BackgroundIdentifying patients in the immunosuppressive phase of sepsis is essential for development of immunomodulatory therapies. Little data exists comparing the ability of the two most well-studied markers of sepsis-induced immunosuppression, human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-ɑ) production, to predict mortality and morbidity. The purpose of this study was to compare HLA-DR expression and LPS-induced TNF-ɑ production as predictors of 28-day mortality and acquisition of secondary infections in adult septic patients.MethodsA single-center, prospective observational study of 83 adult septic patients admitted to a medical or surgical intensive care unit. Blood samples were collected at three time points during the septic course (days 1–2, days 3–4, and days 6–8 after sepsis diagnosis) and assayed for HLA-DR expression and LPS-induced TNF-ɑ production. A repeated measures mixed model analysis was used to compare values of these immunological markers among survivors and non-survivors and among those who did and did not develop a secondary infection.ResultsTwenty-five patients (30.1 %) died within 28 days of sepsis diagnosis. HLA-DR expression was significantly lower in non-survivors as compared to survivors on days 3–4 (p = 0.04) and days 6–8 (p = 0.002). The change in HLA-DR from days 1–2 to days 6–8 was also lower in non-survivors (p = 0.04). Median HLA-DR expression decreased from days 1–2 to days 3–4 in patients who developed secondary infections while it increased in those without secondary infections (p = 0.054). TNF-ɑ production did not differ between survivors and non-survivors or between patients who did and did not develop a secondary infection.ConclusionsMonocyte HLA-DR expression may be a more accurate predictor of mortality and acquisition of secondary infections than LPS-stimulated TNF-ɑ production in adult medical and surgical critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1505-0) contains supplementary material, which is available to authorized users.

Objective We performed a systematic review and meta-analysis to examine the accuracy of bedside ultrasound for confirmation of central venous catheter position and exclusion of pneumothorax compared to chest radiography. Data Sources PubMed, EMBASE, Cochrane Central Register of Controlled Trials, reference lists, conference proceedings and ClinicalTrials.gov Study Selection Articles and abstracts describing the diagnostic accuracy of bedside ultrasound compared with chest radiography for confirmation of central venous catheters in sufficient detail to reconstruct 2×2 contingency tables were reviewed. Primary outcomes included the accuracy of confirming catheter positioning and detecting a pneumothorax. Secondary outcomes included feasibility, inter-rater reliability, and efficiency to complete bedside ultrasound confirmation of central venous catheter position. Data Extraction Investigators abstracted study details including research design and sonographic imaging technique to detect catheter malposition and procedure-related pneumothorax. Diagnostic accuracy measures included pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Data Synthesis 15 studies with 1553 central venous catheter placements were identified with a pooled sensitivity and specificity of catheter malposition by ultrasound of 0.82 [0.77, 0.86] and 0.98 [0.97, 0.99] respectively. The pooled positive and negative likelihood ratios of catheter malposition by ultrasound were 31.12 [14.72, 65.78] and 0.25 [0.13, 0.47]. The sensitivity and specificity of ultrasound for pneumothorax detection was nearly 100% in the participating studies. Bedside ultrasound reduced mean central venous catheter confirmation time by 58.3 minutes. Risk of bias and clinical heterogeneity in the studies were high. Conclusions Bedside ultrasound is faster than radiography at identifying pneumothorax after central venous catheter insertion. When a central venous catheter malposition exists, bedside ultrasound will identify four out of every five earlier than chest radiography.

Objective To evaluate the efficacy of an emergency department (ED)-based lung-protective mechanical ventilation protocol for the prevention of pulmonary complications. Methods This was a quasi-experimental, before-after study that consisted of a pre-intervention period, a run-in period of approximately six months, and a prospective intervention period. The intervention was a multifaceted ED-based mechanical ventilator protocol targeting lung-protective tidal volume, appropriate setting of positive end-expiratory pressure (PEEP), rapid oxygen weaning, and head-of-bed elevation. A propensity score-matched analysis was used to evaluate the primary outcome, which was the composite incidence of acute respiratory distress syndrome and ventilator-associated conditions. Results A total of 1,192 patients in the pre-intervention group and 513 patients in the intervention group were included. Lung-protective ventilation increased by 48.4% in the intervention group. In the propensity score-matched analysis (n= 490 in each group), the primary outcome occurred in 71 patients (14.5%) in the pre-intervention group, as compared with 36 patients (7.4%) in the intervention group [adjusted OR, 0.47 (0.31–0.71)]. There was an increase in ventilator-free days (mean difference 3.7, 95% CI 2.3–5.1), ICU-free days (mean difference 2.4, (95% CI 1.0–3.7), and hospital-free days (mean difference 2.4, 95% CI 1.2–3.6) associated with the intervention. The mortality rate was 34.1% in the pre-intervention group and 19.6% in the intervention group, adjusted OR 0.47 (0.35–0.63). Conclusions Implementing a mechanical ventilator protocol in the ED is feasible, and is associated with significant improvements in the delivery of safe mechanical ventilation and clinical outcome.

BackgroundProviding supplemental oxygen is fundamental in the management of mechanically ventilated patients. Increasing amounts of data show worse clinical outcomes associated with hyperoxia. However, these previous data in the critically ill have not focused on outcomes associated with brief hyperoxia exposure immediately after endotracheal intubation. Therefore, the objectives of this study were to evaluate the impact of isolated early hyperoxia exposure in the emergency department (ED) on clinical outcomes among mechanically ventilated patients with subsequent normoxia in the intensive care unit (ICU).MethodsThis was an observational cohort study conducted in the ED and ICUs of an academic center in the USA. Mechanically ventilated normoxic (partial pressure of arterial oxygen (PaO2) 60–120 mm Hg) ICU patients with mechanical ventilation initiated in the ED were studied. The cohort was categorized into three oxygen exposure groups based on PaO2 values obtained after ED intubation: hypoxia, normoxia, and hyperoxia (defined as PaO2 < 60 mmHg, PaO2 60–120 mm Hg, and PaO2 > 120 mm Hg, respectively, based on previous literature).ResultsA total of 688 patients were included. ED normoxia occurred in 350 (50.9%) patients, and 300 (43.6%) had exposure to ED hyperoxia. The ED hyperoxia group had a median (IQR) ED PaO2 of 189 mm Hg (146–249), compared to an ED PaO2 of 88 mm Hg (76–101) in the normoxia group, P < 0.001. Patients with ED hyperoxia had greater hospital mortality (29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%). After multivariable logistic regression analysis, ED hyperoxia was an independent predictor of hospital mortality (adjusted OR 1.95 (1.34–2.85)).ConclusionsED exposure to hyperoxia is common and associated with increased mortality in mechanically ventilated patients achieving normoxia after admission. This suggests that hyperoxia in the immediate post-intubation period could be particularly injurious, and targeting normoxia from initiation of mechanical ventilation may improve outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1926-4) contains supplementary material, which is available to authorized users.

BackgroundDespite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections.MethodsPatients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated.ResultsTwenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1).ConclusionsCirculating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1182-z) contains supplementary material, which is available to authorized users.

Deep sedation in mechanically ventilated patients, as evaluated in a small number of qualifying heterogeneous randomized controlled trials and observational studies, was associated with increased mortality and lengths of stay. Interventions targeting early sedation depth assessment, starting in the emergency department and subsequent ICU admission, deserve further investigation and could improve outcome.

Early deep sedation is common in mechanically ventilated ED patients and is associated with worse mortality. These data suggest that ED-based sedation is a modifiable variable that could be targeted to improve outcome.

Objective To evaluate the impact of an emergency department (ED) mechanical ventilation protocol on clinical outcomes and adherence to lung-protective ventilation in patients with acute respiratory distress syndrome (ARDS). Design Quasi-experimental, before-after trial. Setting ED and intensive care units (ICU) of an academic center. Patients Mechanically ventilated ED patients experiencing ARDS while in the ED or after admission to the ICU. Interventions An ED ventilator protocol which targeted parameters in need of quality improvement, as identified by prior work: 1) lung-protective tidal volume; 2) appropriate setting of positive end-expiratory pressure (PEEP); 3) oxygen weaning; and 4) head-of-bed elevation. Measurements and Main Results A total of 229 patients (186 pre-intervention group, 43 intervention group) were studied. In the ED, the intervention was associated with significant changes (P < 0.01 for all) in tidal volume, PEEP, respiratory rate, oxygen administration, and head-of-bed elevation. There was a reduction in ED tidal volume from 8.1 mL/kg PBW (7.0 – 9.1) to 6.4 mL/kg PBW (6.1 – 6.7), and an increase in lung-protective ventilation from 11.1% to 61.5%, P < 0.01. The intervention was associated with a reduction in mortality from 54.8% to 39.5% (OR 0.38, 95% CI 0.17 – 0.83, P = 0.02), and a 3.9 day increase in ventilator-free days, P = 0.01. Conclusions This before-after study of mechanically ventilated patients with ARDS demonstrates that implementing a mechanical ventilator protocol in the ED is feasible, and associated with improved clinical outcomes.