Nicolò Patroniti

The application of esophageal pressure measurement in patients with respiratory failure.

This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.

Lung Regional Metabolic Activity and Gas Volume Changes Induced by Tidal Ventilation in Patients with Acute Lung Injury

RATIONALE During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation, metabolic activity can be measured by positron emission tomography imaging of [(18)F]fluoro-2-deoxy-D-glucose. OBJECTIVES To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. METHODS In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolic activity was measured from the [(18)F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. MEASUREMENTS AND MAIN RESULTS Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H(2)O, and with regional Vt normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. CONCLUSIONS In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional Vt normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment-derecruitment and increased metabolic activity.

Sigh improves gas exchange and lung volume in patients with acute respiratory distress syndrome undergoing pressure support ventilation.

Background The aim of our study was to assess the effect of periodic hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume, gas exchange, and respiratory pattern in patients with early acute respiratory distress syndrome (ARDS). Methods Thirteen patients undergoing PSV were enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h each. During baseline 1 and baseline 2, patients underwent PSV. Sighs were administered once per minute by adding to baseline PSV a 3- to 5-s continuous positive airway pressure (CPAP) period, set at a level 20% higher than the peak airway pressure of the PSV breaths or at least 35 cm H2O. Mean airway pressure was kept constant by reducing the positive end-expiratory pressure (PEEP) during the sigh period as required. At the end of each study period, arterial blood gas tensions, air flow and pressures traces, end-expiratory lung volume (EELV), compliance of respiratory system (Crs), and ventilatory parameters were recorded. Results Pao2 improved (P < 0.001) from baseline 1 (91.4 ± 27.4 mmHg) to sigh (133 ± 42.5 mmHg), without changes of Paco2. EELV increased (P < 0.01) from baseline 1 (1,242 ± 507 ml) to sigh (1,377 ± 484 ml). Crs improved (P < 0.01) from baseline 1 (40.2 ± 12.5 ml/cm H2O) to sigh (45.1 ± 15.3 ml/cm H2O). Tidal volume of pressure-supported breaths and the airway occlusion pressure (P0.1) decreased (P < 0.01) during the sigh period. There were no significant differences between baselines 1 and 2 for all parameters. Conclusions The addition of 1 sigh per minute during PSV in patients with early ARDS improved gas exchange and lung volume and decreased the respiratory drive.

Lungs of patients with acute respiratory distress syndrome show diffuse inflammation in normally aerated regions: A [18F]-fluoro-2-deoxy-D-glucose PET/CT study

Objective: Neutrophilic inflammation plays a key role in the pathogenesis of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Positron emission tomography (PET) with [18F]-fluoro-2-deoxy-d-glucose (18FDG) can be used to image cellular metabolism that, during lung inflammatory processes, likely reflects neutrophils activity. The aim of this study was to assess the magnitude and regional distribution of inflammatory metabolic activity in the lungs of patients with ALI/ARDS by PET with 18FDG. Design: Prospective clinical investigation. Patients: Ten patients with ALI/ARDS; four spontaneously breathing and two mechanically ventilated subjects, without known lung disease, served as controls. Interventions: In each individual we performed an 18FDG PET/computed tomography of the thorax. Measurements and Main Results: 18FDG cellular influx rate constant (Ki) was computed for the imaged lung field and for regions of interest, grouping voxels with similar density. In all patients with ALI/ARDS, Ki was higher than in controls, also after accounting for the increased lung density. Ki values differed greatly among patients, but in all patients Ki of the normally aerated regions was much higher (2- to 24-fold) than in controls. Whereas in some patients the highest Ki values corresponded to regions with the lowest aeration, in others these regions had lower Ki than normally and mildly hypoaerated regions. Conclusion: In patients with ALI/ARDS, undergoing mechanical ventilation since days, the metabolic activity of the lungs is markedly increased across the entire lung density spectrum. The intensity of this activation and its regional distribution, however, vary widely within and between patients.

Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO

IntroductionH1N1 influenza can cause severe acute lung injury (ALI). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for H1N1-associated ALI.MethodsCENTRAL, Google Scholar, MEDLINE/PubMed and Scopus (updated 2 January 2012) were systematically searched. Studies reporting on 10 or more patients with H1N1 infection treated with ECMO were included. Baseline, procedural, outcome and validity data were systematically appraised and pooled, when appropriate, with random-effect methods.ResultsFrom 1,196 initial citations, 8 studies were selected, including 1,357 patients with confirmed/suspected H1N1 infection requiring intensive care unit admission, 266 (20%) of whom were treated with ECMO. Patients had a median Sequential Organ Failure Assessment (SOFA) score of 9, and had received mechanical ventilation before ECMO implementation for a median of two days. ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used. ECMO was maintained for a median of 10 days. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features. Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% confidence interval 18% to 37%; I2 = 64%).ConclusionsECMO is feasible and effective in patients with ALI due to H1N1 infection. Despite this, prolonged support (more than one week) is required in most cases, and subjects with severe comorbidities or multiorgan failure remain at high risk of in-hospital death.

Pentraxin 3 in acute respiratory distress syndrome: an early marker of severity.

Objective:Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. Design:We measured circulating pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. Setting:One university medical center general intensive care unit. Patients:The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). Interventions:None. Measurements and Main Results:Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher pentraxin 3 values (p < 0.05). Conclusions:The results presented here show that pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysiological significance of pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.

Measurement of pulmonary edema in patients with acute respiratory distress syndrome

Objective:We measured pulmonary edema by thermal indocyanine green-dye double-dilution technique and quantitative computed tomography (CT) in patients with acute respiratory distress syndrome and compared the two techniques. Design and Setting:Prospective human study in a university hospital. Patients:Fourteen mechanically ventilated patients with acute respiratory distress syndrome (nine primary; nine with intubation <7 days). Interventions:All patients underwent a spiral CT of the thorax. We measured pulmonary thermal volume (PTV) and its components, extravascular lung water and pulmonary blood volume, with an integrated fiberoptic monitoring system (COLD Z-021). Measurements and Results:PTV was tightly correlated with lung weight (LW) measured by CT (PTV = 0.6875 * LWCT + 292.77; correlation coefficient = 0.91; p < .0001; bias −11 ± 8 %). Neither etiology of acute respiratory distress syndrome (primary vs. secondary) nor days of intubation affected the accuracy of thermal dye dilution in comparison with CT. There was no correlation between the extravascular lung water (12.3 ± 3.4 mL/kg) and CT distribution of lung tissue compartments. Extravascular lung water and pulmonary blood volume showed good reproducibility in 32 pairs of thermal dye dilution measurements. Conclusions:Measurements of lung edema by thermal indocyanine green-dye double-dilution method show good correlation with those by quantitative computed tomography and good reproducibility in patients with acute respiratory distress syndrome.

Estimation of Patient’s Inspiratory Effort From the Electrical Activity of the Diaphragm*

Objectives:To calculate an index (termed Pmusc/Eadi index) relating the pressure generated by the respiratory muscles (Pmusc) to the electrical activity of the diaphragm (Eadi), during assisted mechanical ventilation and to assess if the Pmusc/Eadi index is affected by the type and level of ventilator assistance. The Pmusc/Eadi index was also used to measure the patient’s inspiratory effort from Eadi without esophageal pressure. Design:Crossover study. Setting:One general ICU. Patients:Ten patients undergoing assisted ventilation. Intervention:Pressure support and neurally adjusted ventilator assist delivered, each, at three levels of ventilatory assistance. Measurement and Main Results:Airways flow and pressure, esophageal pressure, and Eadi were continuously recorded. Sixty tidal volumes for each ventilator settings were analyzed off-line, at three time points during inspiration. For each time point, Pmusc/Eadi index was calculated. Pmusc/Eadi index was also calculated from airway pressure drop during end-expiratory occlusions. Pmusc/Eadi index was very variable among patients, but within one patient it was not affected by type and level of ventilator assistance. Pmusc/Eadi index decreased during the inspiration. Pmusc/Eadi index obtained during an occlusion from airway pressure swing was tightly correlated with that derived from esophageal pressure during tidal ventilation and allowed to estimate pressure time product. Conclusions:Pmusc is tightly related to Eadi, by a proportionality coefficient that we termed Pmusc/Eadi index, stable within each patient under different conditions of ventilator assistance. The derivation of the Pmusc/Eadi index from Eadi and airway pressure during an expiratory occlusion enables a continuous estimate of patient’s inspiratory effort.

Implications of ICU triage decisions on patient mortality: a cost-effectiveness analysis

IntroductionIntensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors.MethodsThis multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (< 5%, 5% to 40% and >40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved.ResultsAdmission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for <5%, 5% to 40% and >40% predicted mortality, respectively. Average cost per life saved for all patients was

Topographic distribution of tidal ventilation in acute respiratory distress syndrome: effects of positive end-expiratory pressure and pressure support.

103,771 (€82,358) and cost per life-year saved was