Prognostic Performance of Bedside Lung Ultrasound Score (LUSS) and ROX Index in Hypoxemic Respiratory Failure Due to COVID-19.

Background: Noninvasive ventilation, mainly helmet CPAP, was widely used during the COVID-19 pandemic, even outside of intensive care units. Both the ROX index and the LUS score (LUSS) have been proposed as tools to predict negative outcomes in patients with hypoxemia treated with noninvasive ventilation (NIV) outside of ICUs. We aim to evaluate whether the combination of LUSS with the ROX index improves the predictive performance of these indices in patients with hypoxemia due to COVID-19 pneumonia, treated with NIV outside of ICUs. Methods: This is a monocentric prospective observational study conducted at the university teaching hospital Fondazione IRCCS San Gerardo dei Tintori (Monza, Italy) from February to April 2021. LUSS and ROX were collected at the same time in noninvasively ventilated patients outside of the ICU. An LUS exam was performed by 3 emergency medicine attending physicians with at least 5 years' experience in point-of-care ultrasonography using a 12-zone system. To evaluate the accuracy of the prognostic indices in predicting a composite outcome (endotracheal intubation and mortality), ROC curves were used. A logistic multivariable model was used to explore the predictors of the composite outcome of endotracheal intubation and in-hospital mortality. An unadjusted Kaplan-Meier analysis was used to explore the association with the composite outcome of survival without invasive mechanical ventilation at the 30-day follow-up by stratifying the 3 indices by their best cut-offs. Results: A total of 79 patients were included in the statistical analysis and stratified into 2 groups based on the presence of a negative outcome, which was reported in 24 patients out of 79 (30%). A great proportion of patients (66 patients-84%) were treated with helmet CPAP. All three indices (LUSS, ROX and LUSS/ROX) were independently associated with negative outcomes in the multivariable analyses. Although the comparison between the AUROC of LUSS or ROX versus LUSS/ROX did not reveal a statistically significant difference, we observed a trend toward a higher accuracy for predicting negative outcomes using the LUSS/ROX index as compared to using LUSS. With the Kaplan-Maier approach, all three indices stratified by the best cut-off reported a significant association with the outcome of 30-day survival without mechanical ventilation. Conclusions: A multimodal noninvasive approach that combines ultrasound (i.e., LUSS) and a bedside clinical evaluation (i.e., the ROX index) may help clinicians to predict outcomes and to identify patients who would benefit the most from invasive respiratory support.

Dynamic bedside assessment of the physiologic effects of prone position in acute respiratory distress syndrome patients by electrical impedance tomography.

BACKGROUND: Prone position (PP) improves acute respiratory distress syndrome (ARDS) survival by reducing the risk of ventilation-induced lung injury. However, inter-individual variability is a hallmark of ARDS and lung protection by PP might not be optimal in all patients. In the present study, we dynamically assessed physiologic effects of PP by electrical impedance tomography (EIT) and identified predictors of improved lung protection by PP in ARDS patients. METHODS: Prospective physiologic study on 16 intubated, sedated and paralyzed patients with ARDS undergoing PP as per clinical decision. EIT data were recorded during two consecutive steps: 1) baseline supine position before and after a recruitment maneuver (RM); 2) prone position before and after a RM. "Improved lung protection" by PP was defined in the presence of simultaneous improvement of ventilation homogeneity (Hom), alveolar overdistension and collapse (ODCL) and amount of recruitable lung volume by RM in comparison to supine. RESULTS: PP versus supine increased the tidal volume distending the dependent regions (Vtdep), resulting in improved Hom (1.1±0.9 vs. 1.7±0.9, P=0.021). PP also reduced ODCL (19±9% vs. 28±8%, P=0.005) and increased the recruitable lung volume (80 [71-157] vs. 59 [1-110] mL, P=0.025). "Improved lung protection" by PP was predicted by lower Vtdep, higher Vtndep and poorer Hom measured during baseline supine position (P<0.05). CONCLUSIONS: EIT enables dynamic bedside assessment of the physiologic effects of PP and might support early recognition of ARDS patients more likely to benefit from PP.

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.

Measurement of Diaphragmatic Electrical Activity by Surface Electromyography in Intubated Subjects and Its Relationship With Inspiratory Effort.

BACKGROUND: Quantification of patient effort during spontaneous breathing is important to tailor ventilatory assistance. Because a correlation between inspiratory muscle pressure (Pmus) and electrical activity of the diaphragm (EAdi) has been described, we aimed to assess the reliability of surface electromyography (EMG) of the respiratory muscles for monitoring diaphragm electrical activity and subject effort during assisted ventilation. METHODS: At a general ICU of a single university-affiliated hospital, we enrolled subjects who were intubated and on pressure support ventilation (PSV) and were on mechanical ventilation for > 48 h. The subjects were studied at 3 levels of pressure support. Airway flow and pressure; esophageal pressure; EAdi; and surface EMG of the diaphragm (surface EAdi), intercostal, and sternocleidomastoid muscles were recorded. Respiratory cycles were sampled for off-line analysis. The Pmus/EAdi index (PEI) was calculated by relying on EAdi and surface EAdi (surface PEI) from an airway pressure drop during end-expiratory occlusions performed every minute. RESULTS: surface EAdi well correlated with EAdi and Pmus, in particular, after averaging breaths into deciles (R = 0.92 and R = 0.84). When surface PEI was used with surface EAdi, it provided a reliable estimation of Pmus (R = 0.94 in comparison with measured Pmus). CONCLUSIONS: During assisted mechanical ventilation, EAdi can be reliably monitored by both EAdi and surface EMG. The measurement of Pmus based on the calibration of EAdi was also feasible by the use of surface EMG.

Bedside selection of positive end-expiratory pressure by electrical impedance tomography in hypoxemic patients: a feasibility study.

BACKGROUND: Positive end-expiratory pressure (PEEP) is a key element of mechanical ventilation. It should optimize recruitment, without causing excessive overdistension, but controversy exists on the best method to set it. The purpose of the study was to test the feasibility of setting PEEP with electrical impedance tomography in order to prevent lung de-recruitment following a recruitment maneuver. We enrolled 16 patients undergoing mechanical ventilation with PaO2/FiO2 <300 mmHg. In all patients, under constant tidal volume (6-8 ml/kg) PEEP was set based on the PEEP/FiO2 table proposed by the ARDS network (PEEPARDSnet). We performed a recruitment maneuver and monitored the end-expiratory lung impedance (EELI) over 10 min. If the EELI signal decreased during this period, the recruitment maneuver was repeated and PEEP increased by 2 cmH2O. This procedure was repeated until the EELI maintained a stability over time (PEEPEIT). RESULTS: The procedure was feasible in 87% patients. PEEPEIT was higher than PEEPARDSnet (13 ± 3 vs. 9 ± 2 cmH2O, p < 0.001). PaO2/FiO2 improved during PEEPEIT and driving pressure decreased. Recruited volume correlated with the decrease in driving pressure but not with oxygenation improvement. Finally, regional alveolar hyperdistention and collapse was reduced in dependent lung layers and increased in non-dependent lung layers. CONCLUSIONS: In hypoxemic patients, a PEEP selection strategy aimed at stabilizing alveolar recruitment guided by EIT at the bedside was feasible and safe. This strategy led, in comparison with the ARDSnet table, to higher PEEP, improved oxygenation and reduced driving pressure, allowing to estimate the relative weight of overdistension and recruitment.

Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure.

RATIONALE: High-flow nasal cannula (HFNC) improves the clinical outcomes of nonintubated patients with acute hypoxemic respiratory failure (AHRF). OBJECTIVES: To assess the effects of HFNC on gas exchange, inspiratory effort, minute ventilation, end-expiratory lung volume, dynamic compliance, and ventilation homogeneity in patients with AHRF. METHODS: This was a prospective randomized crossover study in nonintubated patients with AHRF with PaO2/setFiO2 less than or equal to 300 mm Hg admitted to the intensive care unit. We randomly applied HFNC set at 40 L/min compared with a standard nonocclusive facial mask at the same clinically set FiO2 (20 min/step). MEASUREMENTS AND MAIN RESULTS: Toward the end of each phase, we measured arterial blood gases, inspiratory effort, and work of breathing by esophageal pressure swings (ΔPes) and pressure time product, and we estimated changes in lung volumes and ventilation homogeneity by electrical impedance tomography. We enrolled 15 patients aged 60 ± 14 years old with PaO2/setFiO2 130 ± 35 mm Hg. Seven (47%) had bilateral lung infiltrates. Compared with the facial mask, HFNC significantly improved oxygenation (P < 0.001) and lowered respiratory rate (P < 0.01), ΔPes (P < 0.01), and pressure time product (P < 0.001). During HFNC, minute ventilation was reduced (P < 0.001) at constant arterial CO2 tension and pH (P = 0.27 and P = 0.23, respectively); end-expiratory lung volume increased (P < 0.001), and tidal volume did not change (P = 0.44); the ratio of tidal volume to ΔPes (an estimate of dynamic lung compliance) increased (P < 0.05); finally, ventilation distribution was more homogeneous (P < 0.01). CONCLUSIONS: In patients with AHRF, HFNC exerts multiple physiologic effects including less inspiratory effort and improved lung volume and compliance. These benefits might underlie the clinical efficacy of HFNC.

Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography.

PURPOSE: Higher positive end-expiratory pressure might induce lung inflation and recruitment, yielding enhanced regional lung protection. We measured positive end-expiratory pressure-related lung volume changes by electrical impedance tomography and by the helium dilution technique. We also used electrical impedance tomography to assess the effects of positive end-expiratory pressure on regional determinants of ventilator-induced lung injury. METHODS: A prospective randomized crossover study was performed on 20 intubated adult patients: 12 with acute hypoxemic respiratory failure and 8 with acute respiratory distress syndrome. Each patient underwent protective controlled ventilation at lower (7 [7, 8] cmH2O) and higher (12 [12, 13] cmH2O) positive end-expiratory pressures. At the end of each phase, we collected ventilation, helium dilution, and electrical impedance tomography data. RESULTS: Positive end-expiratory pressure-induced changes in lung inflation and recruitment measured by electrical impedance tomography and helium dilution showed close correlations (R (2) = 0.78, p < 0.001 and R (2) = 0.68, p < 0.001, respectively) but with relatively variable limits of agreement. At higher positive end-expiratory pressure, recruitment was evident in all lung regions (p < 0.01) and heterogeneity of tidal ventilation distribution was reduced by increased tidal volume distending the dependent lung (p < 0.001); in the non-dependent lung, on the other hand, compliance decreased (p < 0.001) and tidal hyperinflation significantly increased (p < 0.001). In the subgroup of ARDS patients (but not in the whole study population) tidal hyperinflation in the dependent lung regions decreased at higher positive end-expiratory pressure (p = 0.05), probably indicating higher potential for recruitment. CONCLUSIONS: Close correlations exist between bedside assessment of positive end-expiratory pressure-induced changes in lung inflation and recruitment by the helium dilution and electrical impedance tomography techniques. Higher positive end-expiratory pressure exerts mixed effects on the regional determinants of ventilator-induced lung injury; these merit close monitoring.

Control of Respiratory Drive and Effort in Extracorporeal Membrane Oxygenation Patients Recovering from Severe Acute Respiratory Distress Syndrome.

BACKGROUND: The amount of extracorporeal carbon dioxide removal may influence respiratory drive in acute respiratory distress syndrome (ARDS) patients undergoing extracorporeal membrane oxygenation (ECMO). The authors evaluated the effects of different levels of extracorporeal carbon dioxide removal in patients recovering from severe ARDS undergoing pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). METHODS: The authors conducted a prospective, randomized, crossover study on eight spontaneously breathing ARDS patients undergoing venovenous ECMO since 28 ± 20 days. To modulate carbon dioxide extraction, ECMO gas flow (GF) was decreased from baseline resting protective conditions (i.e., GF100%, set to obtain pressure generated in the first 100 ms of inspiration against an occluded airway less than 2 cm H2O, respiratory rate less than or equal to 25 bpm, tidal volume less than 6 ml/kg, and peak airway pressure less than 25 cm H2O) to GF50%-GF25%-GF0% during both PSV and NAVA (random order for ventilation mode). Continuous recordings of airway pressure and flow and esophageal pressure were obtained and analyzed during all study phases. RESULTS: At higher levels of extracorporeal carbon dioxide extraction, pressure generated in the first 100 ms of inspiration against an occluded airway decreased from 2.8 ± 2.7 cm H2O (PSV, GF0%) and 3.0 ± 2.1 cm H2O (NAVA, GF0%) to 0.9 ± 0.5 cm H2O (PSV, GF100%) and 1.0 ± 0.8 cm H2O (NAVA, GF100%; P < 0.001) and patients' inspiratory muscle pressure passed from 8.5 ± 6.3 and 6.5 ± 5.5 cm H2O to 4.5 ± 3.1 and 4.2 ± 3.7 cm H2O (P < 0.001). In time, decreased inspiratory drive and effort determined by higher carbon dioxide extraction led to reduction of tidal volume from 6.6 ± 0.9 and 7.5 ± 1.2 ml/kg to 4.9 ± 0.8 and 5.3 ± 1.3 ml/kg (P < 0.001) and of peak airway pressure from 21 ± 3 and 25 ± 4 cm H2O to 21 ± 3 and 21 ± 5 cm H2O (P < 0.001). Finally, transpulmonary pressure linearly decreased when the amount of carbon dioxide extracted by ECMO increased (R = 0.823, P < 0.001). CONCLUSIONS: In patients recovering from ARDS undergoing ECMO, the amount of carbon dioxide removed by the artificial lung may influence spontaneous breathing. The effects of carbon dioxide removal on spontaneous breathing during the earlier acute phases of ARDS remain to be elucidated.

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.

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.