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Purpose: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure., Methods: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality., Results: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies., Conclusions: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Purpose: The use of noninvasive ventilation (NIV) to facilitate discontinuation of mechanical ventilation in patients with acute hypoxemic respiratory failure (hypoxemic ARF) has never been explored. This pilot study aims to assess the feasibility of early extubation followed by immediate NIV, compared conventional weaning, in patients with resolving hypoxemic ARF., Methods: Twenty consecutive hypoxemic patients were randomly assigned to receive either conventional weaning or NIV. The changes in arterial blood gases and respiratory rate were compared between the two groups at 1, 12, 24 and 48 h. Differences in the rate of extubation failure, ICU and hospital mortality, number of invasive-ventilation-free-days at day 28, septic complications, number of tracheotomies, days and rates of continuous intravenous sedation, and ICU length of stay were also determined., Results: No patient interrupted the study protocol. Arterial blood gases were similar during invasive mechanical ventilation, 1 h after NIV application following extubation, and after 12, 24 and 48 h. Respiratory rate was higher after 1 h in the NIV group, but no different after 12, 24 and 48 h. The number of invasive-ventilation-free-days at day 28 was 20 ± 8 (min = 0, max = 25) days in the treatment group and 10 ± 9 (min = 0, max = 25) days in the control group (p = 0.014). The rate of extubation failure, ICU and hospital mortality, tracheotomies, septic complications, days and rates of continuous sedation, and ICU length of stay were not significantly different between the two groups., Conclusions: In a highly experienced centre NIV may be used to facilitate discontinuation of mechanical ventilation in selected patients with resolving hypoxemic ARF.

Purpose: Neurally adjusted ventilatory assist (NAVA) has been shown to improve patient-ventilator interaction and reduce asynchronies in intubated patients, as opposed to pressure support ventilation (PSV). This is a short-term head-to-head physiologic comparison between PSV and NAVA in delivering noninvasive ventilation through a helmet (h-NIV), in patients with postextubation hypoxemic acute respiratory failure., Methods: Ten patients underwent three 20-min trials of h-NIV in PSV, NAVA, and PSV again. Arterial blood gases (ABGs) were assessed at the end of each trial. Diaphragm electrical activity (EAdi) and airway pressure (P (aw)) were recorded to derive neural and mechanical respiratory rate and timing, inspiratory (delay(TR-insp)) and expiratory trigger delays (delay(TR-exp)), time of synchrony between diaphragm contraction and ventilator assistance (time(synch)), and the asynchrony index (AI)., Results: ABGs, peak EAdi, peak P (aw), respiratory rate, either neural or mechanical, neural timing, and delay(TR-exp) were not different between trials. Compared with PSV, with NAVA the mechanical expiratory time was significantly shorter, while the inspiratory time and duty cycle were greater. Time(synch) was 0.79 ± 0.35 s in NAVA versus 0.60 ± 0.30 s and 0.55 ± 0.29 s during the PSV trials (p < 0.01 for both). AI exceeded 10% during both PSV trials, while not in NAVA (p < 0.001)., Conclusions: Compared with PSV, NAVA improves patient-ventilator interaction and synchrony, with no difference in gas exchange, respiratory rate, and neural drive and timing.

Purpose: Noninvasive continuous positive airway pressure (n-CPAP) has been proposed for the treatment of hypoxemic acute respiratory failure (h-ARF). Recruitment maneuvers were shown to improve oxygenation, i.e., the ratio of arterial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2), during either invasive mechanical ventilation, and n-CPAP, with a response depending on the distribution of lung collapse. We hypothesized that, during n-CPAP, early h-ARF patients with bilateral (B(L)) distribution of lung involvement would benefit from recruitment maneuvers more than those with unilateral (U(L)) involvement., Methods: To perform a recruitment maneuver, once a minute we increased the pressure applied to the airway from 10 cmH2O to 25 cmH2O for 8 s (SIGH). We enrolled 24 patients with h-ARF (12 B(L) and 12 U(L)) who underwent four consecutive trials: (1) 30 min breathing through a Venturi mask (V(MASK)), (2) 1 h n-CPAP (n-CPAP1), (3) 1 h n-CPAP plus SIGH (n-CPAP(SIGH)), and (4) 1 h n-CPAP (n-CPAP2)., Results: Compared to V(MASK), n-CPAP at 10 cmH2O delivered via a helmet, increased PaO2/FiO2 and decreased dyspnea in both B(L) and U(L); furthermore, it reduced the respiratory rate and brought PaCO2 up to normal in B(L) only. Compared to n-CPAP, n-CPAP(SIGH) significantly improved PaO2/FiO2 in B(L) (225 ± 88 vs. 308 ± 105, respectively), whereas it produced no further improvement in PaO2/FiO2 in U(L) (232 ± 72 vs. 231 ± 77, respectively). SIGH did not affect hemodynamics in both groups., Conclusions: Compared to n-CPAP, n-CPAP(SIGH) further improved arterial oxygenation in B(L) patients, whereas it produced no additional benefit in those with U(L).

Objective: To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (VC), low tidal volume (Vt), high positive end-expiratory pressure (PEEP) ventilation., Design: Prospective, randomized, laboratory animal study., Subjects: Twenty-seven male New Zealand white rabbits., Interventions: Anesthetized rabbits with hydrochloric acid-induced ALI were randomized (n = 9 per group) to 5.5 h NAVA (non-paralyzed), VC (paralyzed; Vt 6-ml/kg), or VC (paralyzed; Vt 15-ml/kg). PEEP was adjusted to hemodynamic goals in NAVA and VC6-ml/kg, and was 1 cmH2O in VC15-ml/kg., Measurements and Main Results: PaO2/FiO2; lung wet-to-dry ratio; lung histology; interleukin-8 (IL-8) concentrations in broncho-alveolar-lavage (BAL) fluid, plasma, and non-pulmonary organs; plasminogen activator inhibitor type-1 and tissue factor in BAL fluid and plasma; non-pulmonary organ apoptosis rate; creatinine clearance; echocardiography. PEEP was similar in NAVA and VC6-ml/kg. During NAVA, Vt was lower (3.1 +/- 0.9 ml/kg), whereas PaO2/ FiO2, respiratory rate, and PaCO2 were higher compared to VC6-ml/kg (p<0.05 for all). Variables assessing ventilator-induced lung injury (VILI), IL-8 levels, non-pulmonary organ apoptosis rate, and kidney as well as cardiac performance were similar in NAVA compared to VC6-ml/kg. VILI and non-pulmonary organ dysfunction was attenuated in both groups compared to VC15-ml/kg., Conclusions: In anesthetized rabbits with early experimental ALI, NAVA is as effective as VC6-ml/kg in preventing VILI, in attenuating excessive systemic and remote organ inflammation, and in preserving cardiac and kidney function.

Objective: In sepsis, dysregulation of the immune response leads to rapid multiorgan failure and death. Accurate and timely diagnosis is lifesaving and should discriminate sepsis from the systemic inflammatory response syndrome (SIRS) caused by non-infectious agents. Osteopontin acts as an extracellular matrix component or a soluble cytokine in inflamed tissues. Its exact role in immune response and sepsis remains to be elucidated. Therefore, we investigated the role of osteopontin in SIRS and sepsis., Design: Prospective, observational study., Setting: Intensive care unit of a university hospital., Patients and Participants: Fifty-six patients with SIRS or sepsis and 56 healthy subjects were enrolled., Interventions: We analyzed the serum levels of osteopontin and TH1-TH2 cytokines and investigated the role of osteopontin on interleukin 6 secretion by monocytes., Measurements and Main Results: Serum osteopontin levels were strikingly higher in patients than in controls and in sepsis than in SIRS, and decreased during the resolution of both the disorders. Receiver operating characteristic curves showed that osteopontin levels have discriminative power between SIRS and sepsis with an area under the curve of 0.796. Osteopontin levels directly correlated with those of interleukin 6 and in vitro, recombinant osteopontin increased interleukin 6 secretion by monocytes in both the absence and presence of high doses of lipopolysaccharide., Conclusion: These data suggest that osteopontin might be a mediator involved in the pathogenesis of SIRS and sepsis, possibly by supporting interleukin 6 secretion., Descriptor: 45. SIRS/Sepsis: clinical studies.