Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes. DESIGN: Retrospective cohort study with propensity score overlap weighting analysis. SETTING: Three ICUs in a 1,500-bed tertiary university hospital. PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias. MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001). CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.

Risk factors for ventilator-associated pneumonia due to Staphylococcus aureus in patients with severe brain injury: A multicentre retrospective cohort study.

BACKGROUND: The present study aims at identifying the risk factors for ventilator-associated pneumonia (VAP) Staphylococcus aureus (S. aureus) in patients with severe brain injury (SBI). METHODS: In this multicentre, retrospective, observational study, patients ≥ 18 year old who had SBI (Glasgow coma scale GCS score < 9) who received mechanical ventilation for at least 48 h were analysed. The main objective was to identify risk factors for S. aureus VAP vs VAP due to other pathogens and to identify risk factors for S. aureus VAP vs patients who did not experience VAP. RESULTS: Eight hundred and forty-seven patients with SBI were admitted in ICU after severe traumatic brain injury (n = 489, 58%), aneurysmal SAH (n = 156, 18%), stroke (n = 27, 3%), spontaneous intracranial haemorrhage (n = 80, 9%), arteriovenous malformation rupture (n = 25, 3%), and other causes (n = 70, 8%). Three hundred fifty of 847 patients (41%) had VAP with S. aureus (n = 161) or other pathogens (n = 189). In patients with VAP, the multivariate analysis shows that age per 10 years of ageing (OR 0.80, 95% CI [0.70; 0.90]; p < 0.001) and tobacco use (OR 0.54, 95%CI [0.33;0.88]; p = 0.014) were protective factors against S. aureus. Age per 10 years of ageing remained a protective factor against S. aureus VAP vs no VAP (OR 0.80, 95%CI [0.73; 0.89], p < 0.001). CONCLUSIONS: In this retrospective study involving patients with SBI and who experienced VAP, increased age and tobacco use were protective factors against VAP due to S. aureus. Increased age remained protective against S. aureus in VAP vs no VAP analysis.

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.

Risk factors for mortality in postoperative peritonitis in critically ill patients.

AIM: To identify the risk factors for mortality in intensive care patients with postoperative peritonitis (POP). METHODS: This was a retrospective analysis using a prospective database that includes all patients hospitalized in a surgical intensive care unit for POP from September 2006 to August 2011. The data collected included demographics, comorbidities, postoperative severity parameters, bacteriological findings, adequacy of antimicrobial therapy and surgical treatments. Adequate source control was defined based on a midline laparotomy, infection source control and intraoperative peritoneal lavage. The number of reoperations needed was also recorded. RESULTS: A total of 201 patients were included. The overall mortality rate was 31%. Three independent risk factors for mortality were identified: The Simplified Acute Physiological II Score (OR = 1.03; 95%CI: 1.02-1.05, P < 0.001), postoperative medical complications (OR = 6.02; 95%CI: 1.95-18.55, P < 0.001) and the number of reoperations (OR = 2.45; 95%CI: 1.16-5.17, P = 0.015). Surgery was considered as optimal in 69% of the cases, but without any significant effect on mortality. CONCLUSION: The results from the large cohort in this study emphasize the role of the initial postoperative severity parameters in the prognosis of POP. No predefined criteria for optimal surgery were significantly associated with increased mortality, although the number of reoperations appeared as an independent risk factor of mortality.

Modulation by Polymyxin-B Hemoperfusion of Inflammatory Response Related to Severe Peritonitis.

Conflicting results have been reported on the influence of Polymyxin-B hemoperfusion treatment on systemic inflammation markers. The aim of the study was to assess in a randomized control trial the influence on plasma cytokine concentrations of Polymyxin-B hemoperfusion in septic shock due to peritonitis. A panel of 10 pro- or anti-inflammatory cytokines was measured in 213 patients with peritonitis-induced septic shock enrolled in the randomized trial ABDOMIX testing the impact of 2 Polymyxin-B hemoperfusion sessions with standard treatment. Gram-negative bacteria were identified in 69% of patients. In the overall population, baseline plasma cytokine concentrations were not different between the two groups. Circulating tumor necrosis factor-α, interleukin (IL)-1ß, IL-10, IL-6, and IL-1RA decreased significantly over time in both groups (P <0.0001 for all in controls, and P = 0.0002, 0.003, and <0.0001 in patients treated with Polymyxin-B hemoperfusion). IL-17A decreased significantly in patients treated with Polymyxin B hemoperfusion (P = 0.045) but not in controls. At the end of the second Polymyxin-B hemoperfusion session or at corresponding time in controls, plasma levels of cytokines did not differ between the two groups. Similar results were found in the subgroup of patients with gram-negative peritonitis who completed two Polymyxin-B hemoperfusion sessions. These results do not support a significant influence of Polymyxin-B hemoperfusion on circulating cytokines assessed except for IL-17A which clinical significance remains to be elucidated.

Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial.

PURPOSE: To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. METHOD: Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. PRIMARY OUTCOME: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5% in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95% CI 0.8583-2.935). Secondary endpoints: mortality rate at day 90 was 33.6% in PMX-HP versus 24% in conventional groups, p = 0.10 (OR 1.6128, 95% CI 0.9067-2.8685); reduction in SOFA score from day 0 to day 7 was -5 (-11 to 6) in PMX-HP versus -5 (-11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. CONCLUSION: This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.

High-dose continuous oxacillin infusion results in achievement of pharmacokinetics targets in critically ill patients with deep sternal wound infections following cardiac surgery.

Knowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive for Staphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site.

Atrial fibrillation is not just an artefact in the ICU.

Atrial fibrillation (AF) is common in the intensive care unit (ICU) and is particularly frequent (46%) in septic shock patients. Inflammation favours AF in the general population, and there is a growing body of evidence that inflammation also plays a role in AF occurring after cardiac surgery but also in the general ICU. How such a finding could modify the therapeutic approach remains elusive. The impact of AF on mortality is not clearly demonstrated in the ICU, with AF reflecting essentially the severity of the underlying disease.