Etiological diagnosis of nosocomial pneumonia in a large sample of European intensive care units was based mainly on noninvasive techniques. However, there was high variability in bronchoscopy use between the participating intensive care units.
While sustaining a load that leads to task failure, it is unclear whether diaphragmatic fatigue develops progressively or occurs only at task failure. We hypothesized that incremental loading produces a progressive decrease in diaphragmatic contractility ever before task failure. Ten subjects generated 60% of maximal transdiaphragmatic pressure (Pdimax) for 2 min, 4 min, and until task failure. Before loading, 20 min after each period of loading, and approximately 20 h after the last period of loading, Pdimax, nonpotentiated and potentiated Pdi twitch pressure (Pditw), and the pattern of respiratory muscle recruitment during a CO2 challenge were recorded. Sensation of inspiratory effort at the 4th min of the task-failure protocol was greater than at the same time in the preceding 4-min protocol. Surprisingly, potentiated Pditw and Pdimax were reduced after 2 min of loading and decreased further after 4 min of loading and after task failure; nonpotentiated Pditw was reduced after 4 min of loading and after task failure. The gastric pressure contribution to tidal breathing during a CO2 challenge decreased progressively in relation to duration of the preceding loading period, whereas expiratory muscle recruitment progressively increased. A rest period of approximately 20 h after task failure was not sufficient to normalize these alterations in respiratory muscle recruitment or fatigue-induced changes in diaphragmatic contractility. In conclusion, while sustaining a mechanical load, the diaphragm progressively fatigued, ever before task failure, and when challenged the rib cage-to-diaphragmatic contribution to tidal breathing and recruitment of the expiratory muscles increased pari passu with duration of the preceding loading.
The mechanisms for symptomatic improvement following lung volume reduction surgery for emphysema are poorly understood. We hypothesized that enhanced neuromechanical coupling of the diaphragm is an important factor in this improvement. We studied seven patients with diffuse emphysema before and 3 mo after surgery. Patients showed improvements in 6-min walking distance (p = 0.002) and dyspnea (p = 0.04). The pressure output of the respiratory muscles, quantified as pressure-time product per minute (PTP/min), decreased after surgery (p = 0.03), as did PaCO2 (p = 0.02). Maximal transdiaphragmatic pressures (Pdi(max)) increased from 80.3 +/- 9.5 (SE) to 110.8 +/- 9.3 cm H2O after surgery (p = 0.03), and the twitch transdiaphragmatic pressure response to phrenic nerve stimulation (Pdi(tw)) increased from 17.2 +/- 2.4 to 25.9 +/- 3.0 cm H2O (p = 0.02); these increases were greater than could be accounted for by a decrease in lung volume. The contribution of the diaphragm to tidal breathing, assessed by relative changes in gastric and transdiaphragmatic pressures, increased after surgery (p = 0.008). Net diaphragmatic neuromechanical coupling, quantified as the quotient of tidal volume (normalized to total lung capacity) to tidal change in Pdi (normalized to Pdi(max)), improved after surgery (p = 0.03) and was related to the increase in 6-min walking distance (r = 0.86, p = 0.03) and decrease in dyspnea (r = 0.76, p = 0.08). In conclusion, lung volume reduction surgery effects an improvement in diaphragmatic function, greater than can be accounted for by a decrease in operating lung volume, and enhances diaphragmatic neuromechanical coupling.
BackgroundCurrently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients.MethodsWe conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days.ResultsHigher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups.ConclusionThis phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns.Trial registrationClinicalTrials.gov, NCT00876252. Registered on 3 April 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1601-9) contains supplementary material, which is available to authorized users.
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