Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy.

We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2.

We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F).

We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

Rationale: Patients with acute respiratory distress syndrome (ARDS) have a reduction in functional lung volume that results in increased respiratory system elastance (Ers); however, the extent of this increase varies by patient. Patients with high Ers are at risk of excess lung-distending pressures and may derive greater clinical benefit from neuromuscular blockade (NMB). Objectives: We sought to evaluate whether the effect of early NMB administration on mortality varies according to baseline physiological and biological biomarkers of lung injury, including Ers. Methods: We conducted a secondary analysis of the Reevaluation of Systemic Early Neuromuscular Blockade, or ROSE, trial. Bayesian logistic regression modeling was used to estimate the posterior probability of NMB effect moderation by baseline Ers, ventilatory ratio, and select ARDS plasma biomarkers on 90-day mortality. Measurements and Main Results: The probability of mortality benefit with NMB increased substantially with higher baseline Ers (posterior probability of interaction, 92%; interaction odds ratio = 0.76; 90% credible interval = 0.59-0.99). In patients with an Ers ⩾2 cm H2O/(ml/kg), the posterior probability of benefit was 96% (median absolute risk reduction, 9%; 90% credible interval = 0.5-17.9). The effect of NMB did not vary meaningfully according to ventilatory ratio (posterior probability of interaction, 62%) or baseline plasma levels of receptor for advanced glycation end-products, tumor necrosis factor receptor-1, IL-6, or IL-8 (posterior probabilities of interaction: 12%, 18%, 44%, and 22% respectively). Conclusions: These findings suggest that the mortality benefit of NMB varies with baseline Ers. High Ers may represent a physiological phenotype of acute respiratory distress syndrome. Future prospective testing to confirm benefit in this potentially treatment-responsive group is needed.

Background: The Flow Index was recently developed as a bedside method based on flow waveforms to assess patient inspiratory effort during invasive mechanical ventilation. The aim of this study is to externally validate the Flow Index by assessing its ability to identify low and high inspiratory effort breaths. Methods: Secondary analysis of a randomized controlled trial. The association between Flow Index and patient inspiratory effort (pressure generated by the respiratory muscles [ΔPmus] and pressure-time product from the start of inspiratory flow [PTPinsp]) was evaluated using linear mixed effects models. The discrimination capacity (area under the curve [AUC]) of the Flow Index to identify low and high inspiratory effort breaths was analyzed. Results: A total of 1,095 breaths from 38 subjects were included in the analysis. Flow Index had moderate discriminatory power in identifying low inspiratory effort breaths (AUC of 0.73 and 0.77 for low inspiratory effort defined with ΔPmus and PTPinsp, respectively). Discriminatory power in identifying high inspiratory effort breaths was low (AUC of 0.68 and 0.65 for ΔPmus and PTPinsp, respectively). Conclusions: Flow Index demonstrated moderate discriminatory power in identifying low inspiratory effort breaths, whereas discriminatory power in identifying high inspiratory effort breaths was low.

Non-invasive respiratory support (NRS), including high flow nasal oxygen therapy, continuous positive airway pressure and non-invasive ventilation, is a cornerstone in the management of critically ill patients who develop acute respiratory failure (ARF). Overall, NRS reduces the work of breathing and relieves dyspnea in many patients with ARF, sometimes avoiding the need for intubation and invasive mechanical ventilation with variable efficacy across diverse clinical scenarios. Nonetheless, prolonged exposure to NRS in the presence of sustained high respiratory drive and effort can result in respiratory muscle fatigue, cardiovascular collapse, and impaired oxygen delivery to vital organs, leading to poor outcomes in patients who ultimately fail NRS and require intubation. Assessment of patients' baseline characteristics before starting NRS, close physiological monitoring to evaluate patients' response to respiratory support, adjustment of device settings and interface, and, most importantly, early identification of failure or of paramount importance to avoid the negative consequences of delayed intubation. This review highlights the role of respiratory monitoring across various modalities of NRS in patients with ARF including dyspnea, general respiratory parameters, measures of drive and effort, and lung imaging. It includes technical specificities related to the target population and emphasizes the importance of clinicians' physiological understanding and tailoring clinical decisions to individual patients' needs.

This review summarizes the evidence on clinical outcomes related to diaphragm dysfunction, providing an overview on available monitoring tools and strategies for its prevention and treatment.

Long-term adverse functional outcomes in intensive care survivors are well documented, especially in patients with prolonged mechanical ventilation. Because diaphragm weakness is highly prevalent and strongly associated with weaning failure, a link between diaphragm weakness and adverse functional outcomes is probable. Mechanisms of critical illness-associated diaphragm weakness are complex and include ventilator-related myotrauma through various pathways (i.e. over-assistance, under-assistance, eccentric, expiratory). Given this potential clinical impact, research on preventive and therapeutic strategies is growing including the development of ventilation strategies aiming at protecting both the lung and the diaphragm. Phrenic nerve stimulation and specific rehabilitation strategies also appear promising.

Diaphragm dysfunction is associated with adverse clinical outcomes in ventilated patients; therefore, their inspiratory effort and function should be monitored. Whenever possible, and without compromising lung protection, moderate inspiratory effort should be targeted. Phrenic nerve stimulation and specific rehabilitation strategies are promising to prevent and treat diaphragm dysfunction, but further evidence is needed before widespread implementation.

Accurate monitoring of respiratory drive and inspiratory effort is crucial for optimizing ventilatory support during acute respiratory failure. This review evaluates current and emerging bedside methods for assessing respiratory drive and effort.

While electrical activity of the diaphragm and esophageal pressure remain the reference standards for assessing respiratory drive and effort, their clinical utility is largely limited to research. At the bedside, airway occlusion maneuvers are the most useful tools: P0.1 is a reliable marker of drive and detects abnormal inspiratory efforts, while occlusion pressure (Pocc) may outperform P0.1 in identifying excessive effort. The Pressure-Muscle-Index (PMI) can help detecting insufficient inspiratory effort, though its accuracy depends on obtaining a stable plateau pressure. Other techniques, such as central venous pressure swings (ΔCVP), are promising but require further investigation. Emerging machine learning and artificial intelligence based algorithms could play a pivotal role in automated respiratory monitoring in the near future.

Although Pes and EAdi remain reference methods, airway occlusion maneuvers are currently the most practical bedside tools for monitoring respiratory drive and effort. Noninvasive alternatives such as ΔCVP deserve further evaluation. Artificial intelligence and machine learning may soon provide automated solutions for bedside monitoring of respiratory drive and effort.

Background: The airway-occlusion pressure is used to estimate the muscle pressure (P mus ) and the occlusion pressure at 100 ms (P 0 .1 ) to assess respiratory drive in patients on mechanical ventilation. However, the validity of these maneuvers during noninvasive ventilation (NIV) has not been evaluated. This study was designed to validate the airway-occlusion pressure and the P 0 .1 described for mechanical ventilation during NIV in a bench model. Methods: This was a bench observational prospective study carried out during January and February 2024 in the ICU laboratory of the Hospital Británico of Buenos Aires. Results: In the non-leakage NIV scenarios with oronasal and total face mask, the NIV-airway-occlusion pressure increased with greater P mus (P < .001). For a programmed P mus of 5 cm H2O, values around 4.5 cm H2O were recorded for both oronasal and total face masks. At 10 cm H2O, the values were ∼8 cm H2O, and at 15 cm H2O, they were ∼11 cm H2O. With leaks, this difference worsened as leakage increased and the effort decreased. In the Bland-Altman analysis between mechanical ventilation-airway-occlusion pressure and NIV-airway-occlusion pressure without leakage for oronasal and total face masks, we found a good agreement for the 3 levels of P mus with both types of masks. With regard to the values of NIV-airway-occlusion pressure with the helmet, Bland-Altman analysis showed a high bias and random error. Multivariate analysis found that NIV-airway-occlusion pressure depends on the type of interface, increased with P mus , and decreased as leakage increased. The agreement of NIV-P 0 .1 was not good across all noninvasive measurements. Conclusions: This study constitutes a relevant contribution in the validation of indices to assess P mus during NIV. In a laboratory setting, the measurement of airway-occlusion pressure in NIV may be used to assess effort estimation in the absence of leakage; however, it will likely be underestimated. P 0 .1 proved to be an unreliable method. These findings suggest the feasibility of assessing muscle effort during NIV.

To compare the level of agreement between proximal (near the subject) and distal (inside the ventilator) measured airway occlusion pressure at 100 ms (P0.1) and occlusion pressure (Δ Pocc ), and to study the correlation between Δ Pocc and peak-to-trough esophageal pressure (Δ Pes ).

Secondary analysis of prospectively collected physiology dataset (2021-2022).

Medical-surgical 20-bed PICU.

Children younger than 18 years with and without acute lung injury ventilated greater than 24 hours and spontaneously breathing with appropriate triggering of the ventilator.

None.

Data from three expiratory hold maneuvers (with a maximum of three breaths during each maneuver) in 74 subjects (118 measurements) with median age 3 months (interquartile range 1-17), and primary respiratory failure due to a pulmonary infection in 41/74 (55.4%) were studied. The median proximal ∆ Pocc was 6.7 cm H 2 O (3.1-10.7) and median P0.1 4.9 cm H 2 O (4.1-6.0) for the first breath from the maneuver; both increased significantly ( p < 0.001) with the subsequent two breaths during the same maneuver. Median distal ∆ Pocc was 6.8 (2.9-10.8) and P0.1 4.6 (3.9-5.6) cm H 2 O; both increased significantly ( p < 0.001) with the two subsequent breaths. Proximal and distal Δ Pocc ( r > 0.99, p < 0.001) and P0.1 ( r > 0.80, p < 0.001) were correlated. Correlation between ventilator displayed and Y-piece measured Δ Pocc ( r > 0.99) and P0.1 ( r = 0.85) was good. Mean ( sd ) difference for Δ Pocc was 0.13 (0.21); levels of agreement were -0.28 and 0.54. For P0.1, mean ( sd ) difference was -0.36 (1.14) and levels of agreement -2.61 and 1.88. There was a high correlation between Δ Pes and ∆ Pocc ( r = 0.92) for the same breath and a good correlation with Δ Pes from the preceding breath ( r = 0.76). There was a poor correlation with the transpulmonary pressure ( r = 0.37).

Δ Pocc is not affected by measurement site, whereas P0.1 may be overestimated or underestimated. Δ Pocc was highly correlated with the peak-to-trough esophageal pressure, supporting the concept that inspiratory effort can also be quantified noninvasively by measuring Δ Pocc .

During pressure support ventilation (PSV), the accuracy of non-invasive indicators in diagnosing high or low inspiratory effort has been validated. However, the correlation and agreement of these indicators remain unclear. This study aims to investigate the correlation and agreement among non-invasive inspiratory effort indicators, and to compare characteristics of inspiratory effort in neurocritical and non-neurocritical patients.

This was a single-centre prospective observational study. We collected three non-invasive inspiratory effort indicators, pressure muscular index (PMI), the maximal negative swing of airway pressure during expiratory occlusion (ΔPocc), and the airway occlusion pressure during the first 100ms (P0.1). Cutoff values for these indicators derived from esophageal pressure-time product (PTPmus) were chosen for this study. The correlation and agreement of these indicators were analyzed using Spearman's rank correlation test and linear weighted Kappa analysis. Characteristics of PSV settings and inspiratory effort in neurocritical and non-neurocritical patients were compared.

Ninety-seven patients were enrolled in this study. Correlation analysis showed a moderate correlation between PMI and ΔPocc (rho = -0.524, p < 0.001), ΔPocc and P0.1 (rho = 0.588, p < 0.001), while no correlation between PMI and P0.1 (rho = -0.140, p = 0.172). There was a moderate agreement between ΔPocc and P0.1 (k = 0.459, p < 0.001), a fair agreement between PMI and ΔPocc (k = 0.362, p < 0.001), but no agreement between PMI and P0.1 (k = 0.134, p = 0.072). The correlation of these indicators was similar in neurocritical patients compared with non-neurocritical patients, but agreement was poor.

The study showed that PMI and ΔPocc had moderate correlation and fair agreement, ΔPocc and P0.1 had moderate correlation and agreement, while PMI and P0.1 had no correlation and agreement.

Cipepofol is a highly selective gamma-aminobutyric acid A receptor potentiator. As a new sedative drug, detailed studies on its respiratory effects are further needed. The present study aims to investigate the effects of cipepofol on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.

In this one-arm physiological study, cipepofol was initiated at 0.3 mg/kg/h and increased by 0.1 mg/kg/h every 30 min until reaching 0.8 mg/kg/h. Discontinuation criteria were Richmond Agitation and Sedation Scale (RASS) score ≤ -4 or respiratory rate (RR) < 8 breaths/min or pulse oxygen saturation (SpO2) < 90%. The primary outcomes were changes from baseline in respiratory variables [RR, tidal volume (VT), minute ventilation (Vmin), airway occlusion pressure at 100 msec (P0.1), pressure muscle index (PMI), expiratory occlusion pressure (Pocc)] at 30 min after 0.3 mg/kg/h cipepofol infusion. The secondary outcomes included changes in respiratory variables, cardiorespiratory variables, and RASS scores at rates of cipepofol from 0.3 to 0.8 mg/kg/h.

20 patients were enrolled and all of them completed the cipepofol infusion rate at 0.3 mg/kg/h, achieving RASS score of -2 to +1. For the primary outcomes, there was a significant reduction in VT (390.9, [356.6-511.0] vs. 451.6 [393.5-565.9], p = 0.002), while changes in RR (16.7 ± 2.7 vs. 16.2 ± 3.4, p = 0.465) and Vmin (7.2 ± 1.8 vs. 7.5 ± 1.9, p = 0.154) were not significant. The reductions in P0.1 (p = 0.020), PMI (p = 0.019), and Pocc (p = 0.007) were significant. For secondary outcomes, as the infusion rate of cipepofol increased from 0.3 to 0.8 mg/kg/h, there was a further decrease in VT (p = 0.002) and an increase in RR (p < 0.001), while the change in Vmin (p = 0.430) was not significant. RASS score (p < 0.001) was further decreased.

Cipepofol demonstrates the capability to achieve RASS score -2 to +1 in mechanically ventilated adult patients. The effect of cipepofol on breathing patterns was a decrease in VT, while changes in RR and Vmin were insignificant. The effect on respiratory drive and inspiratory effort significantly reduced P0.1, PMI, and Pocc.

ClinicalTrials.gov, identifier NCT06287138. https://clinicaltrials.gov/study/NCT06287138.

Mechanical ventilation may have adverse effects on diaphragm and lung function. Lung- and diaphragm-protective ventilation is an approach that challenges the clinician to facilitate physiological respiratory efforts, while maintaining minimal lung stress and strain. Here, we discuss the latest advances in monitoring and interventions to achieve lung- and diaphragm protective ventilation.

Noninvasive ventilator maneuvers (P0.1, airway occlusion pressure, pressure-muscle index) can accurately detect low and excessive respiratory efforts and high lung stress. Additional monitoring techniques include esophageal manometry, ultrasound, electrical activity of the diaphragm, and electrical impedance tomography. Recent trials demonstrate that a systematic approach to titrating inspiratory support and sedation facilitates lung- and diaphragm protective ventilation. Titration of positive-end expiratory pressure and, if available, veno-venous extracorporeal membrane oxygenation sweep gas flow may further modulate neural respiratory drive and effort to facilitate lung- and diaphragm protective ventilation.

Achieving lung- and diaphragm-protective ventilation may require more than a single intervention; it demands a comprehensive understanding of the (neuro)physiology of breathing and mechanical ventilation, along with the application of a series of interventions under close monitoring. We suggest a bedside-approach to achieve lung- and diaphragm protective ventilation targets.

The diaphragm is crucial for ventilator weaning, but its specific impact on weaning indicators needs further clarification. This study investigated the variability in weaning outcomes across different diaphragm function populations and the value of respiratory drive and inspiratory effort in weaning.

This observational case-control study enrolled patients on mechanical ventilation for more than 48 h and completed a 30-minute spontaneous breathing trial (SBT) with pressure-support ventilation for the first time. After the SBT, airway pressure at 100 ms during occlusion (P0.1), inspiratory effort, and diaphragmatic ultrasound were evaluated to predict weaning outcomes. Weaning failure was defined as re-intubation within 48 h of weaning, the need for therapeutic non-invasive ventilation, or death.

68 patients with a mean age of 63.21 ± 15.15 years were included. In patients with diaphragm thickness (DT) ≥ 2 mm, P0.1 (P=0.002), pressure-muscle index (PMI) (P=0.012), and occluded expiratory airway pressure swing (ΔPocc) (P=0.030) were significantly higher in those who failed weaning. Conversely, for patients with DT<2 mm, PMI (P=0.003) and ΔPocc (P=0.002) were lower in the weaning failure group. Additionally, within the DT≥2 mm group, P0.1 demonstrated a higher area under the curve (AUC) for weaning prediction (0.889 vs. 0.739) compared to those with DT<2 mm.

PMI and ΔPocc are predictive of weaning outcomes in patients with diaphragm thickness ≥ 2 mm, where the assessment value of P0.1 is notably higher. Diaphragm function significantly influences the accuracy of weaning predictions based on respiratory drive and inspiratory effort.

Our findings indicate that the effectiveness of respiratory drive and inspiratory effort in predicting successful weaning from mechanical ventilation may vary across different patient populations. Diaphragm function plays a crucial role in weaning assessments, particularly when using P0.1, the pressure-muscle index (PMI), and occluded expiratory airway pressure swing (ΔPocc).

To summarize basic physiological concepts of breathing effort and outline various methods for monitoring effort of inspiratory and expiratory muscles.

Esophageal pressure (Pes) measurement is the reference standard for respiratory muscle effort quantification, but various noninvasive screening tools have been proposed. Expiratory occlusion pressures (P0.1 and Pocc) could inform about low and high effort and the resulting lung stress, with Pocc outperforming P0.1 in identifying high effort. The pressure muscle index during an inspiratory hold could unveil inspiratory muscle effort, however obtaining a reliable inspiratory plateau can be difficult. Surface electromyography has the potential for inspiratory effort estimation, yet this is technically challenging for real-time assessment. Expiratory muscle activation is common in the critically ill warranting their assessment, that is, via gastric pressure monitoring. Expiratory muscle activation also impacts inspiratory effort interpretation which could result in both under- and overestimation of the resulting lung stress. There is likely a future role for machine learning applications to automate breathing effort monitoring at the bedside.

Different tools are available for monitoring the respiratory muscles' effort during mechanical ventilation - from noninvasive screening tools to more invasive quantification methods. This could facilitate a lung and respiratory muscle-protective ventilation approach.

Background: In acute hypoxemic respiratory failure (AHRF), spontaneous breathing effort can generate excessive regional lung stress and strain manifesting as pendelluft. Higher PEEP may reduce pendelluft and reduce regional lung stress and strain during spontaneous breathing. This study aimed to establish whether higher or lower PEEP ameliorates pendelluft and to characterize factors determining the presence and magnitude of pendelluft during spontaneous breathing efforts. Methods: This study was a randomized crossover trial of higher versus lower PEEP applied after systematically initiating spontaneous breathing in subjects with moderate or severe AHRF. The presence and volume of pendelluft were assessed by electrical impedance tomography (EIT). Results: EIT recordings were available for 20 of 30 subjects enrolled in the trial. After initiating spontaneous breathing, 11/20 exhibited pendelluft (proportion 55% [95% CI 32-76]). Following PEEP titration, the prevalence of pendelluft was not different between higher versus lower PEEP levels (50% vs 50%, P = .55). When present, pendelluft volume was generally small (median 28 [interquartile range 8-93] mL) but ranged as high as 364 mL. Pendelluft was associated with higher respiratory effort (esophageal pressure [Pes] swing [ΔPes] median -15 cm H2O vs ΔPes median -8 cm H2O, P = .01), higher pulmonary flow resistance (median 8 cm H2O/L/s vs median 3 cm H2O/L/s, P < .001), and higher dynamic pulmonary elastance (median 5.0 cm H2O/mL/kg predicted body weight vs median 3.2 cm H2O/mL/kg predicted body weight, P = .03). Conclusions: Pendelluft reflecting increased regional lung stress and strain is likely common during spontaneous breathing effort in patients with AHRF but was not systematically affected by applying higher PEEP. The presence and magnitude of pendelluft depended on respiratory effort and lung mechanics.

Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches. The concept of mechanical power has emerged as a comprehensive metric encompassing key ventilator parameters associated with the genesis of ventilator-induced lung injury, including volume, pressure, flow, resistance, and respiratory rate. While numerous animal and human studies have linked mechanical power and ventilator-induced lung injury, its practical implementation at the bedside is hindered by calculation challenges, lack of equation consensus, and the absence of an optimal threshold. To overcome the constraints of measuring static respiratory parameters, dynamic mechanical power is proposed for all patients, regardless of their ventilation mode. However, establishing a causal relationship is crucial for its potential implementation, and requires further research. The objective of this review is to explore the role of mechanical power in ventilator-induced lung injury, its association with patient outcomes, and the challenges and potential benefits of implementing a ventilation strategy based on mechanical power.

Fluids are given with the purpose of increasing cardiac output (CO), but approximately only 50% of critically ill patients are fluid responders. Since the effect of a fluid bolus is time-sensitive, it diminuish within few hours, following the initial fluid resuscitation. Several functional hemodynamic tests (FHTs), consisting of maneuvers affecting heart-lung interactions, have been conceived to discriminate fluid responders from non-responders. Three main variables affect the reliability of FHTs in predicting fluid responsiveness: (1) tidal volume; (2) spontaneous breathing activity; (3) cardiac arrythmias. Most FTHs have been validated in sedated or even paralyzed ICU patients, since, historically, controlled mechanical ventilation with high tidal volumes was the preferred mode of ventilatory support. The transition to contemporary methods of invasive mechanical ventilation with spontaneous breathing activity impacts heart-lung interactions by modifying intrathoracic pressure, tidal volumes and transvascular pressure in lung capillaries. These alterations and the heterogeneity in respiratory mechanics (that is present both in healthy and injured lungs) subsequently influence venous return and cardiac output. Cardiac arrythmias are frequently present in critically ill patients, especially atrial fibrillation, and intuitively impact on FHTs. This is due to the random CO fluctuations. Finally, the presence of continuous CO monitoring in ICU patients is not standard and the assessment of fluid responsiveness with surrogate methods is clinically useful, but also challenging. In this review we provide an algorithm for the use of FHTs in different subgroups of ICU patients, according to ventilatory setting, cardiac rhythm and the availability of continuous hemodynamic monitoring.

Predicting complete liberation from mechanical ventilation (MV) is still challenging. Electrical impedance tomography (EIT) offers a non-invasive measure of regional ventilation distribution and could bring additional information.

Whether the display of regional ventilation distribution during a Spontaneous Breathing Trial (SBT) could help at predicting early and successful liberation from MV.

Patients were monitored with EIT during the SBT. The tidal image was divided into ventral and dorsal regions and displayed simultaneously. We explored the ventral-to-dorsal ventilation difference in percentage, and its association with clinical outcomes. Liberation success was defined pragmatically as passing SBT followed by extubation within 24 h without reintubation for 7 days. Failure included use of rescue therapy, reintubation within 7 days, tracheostomy, and not being extubated within 24 h after succesful SBT. A training cohort was used for discovery, followed by a validation cohort.

Among a total of 98 patients analyzed, 85 passed SBT (87%), but rapid liberation success occurred only in 40; 13.5% of extubated patients required reintubation. From the first minutes to the entire SBT duration, the absolute ventral-to-dorsal difference was consistently smaller in liberation success compared to all subgroups of failure (p < 0.0001). An absolute difference at 5 min of SBT > 20% was associated with failure of liberation, with sensitivity and specificity of 71% and 78% and positive predictive value 81% in a validation cohort.

During SBT, a large ventral-to-dorsal difference in ventilation indicated by EIT may help to rapidly identify patients at risk of liberation failure.

Assessing the respiratory system of a patient receiving mechanical ventilation is complex. We provide an overview of an approach at the bedside underpinned by physiology. We discuss the importance of distinguishing between extensive and intensive ventilatory variables. We outline methods to evaluate both passive patients and those making spontaneous respiratory efforts during assisted ventilation. We believe a comprehensive assessment can influence setting mechanical ventilatory support to achieve lung and diaphragm protective ventilation.

Acute respiratory distress syndrome (ARDS) presents significant challenges in critical care, primarily due to its inflammatory nature, which leads to impaired gas exchange and respiratory mechanics. While mechanical ventilation (MV) is essential for patient support, the transition from controlled to assisted ventilation is complex and may be associated with intensive care unit-acquired weakness, ventilator-induced diaphragmatic dysfunction and patient self-inflicted lung injury. This paper explores the multifaceted challenges encountered during this transition, with a focus on respiratory effort, sedation management, and monitoring techniques, and investigates innovative approaches to enhance patient outcomes. The key strategies include optimizing sedation protocols, employing advanced monitoring methods like esophageal pressure measurements, and implementing partial neuromuscular blockade to prevent excessive respiratory effort. We also emphasize the importance of personalized treatment plans and the integration of artificial intelligence to facilitate timely transitions. By highlighting early rehabilitation techniques, continuously assessing the respiratory drive, and fostering collaboration among multidisciplinary teams, clinicians can improve the transition from controlled to assisted MV, ultimately enhancing recovery and long-term respiratory health in patients with ARDS.

Personalized positive end-expiratory pressure (PEEP) might foster lung and diaphragm protection in patients with acute respiratory distress syndrome (ARDS) who are undergoing pressure support ventilation (PSV). We aimed to compare the physiologic effects of personalized PEEP set according to synchronized electrical impedance tomography (EIT) and driving transpulmonary pressure (∆PL) monitoring against a classical lower PEEP/FiO2 table in intubated ARDS patients undergoing PSV.

A cross-over randomized multicenter study was conducted in 30 ARDS patients with simultaneous recording of the airway, esophageal and transpulmonary pressure, together with EIT during PSV. Following a decremental PEEP trial (18 cmH2O to 4 cmH2O), PEEPEIT-∆PL was identified as the level with the smallest difference between lung overdistension and collapse. A low PEEP/FiO2 table was used to select PEEPTABLE. Each PEEP strategy was applied for 20 min, and physiologic data were collected at the end of each step.

The PEEP trial was well tolerated. Median PEEPEIT-∆PL was higher than PEEPTABLE (10 [8-12] vs. 8 [5-10] cmH2O; P = 0.021) and, at the individual patient level, PEEPEIT-∆PL level differed from PEEPTABLE in all patients. Overall, PEEPEIT-∆PL was associated with lower dynamic ∆PL (P < 0.001) and pressure-time product (P < 0.001), but there was variability among patients. PEEPEIT-∆PL also decreased respiratory drive and effort (P < 0.001), improved regional lung mechanics (P < 0.05) and reversed lung collapse (P = 0.007) without increasing overdistension (P = 0.695).

Personalized PEEP selected using synchronized EIT and transpulmonary pressure monitoring could be associated with reduced dynamic lung stress and metabolic work of breathing in ARDS patients undergoing PSV.

This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS).

A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH2O. PEEP was adjusted to maintain oxygen saturation (SaO2) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH2O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients.

In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group's PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999).

Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach.

Patients with acute respiratory distress syndrome often require mechanical ventilation to maintain adequate gas exchange and to reduce the workload of the respiratory muscles. Although lifesaving, positive pressure mechanical ventilation can potentially injure the lungs and diaphragm, further worsening patient outcomes. While the effect of mechanical ventilation on the risk of developing lung injury is widely appreciated, its potentially deleterious effects on the diaphragm have only recently come to be considered by the broader intensive care unit community. Importantly, both ventilator-induced lung injury and ventilator-induced diaphragm dysfunction are associated with worse patient-centered outcomes.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.

Assessing and treating respiratory muscle dysfunction is crucial for patients with both acute and chronic respiratory failure. Respiratory muscle dysfunction can contribute to the onset of respiratory failure and may also worsen due to interventions aimed at treatment. Evaluating respiratory muscle function is particularly valuable for diagnosing, phenotyping and assessing treatment efficacy in these patients. This review outlines established methods, such as measuring respiratory pressures, and explores novel techniques, including respiratory muscle neurophysiology assessments using electromyography and imaging with ultrasound.Additionally, we review various treatment strategies designed to support and alleviate the burden on overworked respiratory muscles or to enhance their capacity through training interventions. These strategies range from invasive and noninvasive mechanical ventilation approaches to specialised respiratory muscle training programmes. By summarising both established techniques and recent methodological advancements, this review aims to provide a comprehensive overview of the tools available in clinical practice for evaluating and treating respiratory muscle dysfunction. Our goal is to present a clear understanding of the current capabilities and limitations of these diagnostic and therapeutic approaches. Integrating advanced diagnostic methods and innovative treatment strategies should help improve patient management and outcomes. This comprehensive review serves as a resource for clinicians, equipping them with the necessary knowledge to effectively diagnose and treat respiratory muscle dysfunction in both acute and chronic respiratory failure scenarios.

During mechanical ventilation, post-insufflation diaphragm contractions (PIDCs) are non-physiologic and could be injurious. PIDCs could be frequent during reverse-triggering, where diaphragm contractions follow the ventilator rhythm. Whether PIDCs happens with different modes of assisted ventilation is unknown. In mechanically ventilated patients with hypoxemic respiratory failure, we aimed to examine whether PIDCs are associated with ventilator settings, patients' characteristics or both.

One-hour recordings of diaphragm electromyography (EAdi), airway pressure and flow were collected once per day for up to five days from intubation until full recovery of diaphragm activity or death. Each breath was classified as mandatory (without-reverse-triggering), reverse-triggering, or patient triggered. Reverse triggering was further subclassified according to EAdi timing relative to ventilator cycle or reverse triggering leading to breath-stacking. EAdi timing (onset, offset), peak and neural inspiratory time (Tineuro) were measured breath-by-breath and compared to the ventilator expiratory time. A multivariable logistic regression model was used to investigate factors independently associated with PIDCs, including EAdi timing, amplitude, Tineuro, ventilator settings and APACHE II.

Forty-seven patients (median[25%-75%IQR] age: 63[52-77] years, BMI: 24.9[22.9-33.7] kg/m2, 49% male, APACHE II: 21[19-28]) contributed 2 ± 1 recordings each, totaling 183,962 breaths. PIDCs occurred in 74% of reverse-triggering, 27% of pressure support breaths, 21% of assist-control breaths, 5% of Neurally Adjusted Ventilatory Assist (NAVA) breaths. PIDCs were associated with higher EAdi peak (odds ratio [OR][95%CI] 1.01[1.01;1.01], longer Tineuro (OR 37.59[34.50;40.98]), shorter ventilator inspiratory time (OR 0.27[0.24;0.30]), high peak inspiratory flow (OR 0.22[0.20;0.26]), and small tidal volumes (OR 0.31[0.25;0.37]) (all P ≤ 0.008). NAVA was associated with absence of PIDCs (OR 0.03[0.02;0.03]; P < 0.001). Reverse triggering was characterized by lower EAdi peak than breaths triggered under pressure support and associated with small tidal volume and shorter set inspiratory time than breaths triggered under assist-control (all P < 0.05). Reverse triggering leading to breath stacking was characterized by higher peak EAdi and longer Tineuro and associated with small tidal volumes compared to all other reverse-triggering phenotypes (all P < 0.05).

In critically ill mechanically ventilated patients, PIDCs and reverse triggering phenotypes were associated with potentially modifiable factors, including ventilator settings. Proportional modes like NAVA represent a solution abolishing PIDCs.

Objectives: To investigate the impact of patient characteristics and treatment factors on excessive respiratory drive, effort, and lung-distending pressure during transitioning from controlled to spontaneous assisted ventilation in patients with acute respiratory distress syndrome (ARDS). Methods: Multicenter cohort observational study of patients with ARDS at four academic intensive care units. Respiratory drive (P0.1), diaphragm electrical activity (EAdi), inspiratory effort derived from EAdi (∆PmusEAdi) and from occlusion of airway pressure (∆Pocc) (PmusΔPocc), and dynamic transpulmonary driving pressure (ΔPL,dyn) were measured at the first transition to assisted spontaneous breathing. Results: A total of 4171 breaths were analyzed in 48 patients. P0.1 was >3.5 cmH2O in 10%, EAdiPEAK > 15 µV in 29%, ∆PmusEAdi > 15 cmH2O in 28%, and ΔPL,dyn > 15 cmH2O in 60% of the studied breaths. COVID-19 etiology of ARDS was the strongest independent risk factor for a higher proportion of breaths with excessive respiratory drive (RR 3.00 [2.43-3.71], p < 0.0001), inspiratory effort (RR 1.84 [1.58-2.15], p < 0.0001), and transpulmonary driving pressure (RR 1.48 [1.36-1.62], p < 0.0001). The P/F ratio at ICU admission, days of deep sedation, and dose of steroids were additional risk factors for vigorous inspiratory effort. Age and dose of steroids were risk factors for high transpulmonary driving pressure. Days of deep sedation (aHR 1.15 [1.07-1.24], p = 0.0002) and COVID-19 diagnosis (aHR 6.96 [1-48.5], p = 0.05) of ARDS were independently associated with composite outcome of transitioning from light to deep sedation (RASS from 0/-3 to -4/-5) or return to controlled ventilation within 48 h of spontaneous assisted breathing. Conclusions: This study identified that specific patient characteristics, including age, COVID-19-related ARDS, and P/F ratio, along with treatment factors such as the duration of deep sedation and the dosage of steroids, are independently associated with an increased likelihood of assisted breaths reaching potentially harmful thresholds of drive, effort, and lung-distending pressure during the initial transition to spontaneous assisted breathing. It is noteworthy that patients who were subjected to prolonged deep sedation under controlled mechanical ventilation, as well as those with COVID-19, were more susceptible to failing the transition from controlled to assisted breathing.

Electromagnetic stimulation of the phrenic nerve induces diaphragm contractions, but no coils for clinical use have been available. We recently demonstrated the feasibility of ventilation using bilateral transcutaneous noninvasive electromagnetic phrenic nerve stimulation (NEPNS) before surgery in lung-healthy patients with healthy weight in a dose-dependent manner.

Is NEPNS feasible in critically ill patients in an ICU setting?

This feasibility nonrandomized controlled study aimed to enroll patients within 36 h of intubation who were expected to remain ventilated for ≥ 72 h. The intervention group received 15-min bilateral transcutaneous NEPNS bid, whereas the control group received standard care. If sufficient, NEPNS was used without pressure support to ventilate the patient; pressure support was added if necessary to ventilate the patient adequately. The primary outcome was feasibility, measured as time to find the optimal stimulation position. Further end points were sessions performed according to the protocol or allowing a next-day catch-up session and tidal volume achieved with stimulation reaching only 3 to 6 mL/kg ideal body weight (IBW). A secondary end point was expiratory diaphragm thickness measured with ultrasound from days 1 to 10 (or extubation).

The revised European Union regulation mandated reapproval of medical devices, prematurely halting the study. Eleven patients (five in the intervention group, six in the control group) were enrolled. The median time to find an adequate stimulation position was 23 s (interquartile range, 12-62 s). The intervention bid was executed in 87% of patients, and 92% of patients including a next-day catch-up session. Ventilation with 3 to 6 mL/kg IBW was achieved in 732 of 1,701 stimulations (43.0%) with stimulation only and in 2,511 of 4,036 stimulations (62.2%) with additional pressure support. A decrease in diaphragm thickness was prevented by bilateral NEPNS (P = .034) until day 10.

Bilateral transcutaneous NEPNS was feasible in the ICU setting with the potential benefit of preventing diaphragm atrophy during mechanical ventilation. NEPNS ventilation effectiveness needs further assessment.

ClinicalTrials.gov; No.: NCT05238753; URL: www.

gov.

This review explores the complex interactions between sedation and invasive ventilation and examines the potential of volatile anesthetics for lung- and diaphragm-protective sedation. In the early stages of invasive ventilation, many critically ill patients experience insufficient respiratory drive and effort, leading to compromised diaphragm function. Compared with common intravenous agents, inhaled sedation with volatile anesthetics better preserves respiratory drive, potentially helping to maintain diaphragm function during prolonged periods of invasive ventilation. In turn, higher concentrations of volatile anesthetics reduce the size of spontaneously generated tidal volumes, potentially reducing lung stress and strain and with that the risk of self-inflicted lung injury. Taken together, inhaled sedation may allow titration of respiratory drive to maintain inspiratory efforts within lung- and diaphragm-protective ranges. Particularly in patients who are expected to require prolonged invasive ventilation, in whom the restoration of adequate but safe inspiratory effort is crucial for successful weaning, inhaled sedation represents an attractive option for lung- and diaphragm-protective sedation. A technical limitation is ventilatory dead space introduced by volatile anesthetic reflectors, although this impact is minimal and comparable to ventilation with heat and moisture exchangers. Further studies are imperative for a comprehensive understanding of the specific effects of inhaled sedation on respiratory drive and effort and, ultimately, how this translates into patient-centered outcomes in critically ill patients.

The optimal timing of intubation in acute hypoxaemic respiratory failure is uncertain and became a point of controversy during the COVID-19 pandemic. Invasive mechanical ventilation is a potentially life-saving intervention but carries substantial risks, including injury to the lungs and diaphragm, pneumonia, intensive care unit-acquired muscle weakness, and haemodynamic impairment. In deciding when to intubate, clinicians must balance premature exposure to the risks of ventilation with the potential harms of unassisted breathing, including disease progression and worsening multiorgan failure. Currently, the optimal timing of intubation is unclear. In this Personal View, we examine a range of parameters that could serve as triggers to initiate invasive mechanical ventilation. The utility of a parameter (eg, the ratio of arterial oxygen tension to fraction of inspired oxygen) to predict the likelihood of a patient undergoing intubation does not necessarily mean that basing the timing of intubation on that parameter will improve therapeutic outcomes. We examine options for clinical investigation to make progress on establishing the optimal timing of intubation.

Even though much progress has been made to improve clinical outcomes, acute respiratory distress syndrome (ARDS) remains a significant cause of acute respiratory failure. Protective mechanical ventilation is the backbone of supportive care for these patients; however, there are still many unresolved issues in its setting. The primary goal of mechanical ventilation is to improve oxygenation and ventilation. The use of positive pressure, especially positive end-expiratory pressure (PEEP), is mandatory in this approach. However, PEEP is a double-edged sword. How to safely set positive end-inspiratory pressure has long been elusive to clinicians. We hereby propose a pressure-volume curve measurement-based method to assess whether injured lungs are recruitable in order to set an appropriate PEEP. For the most severe form of ARDS, extracorporeal membrane oxygenation (ECMO) is considered as the salvage therapy. However, the high level of medical resources required and associated complications make its use in patients with severe ARDS controversial. Our proposed protocol also attempts to propose how to improve patient outcomes by balancing the possible overuse of resources with minimizing patient harm due to dangerous ventilator settings. A recruitment-potential-oriented evaluation-based protocol can effectively stabilize hypoxemic conditions quickly and screen out truly serious patients.

Patient self-inflicted lung injury (P-SILI) is a major challenge for the ICU physician: although spontaneous breathing is associated with physiological benefits, in patients with acute respiratory distress syndrome (ARDS), the risk of uncontrolled inspiratory effort leading to additional injury needs to be assessed to avoid delayed intubation and increased mortality. In the present review, we analyze the available clinical and experimental evidence supporting the existence of lung injury caused by uncontrolled high inspiratory effort, we discuss the pathophysiological mechanisms by which increased effort causes P-SILI, and, finally, we consider the measurements and interpretation of bedside physiological measures of increased drive that should alert the clinician. The data presented in this review could help to recognize injurious respiratory patterns that may trigger P-SILI and to prevent it.

Respiratory effort should be closely monitored in mechanically ventilated ICU patients to avoid both overassistance and underassistance. Surface electromyography of the diaphragm (sEMGdi) offers a continuous and non-invasive modality to assess respiratory effort based on neuromuscular coupling (NMCdi). The sEMGdi derived electrical activity of the diaphragm (sEAdi) is prone to distortion by crosstalk from other muscles including the heart, hindering its widespread use in clinical practice. We developed an advanced analysis as well as quality criteria for sEAdi waveforms and investigated the effects of clinically relevant levels of PEEP on non-invasive NMCdi.

NMCdi was derived by dividing end-expiratory occlusion pressure (Pocc) by sEAdi, based on three consecutive Pocc manoeuvres at four incremental (+ 2 cmH2O/step) PEEP levels in stable ICU patients on pressure support ventilation. Pocc and sEAdi quality was assessed by applying a novel, automated advanced signal analysis, based on tolerant and strict cut-off criteria, and excluding inadequate waveforms. The coefficient of variations (CoV) of NMCdi after basic manual and automated advanced quality assessment were evaluated, as well as the effect of an incremental PEEP trial on NMCdi.

593 manoeuvres were obtained from 42 PEEP trials in 17 ICU patients. Waveform exclusion was primarily based on low sEAdi signal-to-noise ratio (Ntolerant = 155, 37%, Nstrict = 241, 51% waveforms excluded), irregular or abrupt cessation of Pocc (Ntolerant = 145, 35%, Nstrict = 145, 31%), and high sEAdi area under the baseline (Ntolerant = 94, 23%, Nstrict = 79, 17%). Strict automated assessment allowed to reduce CoV of NMCdi to 15% from 37% for basic quality assessment. As PEEP was increased, NMCdi decreased significantly by 4.9 percentage point per cmH2O.

Advanced signal analysis of both Pocc and sEAdi greatly facilitates automated and well-defined identification of high-quality waveforms. In the critically ill, this approach allowed to demonstrate a dynamic NMCdi (Pocc/sEAdi) decrease upon PEEP increments, emphasising that sEAdi-based assessment of respiratory effort should be related to PEEP dependent diaphragm function. This novel, non-invasive methodology forms an important methodological foundation for more robust, continuous, and comprehensive assessment of respiratory effort at the bedside.

Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery.

We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates.

The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups.

The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury.

Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation?

Sixteen patients with Pao2/Fio2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography.

ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H2O; interquartile range (IQR), 15-24 cm H2O vs median, 15 cm H2O; IQR, 13-23 cm H2O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance.

The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance.

ClinicalTrials.gov; No.: NCT04241874; URL: www.

gov.

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.

The successful implementation of assisted ventilation depends on matching the patient's effort with the ventilator support. Pressure muscle index (PMI), an airway pressure based measurement, has been used as noninvasive monitoring to assess the patient's inspiratory effort. The authors aimed to evaluate the feasibility of pressure support adjustment according to the PMI target and the diagnostic performance of PMI to predict the contribution of the patient's effort during ventilator support.

In this prospective physiological study, 22 adult patients undergoing pressure support ventilation were enrolled. After an end-inspiratory airway occlusion, airway pressure reached a plateau, and the magnitude of change in plateau from peak airway pressure was defined as PMI. Pressure support was adjusted to obtain the PMI which was closest to -1, 0, +1, +2, and + 3 cm H2O. Each pressure support level was maintained for 20 min. Esophageal pressure was monitored. Pressure-time products of respiratory muscle and ventilator insufflation were measured, and the fraction of pressure generated by the patient was calculated to represent the contribution of the patient's inspiratory effort.

A total of 105 datasets were collected at different PMI-targeted pressure support levels. The differences in PMI between the target and the obtained value were all within ±1 cm H2O. As targeted PMI increased, pressure support settings decreased significantly from a median (interquartile range) of 11 (10-12) to 5 (4-6) cm H2O (p < 0.001), which resulted in a significant increase in pressure-time products of respiratory muscle [from 2.9 (2.1-5.0) to 6.8 (5.3-8.1) cm H2O•s] and the fraction of pressure generated by the patient [from 25% (19-31%) to 72% (62-87%)] (p < 0.001). The area under receiver operating characteristic curves for PMI to predict 30 and 70% contribution of patient's effort were 0.93 and 0.95, respectively. High sensitivity (all 1.00), specificity (0.86 and 0.78), and negative predictive value (all 1.00), but low positive predictive value (0.61 and 0.43) were obtained to predict either high or low contribution of patient's effort.

Our results preliminarily suggested the feasibility of pressure support adjustment according to the PMI target from the ventilator screen. PMI could reliably predict the high and low contribution of a patient's effort during assisted ventilation.Clinical trial registration: ClinicalTrials.gov, identifier NCT05970393.

Respiratory drive is defined as the intensity of respiratory centers output during the breath and is primarily affected by cortical and chemical feedback mechanisms. During the involuntary act of breathing, chemical feedback, primarily mediated through CO2, is the main determinant of respiratory drive. Respiratory drive travels through neural pathways to respiratory muscles, which execute the breathing process and generate inspiratory flow (inspiratory flow-generation pathway). In a healthy state, inspiratory flow-generation pathway is intact, and thus respiratory drive is satisfied by the rate of volume increase, expressed by mean inspiratory flow, which in turn determines tidal volume. In this review, we will explain the pathophysiology of altered respiratory drive by analyzing the respiratory centers response to arterial partial pressure of CO2 (PaCO2) changes. Both high and low respiratory drive have been associated with several adverse effects in critically ill patients. Hence, it is crucial to understand what alters the respiratory drive. Changes in respiratory drive can be explained by simultaneously considering the (1) ventilatory demands, as dictated by respiratory centers activity to CO2 (brain curve); (2) actual ventilatory response to CO2 (ventilation curve); and (3) metabolic hyperbola. During critical illness, multiple mechanisms affect the brain and ventilation curves, as well as metabolic hyperbola, leading to considerable alterations in respiratory drive. In critically ill patients the inspiratory flow-generation pathway is invariably compromised at various levels. Consequently, mean inspiratory flow and tidal volume do not correspond to respiratory drive, and at a given PaCO2, the actual ventilation is less than ventilatory demands, creating a dissociation between brain and ventilation curves. Since the metabolic hyperbola is one of the two variables that determine PaCO2 (the other being the ventilation curve), its upward or downward movements increase or decrease respiratory drive, respectively. Mechanical ventilation indirectly influences respiratory drive by modifying PaCO2 levels through alterations in various parameters of the ventilation curve and metabolic hyperbola. Understanding the diverse factors that modulate respiratory drive at the bedside could enhance clinical assessment and the management of both the patient and the ventilator.