Transpulmonary pressure monitoring in critically ill patients: pros and cons.

The use of transpulmonary pressure monitoring based on measurement of esophageal pressure has contributed importantly to the personalization of mechanical ventilation based on respiratory pathophysiology in critically ill patients. However, esophageal pressure monitoring is still underused in the clinical practice. This technique allows partitioning of the respiratory mechanics between the lungs and the chest wall, provides information on lung recruitment and risk of barotrauma, and helps titrating mechanical ventilation settings in patients with respiratory failure. In assisted ventilation modes and during non-invasive respiratory support, esophageal pressure monitoring provides important information on the inspiratory effort and work of breathing. Nonetheless, several controversies persist on technical aspects, interpretation and clinical decision-making based on values derived from this monitoring technique. The aim of this review is to summarize the physiological bases of esophageal pressure monitoring, discussing the pros and cons of its clinical applications and different interpretations in critically ill patients undergoing invasive and non-invasive respiratory support.

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

BACKGROUND: Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100 ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. METHODS: Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. RESULTS: We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). CONCLUSIONS: In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. TRIAL REGISTRATION: NCT03266016; August 23, 2017.

The effects of real-time waveform analysis software on patient ventilator synchronization during pressure support ventilation: a randomized crossover physiological study.

BACKGROUND: Patient-ventilator asynchrony commonly occurs during pressure support ventilation (PSV). IntelliSync + software (Hamilton Medical AG, Bonaduz, Switzerland) is a new ventilation technology that continuously analyzes ventilator waveforms to detect the beginning and end of patient inspiration in real time. This study aimed to evaluate the physiological effect of IntelliSync + software on inspiratory trigger delay time, delta airway (Paw) and esophageal (Pes) pressure drop during the trigger phase, airway occlusion pressure at 0.1 s (P0.1), and hemodynamic variables. METHODS: A randomized crossover physiologic study was conducted in 14 mechanically ventilated patients under PSV. Patients were randomly assigned to receive conventional flow trigger and cycling, inspiratory trigger synchronization (I-sync), cycle synchronization (C-sync), and inspiratory trigger and cycle synchronization (I/C-sync) for 15 min at each step. Other ventilator settings were kept constant. Paw, Pes, airflow, P0.1, respiratory rate, SpO2, and hemodynamic variables were recorded. The primary outcome was inspiratory trigger and cycle delay time between each intervention. Secondary outcomes were delta Paw and Pes drop during the trigger phase, P0.1, SpO2, and hemodynamic variables. RESULTS: The time to initiate the trigger was significantly shorter with I-sync compared to baseline (208.9±91.7 vs. 301.4±131.7 msec; P = 0.002) and I/C-sync compared to baseline (222.8±94.0 vs. 301.4±131.7 msec; P = 0.005). The I/C-sync group had significantly lower delta Paw and Pes drop during the trigger phase compared to C-sync group (-0.7±0.4 vs. -1.2±0.8 cmH2O; P = 0.028 and - 1.8±2.2 vs. -2.8±3.2 cmH2O; P = 0.011, respectively). No statistically significant differences were found in cycle delay time, P0.1 and other physiological variables between the groups. CONCLUSIONS: IntelliSync + software reduced inspiratory trigger delay time compared to the conventional flow trigger system during PSV mode. However, no significant improvements in cycle delay time and other physiological variables were observed with IntelliSync + software. TRIAL REGISTRATION: This study was registered in the Thai Clinical Trial Registry (TCTR20200528003; date of registration 28/05/2020).

Comparison of Laryngeal Mask Airway Seal Between Anesthesiologists and Individuals Without Previous Airway Experience.

BACKGROUND: Tracheal intubation is the gold standard for airway management in emergency medicine, but more difficult to apply for inexperienced individuals than laryngeal mask airway (LMA). OBJECTIVE: The aim of our study was to investigate if inexperienced individuals are able to secure the airway with the help of LMA after a short introduction. A second aim was to evaluate Thiel-fixed specimens against unfixed ones. METHODS: In a body donor model, LMA application was evaluated between medical students without previous airway experience and anesthesiologists by comparing the sealing of the larynx using a water column applied to the esophagus. RESULTS: LMAs were successfully applied in 46 out of 55 (83.6%) attempts by medical students and in 30 out of 39 (76.9%) attempts by anesthesiologists. Among medical students, 14.1% of all LMA applications were primarily leaky, compared with 18.8% in anesthesiologists. Esophageal sealing was better in Thiel-fixed specimens (leakage 10.9%) compared with unfixed specimens (leakage 22.9%). Our data showed no significant difference between anesthesiologists and medical students in terms of sealing of LMA. Therefore, we conclude that medical students without previous airway experience can quickly learn to apply LMA sufficiently and thus, achieve aspiration protection similar to anesthesiologists. CONCLUSION: Medical students without previous airway experience can successfully insert LMAs after a short introduction. Thiel-fixed specimens are suitable for studies as well as for training in LMA application.

Intraoperative individualization of positive-end-expiratory pressure through electrical impedance tomography or esophageal pressure assessment: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review of randomized-controlled trials (RCTs) with meta-analyses aimed to compare the effects on intraoperative arterial oxygen tension to inspired oxygen fraction ratio (PaO2/FiO2), exerted by positive end-expiratory pressure (PEEP) individualized trough electrical impedance tomography (EIT) or esophageal pressure (Pes) assessment (intervention) vs. PEEP not tailored on EIT or Pes (control), in patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach. METHODS: PUBMED®, EMBASE®, and Cochrane Controlled Clinical trials register were searched for observational studies and RCTs from inception to the end of August 2022. Inclusion criteria were: RCTs comparing PEEP titrated on EIT/Pes assessment vs. PEEP not individualized on EIT/Pes and reporting intraoperative PaO2/FiO2. Two authors independently extracted data from the enrolled investigations. Data are reported as mean difference and 95% confidence interval (CI). RESULTS: Six RCTs were included for a total of 240 patients undergoing general anesthesia for surgery, of whom 117 subjects in the intervention group and 123 subjects in the control group. The intraoperative mean PaO2/FiO2 was 69.6 (95%CI 32.-106.4 ) mmHg higher in the intervention group as compared with the control group with 81.4% between-study heterogeneity (p < 0.01). However, at meta-regression, the between-study heterogeneity diminished to 44.96% when data were moderated for body mass index (estimate 3.45, 95%CI 0.78-6.11, p = 0.011). CONCLUSIONS: In patients undergoing abdominal or pelvic surgery with an open or laparoscopic/robotic approach, PEEP personalized by EIT or Pes allowed the achievement of a better intraoperative oxygenation compared to PEEP not individualized through EIT or Pes. PROSPERO REGISTRATION NUMBER: CRD 42021218306, 30/01/2023.

A novel adaptive filter with a heart-rate-based reference signal for esophageal pressure signal denoising.

Esophageal pressure (Peso) is one of the most common and minimally invasive methods used to assess the respiratory and lung mechanics in patients receiving mechanical ventilation. However, the Peso measurement is contaminated by cardiogenic oscillations (CGOs), which cannot be easily eliminated in real-time. The field of study dealing with the elimination of CGO from Peso signals is still in the early stages of its development. In this study, we present an adaptive filtering-based method by constructing a reference signal based on the heart rate and sine function to remove CGOs in real-time. The proposed technique is tested using clinical data acquired from 20 patients admitted to the intensive care unit. Lung compliance ( QUOTE ) and esophageal pressure swings (△Pes) are used to evaluate the performance and efficiency of the proposed technique. The CGO can be efficiently suppressed when the constructional reference signal contains the fundamental, and second and third harmonic frequencies of the heart rate signal. The analysis of the data of 8 patients with controlled mechanical ventilation reveals that the standard deviation/mean of the QUOTE is reduced by 28.4-79.2% without changing the QUOTE and the △Pes measurement is more accurate, with the use of our proposed technique. The proposed technique can effectively eliminate the CGOs from the measured Peso signals in real-time without requiring additional equipment to collect the reference signal.

Estimation of the transpulmonary pressure from the central venous pressure in mechanically ventilated patients.

Transpulmonary pressure (PL) calculation requires esophageal pressure (PES) as a surrogate of pleural pressure (Ppl), but its calibration is a cumbersome technique. Central venous pressure (CVP) swings may reflect tidal variations in Ppl and could be used instead of PES, but the interpretation of CVP waveforms could be difficult due to superposition of heartbeat-induced pressure changes. Thus, we developed a digital filter able to remove the cardiac noise to obtain a filtered CVP (f-CVP). The aim of the study was to evaluate the accuracy of CVP and filtered CVP swings (ΔCVP and Δf-CVP, respectively) in estimating esophageal respiratory swings (ΔPES) and compare PL calculated with CVP, f-CVP and PES; then we tested the diagnostic accuracy of the f-CVP method to identify unsafe high PL levels, defined as PL>10 cmH2O. Twenty patients with acute respiratory failure (defined as PaO2/FiO2 ratio below 200 mmHg) treated with invasive mechanical ventilation and monitored with an esophageal balloon and central venous catheter were enrolled prospectively. For each patient a recording session at baseline was performed, repeated if a modification in ventilatory settings occurred. PES, CVP and airway pressure during an end-inspiratory and -expiratory pause were simultaneously recorded; CVP, f-CVP and PES waveforms were analyzed off-line and used to calculate transpulmonary pressure (PLCVP, PLf-CVP, PLPES, respectively). Δf-CVP correlated better than ΔCVP with ΔPES (r = 0.8, p = 0.001 vs. r = 0.08, p = 0.73), with a lower bias in Bland Altman analysis in favor of PLf-CVP (mean bias - 0.16, Limits of Agreement (LoA) -1.31, 0.98 cmH2O vs. mean bias - 0.79, LoA - 3.14, 1.55 cmH2O). Both PLf-CVP and PLCVP correlated well with PLPES (r = 0.98, p < 0.001 vs. r = 0.94, p < 0.001), again with a lower bias in Bland Altman analysis in favor of PLf-CVP (0.15, LoA - 0.95, 1.26 cmH2O vs. 0.80, LoA - 1.51, 3.12, cmH2O). PLf-CVP discriminated high PL value with an area under the receiver operating characteristic curve 0.99 (standard deviation, SD, 0.02) (AUC difference = 0.01 [-0.024; 0.05], p = 0.48). In mechanically ventilated patients with acute respiratory failure, the digital filtered CVP estimated ΔPES and PL obtained from digital filtered CVP represented a reliable value of standard PL measured with the esophageal method and could identify patients with non-protective ventilation settings.

Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).

Effects of an asymmetrical high flow nasal cannula interface in hypoxemic patients.

BACKGROUND: Optimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics. METHODS: We enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2 < 300 mmHg during HFNC support with a conventional cannula. We investigated whether the asymmetrical interface, compared to a conventional high flow nasal cannula, reduces minute ventilation and work of breathing. Each patient underwent support with the asymmetrical interface and the conventional interface, applied in a randomized sequence. Each interface was provided at a flow rate of 40 l/min followed by 60 l/min. Patients were continuously monitored with esophageal manometry and electrical impedance tomography. RESULTS: Application of the asymmetrical interface resulted in a -13.5 [-19.4 to (-4.5)] % change in minute ventilation at a flow rate of 40 l/min, p = 0.006 and a -19.6 [-28.0 to (-7.5)] % change at 60 l/min, p = 0.002, that occurred despite no change in PaCO2 (35 [33-42] versus 35 [33-43] mmHg at 40 l/min and 35 [32-41] versus 36 [32-43] mmHg at 60 l/min). Correspondingly, the asymmetrical interface lowered the inspiratory esophageal pressure-time product from 163 [118-210] to 140 [84-159] (cmH2O*s)/min at a flow rate of 40 l/min, p = 0.02 and from 142 [123-178] to 117 [90-137] (cmH2O*s)/min at a flow rate of 60 l/min, p = 0.04. The asymmetrical cannula did not have any impact on oxygenation, the dorsal fraction of ventilation, dynamic lung compliance, or end-expiratory lung impedance, suggesting no major effect on PEEP, lung mechanics, or alveolar recruitment. CONCLUSIONS: An asymmetrical HFNC interface reduces minute ventilation and work of breathing in patients with mild-to-moderate hypoxemic respiratory failure supported with a conventional interface. This appears to be primarily driven by increased ventilatory efficiency due to enhanced CO2 clearance from the upper airway.

Estimation of transpulmonary driving pressure during synchronized mechanical ventilation using a single lower assist maneuver (LAM) in rabbits: a comparison to measurements made with an esophageal balloon.

BACKGROUND: Mechanical ventilation is applied to unload the respiratory muscles, but knowledge about transpulmonary driving pressure (ΔPL) is important to minimize lung injury. We propose a method to estimate ΔPL during neurally synchronized assisted ventilation, with a simple intervention of lowering the assist for one breath ("lower assist maneuver", LAM). METHODS: In 24 rabbits breathing spontaneously with imposed loads, titrations of increasing assist were performed, with two neurally synchronized modes: neurally adjusted ventilatory assist (NAVA) and neurally triggered pressure support (NPS). Two single LAM breaths (not sequentially, but independently) were performed at each level of assist by acutely setting the assist to zero cm H2O (NPS) or NAVA level 0 cm H2O/uV (NAVA) for one breath. NPS and NAVA titrations were followed by titrations in controlled-modes (volume control, VC and pressure control, PC), under neuro-muscular blockade. Breaths from the NAVA/NPS titrations were matched (for flow and volume) to VC or PC. Throughout all runs, we measured diaphragm electrical activity (Edi) and esophageal pressure (PES). We measured ΔPL during the spontaneous modes (PL_PES) and controlled mechanical ventilation (CMV) modes (PL_CMV) with the esophageal balloon. From the LAMs, we derived an estimation of ΔPL ("PL_LAM") using a correction factor (ratio of volume during the LAM and volume during assist) and compared it to measured ΔPL during passive (VC or PC) and spontaneous breathing (NAVA or NPS). A requirement for the LAM was similar Edi to the assisted breath. RESULTS: All animals successfully underwent titrations and LAMs for NPS/NAVA. One thousand seven-hundred ninety-two (1792) breaths were matched to passive ventilation titrations (matched Vt, r = 0.99). PL_LAM demonstrated strong correlation with PL_CMV (r = 0.83), and PL_PES (r = 0.77). Bland-Altman analysis revealed little difference between the predicted PL_LAM and measured PL_CMV (Bias = 0.49 cm H2O and 1.96SD = 3.09 cm H2O). For PL_PES, the bias was 2.2 cm H2O and 1.96SD was 3.4 cm H2O. Analysis of Edi and PES at peak Edi showed progressively increasing uncoupling with increasing assist. CONCLUSION: During synchronized mechanical ventilation, a LAM breath allows for estimations of transpulmonary driving pressure, without measuring PES, and follows a mathematical transfer function to describe respiratory muscle unloading during synchronized assist.

Respiratory Monitoring During Mechanical Ventilation: The Present and the Future.

The increased application of mechanical ventilation, the recognition of its harms and the interest in individualization raised the need for an effective monitoring. An increasing number of monitoring tools and modalities were introduced over the past 2 decades with growing insight into asynchrony, lung and chest wall mechanics, respiratory effort and drive. They should be used in a complementary rather than a standalone way. A sound strategy can guide a reduction in adverse effects like ventilator-induced lung injury, ventilator-induced diaphragm dysfunction, patient-ventilator asynchrony and helps early weaning from the ventilator. However, the diversity, complexity, lack of expertise, and associated cost make formulating the appropriate monitoring strategy a challenge for clinicians. Most often, a big amount of data is fed to the clinicians making interpretation difficult. Therefore, it is fundamental for intensivists to be aware of the principle, advantages, and limits of each tool. This analytic review includes a simplified narrative of the commonly used basic and advanced respiratory monitors along with their limits and future prospective.

Breath-by-breath P0.1 measured on quasi-occlusion via Hamilton C6 may result in underestimation of respiratory drive and inspiratory effort.

We aimed to identify the threshold for P0.1 in a breath-by-breath manner measured by the Hamilton C6 on quasi-occlusion for high respiratory drive and inspiratory effort. In this prospective observational study, we analyzed the relationships between airway P0.1 on quasi-occlusion and esophageal pressure (esophageal P0.1 and esophageal pressure swing). We also conducted a linear regression analysis and derived the threshold of airway P0.1 on quasi-occlusion for high respiratory drive and inspiratory effort. We found that airway P0.1 measured on quasi-occlusion had a strong positive correlation with esophageal P0.1 measured on quasi-occlusion and esophageal pressure swing, respectively. Additionally, the P0.1 threshold for high respiratory drive and inspiratory effort were calculated at approximately 1.0 cmH2O from the regression equations. Our calculations suggest a lower threshold of airway P0.1 measured by the Hamilton C6 on quasi-occlusion than that which has been previously reported.

Nasal pressure swings as the measure of inspiratory effort in spontaneously breathing patients with de novo acute respiratory failure.

BACKGROUND: Excessive inspiratory effort could translate into self-inflicted lung injury, thus worsening clinical outcomes of spontaneously breathing patients with acute respiratory failure (ARF). Although esophageal manometry is a reliable method to estimate the magnitude of inspiratory effort, procedural issues significantly limit its use in daily clinical practice. The aim of this study is to describe the correlation between esophageal pressure swings (ΔPes) and nasal (ΔPnos) as a potential measure of inspiratory effort in spontaneously breathing patients with de novo ARF. METHODS: From January 1, 2021, to September 1, 2021, 61 consecutive patients with ARF (83.6% related to COVID-19) admitted to the Respiratory Intensive Care Unit (RICU) of the University Hospital of Modena (Italy) and candidate to escalation of non-invasive respiratory support (NRS) were enrolled. Clinical features and tidal changes in esophageal and nasal pressure were recorded on admission and 24 h after starting NRS. Correlation between ΔPes and ΔPnos served as primary outcome. The effect of ΔPnos measurements on respiratory rate and ΔPes was also assessed. RESULTS: ΔPes and ΔPnos were strongly correlated at admission (R2 = 0.88, p < 0.001) and 24 h apart (R2 = 0.94, p < 0.001). The nasal plug insertion and the mouth closure required for ΔPnos measurement did not result in significant change of respiratory rate and ΔPes. The correlation between measures at 24 h remained significant even after splitting the study population according to the type of NRS (high-flow nasal cannulas [R2 = 0.79, p < 0.001] or non-invasive ventilation [R2 = 0.95, p < 0.001]). CONCLUSIONS: In a cohort of patients with ARF, nasal pressure swings did not alter respiratory mechanics in the short term and were highly correlated with esophageal pressure swings during spontaneous tidal breathing. ΔPnos might warrant further investigation as a measure of inspiratory effort in patients with ARF. TRIAL REGISTRATION: NCT03826797 . Registered October 2016.

Endotyping Sleep Apnea One Breath at a Time: An Automated Approach for Separating Obstructive from Central Sleep-disordered Breathing.

Rationale: Determining whether an individual has obstructive or central sleep apnea is fundamental to selecting the appropriate treatment. Objectives: Here we derive an automated breath-by-breath probability of obstruction, as a surrogate of gold-standard upper airway resistance, using hallmarks of upper airway obstruction visible on clinical sleep studies. Methods: From five nocturnal polysomnography signals (airflow, thoracic and abdominal effort, oxygen saturation, and snore), nine features were extracted and weighted to derive the breath-by-breath probability of obstruction (Pobs). A development and initial test set of 29 subjects (development = 6, test = 23) (New York, NY) and a second test set of 39 subjects (Solingen, Germany), both with esophageal manometry, were used to develop Pobs and validate it against gold-standard upper airway resistance. A separate dataset of 114 subjects with 2 consecutive nocturnal polysomnographies (New York, NY) without esophageal manometry was used to assess the night-to-night variability of Pobs. Measurements and Main Results: A total of 1,962,229 breaths were analyzed. On a breath-by-breath level, Pobs was strongly correlated with normalized upper airway resistance in both test sets (set 1: cubic adjusted [adj.] R2 = 0.87, P < 0.001, area under the receiver operating characteristic curve = 0.74; set 2: cubic adj. R2 = 0.83, P < 0.001, area under the receiver operating characteristic curve = 0.7). On a subject level, median Pobs was associated with the median normalized upper airway resistance (set 1: linear adj. R2 = 0.59, P < 0.001; set 2: linear adj. R2 = 0.45, P < 0.001). Median Pobs exhibited low night-to-night variability [intraclass correlation(2, 1) = 0.93]. Conclusions: Using nearly 2 million breaths from 182 subjects, we show that breath-by-breath probability of obstruction can reliably predict the overall burden of obstructed breaths in individual subjects and can aid in determining the type of sleep apnea.

Role of Positive End-Expiratory Pressure and Regional Transpulmonary Pressure in Asymmetrical Lung Injury.

Rationale: Asymmetrical lung injury is a frequent clinical presentation. Regional distribution of Vt and positive end-expiratory pressure (PEEP) could result in hyperinflation of the less-injured lung. The validity of esophageal pressure (Pes) is unknown.Objectives: To compare, in asymmetrical lung injury, Pes with directly measured pleural pressures (Ppl) of both sides and investigate how PEEP impacts ventilation distribution and the regional driving transpulmonary pressure (inspiratory - expiratory).Methods: Fourteen mechanically ventilated pigs with lung injury were studied. One lung was blocked while the contralateral one underwent surfactant lavage and injurious ventilation. Airway pressure and Pes were measured, as was Ppl in the dorsal and ventral pleural space adjacent to each lung. Distribution of ventilation was assessed by electrical impedance tomography. PEEP was studied through decremental steps.Measurements and Results: Ventral and dorsal Ppl were similar between the injured and the noninjured lung across all PEEP levels. Dorsal Ppl and Pes were similar. The driving transpulmonary pressure was similar in the two lungs. Vt distribution between lungs was different at zero end-expiratory pressure (≈70% of Vt going in noninjured lung) owing to different respiratory system compliance (8.3 ml/cm H2O noninjured lung vs. 3.7 ml/cm H2O injured lung). PEEP at 10 cm H2O with transpulmonary pressure around zero homogenized Vt distribution opening the lungs. PEEP ≥16 cm H2O equalized distribution of Vt but with overdistension for both lungs.Conclusions: Despite asymmetrical lung injury, Ppl between injured and noninjured lungs is equalized and esophageal pressure is a reliable estimate of dorsal Ppl. Driving transpulmonary pressure is similar for both lungs. Vt distribution results from regional respiratory system compliance. Moderate PEEP homogenizes Vt distribution between lungs without generating hyperinflation.

Central venous pressure swing outperforms diaphragm ultrasound as a measure of inspiratory effort during pressure support ventilation in COVID-19 patients.

PURPOSE: The COVID-19-related shortage of ICU beds magnified the need of tools to properly titrate the ventilator assistance. We investigated whether bedside-available indices such as the ultrasonographic changes in diaphragm thickening ratio (TR) and the tidal swing in central venous pressure (ΔCVP) are reliable estimates of inspiratory effort, assessed as the tidal swing in esophageal pressure (ΔPes). METHODS: Prospective, observational clinical investigation in the intensive care unit of a tertiary care Hospital. Fourteen critically-ill patients were enrolled (age 64 ± 7 years, BMI 29 ± 4 kg/m2), after 6 [3; 9] days from onset of assisted ventilation. A three-level pressure support trial was performed, at 10 (PS10), 5 (PS5) and 0 cmH2O (PS0). In each step, the esophageal and central venous pressure tidal swing were recorded, as well as diaphragm ultrasound. RESULTS: The reduction of pressure support was associated with an increased respiratory rate and a reduced tidal volume, while minute ventilation was unchanged. ΔPes significantly increased with reducing support (5 [3; 8] vs. 8 [14; 13] vs. 12 [6; 16] cmH2O, p < 0.0001), as did the diaphragm TR (9.2 ± 6.1 vs. 17.6 ± 7.2 vs. 28.0 ± 10.0%, p < 0.0001) and the ΔCVP (4 [3; 7] vs. 8 [5; 9] vs. 10 [7; 11] cmH2O, p < 0.0001). ΔCVP was significantly associated with ΔPes (R2 = 0.810, p < 0.001), as was diaphragm TR, albeit with a lower coefficient of determination (R2 = 0.399, p < 0.001). CONCLUSIONS: In patients with COVID-19-associated respiratory failure undergoing assisted mechanical ventilation, ΔCVP is a better estimate of inspiratory effort than diaphragm ultrasound.

Surface EMG-based quantification of inspiratory effort: a quantitative comparison with Pes.

BACKGROUND: Inspiratory patient effort under assisted mechanical ventilation is an important quantity for assessing patient-ventilator interaction and recognizing over and under assistance. An established clinical standard is respiratory muscle pressure [Formula: see text], derived from esophageal pressure ([Formula: see text]), which requires the correct placement and calibration of an esophageal balloon catheter. Surface electromyography (sEMG) of the respiratory muscles represents a promising and straightforward alternative technique, enabling non-invasive monitoring of patient activity. METHODS: A prospective observational study was conducted with patients under assisted mechanical ventilation, who were scheduled for elective bronchoscopy. Airway flow and pressure, esophageal/gastric pressures and sEMG of the diaphragm and intercostal muscles were recorded at four levels of pressure support ventilation. Patient efforts were quantified via the [Formula: see text]-time product ([Formula: see text]), the transdiaphragmatic pressure-time product ([Formula: see text]) and the EMG-time products (ETP) of the two sEMG channels. To improve the signal-to-noise ratio, a method for automatically selecting the more informative of the sEMG channels was investigated. Correlation between ETP and [Formula: see text] was assessed by determining a neuromechanical conversion factor [Formula: see text] between the two quantities. Moreover, it was investigated whether this scalar can be reliably determined from airway pressure during occlusion maneuvers, thus allowing to quantify inspiratory effort based solely on sEMG measurements. RESULTS: In total, 62 patients with heterogeneous pulmonary diseases were enrolled in the study, 43 of which were included in the data analysis. The ETP of the two sEMG channels was well correlated with [Formula: see text] ([Formula: see text] and [Formula: see text] for diaphragm and intercostal recordings, respectively). The proposed automatic channel selection method improved correlation with [Formula: see text] ([Formula: see text]). The neuromechanical conversion factor obtained by fitting ETP to [Formula: see text] varied widely between patients ([Formula: see text]) and was highly correlated with the scalar determined during occlusions ([Formula: see text], [Formula: see text]). The occlusion-based method for deriving [Formula: see text] from ETP showed a breath-wise deviation to [Formula: see text] of [Formula: see text] across all datasets. CONCLUSION: These results support the use of surface electromyography as a non-invasive alternative for monitoring breath-by-breath inspiratory effort of patients under assisted mechanical ventilation.

Early Inspiratory Effort Assessment by Esophageal Manometry Predicts Noninvasive Ventilation Outcome in De Novo Respiratory Failure. A Pilot Study.

Rationale: The role of inspiratory effort still has to be determined as a potential predictor of noninvasive mechanical ventilation (NIV) failure in acute hypoxic de novo respiratory failure.Objectives: To explore the hypothesis that inspiratory effort might be a major determinant of NIV failure in these patients.Methods: Thirty consecutive patients with acute hypoxic de novo respiratory failure admitted to a single center and candidates for a 24-hour NIV trial were enrolled. Clinical features, tidal change in esophageal pressure (ΔPes), tidal change in dynamic transpulmonary pressure (ΔPl), expiratory Vt, and respiratory rate were recorded on admission and 2-4 to 12-24 hours after NIV start and were tested for correlation with outcomes.Measurements and Main Results: ΔPes and ΔPes/ΔPl ratio were significantly lower 2 hours after NIV start in patients who successfully completed the NIV trial (n = 18) compared with those who needed endotracheal intubation (n = 12) (median [interquartile range], 11 [8-15] cm H2O vs. 31.5 [30-36] cm H2O; P < 0.0001), whereas other variables differed later. ΔPes was not related to other predictors of NIV failure at baseline. NIV-induced reduction in ΔPes of 10 cm H2O or more after 2 hours of treatment was strongly associated with avoidance of intubation and represented the most accurate predictor of treatment success (odds ratio, 15; 95% confidence interval, 2.8-110; P = 0.001 and area under the curve, 0.97; 95% confidence interval, 0.91-1; P < 0.0001).Conclusions: The magnitude of inspiratory effort relief as assessed by ΔPes variation within the first 2 hours of NIV was an early and accurate predictor of NIV outcome at 24 hours.Clinical trial registered with www.clinicaltrials.gov (NCT03826797).

Non-invasive assessment of respiratory muscle activity during pressure support ventilation: accuracy of end-inspiration occlusion and least square fitting methods.

Pressure support ventilation (PSV) should be titrated considering the pressure developed by the respiratory muscles (Pmusc) to prevent under- and over-assistance. The esophageal pressure (Pes) is the clinical gold standard for Pmusc assessment, but its use is limited by alleged invasiveness and complexity. The least square fitting method and the end-inspiratory occlusion method have been proposed as non-invasive alternatives for Pmusc assessment. The aims of this study were: (1) to compare the accuracy of Pmusc estimation using the end-inspiration occlusion (Pmusc,index) and the least square fitting (Pmusc,lsf) against the reference method based on Pes; (2) to test the accuracy of Pmusc,lsf and of Pmusc,index to detect overassistance, defined as Pmusc ≤ 1 cmH2O. We studied 18 patients at three different PSV levels. At each PSV level, Pmusc, Pmusc,lsf, Pmusc,index were calculated on the same breaths. Differences among Pmusc, Pmusc,lsf, Pmusc,index were analyzed with linear mixed effects models. Bias and agreement were assessed by Bland-Altman analysis for repeated measures. The ability of Pmusc,lsf and Pmusc,index to detect overassistance was assessed by the area under the receiver operating characteristics curve. Positive and negative predictive values were calculated using cutoff values that maximized the sum of sensitivity and specificity. At each PSV level, Pmusc,lsf was not different from Pmusc (p = 0.96), whereas Pmusc,index was significantly lower than Pmusc. The bias between Pmusc and Pmusc,lsf was zero, whereas Pmusc,index systematically underestimated Pmusc of 6 cmH2O. The limits of agreement between Pmusc and Pmusc,lsf and between Pmusc and Pmusc,index were ± 12 cmH2O across bias. Both Pmusc,lsf ≤ 4 cmH2O and Pmusc,index ≤ 1 cmH2O had excellent negative predictive value [0.98 (95% CI 0.94-1) and 0.96 (95% CI 0.91-0.99), respectively)] to identify over-assistance. The inspiratory effort during PSV could not be accurately estimated by the least square fitting or end-inspiratory occlusion method because the limits of agreement were far above the signal size. These non-invasive approaches, however, could be used to screen patients at risk for absent or minimal respiratory muscles activation to prevent the ventilator-induced diaphragmatic dysfunction.

Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation.

BACKGROUND: The driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined. METHODS: Retrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a "passive-like" decrease followed by plateau, a pattern with "clear plateau," and an "irregular rise" pattern, which included all cases of late or continuous increase, with or without plateau. RESULTS: Data from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively. CONCLUSIONS: The pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.