Cristina Mietto

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.

Lung stress and strain during mechanical ventilation: any safe threshold?

RATIONALE Unphysiologic strain (the ratio between tidal volume and functional residual capacity) and stress (the transpulmonary pressure) can cause ventilator-induced lung damage. OBJECTIVES To identify a strain-stress threshold (if any) above which ventilator-induced lung damage can occur. METHODS Twenty-nine healthy pigs were mechanically ventilated for 54 hours with a tidal volume producing a strain between 0.45 and 3.30. Ventilator-induced lung damage was defined as net increase in lung weight. MEASUREMENTS AND MAIN RESULTS Initial lung weight and functional residual capacity were measured with computed tomography. Final lung weight was measured using a balance. After setting tidal volume, data collection included respiratory system mechanics, gas exchange and hemodynamics (every 6 h); cytokine levels in serum (every 12 h) and bronchoalveolar lavage fluid (end of the experiment); and blood laboratory examination (start and end of the experiment). Two clusters of animals could be clearly identified: animals that increased their lung weight (n = 14) and those that did not (n = 15). Tidal volume was 38 ± 9 ml/kg in the former and 22 ± 8 ml/kg in the latter group, corresponding to a strain of 2.16 ± 0.58 and 1.29 ± 0.57 and a stress of 13 ± 5 and 8 ± 3 cm H(2)O, respectively. Lung weight gain was associated with deterioration in respiratory system mechanics, gas exchange, and hemodynamics, pulmonary and systemic inflammation and multiple organ dysfunction. CONCLUSIONS In healthy pigs, ventilator-induced lung damage develops only when a strain greater than 1.5-2 is reached or overcome. Because of differences in intrinsic lung properties, caution is warranted in translating these findings to humans.

Ventilator associated pneumonia: evolving definitions and preventive strategies.

Ventilator-associated pneumonia (VAP) is one of the most frequent hospital-acquired infections occurring in intubated patients. Because VAP is associated with higher mortality, morbidity, and costs, there is a need to solicit further research for effective preventive measures. VAP has been proposed as an indicator of quality of care. Clinical diagnosis has been criticized to have poor accuracy and reliability. Thus, the Centers for Disease Control and Prevention has introduced a new definition based upon objective and recordable data. Institutions are nowadays reporting a VAP zero rate in surveillance programs, which is in discrepancy with clinical data. This reduction has been highlighted in epidemiological studies, but it can only be attributed to a difference in patient selection, since no additional intervention has been taken to modify pathogenic mechanisms in these studies. The principal determinant of VAP development is the presence of the endotracheal tube (ETT). Contaminated oropharyngeal secretions pool over the ETT cuff and subsequently leak down to the lungs through a hydrostatic gradient. Impairment of mucociliary motility and cough reflex cannot counterbalance with a proper clearance of secretions. Lastly, biofilm develops on the inner ETT surface and acts as a reservoir for microorganism inoculum to the lungs. New preventive strategies are focused on the improvement of secretions drainage and prevention of bacterial colonization. The influence of gravity on mucus flow and body positioning can facilitate the clearance of distal airways, with decreased colonization of the respiratory tract. A different approach proposes ETT modifications to limit the leakage of oropharyngeal secretions: subglottic secretion drainage and cuffs innovations have been addressed to reduce VAP incidence. Moreover, coated-ETTs have been shown to prevent biofilm formation, although there is evidence that ETT clearance devices (Mucus Shaver) are required to preserve the antimicrobial properties over time. Here, after reviewing the most noteworthy issues in VAP definition and pathophysiology, we will present the more interesting proposals for VAP prevention.

Nitrogen washout/washin, helium dilution and computed tomography in the assessment of end expiratory lung volume.

IntroductionEnd expiratory lung volume (EELV) measurement in the clinical setting is routinely performed using the helium dilution technique. A ventilator that implements a simplified version of the nitrogen washout/washin technique is now available. We compared the EELV measured by spiral computed tomography (CT) taken as gold standard with the lung volume measured with the modified nitrogen washout/washin and with the helium dilution technique.MethodsPatients admitted to the general intensive care unit of Ospedale Maggiore Policlinico Mangiagalli Regina Elena requiring ventilatory support and, for clinical reasons, thoracic CT scanning were enrolled in this study. We performed two EELV measurements with the modified nitrogen washout/washin technique (increasing and decreasing inspired oxygen fraction (FiO2) by 10%), one EELV measurement with the helium dilution technique and a CT scan. All measurements were taken at 5 cmH2O airway pressure. Each CT scan slice was manually delineated and gas volume was computed with custom-made software.ResultsThirty patients were enrolled (age = 66 +/- 10 years, body mass index = 26 +/- 18 Kg/m2, male/female ratio = 21/9, partial arterial pressure of carbon dioxide (PaO2)/FiO2 = 190 +/- 71). The EELV measured with the modified nitrogen washout/washin technique showed a very good correlation (r2 = 0.89) with the data computed from the CT with a bias of 94 +/- 143 ml (15 +/- 18%, p = 0.001), within the limits of accuracy declared by the manufacturer (20%). The bias was shown to be highly reproducible, either decreasing or increasing the FiO2 being 117+/-170 and 70+/-160 ml (p = 0.27), respectively. The EELV measured with the helium dilution method showed a good correlation with the CT scan data (r2 = 0.91) with a negative bias of 136 +/- 133 ml, and appeared to be more correct at low lung volumes.ConclusionsThe EELV measurement with the helium dilution technique (at low volumes) and modified nitrogen washout/washin technique (at all lung volumes) correlates well with CT scanning and may be easily used in clinical practice.Trial RegistrationCurrent Controlled Trials NCT00405002.

Autologous Transfusion of Stored Red Blood Cells Increases Pulmonary Artery Pressure

RATIONALE Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. OBJECTIVES We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure. METHODS Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide. MEASUREMENTS AND MAIN RESULTS The age of volunteers was 41 ± 4 years (mean ± SEM), and their body mass index was 33.4 ± 1.3 kg/m(2). Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 ± 2 to 23 ± 2 mm Hg; P < 0.05) but did not change after transfusing 3-day blood (17 ± 2 to 18 ± 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 ± 2 to 12 ± 1 mm Hg; P < 0.05). CONCLUSIONS Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. Clinical trial registered with www.clinicaltrials.gov (NCT 01529502).

Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients.

Objective:The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients frequently require prolonged mechanical ventilation, increasing the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved gas exchange. Design:Prospective, crossover, nonrandomized interventional study. Setting:Medical and surgical ICUs at Massachusetts General Hospital. Patients:Critically ill, mechanically ventilated morbidly obese (body mass index > 35 kg/m2) patients (n = 14). Interventions:This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through esophageal pressure measurement before and after a recruitment maneuver, and at best positive end-expiratory pressure identified through a best decremental positive end-expiratory pressure trial. Measurements and Main Results:The average body mass index was 50.7 ± 16.0 kg/m2. The two methods of evaluating positive end-expiratory pressure identified similar optimal positive end-expiratory pressure levels (20.7 ± 4.0 vs 21.3 ± 3.8 cm H2O; p = 0.40). End-expiratory pressure titration increased end-expiratory lung volumes (&Dgr;11 ± 7 mL/kg; p < 0.01) and oxygenation (&Dgr;86 ± 50 torr; p < 0.01) and decreased lung elastance (&Dgr;5 ± 5 cm H2O/L; p < 0.01). Recruitment maneuvers followed by titrated positive end-expiratory pressure were effective at increasing end-expiratory lung volumes while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the clinicians (11.6 ± 2.9 cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation. Conclusions:Commonly used positive end-expiratory pressure by clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by end-expiratory pressure titration was found to significantly improve lung volumes, respiratory system elastance, and oxygenation.

Pleural effusion in patients with acute lung injury : a CT scan study

Objectives:Pleural effusion is a frequent finding in patients with acute respiratory distress syndrome. To assess the effects of pleural effusion in patients with acute lung injury on lung volume, respiratory mechanics, gas exchange, lung recruitability, and response to positive end-expiratory pressure. Design, Setting, and Patients:A total of 129 acute lung injury or acute respiratory distress syndrome patients, 68 analyzed retrospectively and 61 prospectively, studied at two University Hospitals. Interventions:Whole-lung CT was performed during two breath-holding pressures (5 and 45 cm H2O). Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied. Measurements:Pleural effusion volume was determined on each CT scan section; respiratory system mechanics, gas exchange, and hemodynamics were measured at 5 and 15 cm H2O positive end-expiratory pressure. In 60 patients, elastances of lung and chest wall were computed, and lung and chest wall displacements were estimated. Results:Patients were divided into higher and lower pleural effusion groups according to the median value (287 mL). Patients with higher pleural effusion were older (62 ± 16 yr vs. 54 ± 17 yr, p < 0.01) with a lower minute ventilation (8.8 ± 2.2 L/min vs. 10.1 ± 2.9 L/min, p < 0.01) and respiratory rate (16 ± 5 bpm vs. 19 ± 6 bpm, p < 0.01) than those with lower pleural effusion. Both at 5 and 15 cm H2O of positive end-expiratory pressure PaO2/FIO2, respiratory system elastance, lung weight, normally aerated tissue, collapsed tissue, and lung and chest wall elastances were similar between the two groups. The thoracic cage expansion (405 ± 172 mL vs. 80 ± 87 mL, p < 0.0001, for higher pleural effusion group vs. lower pleural effusion group) was greater than the estimated lung compression (178 ± 124 mL vs. 23 ± 29 mL, p < 0.0001 for higher pleural effusion group vs. lower pleural effusion group, respectively). Conclusions:Pleural effusion in acute lung injury or acute respiratory distress syndrome patients is of modest entity and leads to a greater chest wall expansion than lung reduction, without affecting gas exchange or respiratory mechanics.

Effect of body mass index in acute respiratory distress syndrome.

BACKGROUND Obesity is associated in healthy subjects with a great reduction in functional residual capacity and with a stiffening of lung and chest wall elastance, which promote alveolar collapse and hypoxaemia. Likewise, obese patients with acute respiratory distress syndrome (ARDS) could present greater derangements of respiratory mechanics than patients of normal weight. METHODS One hundred and one ARDS patients were enrolled. Partitioned respiratory mechanics and gas exchange were measured at 5 and 15 cm H2O of PEEP with a tidal volume of 6-8 ml kg(-1) of predicted body weight. At 5 and 45 cm H2O of PEEP, two lung computed tomography scans were performed. RESULTS Patients were divided as follows according to BMI: normal weight (BMI≤25 kg m(-2)), overweight (BMI between 25 and 30 kg m(-2)), and obese (BMI>30 kg m(-2)). Obese, overweight, and normal-weight groups presented a similar lung elastance (median [interquartile range], respectively: 17.7 [14.2-24.8], 20.9 [16.1-30.2], and 20.5 [15.2-23.6] cm H2O litre(-1) at 5 cm H2O of PEEP and 19.3 [15.5-26.3], 21.1 [17.4-29.2], and 17.1 [13.4-20.4] cm H2O litre(-1) at 15 cm H2O of PEEP) and chest elastance (respectively: 4.9 [3.1-8.8], 5.9 [3.8-8.7], and 7.8 [3.9-9.8] cm H2O litre(-1) at 5 cm H2O of PEEP and 6.5 [4.5-9.6], 6.6 [4.2-9.2], and 4.9 [2.4-7.6] cm H2O litre(-1) at 15 cm H2O of PEEP). Lung recruitability was not affected by the body weight (15.6 [6.3-23.4], 15.7 [9.8-22.2], and 11.3 [6.2-15.6]% for normal-weight, overweight, and obese groups, respectively). Lung gas volume was significantly lower whereas total superimposed pressure was significantly higher in the obese compared with the normal-weight group (1148 [680-1815] vs 827 [686-1213] ml and 17.4 [15.8-19.3] vs 19.3 [18.6-21.7] cm H2O, respectively). CONCLUSIONS Obese ARDS patients do not present higher chest wall elastance and lung recruitability.

Respiratory therapy device modifications to prevent ventilator-associated pneumonia.

Purpose of review Ventilator-associated pneumonia (VAP) is a controversial entity in the field of critical care. After years of research and significant efforts from regulatory agencies and hospitals, this complication is still frequently affecting mechanically ventilated patients, making VAP an active battleground for research. As a result, several preventive measures have recently been tested in experimental and clinical trials. Our interest is focused on those innovations related to the endotracheal tube (ETT). Recent findings Four ETT-related VAP causative mechanisms are reviewed, together with different associated potential solutions. Technologies such as the subglottic secretion drainage and the Mucus Slurper have been studied to eliminate subglottic secretion pooling. Novel designs for the cuff and the management of its pressure may avoid leakage. Antimicrobial coatings can prevent endoluminal biofilm formation, whereas using an ETT cleaning device may also be beneficial. Finally, preserving the tracheal ciliary function will keep our best physiologic protection active. Summary VAP prevention strategies are a continuously evolving field. Being able to identify the most valuable ideas needs a deep understanding of the disease pathophysiology. The role of the ETT is crucial and there is need for our standards of care to improve. This may soon be possible with newer technologies becoming increasingly available to clinicians.

Removal of Endotracheal Tube Obstruction With a Secretion Clearance Device

Accumulation of secretions may suddenly occlude an endotracheal tube (ETT), requiring immediate medical attention. The endOclear catheter (Endoclear LLC, Petoskey, Michigan) is a novel device designed to clear mucus and debris from an ETT and restore luminal patency. We present 3 subsequent cases of life-threatening partial ETT occlusions recorded over a period of 6 months at Massachusetts General Hospital. After conventional methods (standard tracheal suctioning and bronchoscopy) failed, the endOclear was used, with successful restoration of the airways in all 3 cases. The respiratory conditions rapidly improved, and all 3 patients tolerated the ETT-cleaning maneuver. These results show that such a device is safe and easy to use during an emergency airway situation for efficient and rapid removal of secretions from obstructed ETTs by respiratory therapists.