Lluis Blanch

Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial.

CONTEXT Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS). OBJECTIVE To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS. DESIGN, SETTING, AND PATIENTS The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia. INTERVENTIONS Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation. MAIN OUTCOME MEASURES The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning. RESULTS Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19). CONCLUSION Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00159939.

Short-term effects of prone position in critically ill patients with acute respiratory distress syndrome

Abstract.Objective: Changing the position from supine to prone is an emerging strategy to improve gas exchange in patients with the acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the acute effects on gas exchange, hemodynamics, and respiratory system mechanics of turning critically ill patients with ARDS from supine to prone. Design: Open, prospective study. Setting: General intensive care units. Patients: 23 patients [mean age 56 ± 17 (SD) years] who met ARDS criteria and had a Lung Injury Score > 2.5 (mean 3.25 ± 0.3). Interventions: The decision to turn a patient was made using a protocol based on impaired oxygenation despite the use of positive end-expiratory pressure and a fractional inspired oxygen (FIO2) of 1. Measurements and results: We measured gas exchange and hemodynamic variables in all patients and in 16 patients calculated respiratory system compliance when they were supine and 60 to 90 min after turning them to a prone position. This latter position was remarkably well tolerated, and no clinically relevant complications or events were detected either during turning or while prone. The partial pressure of oxygen in arterial blood (PaO2)/FIO2 ratio improved from 78 ± 37 mm Hg supine to 115 ± 31 mm Hg prone (p < 0.001), and intrapulmonary shunt decreased from 43 ± 11 to 34 ± 8 % (p < 0.001). Cardiac output and other hemodynamic parameters were not affected. Respiratory system compliance slightly improved from 24.7 ± 10.2 ml/cmH2O supine to 27.8 ± 13.2 ml/cmH2O prone (p < 0.05). An improvement in PaO2/FIO2 of more than 15 % from changing from supine to prone was found in 16 patients (responders). Responders had more hypoxemia (PaO2/FIO2 70 ± 23 vs 99 ± 53 mm Hg in non-responders, p < 0.01), more hypercapnia (partial pressure of carbon dioxide in arterial blood (70 ± 27 vs 64 ± 9 mm Hg, p < 0.01), and a shorter elapsed time to the onset of ARDS and turning to the prone position (11.8 ± 16 vs 32.8 ± 42 days, p < 0.01). Conclusions: Turning critically ill, severely hypoxemic patients from the supine to the prone position is a safe and useful therapeutic intervention. Our data suggest that prone positioning should be carried out early in the course of ARDS.

Clinical consequences of the implementation of a weaning protocol

ObjectiveTo analyze the clinical and economic consequences of the implementation of a weaning protocol in patients mechanically ventilated (MV) for more than 48 h.DesignComparative studySettingGeneral intensive care unit (ICU) in a county hospital covering 360 000 inhabitants.Patients51 patients weaned by a fixed protocol were studied prospectively and compared with 50 retrospective controls.MeasurementsThe following variables were assessed: Acute Physiology and Chronic Health Evaluation (APACHE) II score, age, cause of respiratory failure, type of extubation (direct extubation or extubation using a weaning technique), number of days on MV before the weaning trial, weaning time, total duration of MV, complications (reintubations and tracheostomies), length of ICU stay, and mortality.ResultsThe groups were comparble in terms of age, APACHE II score, and main cause of acute respiratory failure. Number of days on MV up to the weaning trial were similar in the two groups (8.4±7.7 in the protocol group vs 7.5±5.5 in the control group, NS). Most of the patients (80%) in the protocol group were directly extubated without a weaning technique, unlike the control group (10%) (p<0.01). When a weaning technique was used, the weaning time was similar in both groups (3.5±3.9 days vs 3.6±2.2 days in the control group). Duration of MV was shorter in the protocol group (10.4±11.6 days) than in the control group (14.4±10.3 days) (p<0.05). As a result, the ICU stay was reduced by using the weaning protocol (16.7±16.5 days vs 20.3±13.2 days in the control group,p<0.05). We found no differences in reintubation rate (17 vs 14% in the control group) and need for tracheostomies (2 vs 8% in the control group).ConclusionThe implementation of a weaning protocol decreased the duration of MV and ICU stay by increasing the number of safe, direct extubations.

Effect of acute moderate changes in PaCO2 on global hemodynamics and gastric perfusion.

Objective: To describe global hemodynamics and splanchnic perfusion changes in response to acute modifications in PaCO2 in hemodynamically stable patients. Design: Prospective, randomized crossover study. Setting: Medical‐surgical intensive care unit at a community hospital (400,000 inhabitants). Patients: Ten critically III patients who were sedated, paralyzed, and mechanically ventilated. Interventions: Hypercapnia and hypocapnia were obtained by increasing and reducing instrumental deadspace in random order. After each intervention, patients returned to the basal condition. Each period lasted 80 min: 20 min to achieve stable PaCO2 and 60 min for tonometer equilibration. In each period, global hemodynamic variables and tonometric data were collected. The periods were compared using analysis of variance. Measurements and Main Results: Acute hypercapnia (PaCO2 from 40 ± 3 to 52 ± 3 torr, p < .05) increased cardiac index (3.43 ± 0.37 vs. 3.97 ± 0.43 mL/min/m2, p < .05), heart rate (95 ± 6 vs. 105 ± 3 beats/min, p < .05), and mean pulmonary artery pressure (21 ± 1 vs. 24 ± 1 mm Hg, p < .05) and reduced systemic vascular resistance (992 ± 98 vs. 813 ± 93 dyne‐sec/cm5, p < .05) and oxygen extraction ratio (27 ± 3% vs. 22 ± 2%, p < .05). Standardized intramucosal PCO2 increased from 49 ± 2 to 61 ± 3 torr (p < .05) with an associated decrease in calculated intramucosal pH ([pHi] 7.35 ± 0.03 vs. 7.25 ± 0.02, p < .05), but the gastro‐arterial PCO2 gradient (ΔPCO2) did not change. Acute hypocapnia (PaCO2 from 41 ± 3 to 34 ± 3 torr, p < .05; pH 7.41 ± 0.01 to 7.47 ± 0.02, p < .05) induced slight increments in systemic vascular resistance (995 ± 117 vs. 1088 ± 160 dyne·sec/cm5, p < .05) and oxygen extraction ratio (28 ± 2% vs. 30 ± 2%, p < .05). Standardized intramucosal PCO2 decreased (50 ± 4 vs. 44 ± 3 torr, p < .05), pHi increased (7.33 ± 0.03 vs. 7.36 ± 0.02; p < .05), but ΔPCO2 did not change. Conclusions: In this small group of stable patients, moderate acute variations in PaCO2 had a significant effect on global hemodynamics, but splanchnic perfusion, assessed by ΔPCO2, did not change. In these conditions, the use of pHi to evaluate gastric perfusion appears unreliable.

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury

Objective:To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. Design:Prospective experimental study. Setting:Animal research laboratory. Subjects:Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. Interventions:After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. Measurements and Main Results:No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). Conclusions:Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.

Relative roles of vascular and airspace pressures in ventilator-induced lung injury.

ObjectiveTo determine whether elevations in pulmonary vascular pressure induced by mechanical ventilation are more injurious than elevations of pulmonary vascular pressure of similar magnitude occurring in the absence of mechanical ventilation. DesignProspective comparative laboratory investigation. SettingUniversity research laboratory. SubjectsMale New Zealand white rabbits. InterventionsThree groups of isolated, perfused rabbit lungs were exposed to cyclic elevation of pulmonary artery pressures arising from either intermittent positive pressure mechanical ventilation or from pulsatile perfusion of lungs held motionless by continuous positive airway pressure. Peak, mean, and nadir pulmonary artery pressures and mean airway pressure were matched between groups (35, 27.4 ± 0.74, and 20.8 ± 1.5 mm Hg, and 17.7 ± 0.22 cm H2O, respectively). Measurements and Main Results Lungs exposed to elevated pulmonary artery pressures attributable to intermittent positive pressure mechanical ventilation formed more edema (6.8 ± 1.3 vs. 1.1 ± 0.9 g/g of lung), displayed more perivascular (61 ± 26 vs. 15 ± 13 vessels) and alveolar hemorrhage (76 ± 11% vs. 26 ± 18% of alveoli), and underwent larger fractional declines in static compliance (88 ± 4.4% vs. 48 ± 25.1% decline) than lungs exposed to similar peak and mean pulmonary artery pressures in the absence of tidal positive pressure ventilation. ConclusionsIsolated phasic elevations of pulmonary artery pressure may cause less damage than those occurring during intermittent positive pressure mechanical ventilation, suggesting that cyclic changes in perivascular pressure surrounding extra-alveolar vessels may be important in the genesis of ventilator-induced lung injury.

Improvement in oxygenation by prone position and nitric oxide in patients with acute respiratory distress syndrome.

Objective: Inhaled nitric oxide (NO) and prone position improve arterial oxygenation in patients with the acute respiratory distress syndrome. This study was undertaken to assess the combined effects of NO and prone position in these patients. Design: Prospective clinical study. Setting: General intensive care service in a community teaching hospital. Patients: 14 mechanically ventilated adult patients with the acute respiratory distress syndrome (mean lung injury score 3.23 ± 0.27). Measurements and results: We measured hemodynamic and oxygenation parameters in the supine position and 2 h later in the prone position, before and during inhalation of 10 ppm NO. A positive response in oxygenation was defined as a ≥ 20 % increment in the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2). In the prone position PaO2/FIO2 increased significantly (from 110 ± 55 to 161 ± 89 mmHg, p < 0.01) and venous admixture decreased (from 38 ± 12 to 30 ± 7 %, p < 0.01) compared to the supine position. Ten of the 14 patients were responders in the prone position. In the supine position, inhalation of NO improved oxygenation to a lesser extent, increasing PaO2/FIO2 to 134 ± 64 mmHg (p < 0.01) and decreasing venous admixture to 35 ± 12 %, (p < 0.01). Five of the 14 patients responded to NO inhalation supine and 8 of 14 responded prone (p = 0.22). The combination of NO therapy and prone positioning was additive in increasing PaO2/FIO2 (197 ± 92 mmHg) and decreasing venous admixture (27 ± 8 %) (p < 0.01). This combination also showed a positive oxygenation response on compared to the supine value without NO in 13 of the 14 patients (93 %). NO-induced changes in PaO2/FIO2 were correlated to changes in pulmonary vascular resistance only in the prone position. Conclusions: In patients with the acute respiratory distress syndrome, the combination of NO and prone position is a valuable adjunct to mechanical ventilation.

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletchers efficiency index, Bohrs dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.

Post-neurosurgical and spontaneous gram-negative bacillary meningitis in adults.

In order to evaluate the clinical aspects of gram-negative bacillary meningitis (GNBM) we reviewed the charts of 20 adult patients with the discharge diagnosis of meningitis caused by gram-negative bacilli (bacteriologically proved) seen between 1973 and 1984. Nine patients had post-neurosurgical (post-NS) GNBM and 11 patients spontaneous (S) GNBM; the mean age of the former was 42 +/- 16 years and of the latter 56 +/- 14 years (p less than 0.05). The overall mortality rate was 50% (33% in the post-NS group and 64% in the S group). The glucose levels in CSF were significantly lower in the patients who died. Patients treated with combined aminoglycoside therapy presented a lower mortality rate than those treated with intravenous aminoglycoside only (25% versus 70%). We suggest that if aminoglycoside therapy is employed, these antibiotics must be administered both intravenously and directly into CNS.

Activation of the Wnt/β-Catenin Signaling Pathway by Mechanical Ventilation Is Associated with Ventilator-Induced Pulmonary Fibrosis in Healthy Lungs

Background Mechanical ventilation (MV) with high tidal volumes (VT) can cause or aggravate lung damage, so-called ventilator induced lung injury (VILI). The relationship between specific mechanical events in the lung and the cellular responses that result in VILI remains incomplete. Since activation of Wnt/β-catenin signaling has been suggested to be central to mechanisms of lung healing and fibrosis, we hypothesized that the Wnt/β-catenin signaling plays a role during VILI. Methodology/Principal Findings Prospective, randomized, controlled animal study using adult, healthy, male Sprague-Dawley rats. Animals (n = 6/group) were randomized to spontaneous breathing or two strategies of MV for 4 hours: low tidal volume (VT) (6 mL/kg) or high VT (20 mL/kg). Histological evaluation of lung tissue, measurements of WNT5A, total β-catenin, non-phospho (Ser33/37/Thr41) β-catenin, matrix metalloproteinase-7 (MMP-7), cyclin D1, vascular endothelial growth factor (VEGF), and axis inhibition protein 2 (AXIN2) protein levels by Western blot, and WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, MMP-7, and AXIN2 immunohistochemical localization in the lungs were analyzed. High-VT MV caused lung inflammation and perivascular edema with cellular infiltrates and collagen deposition. Protein levels of WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, MMP-7, cyclin D1, VEGF, and AXIN2 in the lungs were increased in all ventilated animals although high-VT MV was associated with significantly higher levels of WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, MMP-7, cyclin D1, VEGF, and AXIN2 levels. Conclusions/Significance Our findings demonstrate that the Wnt/β-catenin signaling pathway is modulated very early by MV in lungs without preexistent lung disease, suggesting that activation of this pathway could play an important role in both VILI and lung repair. Modulation of this pathway might represent a therapeutic option for prevention and/or management of VILI.