We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).

In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.

We designed a prospective multicenter randomized controlled study in three long-term weaning units (LWU) to evaluate which protocol, inspiratory pressure support ventilation (PSV) or spontaneous breathing trials (SB), is more effective in weaning patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for more than 15 d. Fifty-two of 75 patients, failing an initial T-piece trial at admission, were randomly assigned to PSV or SB (26 in both groups). No significant difference was found in weaning success rate (73% versus 77% in the PSV and SB group, respectively), mortality rate (11.5% versus 7.6%), duration of ventilatory assistance (181 +/- 161 versus 130 +/- 106 h), LWU (33 +/- 12 versus 35 +/- 19 d), or total hospital stay. The results of these defined protocols were retrospectively compared with an "uncontrolled clinical practice" in weaning historical control patients. The overall 30-d weaning success rate was significantly greater (87% versus 70%) and the time spent under mechanical ventilation by survived and weaned patients was shorter in the patients in the study than in historical control patients (103 +/- 144 versus 170 +/- 127 h). The LWU and hospital stays were also significantly shorter (27 +/- 12 versus 38 +/- 18 and 38 +/- 17 versus 47 +/- 18 d). Spontaneous breathing trials and decreasing levels of PSV are equally effective in difficult-to-wean patients with COPD. The application of a well-defined protocol, independent of the mode used, may result in better outcomes than uncontrolled clinical practice.

Different modalities of assisted ventilation improve breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of the addition of assisted ventilation during exercise training on the outcome of a structured pulmonary rehabilitation programme (PRP) in COPD patients. Thirty-three male patients with stable COPD (mean (SD) forced expiratory volume in 1 s (FEV1) 44 (16) % pred), without chronic ventilatory failure, undergoing a 6-week multidisciplinary outpatient PRP including exercise training, were randomised to training during either mask proportional assist ventilation (PAV: 18 patients) or spontaneous breathing (SB: 15 patients). Assessment included exercise tolerance, dyspnoea, leg fatigue, and health-related quality of life (HRQL). Five out of 18 patients (28%) in the PAV group dropped out due to lack of compliance with the equipment. Both groups showed significant post-PRP improvements in exercise tolerance (peak work rate difference: 20 (95% Cl 2.4-37.6) and 14 (3.8% CI to 24.2) W in PAV and SB group, respectively), dyspnoea and leg fatigue, but not in HRQL, without any significant difference between groups. It is concluded that with the modality and in the patients assessed in this study assisted ventilation during training sessions included in a multidisciplinary PRP was not well tolerated by all patients and gave no additional physiological benefit in comparison with exercise training alone.

Despite progressive lost in effectiveness of repeated PRP, COPD patients undergoing those programs do not show any significant worsening in exercise tolerance, dyspnoea and HRQL along a period of 7 years.