Influence of parenteral nutrition delivery system on the development of bloodstream infections in critically ill patients: an international, multicenter, prospective, open-label, controlled study--EPICOS study.

BACKGROUND: Parenteral nutrition (PN) is associated with an increased risk of developing bloodstream infections (BSIs) but the impact of the PN delivery system upon BSI rates remains unclear. This was an international, multicenter, prospective, randomized, open-label, controlled trial that investigated the differences of BSIs associated with 2 different PN systems. METHODS: Patients were randomly allocated in a 2:1:1 ratio to receive either PN delivered by a multichamber bag (MCB group), or by compounded PN made with olive oil (COM1 group) or with MCT/LCT (COM2 group). Blood cultures were performed to evaluate the incidence of BSIs, and catheter use data was collected to calculate CLAB and central venous catheter device use ratio (CVC-DUR). Secondary outcomes included the development of severe sepsis/septic shock, number of intensive care unit (ICU) and hospital days, and all-cause mortality at Day 28. RESULTS: 406 patients were included: 202 in the MCB group, 103 in the COM1 group, and 101 in the COM2 group. Baseline characteristics were well balanced between the 3 groups, BSIs were significantly higher in patients receiving compounded PN (46 BSIs for COM1+COM2 vs 34 BSIs for MCB; p = 0.03).CLAB was higher in patients receiving compounded PN (13.2 for COM1+COM2 vs 10.3 for MCB; p < 0.0001). No differences were observed for the secondary outcomes. CONCLUSION: Compounded PN was associated with a higher incidence of BSIs and CLABs, suggesting that the use of MCB PN may play a role in reducing the incidence of BSIs in patients who receive PN. TRIAL REGISTRATION NUMBER: NCT00798681.

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.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 patients developed 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877.