hospital São Vicente de Paulo (HSVP). The three are tertiary general hospitals, and two of them are university hospitals affiliated with the Universidade de Passo Fundo (UPF) and the Brazilian Health System (SUS). They have from 90 to 550 hospital beds, and 9 to 22 ICU beds. This study was approved by the Ethics in Research Committee of UPF, and all patients or their legal guardians signed an informed consent term.

Patients were included if they were 18 years or older and developed systemic inflammatory response syndrome (SIRS)17 while in the ICU. Exclusion criteria were: ICU stays shorter than 24 hours; and pregnancy. Each new admission was classified as a new patient in this study.

A questionnaire was used to collect data and to keep uniform records for the three ICU. A manual with detailed information about how to fill out the questionnaire and definitions of all variables was handed out to all researchers. The patients were followed up until discharge from ICU, death, or the 28th day after inclusion in the study. Demographic data, the cause of admission, immunosuppression, APACHE II score, SOFA score, and source of infection were collected. APACHE II scores were calculated in the first 24 hours of hospitalization according to the Knaus method15, and the SOFA scores16 were calculated daily during ICU stay. When a variable was absent, it was classified as normal and a value of zero was entered for that variable. The use of antibiotics, predisposing factor for infection, laboratory culture results, ICU length of stay, and ICU mortality rate were also used for the analyses. Patients were classified according to 4 stages: non-infectious SIRS, sepsis, severe sepsis, and septic shock, according to the definitions established by the consensus of the American College of Chest Physicians and the Society of Critical Care Medicine (ACCP/SCCM) in 199117. Patients could change from one severity stage to the other, but did not go back to a previous stage; therefore, their data might be entered in more than one stage. The authors did not play any role in the decisions made by the patients' attending physicians.

Clinical concepts and criteria introduced in the last decade to define SIRS established a more accurate classification of inflammatory events in patients in ICU. SIRS, sepsis, severe sepsis and septic shock were defined according to the consensus of the ACCP/SCCM. Infection was defined as the presence of pathogenic microorganisms in any sterile medium (blood, cerebrospinal fluid, and ascetic fluid) or the clinical suspicion of infection treated with antibiotics or not17.

Statistical Analysis

Data are presented as mean ± SD, median (interquartile range) and percentages. The Student t test was used to analyze normally distributed variables; the Mann-Whitney test, for no normal variables; and the Fisher Exact test, for categorical variables. The evaluate the discriminatory power of APACHE II scores for mortality, a receiver operation characteristic curve (ROC) was used, and values between 0.7 to 0.8 for area under the curve were classified as good discrimination and , between 0.8 and 0.9, as excellent18-20. The level of statistic significance was set at p < 0.05 (two-tailed). The SPSS 13.0 for Windows (Chicago, US) software was used for statistical analyses.

 

RESULTS

This study was conducted in the general ICU of three hospitals in Passo Fundo Brazil. Percentages of total number of admissions were 50.7%, 36.6% and 13% for HSVP, HCPF and HP. The two teaching hospitals affiliated with the Brazilian Health System (SUS) had 87% of all admissions (Table 1). During the study, 971 patients consecutively admitted to the ICU were evaluated, and 560 met inclusion criteria, which corresponds to a prevalence rate of 58%. Mean age was 60.7 ± 18.6 years, and 56.8% of the patients were older than 60 years; 55.5% were men. Four hundred eleven patients (42%) were excluded because they did not develop SIRS, where younger than 18 years, stayed in the ICU for less than 24 hours, or data were missing from their records (Figure 1). Patients were admitted to the ICU due to neurologic (29.8%), respiratory (24.3%) or surgical (17.1) problems; clinical causes were found for 76.1% of all cases. Non-infectious causes were responsible for 28.7% of all cases of SIRS, and infectious causes, for 71.3%; sepsis, severe sepsis and septic shock were found in 36.4%, 27.8% and 35.8% of the cases of infectious SIRS. The most frequent symptoms of SIRS were tachycardia (82.3%) and tachypnea (80%). Overall mean APACHE II score was 18 ± 9; for survivors, it was 15 ± 8; and for no survivors, 24 ± 9 (p < 0.001). According to the receiver operating characteristic (ROC) curve, a cut-off point of 18.5 was established as the value to obtain good sensitivity (67.6%) and specificity (67.1%); area under the curve was 0.734 ± 0.02 (Figure 2). Mean SOFA scores for SIRS, sepsis, severe sepsis and septic shock were 3.99, 2.65, 4.90 and 8.12. Overall mean SOFA score was 5.4 ± 3.5. Mean first and last SOFA scores of patients that survived was statistically different from mean first and last SOFA score of no survivors (p < 0.001) (Figure 3). System or organ failures were most common in the respiratory (60.4%), neurologic (42.1%) and renal (37.1%) systems. Failure in 3 or more organs was found for 36.4% of the patients; mortality rate ranged from 14.6% for patients with fewer than 3 organ failures to 59.8% in patients with 3 or more organ failures (p < 0.001). Of all study patients, 414 (73.9%) developed infection; cultures were made for 340 (60.7%) and were positive in 50.3% of the cases. Nosocomial infection was found in 53.8% of the cases, and the most frequent sites of infection were the lungs (71.6%), urinary tract (4%) and surgical wound (3.0%). Positive cultures were most frequently obtained from sputum (23%), urine (18.8% and blood (12.7%). The most frequent pathogens were gram-negative bacilli (Escherichia coli, Pseudomonas aeruginosa, Enterobacter sp and Acinetobacter sp) in 53.2% of the cases, and gram-positive cocci (Coagulase-negative Staphylococcus and Staphylococcus aureus). More than one pathogen was identified in 2.8% of the cases, and fungi, in 1.3%. The antibiotics used most frequently were cephalosporin (48.4%), antianaerobic agents (36.3%) and beta-lactamic antibiotics (26.4%). Only one antibiotic was used in 26.1% of the cases; 2, in 28.6%; three or more, in 24% of the patients. The most important infection risk factors were urethral catheter in 87% of the cases; nasogastric catheter in 73%; central venous catheter in 61%; and mechanical ventilation in 51%. Overall median number of days in the ICU was 6 (3-11), and median ICU stay of patients classified according to stages was 6 (2-14). Overall ICU mortality was 31.1%, and on the 28th day after inclusion in the study, 34.6%. Mortality for non-infectious SIRS, sepsis, severe sepsis, and septic shock was 6.1%, 10.1%, 22.6% and 64.8% (Table 2).

 

DISCUSSION

This is the first prospective study in our region to analyze the occurrence of sepsis in patients admitted to the ICU. Sepsis remains a global medical challenge and one of the main causes of death in ICU. This study found a high frequency of sepsis, an overall ICU mortality rate of 31.1% and a rate of 34.6% on the 28th day after inclusion in the study (p = 0.237). Studies in Europe and the US with patients with sepsis reported general mortality rates that ranged from 13.5% to 53.6%1,21-23. Brazilian studies found a general ICU mortality rate of 21.8% and 46.4%12,13. When patients were divided into groups of non-infectious SIRS, sepsis, severe sepsis or septic shock, ICU mortality rates were 6.1%, 10.1%, 22% and 64.8%. Rangel-Frausto et al.24 and Salvo et al.10 found mortality rates of 7% and 26.5% for non-infectious SIRS, 36% and 16% for sepsis, 20% and 52% for severe sepsis, and 46% and 82% for septic shock. The SOAP study21, conducted in 198 ICU in Europe, found a mortality rate of 32.2% for severe sepsis and of 54.1% for septic shock. Brazilian studies reported mortality rates of 11.3% for non-infectious SIRS, of 16.7% to 33.9% for sepsis, 34.4% to 46.9% for severe sepsis, and 52.2% to 65.3% for septic shock12,13. Our overall mortality rates and rates according to sepsis stages were similar to those reported in the literature25,26. Overall mean APACHE II score was 18 ± 9; for survivors, it was 15 ± 8, and for no survivors, 24 ± 9, and the difference was statistically significant (p < 0.001). APACHE II scores were significantly associated with death, and a greater score was associated with greater likelihood of death. A cut-off point of 18 was found using the ROC curve, a value that was adequate to obtain good sensitivity (67.6%) and specificity (66.6%); area under the curve was 0.734 ± 0.0220 (Figure 3). The use of the APACHE II score as a predictor of mortality is controversial. Some studies reported that it successfully predicted outcome for their patients19,20,26, but Lundeberg et al.27 failed to demonstrate the efficacy of APACHE II as a predictor of mortality of patients with sepsis. The SOFA score was associated with overall mortality in our study. The comparison of means, of the first and last SOFA scores of survivors and no survivors revealed a statistically significant difference (p < 0.001) (Table 2), results that are similar to those reported in Brazilian and European studies14,16. In our study, patients with two or fewer organ failures had a mortality rate of 14.6%, and those with three or more, 59.8% (p < 0.001). These findings are similar to those reported in a study conducted by Vincent et al.21, in which patients without any organ dysfunction had a mortality rate of 6%, whereas those with 4 or more organ dysfunctions had a rate of 65%. In this study, gram-negative bacteria were found in 53.2% of the cases, gram-positive bacteria, in 30.4%, and fungi, in 1.3%. Martin et al.6 studied the epidemiology of sepsis in the US and reported that gram-positive bacteria were the most frequent in the ICU. The most frequent site of infection was the lungs (71.6%), which is in agreement with findings in the literature12,13,21. The mortality rate in the group of patients on mechanical ventilation or immunosuppressed patients was significantly greater than that of patients not on ventilation or immunosuppressed (47.6% and 18.2% p < 0.001; 40.9% and 28.7%, p = 0.018). Vincent et al.21 also found a significantly greater mortality rate for patients on mechanical ventilation or immunosuppressed. Median length of ICU stay was 63,4-10 days, similar to those reported in the literature5,8,28.

One of the limitations of this study was that it was conducted in a period of 6 months (August to February). As the prevalence of infections may be affected by season, this study may have failed to demonstrate the actual prevalence of germs that cause such infections or even of sites of infection29,30. Another limitation was that patients were followed up only up to the 28th day after inclusion in the study, and data may have failed to demonstrate actual middle- and long-term morbidity and mortality. Moreover, the study was conducted in only 3 ICU in the city of Passo Fundo, which receives patients only from parts of two Brazilian states. However, few studies investigated the epidemiology of sepsis in Brazil before, and this is the first study on the epidemiology of sepsis in this region.

This study described the epidemiologic profile of patients with sepsis in ICU in the city of Passo Fundo, Brazil, and found a high prevalence of sepsis and an unacceptable high mortality rate in the region. Future studies should include a larger number of patients and ICU to better understand and treat patients with sepsis.

 

ACKNOWLEDGEMENTS

We are grateful to the statisticians of the Graduate Research Group of Hospital de Clínicas de Porto Alegre for the help provided in the analysis of data.

 

REFERENCES

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Received from Hospital da Cidade de Passo Fundo (HCPF), Hospital Prontoclínica (HP) and Hospital São Vicente de Paulo (HSVP), Passo Fundo, RS

 

 

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