D.S.Y. Ong

Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis

Rationale We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and that the thereby identified biological phenotypes are associated with mortality. Methods Consecutive patients with ARDS were included in this prospective observational cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and endothelial activation provided the phenotypes in a training cohort, not taking any outcome data into account. Logistic regression with backward selection was used to select the most predictive biomarkers, and these predicted phenotypes were validated in a separate cohort. Multivariable logistic regression was used to quantify the independent association with mortality. Results Two phenotypes were identified in 454 patients, which we named ‘uninflamed’ (N=218) and ‘reactive’ (N=236). A selection of four biomarkers (interleukin-6, interferon gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to accurately predict the phenotype in the training cohort (area under the receiver operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were 15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in the validation cohort (N=207). The ‘reactive phenotype’ was independent from confounders associated with intensive care unit mortality (training cohort: OR 1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31). Conclusions Patients with ARDS can be clustered into two biological phenotypes, with different mortality rates. Four biomarkers can be used to predict the phenotype with high accuracy. The phenotypes were very similar to those found in cohorts derived from randomised controlled trials, and these results may improve patient selection for future clinical trials targeting host response in patients with ARDS.

Respiratory syncytial virus in critically ill adult patients with community-acquired respiratory failure: a prospective observational study.

The incidence of respiratory syncytial virus (RSV) and influenza virus infection was determined during three RSV seasons in 158 adult patients consecutively admitted to the intensive care unit with community-acquired respiratory failure. Nasopharyngeal swabs were tested for the presence of RSV and influenza virus by real-time polymerase chain reaction. Six patients (4%) were positive for RSV and all recovered. This finding was in sharp contrast to influenza (23 (15%) patients, 4 (17%) deaths). In conclusion, even in the midst of the RSV season, RSV is an infrequent cause of respiratory failure in adults admitted to the intensive care unit.

Is a randomized trial of a short course of aminoglycoside added to β-lactam antibiotics for empirical treatment in critically ill patients with sepsis justified?

Abstract Short-term adjunctive treatment with aminoglycosides in critically ill patients is advocated in guidelines for the empirical treatment of sepsis, despite lack of evidence from randomized trials. A large observational study recently reported more nephrotoxicity and a trend to worse patient outcome in critically ill patients receiving aminoglycosides added to beta-lactam antibiotics. Here, we discuss if a randomized controlled trial to obtain a more definite answer is justified and how it could be performed.

O064: Validation and assessment of the new surveillance paradigm for ventilator-associated events

Reliable, meaningful surveillance methods are essential for benchmarking of healthcare-associated infection rates. However case-definitions for ventilator-associated pneumonia (VAP) are complex and subjective. A novel surveillance paradigm for detection of ventilator-associated events (VAE) was recently proposed by the National Healthcare Safety Network (NHSN).

ARDS: Reaktivierung von CMV-Infektion

Cytomegalievirus-Infektionen sind bei immunsupprimierten Patienten haufig. Studien zeigen auch bei immunkompetenten Intensivpatienten eine Reaktivierungsrate von bis zu 40 %. Unklar ist jedoch, ob das ein unabhangiger Risikofaktor fur eine erhohte Mortalitat der Patienten ist.

A high anti-inflammatory response is associated with intermediate-term mortality in patients with sepsis

Sepsis is characterized by a complex systemic inflammatory response to infection. While an overwhelming pro-inflammatory response is held responsible for early deaths, subsequent anti-inflammatory cytokine production may lead to immunosuppression and secondary infections. This has been suggested as a cause of intermediate-term deaths[1].