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Objectives: Nebulized colistimethate sodium (CMS) can be used to treat ventilator-associated pneumonia caused by MDR bacteria. The influence of the diluent volume of CMS on aerosol delivery has never been studied. The main objectives of the study were to compare aerosol particle characteristics and plasma and urine pharmacokinetics between two diluent volumes in patients treated with nebulized CMS., Methods: A crossover study was conducted in eight patients receiving nebulized CMS every 8 h. After inclusion, nebulization started with 4 million international units (MIU) of CMS diluted either in 6 mL (experimental dilution) or in 12 mL (recommended dilution) of normal saline in a random order. For each diluent volume, CMS aerosol particle sizes were measured and plasma and urine samples were collected every 2 h. Nebulization time and stability of colistin in normal saline were assessed., Results: The mass median aerodynamic diameters were 1.4 ± 0.2 versus 0.9 ± 0.2 μm (P < 0.001) for 6 and 12 mL diluent volumes, respectively. The plasma area under the concentration-time curve from 0 to 8 h (AUC0-8) of colistinA+B was 6.6 (4.3-17.0) versus 6.7 (3.6-14.0) μg·h/mL (P = 0.461) for each dilution. The total amount of colistin and CMS eliminated in the urine represented, respectively, 17% and 13% of the CMS initially placed in the nebulizer chamber for 6 and 12 mL diluent volumes (P = 0.4). Nebulization time was shorter [66 (58-75) versus 93 (69-136) min, P = 0.042] and colistin stability was better with the 6 mL diluent volume., Conclusions: Nebulization with a higher concentration of CMS in saline (4 MIU in 6 mL) decreases nebulization time and improves colistin stability without changing plasma and urine pharmacokinetics or aerosol particle characteristics for lung deposition.

Purpose: Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO2/FiO2 ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS., Methods: We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed., Results: Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO2 change was found according to oxygenation response or lung morphology., Conclusions: In ARDS patients with a PaO2/FiO2 ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

Introduction: The study was designed to assess the impact of fluid loading on lung aeration, oxygenation and hemodynamics in patients with septic shock and acute respiratory distress syndrome (ARDS)., Methods: During a 1-year period, a prospective observational study was performed in 32 patients with septic shock and ARDS. Cardiorespiratory parameters were measured using Swan Ganz (n = 29) or PiCCO catheters (n = 3). Lung aeration and regional pulmonary blood flows were measured using bedside transthoracic ultrasound. Measurements were performed before (T0), at the end of volume expansion (T1) and 40 minutes later (T2), consisting of 1-L of saline over 30 minutes during the first 48 h following onset of septic shock and ARDS., Results: Lung ultrasound score increased by 23% at T2, from 13 at baseline to 16 (P < 0.001). Cardiac index and cardiac filling pressures increased significantly at T1 (P < 0.001) and returned to control values at T2. The increase in lung ultrasound score was statistically correlated with fluid loading-induced increase in cardiac index and was not associated with increase in pulmonary shunt or regional pulmonary blood flow. At T1, PaO2/FiO2 significantly increased (P < 0.005) from 144 (123 to 198) to 165 (128 to 226) and returned to control values at T2, whereas lung ultrasound score continued to increase., Conclusions: Early fluid loading transitorily improves hemodynamics and oxygenation and worsens lung aeration. Aeration changes can be detected at the bedside by transthoracic lung ultrasound, which may serve as a safeguard against excessive fluid loading.

Objective: Postextubation distress after a successful spontaneous breathing trial is associated with increased morbidity and mortality. Predicting postextubation distress is therefore a major issue in critically ill patients. To assess whether lung derecruitment during spontaneous breathing trial assessed by lung ultrasound is predictive of postextubation distress., Design and Setting: Prospective study in two multidisciplinary intensive care units within University Hospital., Patients and Methods: One hundred patients were included in the study. Lung ultrasound, echocardiography, and plasma B-type natriuretic peptide levels were determined before and at the end of a 60-min spontaneous breathing trial and 4 hrs after extubation. To quantify lung aeration, a lung ultrasound score was calculated. Patients were followed up to hospital discharge., Measurements and Main Results: Fourteen patients failed the spontaneous breathing trial, 86 were extubated, 57 were definitively weaned (group 1), and 29 suffered from postextubation distress (group 2). Loss of lung aeration during the successful spontaneous breathing trial was observed only in group 2 patients: lung ultrasound scores increased from 15 [13;17] to 19 [16; 21] (p < .01). End-spontaneous breathing trial lung ultrasound scores were significantly higher in group 2 than in group 1 patients: 19 [16;21] vs. 10 [7;13], respectively (p < .001) and predicted postextubation distress with an area under the receiver operating characteristic curve of 0.86. Although significantly higher in group 2, B-type natriuretic peptide and echocardiography cardiac filling pressures were not clinically helpful in predicting postextubation distress., Conclusion: Lung ultrasound determination of aeration changes during a successful spontaneous breathing trial may accurately predict postextubation distress.

Rationale: In the critically ill patients, lung ultrasound (LUS) is increasingly being used at the bedside for assessing alveolar-interstitial syndrome, lung consolidation, pneumonia, pneumothorax, and pleural effusion. It could be an easily repeatable noninvasive tool for assessing lung recruitment., Objectives: Our goal was to compare the pressure-volume (PV) curve method with LUS for assessing positive end-expiratory pressure (PEEP)-induced lung recruitment in patients with acute respiratory distress syndrome/acute lung injury (ARDS/ALI)., Methods: Thirty patients with ARDS and 10 patients with ALI were prospectively studied. PV curves and LUS were performed in PEEP 0 and PEEP 15 cm H₂O₂. PEEP-induced lung recruitment was measured using the PV curve method., Measurements and Main Results: Four LUS entities were defined: consolidation; multiple, irregularly spaced B lines; multiple coalescent B lines; and normal aeration. For each of the 12 lung regions examined, PEEP-induced ultrasound changes were measured, and an ultrasound reaeration score was calculated. A highly significant correlation was found between PEEP-induced lung recruitment measured by PV curves and ultrasound reaeration score (Rho = 0.88; P < 0.0001). An ultrasound reaeration score of +8 or higher was associated with a PEEP-induced lung recruitment greater than 600 ml. An ultrasound lung reaeration score of +4 or less was associated with a PEEP-induced lung recruitment ranging from 75 to 450 ml. A statistically significant correlation was found between LUS reaeration score and PEEP-induced increase in Pa(O₂) (Rho = 0.63; P < 0.05)., Conclusions: PEEP-induced lung recruitment can be adequately estimated with bedside LUS. Because LUS cannot assess PEEP-induced lung hyperinflation, it should not be the sole method for PEEP titration.

Purpose of Review: Lung ultrasound at the bedside can provide accurate information on lung status in critically ill patients with acute respiratory distress syndrome., Recent Findings: Lung ultrasound can replace bedside chest radiography and lung computed tomography for assessment of pleural effusion, pneumothorax, alveolar-interstitial syndrome, lung consolidation, pulmonary abscess and lung recruitment/de-recruitment. It can also accurately determine the type of lung morphology at the bedside (focal or diffuse aeration loss), and therefore it is useful for optimizing positive end-expiratory pressure. The learning curve is brief, so most intensive care physicians will be able to use it after a few weeks of training., Summary: Lung ultrasound is noninvasive, easily repeatable and allows assessment of changes in lung aeration induced by the various therapies. It is among the most promising bedside techniques for monitoring patients with acute respiratory distress syndrome.