This is the first prospective cohort epidemiological study of sepsis performed in Brazil, the largest country in South America, and to our knowledge it is the first large cohort of this kind performed in an underdeveloped country. Brazil is heterogeneous in many aspects such as income distribution, educational profiles and use of technology. Even within a particular State, those characteristics can vary significantly. We have initially included five ICUs belonging to the recently created Brazilian Critical Care Clinical Trials Network, because these ICUs already have all personnel and infrastructure for the study. A second phase of our BASES study has already been started in five other ICUs. We have therefore prospectively included 1383 patients admitted to five mixed ICUs from São Paulo and Santa Catarina States, and followed all of them daily, searching for the ACCP/SCCM criteria of SIRS, sepsis, severe sepsis and septic shock, and also for organ dysfunction development (SOFA score). This study design allowed the identification of septic episodes at admission and those beginning during the course of ICU stay. This information can be used to identify risk factors associated with sepsis in patients admitted to the ICU without infection, and also to verify differences in outcome for patients admitted with and without infection.
In general, we found a higher incidence density for sepsis, severe sepsis and septic shock than those reported by other studies [13
]; this could have been due to a more severely ill cohort of patients, resulting in a greater proportional use of invasive devices such as central venous lines, urinary catheters and mechanical ventilation. In addition, our patients had a higher LOS in ICU. Different types of hospital (teaching versus non-teaching), types of ICU (mixed versus surgical), antibiotic use patterns and frequency of antimicrobial-resistant pathogens might also have been factors.
In comparison with the classical study of Rangel-Frausto [10
], we have found a higher severe sepsis occurrence rate (27.3% versus 11.5%), which could be ascribed to the organ dysfunction criteria used in our study and to the fact that we did not enroll ward patients. We defined severe sepsis as any patient with at least one organ dysfunction identified by the SOFA score. In another prospective study, Sands and colleagues [13
] documented an incidence density of sepsis of 2.8 ± 0.17 per 1000 patient-days. This study also included ICU and ward patients. Even in a study that followed only ICU patients [15
], the occurrence rate of clinically suspected sepsis and confirmed severe sepsis was 9.0% and 6.3% of ICU admissions, respectively. In contrast and despite the smaller number of patients in our cohort, we have found a similar occurrence rate of severe sepsis (27.3%) to that found in the larger study of Alberti and colleagues (22.7%) [6
]. This is important for validation of our data. It is noteworthy that both studies included only ICU patients.
There has been great variability in outcome reported in several studies in septic patients. In 1998, Friedman and colleagues published data from 131 studies [4
] involving only septic shock patients. In that study they found a mortality rate of about 50%, with no major change in the previous 20 years. Other studies [10
] reported mortality rates for severe sepsis and septic shock patients ranging from 20% to 81%. One of the major challenges in sepsis studies is to standardize the enrolled population to allow adequate comparison, principally in epidemiologic and therapeutic trials. The severe sepsis mortality rate in our study was similar to those in studies that used the same (ACCP/SCCM Consensus) criteria [6
], but was higher than those found by Rangel-Frausto and colleagues [10
] and Angus and colleagues [5
]. Many factors can explain those differences, for example patient age, associated comorbidities and severity of sepsis (APACHE II score), source and type of infection (community, nosocomial or ICU-acquired), and number and severity of organ dysfunctions. In addition, we must consider access to the best standard of care [18
], which can easily be appraised from the outcomes of private versus public hospitals in our cohort.
Although the ACCP/SCCM Consensus Conference definition categories have received severe criticisms, some authors [10
] have found a close relationship between these categories and outcome. This relationship could be explained by the organ dysfunction presence implicit in this categorization. Thus, to clarify this matter, we measured the SOFA score daily and observed that as the sepsis-related conditions increased from sepsis to septic shock, the first-day and maximum SOFA scores also increased in parallel. This probably suggests that when using the ACCP/SCCM definitions it would be very useful to measure organ dysfunction by means of an organ dysfunction descriptor, to improve the characterization of the progress of the septic patient in ICU.
The lungs and respiratory tract was the main source of infection in our group of septic patients. This finding has been reported by others [6
] and highlights the major role of respiratory infection in ICUs and the need for its prevention. Many of these episodes have been related to ventilator-associated pneumonia [20
]. In our study, the diagnosis of community-acquired or nosocomial respiratory infection was made on the basis of clinical, laboratory and radiographic data. We did not routinely use any kind of tool-based diagnosis, such as protected brush-specimen or broncho-alveolar lavage. The high incidence of lung/respiratory infection in our study might therefore be due, at least in part, to the broad definition criteria we used.
Variability in the time course of sepsis can introduce difficulties in case definition and might consequently explain some discrepancies in incidence rates between studies. In our study, sepsis was diagnosed in 415 patients during their ICU stay, with 281 (67.7%) meeting sepsis diagnostic criteria on admission and 134 (32.3%) on the following days. Similarly, Knaus and colleagues [22
] found that 18% of patients did not meet case definition criteria for sepsis at the time of admission but did meet them within the first week of ICU stay. It is therefore very important to be aware of the case definition criteria used in each study, because the incidence of sepsis can vary according to the follow-up period.
The impact of sepsis in critically ill patients has been underestimated by governmental health services. Quartin and colleagues [23
] showed in their large study that sepsis could jeopardize patients for up to 5 years after a septic episode. In addition, in their model they evaluated the impact of sepsis and common associated comorbidities. They generated a model of how comorbidities could affect survival by studying a large cohort of nonseptic patients. Application of this model to the septic population yielded a prediction of death rates from causes other than sepsis, and mortality beyond this prediction was considered 'sepsis-associated'. They found that although septic patients have many associated comorbidities, sepsis is the cause of many deaths that occur outside the time frame normally associated with this acute disease. In our population, we found that septic patients had higher APACHE II and SOFA scores and a similar number of comorbidities, but higher rates of malignancy, congestive heart failure and chronic obstructive pulmonary disease. Actually, septic patients have severe acute physiological disturbances, as shown by the SOFA score, and probably have chronic diseases, as shown by the APACHE II score, decreasing the possibility of a more rapid recovery free of sequels. In general, acute organ dysfunction is related to early outcome and associated comorbidities are related to late outcome. However, this apparent acute disease could interfere long after its identification. It is therefore possible that septic patients suffer tissue organ derangements leading to prolonged occult risks for mortality. Although this interesting hypothesis has not yet been explored, recent clinical trials in sepsis [2
] have included long-term follow-up.
When comparing data from the private hospital with those from the public hospitals (Table ), we found an incidence of severe sepsis of 16% versus 35%. This difference can be explained by a higher incidence of infection in public hospitals, where patients have a poorer nutritional status and are admitted later in the course of their disease to the ICU. Frequently, studies from developed countries correlate the incidence of severe sepsis with more advanced age and a greater number of underlying diseases and invasive procedures [15
]. Although the private hospital presented all these factors in our study, it showed an incidence of severe sepsis similar to that reported in the literature and lower than that for the public hospitals. We suggest that in Brazil, social and economical factors have a greater influence on the incidence of infection than those classically demonstrated factors. In addition, among septic shock patients we also observed a higher mortality rate in the public hospitals, although the first-day SOFA scores were similar in both groups, namely private and public hospitals. Factors including care provided by the hospitals, delay between hospital (emergency room) and ICU admissions, quality of the multiprofessional ICU team, and access to the best standard of care could explain those discrepant mortality rates. Nevertheless, these data need to be confirmed by specifically designed trials, because we had data from only one private hospital and it could be an outlier institution. Caution should therefore be exercised before drawing definitive conclusions.
Incidence of sepsis and outcome in private and public hospitals
In conclusion, sepsis is an emergent public health problem with a high incidence density and high mortality rates. In our study, the incidence density of sepsis was about 57 per 1000 patient-days, with a high overall mortality rate and a sharp contrast between private and public hospitals. Moreover, there was a close relationship between ACCP/SCCM categories, organ dysfunction development and mortality rate.