Individualized PEEP setting in subjects with ARDS: a randomized controlled pilot study.

BACKGROUND: Low-tidal-volume ventilation may be associated with repetitive opening and closing of terminal airways. The use of PEEP is intended to keep the alveoli open. No method of adjusting the optimal PEEP has shown to be superior or to improve clinical outcomes. We conducted a pilot study to evaluate the effect of setting an individualized level of PEEP at the highest compliance on oxygenation, multiple-organ-dysfunction, and survival in subjects with ARDS. METHODS: Subjects with ARDS ventilated with low tidal volumes and limitation of airway pressure to 30 cm H2O were randomized to either a compliance-guided PEEP group or an FIO2-guided group. RESULTS: Of the 159 patients with ARDS admitted during the study period, 70 met the inclusion criteria. Subjects in the compliance-guided group showed nonsignificant improvements in PaO2/FIO2 during the first 14 days, and in 28-day mortality (20.6% vs. 38.9%, P = .12). Multiple-organ-dysfunction-free days (median 6 vs 20.5 d, P = .02), respiratory-failure-free days (median 7.5 vs 14.5 d, P = .03), and hemodynamic-failure-free days (median 16 vs 22 d, P = .04) at 28 days were significantly lower in subjects with compliance-guided setting of PEEP. CONCLUSIONS: In ARDS subjects, protective mechanical ventilation with PEEP application according to the highest compliance was associated with less organ dysfunction and a strong nonsignificant trend toward lower mortality. ClinicalTrials.gov Number NCT01119872.

A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia.

RATIONALE: Iseganan, an antimicrobial peptide, is active against aerobic and anaerobic gram-positive and gram-negative bacteria as well as fungi and yeasts. The drug has shown little resistance in vitro and to be safe and well tolerated in 800 patients with cancer treated for up to 6 wk. OBJECTIVES: To determine the efficacy of iseganan for the prevention of ventilator-associated pneumonia (VAP). METHODS: Mechanically ventilated patients in the United States and Europe were randomized to oral topical iseganan or placebo (1:1) and treated six times per day while intubated for up to 14 d. Patients were eligible if randomized within 24 h of intubation and estimated to survive and remain mechanically ventilated for 48 h or more. The primary efficacy endpoint of the study was VAP measured among survivors at Day 14. MEASUREMENTS AND MAIN RESULTS: A total of 709 patients were randomized and received at least one dose of study drug. The two groups were comparable at baseline except iseganan-treated patients were, on average, 3 yr older. The rate of VAP among survivors at Day 14 was 16% (45/282) in patients treated with iseganan and 20% (57/284) in those treated with placebo (p = 0.145). Mortality at Day 14 was 22.1% (80/362) in the iseganan group compared with 18.2% (63/347) in the placebo group (p = 0.206). No pattern of excess adverse events in the iseganan group compared with placebo was observed. CONCLUSIONS: Iseganan is not effective in improving outcome in patients on prolonged mechanical ventilation.

Noninvasive vs conventional mechanical ventilation in acute respiratory failure: a multicenter, randomized controlled trial.

STUDY OBJECTIVE: Noninvasive mechanical ventilation (NIMV) is beneficial for patients with acute respiratory failure (ARF) when added to medical treatment. However, its role as an alternative to conventional mechanical ventilation (CMV) remains controversial. Our aim was to compare the efficacy and resource consumption of NIMV against CMV in patients with ARF. DESIGN: A randomized, multicenter, controlled trial. SETTING: Seven multipurpose ICUs. PATIENTS: Sixty-four patients with ARF from various causes who fulfilled criteria for mechanical ventilation. INTERVENTION: The noninvasive group received ventilation through a face mask in pressure-support mode plus positive end-expiratory pressure; the conventional group received ventilation through a tracheal tube. MEASUREMENTS AND RESULTS: Avoidance of intubation, mortality, and consumption of resources were the outcome variables. Thirty-one patients were assigned to the noninvasive group, and 33 were assigned to the conventional group. In the noninvasive group, 58% patients were intubated, vs 100% in the conventional group (relative risk reduction, 43%; p < 0.001). Stratification by type of ARF gave similar results. In the ICU, death occurred in 23% and 39% (p = 0.09) and complications occurred in 52% and 70% (p = 0.07) in the noninvasive and conventional groups, respectively. There were no differences in length of stay. The Therapeutic Intervention Score System-28, but not the direct nursing activity time, was lower in the noninvasive group during the first 3 days. CONCLUSIONS: NIMV reduces the need for intubation and therapeutic intervention in patients with ARF from different causes. There is a nonsignificant trend of reduction in ICUs and hospital mortality together with fewer complications during ICU stay.