Individual response in patient's effort and driving pressure to variations in assistance during pressure support ventilation.

BACKGROUND: During Pressure Support Ventilation (PSV) an inspiratory hold allows to measure plateau pressure (Pplat), driving pressure (∆P), respiratory system compliance (Crs) and pressure-muscle-index (PMI), an index of inspiratory effort. This study aims [1] to assess systematically how patient's effort (estimated with PMI), ∆P and tidal volume (Vt) change in response to variations in PSV and [2] to confirm the robustness of Crs measurement during PSV. METHODS: 18 patients recovering from acute respiratory failure and ventilated by PSV were cross-randomized to four steps of assistance above (+ 3 and + 6 cmH2O) and below (-3 and -6 cmH2O) clinically set PS. Inspiratory and expiratory holds were performed to measure Pplat, PMI, ∆P, Vt, Crs, P0.1 and occluded inspiratory airway pressure (Pocc). Electromyography of respiratory muscles was monitored noninvasively from body surface (sEMG). RESULTS: As PSV was decreased, Pplat (from 20.5 ± 3.3 cmH2O to 16.7 ± 2.9, P < 0.001) and ∆P (from 12.5 ± 2.3 to 8.6 ± 2.3 cmH2O, P < 0.001) decreased much less than peak airway pressure did (from 21.7 ± 3.8 to 9.7 ± 3.8 cmH2O, P < 0.001), given the progressive increase of patient's effort (PMI from -1.2 ± 2.3 to 6.4 ± 3.2 cmH2O) in line with sEMG of the diaphragm (r = 0.614; P < 0.001). As ∆P increased linearly with Vt, Crs did not change through steps (P = 0.119). CONCLUSION: Patients react to a decrease in PSV by increasing inspiratory effort-as estimated by PMI-keeping Vt and ∆P on a desired value, therefore, limiting the clinician's ability to modulate them. PMI appears a valuable index to assess the point of ventilatory overassistance when patients lose control over Vt like in a pressure-control mode. The measurement of Crs in PSV is constant-likely suggesting reliability-independently from the level of assistance and patient's effort.

A technique to measure tidal volume during noninvasive respiratory support by continuous-flow helmet CPAP.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has promoted the use of helmet continuous positive airway pressure (CPAP) for noninvasive respiratory support in hypoxic respiratory failure patients, despite the lack of tidal volume monitoring. We evaluated a novel technique designed to measure tidal volume during noninvasive continuous-flow helmet CPAP. METHODS: A bench model of spontaneously breathing patients undergoing helmet CPAP therapy (three positive end-expiratory pressure [PEEP] levels) at different levels of respiratory distress was used to compare measured and reference tidal volumes. Tidal volume measurement by the novel technique was based on helmet outflow-trace analysis. Helmet inflow was increased from 60 to 75 and 90 L/min to match the patient's peak inspiratory flow; an additional subset of tests was conducted under the condition of purposely insufficient inflow (i.e., high respiratory distress and 60 L/min inflow). RESULTS: The tidal volumes examined herein ranged from 250 to 910 mL. The Bland‒Altman analysis showed a bias of -3.2 ± 29.3 mL for measured tidal volumes compared to the reference, corresponding to an average relative error of -1 ± 4.4%. Tidal volume underestimation correlated with respiratory rate (rho = .411, p = .004) but not with peak inspiratory flow, distress, or PEEP. When the helmet inflow was maintained purposely low, tidal volume underestimation occurred (bias - 93.3 ± 83.9 mL), corresponding to an error of -14.8 ± 6.3%. CONCLUSION: Tidal volume measurement is feasible and accurate during bench continuous-flow helmet CPAP therapy by the analysis of the outflow signal, provided that helmet inflow is adequate to match the patient's inspiratory efforts. Insufficient inflow resulted in tidal volume underestimation. In vivo data are needed to confirm these findings.

A Recirculation System to Reduce the Consumption of Oxygen During CPAP.

BACKGROUND: During continuous flow CPAP for noninvasive respiratory support, a high flow (eg, 60-90 L/min) of gas with FIO2 titratable up to 1.0 is flown within a helmet or face mask, while a PEEP valve maintains the set pressure. A large amount of oxygen is wasted, whereas only a minimal amount is consumed. We describe a recirculation circuit designed to reuse the exhaust gas and save oxygen. METHODS: A standard Venturi-based continuous flow system delivering a flow of ≥ 60 L/min to a helmet, and a modified system designed to recirculate oxygen were tested on the bench during simulated active breathing. The proposed system recirculates the oxygen-enriched gas escaping from the PEEP valve; after CO2 removal, the gas is entrained by the Venturi flow generator and redirected to the helmet. We compared oxygen consumption, pneumatic performance, and gas conditioning of the standard and the recirculation systems. RESULTS: The recirculation system reduced the oxygen consumption up to 80% as compared to the standard system. Oxygen sparing increased with increasing FIO2 and total flow delivered to the helmet. Exhaled CO2 was efficiently removed by a single soda lime canister for about 10 h. Pressure swings during a respiratory cycle slightly worsened when using the recirculation system as compared to the standard one (from 3.5-4.4 cm H2O). At FIO2 1.0, humidity was 6.1 mg/L and 17.3 mg/L with the standard and the recirculation system, respectively. CONCLUSIONS: The recirculation system allowed a 4/5-fold reduction of oxygen consumption during simulated helmet CPAP therapy, whereas CO2 removal was effective for > 10 h. Recirculation minimally affected pneumatic performance of the CPAP continuous flow system, while improving gas conditioning as compared to the standard system.

The use of head helmets to deliver noninvasive ventilatory support: a comprehensive review of technical aspects and clinical findings.

A helmet, comprising a transparent hood and a soft collar, surrounding the patient's head can be used to deliver noninvasive ventilatory support, both as continuous positive airway pressure and noninvasive positive pressure ventilation (NPPV), the latter providing active support for inspiration. In this review, we summarize the technical aspects relevant to this device, particularly how to prevent CO2 rebreathing and improve patient-ventilator synchrony during NPPV. Clinical studies describe the application of helmets in cardiogenic pulmonary oedema, pneumonia, COVID-19, postextubation and immune suppression. A section is dedicated to paediatric use. In summary, helmet therapy can be used safely and effectively to provide NIV during hypoxemic respiratory failure, improving oxygenation and possibly leading to better patient-centred outcomes than other interfaces.

Noninvasive respiratory support outside the intensive care unit for acute respiratory failure related to coronavirus-19 disease: a systematic review and meta-analysis.

BACKGROUND: Noninvasive respiratory support (NIRS) has been diffusely employed outside the intensive care unit (ICU) to face the high request of ventilatory support due to the massive influx of patients with acute respiratory failure (ARF) caused by coronavirus-19 disease (COVID-19). We sought to summarize the evidence on clinically relevant outcomes in COVID-19 patients supported by NIV outside the ICU. METHODS: We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register, along with medRxiv and bioRxiv repositories for pre-prints, for observational studies and randomized controlled trials, from inception to the end of February 2021. Two authors independently selected the investigations according to the following criteria: (1) observational study or randomized clinical trials enrolling ≥ 50 hospitalized patients undergoing NIRS outside the ICU, (2) laboratory-confirmed COVID-19, and (3) at least the intra-hospital mortality reported. Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines were followed. Data extraction was independently performed by two authors to assess: investigation features, demographics and clinical characteristics, treatments employed, NIRS regulations, and clinical outcomes. Methodological index for nonrandomized studies tool was applied to determine the quality of the enrolled studies. The primary outcome was to assess the overall intra-hospital mortality of patients under NIRS outside the ICU. The secondary outcomes included the proportions intra-hospital mortalities of patients who underwent invasive mechanical ventilation following NIRS failure and of those with 'do-not-intubate' (DNI) orders. RESULTS: Seventeen investigations (14 peer-reviewed and 3 pre-prints) were included with a low risk of bias and a high heterogeneity, for a total of 3377 patients. The overall intra-hospital mortality of patients receiving NIRS outside the ICU was 36% [30-41%]. 26% [21-30%] of the patients failed NIRS and required intubation, with an intra-hospital mortality rising to 45% [36-54%]. 23% [15-32%] of the patients received DNI orders with an intra-hospital mortality of 72% [65-78%]. Oxygenation on admission was the main source of between-study heterogeneity. CONCLUSIONS: During COVID-19 outbreak, delivering NIRS outside the ICU revealed as a feasible strategy to cope with the massive demand of ventilatory assistance. REGISTRATION: PROSPERO, https://www.crd.york.ac.uk/prospero/ , CRD42020224788, December 11, 2020.

Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak.

BACKGROUND: Respiratory failure due to COVID-19 pneumonia is associated with high mortality and may overwhelm health care systems, due to the surge of patients requiring advanced respiratory support. Shortage of intensive care unit (ICU) beds required many patients to be treated outside the ICU despite severe gas exchange impairment. Helmet is an effective interface to provide continuous positive airway pressure (CPAP) noninvasively. We report data about the usefulness of helmet CPAP during pandemic, either as treatment, a bridge to intubation or a rescue therapy for patients with care limitations (DNI). METHODS: In this observational study we collected data regarding patients failing standard oxygen therapy (i.e., non-rebreathing mask) due to COVID-19 pneumonia treated with a free flow helmet CPAP system. Patients' data were recorded before, at initiation of CPAP treatment and once a day, thereafter. CPAP failure was defined as a composite outcome of intubation or death. RESULTS: A total of 306 patients were included; 42% were deemed as DNI. Helmet CPAP treatment was successful in 69% of the full treatment and 28% of the DNI patients (P < 0.001). With helmet CPAP, PaO2/FiO2 ratio doubled from about 100 to 200 mmHg (P < 0.001); respiratory rate decreased from 28 [22-32] to 24 [20-29] breaths per minute, P < 0.001). C-reactive protein, time to oxygen mask failure, age, PaO2/FiO2 during CPAP, number of comorbidities were independently associated with CPAP failure. Helmet CPAP was maintained for 6 [3-9] days, almost continuously during the first two days. None of the full treatment patients died before intubation in the wards. CONCLUSIONS: Helmet CPAP treatment is feasible for several days outside the ICU, despite persistent impairment in gas exchange. It was used, without escalating to intubation, in the majority of full treatment patients after standard oxygen therapy failed. DNI patients could benefit from helmet CPAP as rescue therapy to improve survival. TRIAL REGISTRATION: NCT04424992.

A brief airway occlusion is sufficient to measure the patient's inspiratory effort/electrical activity of the diaphragm index (PEI).

Pressure generated by patient's inspiratory muscles (Pmus) during assisted mechanical ventilation is of significant relevance. However, Pmus is not commonly measured since an esophageal balloon catheter is required. We have previously shown that Pmus can be estimated by measuring the electrical activity of the diaphragm (EAdi) through the Pmus/EAdi index (PEI). We investigated whether PEI could be reliably measured by a brief end-expiratory occlusion maneuver to propose an automated PEI measurement performed by the ventilator. Pmus, EAdi, airway pressure (Paw), and flow waveforms of 12 critically ill patients undergoing assisted mechanical ventilation were recorded. Repeated end-expiratory occlusion maneuvers were performed. PEI was measured at 100 ms (PEI0.1) and 200 ms (PEI0.2) from the start of the occlusion and compared to the PEI measured at the maximum Paw deflection (PEIoccl, reference). PEI0.1 and PEI0.2 tightly correlated with PEIoccl, (p < 0.001, R2 = 0.843 and 0.847). At a patient-level analysis, the highest percentage error was -64% and 50% for PEI0.1 and PEI0.2, respectively, suggesting that PEI0.2 might be a more reliable measurement. After correcting the error bias, the PEI0.2 percentage error was lower than ± 30% in all but one subjects (range - 39 to + 29%). It is possible to calculate PEI over a brief airway occlusion of 200 ms at inspiratory onset without the need for a full patient's inspiratory effort. Automated and repeated brief airway occlusions performed by the ventilator can provide a real time measurement of PEI; combining the automatically measured PEI with the EAdi trace could be used to continuously display the Pmus waveform at the bedside without the need of an esophageal balloon catheter.

Occurrence of pendelluft under pressure support ventilation in patients who failed a spontaneous breathing trial: an observational study.

BACKGROUND: Pendelluft, the movement of gas within different lung regions, is present in animal models of assisted mechanical ventilation and associated with lung overstretching. Due to rebreathing of CO2 as compared to fresh gas, pendelluft might reduce ventilatory efficiency possibly exacerbating patient's respiratory workload during weaning. Our aim was to measure pendelluft by electrical impedance tomography (EIT) in patients who failed a spontaneous breathing trial (SBT). METHODS: This is an observational study conducted in a general intensive care unit of a tertiary-level teaching hospital. EIT signal was recorded in 20 patients while pressure support (PS) ventilation was progressively reduced from clinical level (baseline) to 2 cmH2O, as in an SBT; four ventral-to-dorsal lung regions of interest were identified for pendelluft measurement. A regional gas movement (> 6 mL) occurring in a direction opposite to the global EIT signal was considered diagnostic for high pendelluft. RESULTS: Eight patients out of 20 (40%) were classified as high-pendelluft; baseline clinical characteristics did not differ between high- and low-pendelluft patients. At PS reduction, pendelluft and EtCO2 increased more in the high-pendelluft group (p < .001 and .011, respectively). The volume of gas subject to pendelluft moved almost completely from the ventral towards the dorsal lung regions, while the opposite movement was minimal (16.3 [10:32.8] vs. 0 [0:1.8] mL, p = .001). In a subgroup of patients, increased pendelluft volumes positively correlated with markers of respiratory distress such as increased respiratory rate, p0.1, and EtCO2. CONCLUSIONS: Occult pendelluft can be measured by EIT, and is frequently present in patients failing an SBT. When present, pendelluft increases with the reduction of ventilator support and is associated with increased EtCO2, suggesting a reduction of the ability to eliminate CO2.

Event-triggered averaging of electrical impedance tomography (EIT) respiratory waveforms as compared to low-pass filtering for removal of cardiac related impedance changes.

Electrical impedance tomography (EIT) is used for bedside ventilation monitoring; cardiac related impedance changes represent a source of noise superimposed on the ventilation signal, commonly removed by low-pass filtering (LPF). We investigated if an alternative approach, based on an event-triggered averaging (ETA) process, is more effective at preserving the actual ventilation waveform. Ten paralyzed patients undergoing volume-controlled ventilation were studied; 30 breaths for each patient were identified to compare LPF and ETA. For ETA the identified breaths were temporally aligned on the beginning of inspiration; the values of the thirty curves at each time point were averaged. The analysis was conducted on the global EIT signal and on four ventral-to-dorsal regions of interest. Global tidal variations by ETA resulted higher than LPF (average difference 139 ± 88 arbitrary units, p = 0.004). Both for global and regional waveforms, minimum and maximum EIT slopes were steeper by ETA as compared to LPF (average difference respectively - 57 ± 60 mL/s and 144 ± 96 mL/s for global signal, p < 0.05); ventilator inspiratory peak airflow correlated with maximum slope measured by ETA (r = 0.902, p < 0.001), but not LPF (p = 0.319). Beginning of inspiration identified on the ventilator waveform and on the global EIT signal by ETA occurred simultaneously, (+ 0.04 ± 0.07 s, p = 0.081), while occurred earlier by LPF (- 0.26 ± 0.1 s, p < 0.001). Removal of cardiac related impedance changes by ETA results in a ventilation signal more similar to the waveforms recorded by the ventilator, particularly regarding the slope of impedance changes and time at the minimum values as compared to LPF.

Non-Pharmacological Interventions to Prevent Ventilator-Associated Pneumonia: A Literature Review.

Ventilator-associated pneumonia (VAP) is a well-known complication of invasive mechanical ventilation in critically ill patients. The presence of an endotracheal tube (ETT) is one of the major culprits for VAP development: air flow moves pathogens toward the distal airways, while clearance of the trachea is blunted due to reduced tracheal ciliary movement and impaired cough. Several measures are recognized as being useful to prevent VAP, and these are usually grouped in a VAP bundle (ie, avoiding intubation or re-intubation whenever possible; head of bed elevation; hand hygiene; shortening ventilation through sedation interruptions, spontaneous breathing trials, or thromboembolic prophylaxis). However, other interventions have been proposed to reduce VAP rate; some of these interventions have been reported in large clinical trials to be effective, some have been evaluated in small observational studies, and still others at a pre-clinical stage. Some strategies aim to improve the ETT design via a subglottic drainage system, with treatment of the ETT surface to reduce pathogen activity, or by modification of the cuff shape or cuff material to provide a better seal. Another proposed strategy is improving airway care through control of cuff pressure, cleaning the ETT, or use of closed suction systems. Other interventions target a patient's position in the bed to reduce aspiration of digestive content in the airways, or the use of probiotics to modulate gastric flora. Some of these measures are supported by strong evidence, but the impact on relevant outcomes such as duration of ventilation or mortality, as well as cost-benefit ratio, is still unclear, resulting in lack of widespread use.

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data.

PURPOSE: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. METHODS: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. RESULTS: Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01-1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02-1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07-3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT. CONCLUSIONS: Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

Do spontaneous and mechanical breathing have similar effects on average transpulmonary and alveolar pressure? A clinical crossover study.

BACKGROUND: Preservation of spontaneous breathing (SB) is sometimes debated because it has potentially both negative and positive effects on lung injury in comparison with fully controlled mechanical ventilation (CMV). We wanted (1) to verify in mechanically ventilated patients if the change in transpulmonary pressure was similar between pressure support ventilation (PSV) and CMV for a similar tidal volume, (2) to estimate the influence of SB on alveolar pressure (Palv), and (3) to determine whether a reliable plateau pressure could be measured during pressure support ventilation (PSV). METHODS: We studied ten patients equipped with esophageal catheters undergoing three levels of PSV followed by a phase of CMV. For each condition, we calculated the maximal and mean transpulmonary (ΔPL) swings and Palv. RESULTS: Overall, ΔPL was similar between CMV and PSV, but only loosely correlated. The differences in ΔPL between CMV and PSV were explained largely by different inspiratory flows, indicating that the resistive pressure drop caused this difference. By contrast, the Palv profile was very different between CMV and SB; SB led to progressively more negative Palv during inspiration, and Palv became lower than the set positive end-expiratory pressure in nine of ten patients at low PSV. Finally, inspiratory occlusion holds performed during PSV led to plateau and Δ PL pressures comparable with those measured during CMV. CONCLUSIONS: Under similar conditions of flow and volume, transpulmonary pressure change is similar between CMV and PSV. SB during mechanical ventilation can cause remarkably negative swings in Palv, a mechanism by which SB might potentially induce lung injury.

The Ratio of Inspiratory Pressure Over Electrical Activity of the Diaphragm Remains Stable During ICU Stay and is not Related to Clinical Outcome.

BACKGROUND: We previously described an index, defined as the ratio between the inspiratory muscle pressure (Pmus) and the electrical activity of the diaphragm (EA(di)) (Pmus/EA(di) index). In the present work, we describe the trend of Pmus/EA(di) index over time, investigating whether it could be an indicator of muscular efficiency associated with risk factors for diaphragmatic injury and/or clinical outcomes. METHODS: This work is a retrospective analysis of subjects with measurements of Pmus/EA(di) index obtained, on different days, during assisted ventilation. Effects of Pmus/EA(di) index absolute value on clinical outcomes were investigated dividing subjects into those with Pmus/EA(di) index higher or lower than the median. Effects of Pmus/EA(di) index trend over time were analyzed, distinguishing between subjects with Pmus/EA(di) index increasing or decreasing. RESULTS: Mean Pmus/EA(di) index was 1.04 ± 0.67, and the median (interquartile range) was 1.00 (0.59-1.34), without a systematic trend over the days. Demographic, ventilator, or outcome data did not significantly differ between subjects with Pmus/EA(di) index higher or lower than the median. Similarly, we did not find relevant differences in subjects with Pmus/EA(di) index increasing or decreasing over time. CONCLUSIONS: The Pmus/EA(di) index value remained constant in each subject over time, although the inter-individual variability was high. Neither the Pmus/EA(di) index nor its trends appeared to be associated with ventilatory variables or clinical outcome.

The use of a novel cleaning closed suction system reduces the volume of secretions within the endotracheal tube as assessed by micro-computed tomography: a randomized clinical trial.

BACKGROUND: Early after intubation, a layer of biofilm covers the inner lumen of the endotracheal tube (ETT). Cleaning the ETT might prevent airways colonization by pathogens, reduce resistance to airflow, and decrease sudden ETT obstruction. We investigated the effectiveness of a cleaning closed suction system in maintaining the endotracheal tube free from secretions. METHODS: We conducted a single center, randomized controlled trial, in the general intensive care unit of a tertiary-level university hospital. We enrolled 40 adult critically ill patients expected to remain intubated for more than 48 h, within 24 h from intubation. Patients were randomized to receive three ETT cleaning maneuvers/day using a novel device (Airway Medix Closed Suction System™, cleaning group) or to standard care (no ETT cleaning, standard closed suction, control group). After extubation, the amount of secretions in the ETTs was measured by micro-computed tomography. RESULTS: The volume of secretions in the ETTs from the cleaning group was lower than controls (0.081 [0.021-0.306] vs. 0.568 [0.162-0.756] mL, p = 0.001), corresponding to a cross-sectional area reduction six times lower (1[0-3] vs. 6 [2-10] %, p = 0.001). In a subset of 16 patients, the resistance to airflow tended to be lower after 1 day of treatment (p = 0.063) and was lower after 2 days (0.024), while no difference was present at enrollment (p = 0.922). ETT colonization did not differ between the two groups. CONCLUSIONS: The use of a novel cleaning closed suction system proved to be effective in reducing secretions present in the ETT after extubation, possibly reducing resistance to airflow during intubation. TRIAL REGISTRATION: clinicaltrials.gov NCT01912105.

Effects of Sigh on Regional Lung Strain and Ventilation Heterogeneity in Acute Respiratory Failure Patients Undergoing Assisted Mechanical Ventilation.

OBJECTIVE: In acute respiratory failure patients undergoing pressure support ventilation, a short cyclic recruitment maneuver (Sigh) might induce reaeration of collapsed lung regions, possibly decreasing regional lung strain and improving the homogeneity of ventilation distribution. We aimed to describe the regional effects of different Sigh rates on reaeration, strain, and ventilation heterogeneity, as measured by thoracic electrical impedance tomography. DESIGN: Prospective, randomized, cross-over study. SETTING: General ICU of a single university-affiliated hospital. PATIENTS: We enrolled 20 critically ill patients intubated and mechanically ventilated with PaO2/FIO2 up to 300 mm Hg and positive end-expiratory pressure at least 5 cm H2O (15 with acute respiratory distress syndrome), undergoing pressure support ventilation as per clinical decision. INTERVENTIONS: Sigh was added to pressure support ventilation as a 35 cm H2O continuous positive airway pressure period lasting 3-4 seconds at different rates (no-Sigh vs 0.5, 1, and 2 Sigh(s)/min). All study phases were randomly performed and lasted 20 minutes. MEASUREMENTS AND MAIN RESULTS: In the last minutes of each phase, we measured arterial blood gases, changes in end-expiratory lung volume of nondependent and dependent regions, tidal volume reaching nondependent and dependent lung (Vtnondep and Vtdep), dynamic intratidal ventilation heterogeneity, defined as the average ratio of Vt reaching nondependent/Vt reaching dependent lung regions along inspiration (VtHit). With Sigh, oxygenation improved (p < 0.001 vs no-Sigh), end-expiratory lung volume of nondependent and dependent regions increased (p < 0.01 vs no-Sigh), Vtnondep showed a trend to reduction, and Vtdep significantly decreased (p = 0.11 and p < 0.01 vs no-Sigh, respectively). VtHit decreased only when Sigh was delivered at 0.5/min (p < 0.05 vs no-Sigh), while it did not vary during the other two phases. CONCLUSIONS: Sigh decreases regional lung strain and intratidal ventilation heterogeneity. Our study generates the hypothesis that in ventilated acute respiratory failure patients, Sigh may enhance regional lung protection.

A rare case of ALCAPA and rheumatic mitral valve regurgitation in an adult patient.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary artery defect leading to sudden cardiac death. Diagnosis is made after the onset of symptoms, mainly in the pediatric population. We describe an uncommon presentation of ALCAPA and rheumatic mitral valve regurgitation, diagnosed by a coronary 64-CT scan performed before a planned mitral valve repair operation.

Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study.

INTRODUCTION: Timely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute-phase mediator produced by various cell types in the lungs. Animal studies have shown that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbial clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The aim of the present study was to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia. METHODS: We recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy, and Massachusetts General Hospital, Boston, MA, USA) undergoing bronchoalveolar lavage (BAL) as per clinical decision. We collected BAL fluid and plasma samples, together with relevant clinical and microbiological data. We assayed PTX3 and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in BAL fluid and PTX3, sTREM-1, C-reactive protein (CRP) and procalcitonin (PCT) in plasma. Two blinded independent physicians reviewed patient data to confirm pneumonia. We determined the PTX3 threshold in BAL fluid for pneumonia and compared it to other biomarkers. RESULTS: Microbiologically confirmed pneumonia of bacterial (n =12), viral (n =4) or fungal (n =8) etiology was diagnosed in 24 patients (29%). PTX3 levels in BAL fluid predicted pneumonia with an area under the receiving operator curve of 0.815 (95% CI =0.710 to 0.921, P <0.0001), whereas none of the other biomarkers were effective. In particular, PTX3 levels ≥1 ng/ml in BAL fluid predicted pneumonia in univariate analysis (ß =2.784, SE =0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index PTX3 values ≥1 ng/ml in BAL fluid for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 patients who fulfilled the clinical criteria for the diagnosis of pneumonia at BAL fluid sampling, the diagnostic accuracy of PTX levels was confirmed in univariate and ROC curve analysis. CONCLUSIONS: In this hypothesis-generating convenience sample, a PTX3 level ≥1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients.

Clinical assessment of auto-positive end-expiratory pressure by diaphragmatic electrical activity during pressure support and neurally adjusted ventilatory assist.

BACKGROUND: Auto-positive end-expiratory pressure (auto-PEEP) may substantially increase the inspiratory effort during assisted mechanical ventilation. Purpose of this study was to assess whether the electrical activity of the diaphragm (EAdi) signal can be reliably used to estimate auto-PEEP in patients undergoing pressure support ventilation and neurally adjusted ventilatory assist (NAVA) and whether NAVA was beneficial in comparison with pressure support ventilation in patients affected by auto-PEEP. METHODS: In 10 patients with a clinical suspicion of auto-PEEP, the authors simultaneously recorded EAdi, airway, esophageal pressure, and flow during pressure support and NAVA, whereas external PEEP was increased from 2 to 14 cm H2O. Tracings were analyzed to measure apparent "dynamic" auto-PEEP (decrease in esophageal pressure to generate inspiratory flow), auto-EAdi (EAdi value at the onset of inspiratory flow), and IDEAdi (inspiratory delay between the onset of EAdi and the inspiratory flow). RESULTS: The pressure necessary to overcome auto-PEEP, auto-EAdi, and IDEAdi was significantly lower in NAVA as compared with pressure support ventilation, decreased with increase in external PEEP, although the effect of external PEEP was less pronounced in NAVA. Both auto-EAdi and IDEAdi were tightly correlated with auto-PEEP (r = 0.94 and r = 0.75, respectively). In the presence of auto-PEEP at lower external PEEP levels, NAVA was characterized by a characteristic shape of the airway pressure. CONCLUSIONS: In patients with auto-PEEP, NAVA, compared with pressure support ventilation, led to a decrease in the pressure necessary to overcome auto-PEEP, which could be reliably monitored by the electrical activity of the diaphragm before inspiratory flow onset (auto-EAdi).

Measurement of endotracheal tube secretions volume by micro computed tomography (MicroCT) scan: an experimental and clinical study.

BACKGROUND: Biofilm accumulates within the endotracheal tube (ETT) early after intubation. Contaminated secretions in the ETT are associated with increased risk for microbial dissemination in the distal airways and increased resistance to airflow. We evaluated the effectiveness of micro computed tomography (MicroCT) for the quantification of ETT inner volume reduction in critically ill patients. METHODS: We injected a known amount of gel into unused ETT to simulate secretions. We calculated the volume of gel analyzing MicroCT scans for a length of 20 cm. We then collected eleven ETTs after extubation of critically ill patients, recording clinical and demographical data. We assessed the amount of secretions by MicroCT and obtained ETT microbiological cultures. RESULTS: Gel volumes assessed by MicroCT strongly correlated with injected gel volumes (p < 0.001, r2 = 0.999).MicroCT revealed the accumulation of secretions on all the ETTs (median 0.154, IQR:0.02-0.837 mL), corresponding to an average cross-sectional area reduction of 1.7%. The amount of secretions inversely correlated with patients' age (p = 0.011, rho = -0.727) but not with days of intubation, SAPS2, PaO2/FiO2 assessed on admission. Accumulation of secretions was higher in the cuff region (p = 0.003). Microbial growth occurred in cultures from 9/11 ETTs, and did not correlate with secretions amount. In 7/11 cases the same microbes were identified also in tracheal aspirates. CONCLUSIONS: MicroCT appears as a feasible and precise technique to measure volume of secretions within ETTs after extubation. In patients, secretions tend to accumulate in the cuff region, with high variability among patients.

Critical illness is associated with decreased plasma levels of coenzyme Q10: a cross-sectional study.

PURPOSE: Plasma coenzyme Q10 (CoQ10) levels are lower in patients with septic shock (SS) than in healthy controls (HCs). However, CoQ10 status in critically ill patients without SS is unknown. Here, we investigated CoQ10 concentrations in patients with SS and without SS as compared with HCs. MATERIALS AND METHODS: We enrolled 36 critically ill patients and 18 HCs. Plasma CoQ10 concentrations were measured, and patients' clinical and demographical data were collected. RESULTS: Plasma CoQ10 concentrations were lower in critically ill patients (0.50±0.36 µg/mL, P<.001), both in patients with SS (0.37±0.25 µg/mL, P=.002) and patients without SS (0.56±0.39, P=.04), as compared with HCs (0.79±0.19). Coenzyme Q10 levels did not differ between patients with SS and patients without SS (P=.13). In critically ill patients, CoQ10 levels inversely correlated with age (r=-0.40, P=.015) and did not correlate with partial pressure of oxygen in the arterial blood/fraction of inspired oxygen, Simplified Acute Physiology Score II, Systemic Organ Failure Assessment score, or mortality. Lower CoQ10 levels were associated with lower activities of daily living score after discharge (P=.005), independent of age. CONCLUSIONS: Decreased plasma CoQ10 levels are not specific to patients with SS, but rather observed in a broad range of critically ill patients. In critically ill patients, CoQ10 insufficiency may be associated with various conditions; age may be a risk factor.