Low interleukin-10 release after ex vivo stimulation of whole blood is associated with persistent organ dysfunction in sepsis: A prospective observational study.

BACKGROUND: Sepsis profoundly alters immune homeostasis. Cytokine release after whole blood lipopolysaccharide (LPS)-stimulation reflects cell function across multiple immune cell classes and represents the immune response to LPS. The main goal of this study was to evaluate the prognostic value of ex vivo stimulation of whole blood with LPS in sepsis. METHODS: Blood was drawn on day 1 and day 7 after admission, and stimulated ex vivo with LPS. Tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 were measured with and without stimulation. Our primary outcome measure was the persistence of at least one organ dysfunction at day 7. Organ dysfunction was defined according to the SOFA components by a score ≥ 2. RESULTS: Forty-nine patients with sepsis from a 21-bed intensive care unit, and 23 healthy volunteers were enrolled. The blood of septic patients was less responsive to ex vivo stimulation with LPS than that of healthy controls at day 1 and 7, as demonstrated by lower TNF-α, IL-1ß, IL-6 and IL-10 release. Persistent organ dysfunction was more frequent in patients with lower IL-10 release at day 1 but such an association was not found for pro-inflammatory cytokines. A persistent low IL-10 release at day 7 was also associated with persistent organ dysfunction. CONCLUSION: These data suggest that the capacity to produce IL-10 in response to whole blood ex vivo stimulation early in sepsis, as well as persistent low IL-10 response over time, may help in prognostication and patient stratification. These results will need to be confirmed in future studies.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial.

IMPORTANCE: It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE: To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS: Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES: The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS: Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE: Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01971892.