Summary Background The sepsis burden on acute care services in middle-income countries is a cause for concern. We estimated incidence, prevalence, and mortality of sepsis in adult Brazilian intensive care units (ICUs) and association of ICU organisational factors with outcome. Methods We did a 1-day point prevalence study with follow-up of patients in ICU with sepsis in a nationally representative pseudo-random sample. We produced a sampling frame initially stratified by geographical region. Each stratum was then stratified by hospitals' main source of income (serving general public vs privately insured individuals) and ICU size (ten or fewer beds vs more than ten beds), finally generating 40 strata. In each stratum we selected a random sample of ICUs so as to enrol the total required beds in 1690 Brazilian adult ICUs. We followed up patients until hospital discharge censored at 60 days, estimated incidence from prevalence and length of stay, and generated national estimates. We assessed mortality prognostic factors using random-effects logistic regression models. Findings On Feb 27, 2014, 227 (72%) of 317 ICUs that were randomly selected provided data on 2632 patients, of whom 794 had sepsis (30·2 septic patients per 100 ICU beds, 95% CI 28·4–31·9). The ICU sepsis incidence was 36·3 per 1000 patient-days (95% CI 29·8–44·0) and mortality was observed in 439 (55·7%) of 788 patients (95% CI 52·2–59·2). Low availability of resources (odds ratio [OR] 1·67, 95% CI 1·02–2·75, p=0·045) and adequacy of treatment (OR 0·56, 0·37–0·84, p=0·006) were independently associated with mortality. The projected incidence rate is 290 per 100 000 population (95% CI 237·9–351·2) of adult cases of ICU-treated sepsis per year, which yields about 420 000 cases annually, of whom 230 000 die in hospital. Interpretation The incidence, prevalence, and mortality of ICU-treated sepsis is high in Brazil. Outcome varies considerably, and is associated with access to adequate resources and treatment. Our results show the burden of sepsis in resource-limited settings, highlighting the need to establish programmes aiming for sepsis prevention, early diagnosis, and adequate treatment. Funding Fundacao de Apoio a Pesquisa do Estado de Sao Paulo (FAPESP).

https://www.arca.fiocruz.br/bitstream/icict/34602/2/ve_Machado_Flavia_etal_INI_2017.pdf

The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study

Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality. Randomization was concealed, and patients were allocated to receive, for seven days, either an EPA/GLA diet or an isocaloric, isonitrogenous control diet not enhanced with lipids. Patients were continuously tube-fed at a minimum of 75% of basal energy expenditure × 1.3. To evaluate the progression to severe sepsis and/or septic shock, daily screening for individual organ failure was performed. All clinical outcomes were recorded during a 28-day follow-up period. A total of 115 patients in the early stages of sepsis requiring EN were included, among whom 106 were considered evaluable. Intention-to-treat (ITT) analysis demonstrated that patients fed the EPA/GLA diet developed less severe sepsis and/or septic shock than patients fed the control diet (26.3% versus 50%, respectively; P = 0.0259), with similar results observed for the evaluable patients (26.4% versus 50.9% respectively; P = 0.0217). The ITT analysis demonstrated that patients in the study group developed cardiovascular failure (36.2% versus 21%, respectively; P = 0.0381) and respiratory failure (39.6% versus 24.6%, respectively; P = 0.0362) less often than the control group. Similarly, when considering only the evaluable patients, fewer patientsdeveloped cardiovascular failure (20.7% versus 37.7%, respectively; P = 0.03) and respiratory failure (26.4% versus 39.6%, respectively; P = 0.04). The percentage of patients fed the EPA/GLA diet requiring invasive mechanical ventilation was reduced compared with controls (ITT patients: 18.9% versus 33.9%, respectively; P = 0.394; evaluable patients: 17.5% versus 34.5%, respectively; P = 0.295). Patients nourished with the EPA/GLA diet remained in the ICU fewer days than the control population (ITT patients: 21.1 ICU-free days versus 14.7 ICU-free days, respectively; P < 0.0001; evaluable patients: 20.8 ICU-free days versus 14.3 ICU-free days, respectively; P < 0.0001) and fewer days at the hospital (ITT patients: 19.5 hospital-free days versus 10.3 hospital-free days, respectively; P < 0.0001; evaluable patients: 19.1 hospital-free days versus 10.2 hospital-free days, respectively; P < 0.001) (all numbers expressed as means). No significant differences in 28-day all-cause mortality were observed (ITT patients: 26.2% EPA/GLA diet versus 27.6% control diet, respectively; P = 0.72; evaluable: 26.4 EPA/GLA diet versus 30.18 control diet, respectively; P = 0.79). These data suggest that EPA/GLA may play a beneficial role in the treatment of enterally fed patients in the early stages of sepsis without associated organ dysfunction by contributing to slowing the progression of sepsis-related organ dysfunction, especially with regard to cardiovascular and respiratory dysfunction. ClinicalTrials.gov: NCT00981877

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Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT Study

Hospital-related cost of sepsis: A systematic review.

Extracorporeal cytokine adsorption in septic shock: A proof of concept randomized, controlled pilot study.

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.

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

Background
Sepsis has a high prevalence within intensive care units, with elevated rates of morbidity and mortality, and high costs. Data on sepsis costs are scarce in the literature, and in developing countries such as Brazil these data are largely unavailable.

Vilto Michels

Papers

A Multicentre, Prospective Study to Evaluate Costs of Septic Patients in Brazilian Intensive Care Units