Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

Correlation between Serum Biomarkers and Lung Ultrasound in COVID-19: An Observational Study.

Serum biomarkers and lung ultrasound are important measures for prognostication and treatment allocation in patients with COVID-19. Currently, there is a paucity of studies investigating relationships between serum biomarkers and ultrasonographic biomarkers derived from lung ultrasound. This study aims to assess correlations between serum biomarkers and lung ultrasound findings. This study is a secondary analysis of four prospective observational studies in adult patients with COVID-19. Serum biomarkers included markers of epithelial injury, endothelial dysfunction and immune activation. The primary outcome was the correlation between biomarker concentrations and lung ultrasound score assessed with Pearson's (r) or Spearman's (rs) correlations. Forty-four patients (67 [41-88] years old, 25% female, 52% ICU patients) were included. GAS6 (rs = 0.39), CRP (rs = 0.42) and SP-D (rs = 0.36) were correlated with lung ultrasound scores. ANG-1 (rs = -0.39) was inversely correlated with lung ultrasound scores. No correlations were found between lung ultrasound score and several other serum biomarkers. In patients with COVID-19, several serum biomarkers of epithelial injury, endothelial dysfunction and immune activation correlated with lung ultrasound findings. The lack of correlations with certain biomarkers could offer opportunities for precise prognostication and targeted therapeutic interventions by integrating these unlinked biomarkers.

Setting positive end-expiratory pressure: lung and diaphragm ultrasound.

PURPOSE OF REVIEW: The purpose of this review is to summarize the role of lung ultrasound and diaphragm ultrasound in guiding ventilator settings with an emphasis on positive end-expiratory pressure (PEEP). Recent advances for using ultrasound to assess the effects of PEEP on the lungs and diaphragm are discussed. RECENT FINDINGS: Lung ultrasound can accurately diagnose the cause of acute respiratory failure, including acute respiratory distress syndrome and can identify focal and nonfocal lung morphology in these patients. This is essential in determining optimal ventilator strategy and PEEP level. Assessment of the effect of PEEP on lung recruitment using lung ultrasound is promising, especially in the perioperative setting. Diaphragm ultrasound can monitor the effects of PEEP on the diaphragm, but this needs further validation. In patients with an acute exacerbation of chronic obstructive pulmonary disease, diaphragm ultrasound can be used to predict noninvasive ventilation failure. Lung and diaphragm ultrasound can be used to predict weaning outcome and accurately diagnose the cause of weaning failure. SUMMARY: Lung and diaphragm ultrasound are useful for diagnosing the cause of respiratory failure and subsequently setting the ventilator including PEEP. Effects of PEEP on lung and diaphragm can be monitored using ultrasound.

Use of Lung Ultrasound in the New Definitions of Acute Respiratory Distress Syndrome Increases the Occurrence Rate of Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess the effect of incorporating bilateral abnormalities as detected by lung ultrasound (LUS) in the Kigali modification and the New Global definition of acute respiratory distress syndrome (ARDS) on the occurrence rate of ARDS. DESIGN: Post hoc analysis of a previously published prospective cohort study. SETTING: An academic mixed medical-surgical ICU. PATIENTS: The original study included critically ill adults with any opacity on chest radiography in whom subsequent LUS was performed. Patients with ARDS according to the Berlin definition, COVID-19 patients and patients with major thorax trauma were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LUS was performed within 24 hours of chest radiography and the presence of unilateral and bilateral abnormalities on LUS and chest radiograph (opacities) was scored. Subsequently, the Kigali modification and the New Global definition of ARDS were applied by two independent researchers on the patients with newly found bilateral opacities. Of 120 patients, 116 were included in this post hoc analysis. Thirty-three patients had bilateral opacities on LUS and unilateral opacities on chest radiograph. Fourteen of these patients had ARDS according to the Kigali modification and 12 had ARDS according to the New Global definition. The detected LUS patterns were significantly different between patients with and without ARDS ( p = 0.004). An A-profile with a positive PosteroLateral Alveolar and/or Pleural Syndrome was most prevalent in patients without ARDS, whereas heterogeneous and mixed A, B, and C patterns were most prevalent in patients with ARDS. CONCLUSION: The addition of bilateral abnormalities as detected by LUS to the Kigali modification and the New Global definition increases the occurrence rate of the ARDS. The nomenclature for LUS needs to be better defined as LUS patterns differ between patients with and without ARDS. Incorporating well-defined LUS criteria can increase specificity and sensitivity of new ARDS definitions.

Development, feasibility testing, and preliminary evaluation of the Communication with an Artificial airway Tool (CAT): Results of the Crit-CAT pilot study.

BACKGROUND: A purpose-built outcome measure for assessing communication effectiveness in patients with an artificial airway is needed. OBJECTIVES: The objective of this study was to develop the Communication with an Artificial airway Tool (CAT) and to test the feasibility and to preliminary evaluate the clinical metrics of the tool. METHODS: Eligible patients with an artificial airway in the Intensive Care Unit were enrolled in the pilot study (Crit-CAT). The CAT was administered at least twice before and after the communication intervention. Item correlation analysis was performed. Participant and family member acceptability ratings and feedback were solicited. A qualitative thematic analysis was undertaken. RESULTS: Fifteen patients with a mean age of 53 years (standard deviation [SD]: 19.26) were included. The clinician-reported scale was administered on 50 attempts (100%) with a mean completion time of 4.5 (SD: 0.77) minutes. The patient-reported scale was administered on 46 out of 49 attempts (94%) and took a mean of 1.5 (SD: 0.39) minutes to complete. The CAT was feasible for use in the Intensive Care Unit, with patients with either an endotracheal or tracheostomy tube, whilst receiving invasive mechanical ventilation or not, and while using either verbal or nonverbal modes of communication. Preliminary establishment of responsiveness, validity, and reliability was made. The tool was acceptable to participants and their family members. CONCLUSION: The clinician-reported and patient-reported components of the study were feasible for use. The CAT has the potential to enable quantifiable comparison of communication interventions for patients with an artificial airway. Future research is required to determine external validity and reliability.

The diagnostic accuracy of lung ultrasound to determine PiCCO-derived extravascular lung water in invasively ventilated patients with COVID-19 ARDS.

BACKGROUND: Lung ultrasound (LUS) can detect pulmonary edema and it is under consideration to be added to updated acute respiratory distress syndrome (ARDS) criteria. However, it remains uncertain whether different LUS scores can be used to quantify pulmonary edema in patient with ARDS. OBJECTIVES: This study examined the diagnostic accuracy of four LUS scores with the extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution in patients with moderate-to-severe COVID-19 ARDS. METHODS: In this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were enrolled within 48 hours after intubation and underwent LUS and EVLWi measurement on the first and fourth day after enrolment. EVLWi and ∆EVLWi were used as reference standards. Two 12-region scores (global LUS and LUS-ARDS), an 8-region anterior-lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi > 15 mL/kg) was calculated. RESULTS: 26 out of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 out of 29 patients (83%) at time point 2. The global LUS (r = 0.54), LUS-ARDS (r = 0.58) and anterior-lateral score (r = 0.54) correlated significantly with EVLWi, while the B-line score did not (r = 0.32). ∆global LUS (r = 0.49) and ∆anterior-lateral LUS (r = 0.52) correlated significantly with ∆EVLWi. AUROCC for EVLWi > 15 ml/kg was 0.73 for the global LUS, 0.79 for the anterior-lateral and 0.85 for the LUS-ARDS score. CONCLUSIONS: Overall, LUS demonstrated an acceptable diagnostic accuracy for detection of pulmonary edema in moderate-to-severe COVID-19 ARDS when compared with PICCO. For identifying patients at risk of severe pulmonary edema, an extended score considering pleural morphology may be of added value. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04794088, registered on 11 March 2021. European Clinical Trials Database number 2020-005447-23.

Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (∆EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes. RESULTS: 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in ∆EVLWi between the groups (0.19 ml/kg, 95% CI - 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (- 1.17 ml/kg, 95% CI - 1.87 to - 0.44). CONCLUSIONS: IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials. Trial registration NCT04794088 , registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial.

BACKGROUND: Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28. METHODS: The "effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients" (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician's discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1-7 after randomisation and on days 1-7 after start of LUS examination; mean serum lactate on days 1-7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28. DISCUSSION: The CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable. TRIAL REGISTRATION: ClinicalTrials.gov NCT05188092. Registered since January 12, 2022.

Oxygen Consumption with High-Flow Nasal Oxygen versus Mechanical Ventilation- An International Multicenter Observational Study in COVID-19 Patients (PROXY-COVID).

The COVID-19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4-18.4] versus 2.9 [1.8-4.1] L/minute; mean difference = 11.3 [95% CI 11.0-11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Atrial inflammation and microvascular thrombogenicity are increased in deceased COVID-19 patients.

BACKGROUND: Histopathological studies have shown inflammation, cardiomyocyte injury, and microvascular thrombosis in the ventricular myocardium of patients with coronavirus disease 2019 (COVID-19). However, although atrial dysfunction is common in COVID-19, little is known about histopathological changes in the atria of the heart. We therefore analyzed inflammation, cardiomyocyte injury, and microvascular thrombogenicity in the atria of deceased patients with COVID-19. METHODS: Atrial tissue was obtained from autopsied COVID-19 (n=16) patients and control patients (n=10) and analyzed using immunohistochemistry. The infiltration of CD45+ leukocytes, CD3+ T lymphocytes, CD68+ macrophages, MPO+ neutrophils, and Tryptase+ mast cells were quantified as well as cardiomyocyte damage and microvascular thrombosis. In addition, Tissue Factor (TF) and Factor XII (FXII) were quantified as markers of microvascular thrombogenicity. RESULTS: The numbers of lymphocytes, macrophages, and neutrophils were significantly increased in the atrial myocardium and epicardial atrial adipose tissue of COVID-19 patients compared with the control group. This was accompanied by dispersed cardiomyocyte injury, the occasional presence of microvascular thrombosis, and an increased presence of TF and FXII in the microvascular endothelium. CONCLUSIONS: Severe COVID-19 induces inflammation, cardiomyocyte injury, and microvascular thrombosis in the atria of the heart.

Concise Versus Extended Lung Ultrasound Score to Monitor Critically Ill Patients With COVID-19.

BACKGROUND: Lung ultrasound (LUS) can be used to monitor critically ill patients with COVID-19, but the optimal number of examined lung zones is disputed. METHODS: This was a prospective observational study. The objective was to investigate whether concise (6 zones) and extended (12 zones) LUS scoring protocols are clinically equivalent in critically ill ICU subjects with COVID-19. The primary outcome of this study was (statistical) agreement between concise and extended LUS score index evaluated in both supine and prone position. Agreement was determined using correlation coefficients and Bland-Altman plots to detect systematic differences between protocols. Secondary outcomes were difference between LUS score index in supine and prone position using similar methods. RESULTS: We included 130 LUS examinations in 40 subjects (mean age 69.0 ± 8.5y, 75% male). Agreement between concise and extended LUS score index had no clinically relevant constant or proportional bias and limits of agreement were below the smallest detectable change. Across position changes, supine LUS score index was 8% higher than prone LUS score index and had limits above the smallest detectable change, indicating true LUS score index differences between protocols may occur due to the position change itself. Lastly, inter-rater and intra-rater agreement were very good. CONCLUSIONS: Concise LUS was equally informative as extended LUS for monitoring critically ill subjects with COVID-19 in supine or prone position. Clinicians can monitor patients undergoing position changes but must be wary that LUS score index alterations may result from the position change itself rather than disease progression or clinical improvement.

Defining effective communication for critically ill patients with an artificial airway: An international multi-professional consensus.

OBJECTIVES: To define effective communication and identify its key elements specific to critically ill patients with an artificial airway. DESIGN: A modified Consensus Development Panel methodology. SETTING: International video-conferences. MAIN OUTCOME MEASURES: Definition of effective communication and it's key elements. RESULTS: Eight experts across four international regions and three professions agreed to form the Consensus Development Panel together with a Chair and one person with lived experience who reviewed the outputs prior to finalisation. "Communication for critically ill adult patients with an artificial airway (endotracheal or tracheostomy tube) is defined as the degree in which a patient can initiate, impart, receive, and understand information, and can range from an ineffective to effective exchange of basic to complex information between the patient and the communication partner(s). Effective communication encompasses seven key elements including: comprehension, quantity, rate, effort, duration, independence, and satisfaction. In critically ill adults, communication is impacted by factors including medical, physical and cognitive status, delirium, fatigue, emotional status, the communication partner and the nature of the ICU environment (e.g., staff wearing personal protective equipment, noisy equipment, bright lights)." The panel agreed that communication occurs on a continuum from ineffective to effective for basic and complex communication. CONCLUSION: We developed a definition and list of key elements which constitute effective communication for critically ill patients with an artificial airway. These can be used as the basis of standard terminology to support future research on the development of communication-related outcome measurement tools in this population. IMPLICATIONS FOR CLINICAL PRACTICE: This study provides international multi-professional consensus terminology and a definition of effective communication which can be used in clinical practice. This standard definition and key elements of effective communication can be included in our clinical impressions of patient communication, and be used in discussion with the patient themselves, their families and the multi-professional team, to guide care, goal development and intervention.

The Impact of Thoracic Ultrasound on Clinical Management of Critically Ill Patients (UltraMan): An International Prospective Observational Study.

OBJECTIVES: To investigate the impact of thoracic ultrasound (TUS) examinations on clinical management in adult ICU patients. DESIGN: A prospective international observational study. SETTING: Four centers in The Netherlands and Italy. PATIENTS: Adult ICU patients (> 18 yr) that received a clinically indicated lung ultrasound examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinicians performing TUS completed a pre- and post-examination case report form. Patient characteristics, TUS, and resulting clinical effects were recorded. First, change of management, defined as a TUS-induced change in clinical impression leading to a change in treatment plan, was reported. Second, execution of intended management changes within 8 hours was verified. Third, change in fluid balance after 8 hours was calculated. A total of 725 TUS performed by 111 operators across 534 patients (mean age 63 ± 15.0, 70% male) were included. Almost half of TUS caused a change in clinical impression, which resulted in change of management in 39% of cases. The remainder of TUS confirmed the clinical impression, while a minority (4%) did not contribute. Eighty-nine percent of management changes indicated by TUS were executed within 8 hours. TUS examinations that led to a change in fluid management also led to distinct and appropriate changes in patient's fluid balance. CONCLUSIONS: In this international observational study in adult ICU patients, use of TUS had a major impact on clinical management. These results provide grounds for future randomized controlled trials to determine if TUS-induced changes in decision-making also lead to improved health outcomes.

Performance of Noninvasive Airway Occlusion Maneuvers to Assess Lung Stress and Diaphragm Effort in Mechanically Ventilated Critically Ill Patients.

BACKGROUND: Monitoring and controlling lung stress and diaphragm effort has been hypothesized to limit lung injury and diaphragm injury. The occluded inspiratory airway pressure (Pocc) and the airway occlusion pressure at 100 ms (P0.1) have been used as noninvasive methods to assess lung stress and respiratory muscle effort, but comparative performance of these measures and their correlation to diaphragm effort is unknown. The authors hypothesized that Pocc and P0.1 correlate with diaphragm effort and lung stress and would have strong discriminative performance in identifying extremes of lung stress and diaphragm effort. METHODS: Change in transdiaphragmatic pressure and transpulmonary pressure was obtained with double-balloon nasogastric catheters in critically ill patients (n = 38). Pocc and P0.1 were measured every 1 to 3 h. Correlations between Pocc and P0.1 with change in transdiaphragmatic pressure and transpulmonary pressure were computed from patients from the first cohort. Accuracy of Pocc and P0.1 to identify patients with extremes of lung stress (change in transpulmonary pressure > 20 cm H2O) and diaphragm effort (change in transdiaphragmatic pressure < 3 cm H2O and >12 cm H2O) in the preceding hour was assessed with area under receiver operating characteristic curves. Cutoffs were validated in patients from the second cohort (n = 13). RESULTS: Pocc and P0.1 correlate with change in transpulmonary pressure (R2 = 0.62 and 0.51, respectively) and change in transdiaphragmatic pressure (R2 = 0.53 and 0.22, respectively). Area under receiver operating characteristic curves to detect high lung stress is 0.90 (0.86 to 0.94) for Pocc and 0.88 (0.84 to 0.92) for P0.1. Area under receiver operating characteristic curves to detect low diaphragm effort is 0.97 (0.87 to 1.00) for Pocc and 0.93 (0.81 to 0.99) for P0.1. Area under receiver operating characteristic curves to detect high diaphragm effort is 0.86 (0.81 to 0.91) for Pocc and 0.73 (0.66 to 0.79) for P0.1. Performance was similar in the external dataset. CONCLUSIONS: Pocc and P0.1 correlate with lung stress and diaphragm effort in the preceding hour. Diagnostic performance of Pocc and P0.1 to detect extremes in these parameters is reasonable to excellent. Pocc is more accurate in detecting high diaphragm effort.