P0.1 is associated with duration of ventilation and mortality in patients with COVID-19 ARDS

P0.1 is associated with duration of ventilation and mortality in patients with COVID-19 ARDS | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report P0.1 is associated with duration of ventilation and mortality in patients with COVID-19 ARDS Else ter Haar, Maurits Renes, Hendrik Zijlstra, Salvador Recinos, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4919933/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Rationale In acute respiratory distress syndrome (ARDS), optimal timing of transition from controlled to assisted ventilation and the ventilatory parameters which define this are unknown. Premature transition may impair recovery of an injured lung through patient self-inflicted lung injury. Objectives To investigate whether the airway occlusion pressure (P0.1) directly after transition to assisted ventilation is associated with the duration of ventilation and mortality. Methods Invasively ventilated patients with COVID-19 ARDS were retrospectively identified. P0.1 was recorded for 24 hours after transition to assisted ventilation. The primary endpoint was the number of ventilator-free days while being alive in the 28 days following the first transition from controlled to assisted ventilation (VFDav-28). Secondary outcome was ICU mortality. Multivariable logistic regression was used to identify variables independently associated with outcome parameters. ROC curves were generated to assess predictive values. Measurements and Main Results 78 patients with COVID-ARDS were included. Higher (more negative) P0.1 was associated with less VFDav-28 and higher ICU mortality. The predictive value of P0.1 for both VFDav-28 and mortality was good (AUC 0.75). Conclusions This study shows that P0.1 directy after transition to assited ventilation is associated with prolonged duration of invasive ventilation and ICU mortality. COVID-19 acute respiratory distress syndrome pressure support ventilation patient self-inflicted lung injury airway occlusion pressure (P0.1) Figures Figure 1 Introduction Optimal strategies for assisted ventilation in Acute Respiratory Distress Syndrome (ARDS) remain unknown. Notably, the best timing of the transition to pressure support ventilation (PSV) has not been elucidated. Premature transition may inflict injury due to excessive stress and strain on an injured lung caused by excessive inspiratory effort and high respiratory drive. This could lead to patient self-inflicted lung injury (PSILI), which impairs patient outcome ( 1 ). One important determinant of the development of PSILI in animal models is respiratory effort ( 2 ). The airway occlusion pressure at 100ms from the initiation of inspiration (P0.1) is a readily available ventilatory parameter reflecting respiratory effort. In this study, we hypothesized that P0.1 directly after the transition to PSV is associated with clinical outcomes, such as mortality and duration of ventilation. Methods We performed a single-center retrospective study within the University Medical Center Groningen in The Netherlands. The institutional review board waived the requirement for written informed consent (METc2023/10410707). Invasively ventilated adult patients admitted to our ICU with PCR-confirmed COVID-ARDS who experienced a transition from controlled to PSV between March 2020 and April 2022 were retrospectively identified. In our institution, the timing of transition from controlled to PSV is not protocolized and, therefore, depends on the attending clinician. Patient characteristics and ventilation parameters were extracted from the patient record (EPIC, Epic Systems Corporation, Verona, WI, USA). Our ICU is equipped with a SERVO-U (Maquet) ventilator, which estimates the P0.1 and exports these values to the electronic patient record every minute. We calculated the mean P0.1 value over the first 24 hours after transition from controlled to PSV or until failure (whichever came first). The primary outcome was ventilator-free days and alive in the 28 days following the first transition from controlled to PSV (VFDav-28). This modified endpoint is similar to VFD28 used in many ARDS studies ( 3 , 4 ). VFDav-28 was dichotomized with a cut-off at 14 days, in line with outcomes in critically ill COVID-19 patients in previous studies ( 5 , 6 ). The secondary outcome was ICU mortality. Mann-Whitney U and Fisher’s Exact Test were used to test which variables were associated with VFDav-28 < 14 days and ICU mortality. Two multivariable logistic regression models for both outcomes seperately were created, including the covariates P0.1 and predefined potential confounders (age, sex, and ARDS severity using P/F ratio). ROC curves were generated to assess the predictive value of these models. All analyses were performed using IBM SPSS Statistics version 28.0.1.0 (IBM, New York, NY, USA). Results We included 78 patients. Baseline patient characteristics and ventilatory parameters are depicted in Table 1 . Univariate analyses showed that patients with less ventilator-free days (VFDav-28 14 days; P0.1 3.4 (IQR 2.1–4.5) vs 1.6 (IQR 1.2–2.5), p < 0.001. Counterintuitively, these patients with less VFDav-28 days and higher P0.1 values, had lower RASSscores on the day of transition (Table 1 .). Age, gender, BMI, ARDS severity, or other ventilatory parameters on the day of transition were not associated with VFDav-28 < 14 days or ICU mortality. Table 1. Baseline characteristics and ventilatory parameters for the total population and stratified for VFDav-28 <14 days versus ≥14 days. Total population (n = 78) VFDav-28 p-value <14 days (n = 29) ≥14 days (n = 49) Age at ICU admission (years) 58 ± 13 58 ± 13 58 ± 14 0.848 Sex (male) 53 (68%) 22 (76%) 31 (63%) 0.252 Body-mass index (kg/m 2 ) 30.1 ± 6.2 29.1 ± 5.4 30.7 ± 6.6 0.258 Severity of ARDS at initiation of invasive mechanical ventilation (P/F ratio) 135 (105 – 173) 133 (97 – 163) 139 (111 – 180) 0.207 ICU mortality 16 (21%) 16 (55%) 0 (0%) <0.001 ICU length of stay (days) 14 (9 – 27) 28 (18 – 43) 12 (8 – 15) <0.001 Duration of invasive mechanical ventilation (days) 12 (7 – 22) 24 (17 – 39) 9 (6 – 12) <0.001 VFDav-28 (days) 20 (1 – 25) 0 (0 – 5) 24 (21 – 26) <0.001 Time from intubation to PSV (days) 5 (3 – 8) 6 (4 – 12) 4 (3 – 7) 0.043 Prone positioning on the first day of ICU admission 29 (37%) 16 (55%) 13 (27%) 0.016 Extracorporeal membrane oxygenation 6 (8%) 3 (10%) 3 (6%) 0.665 Ventilatory parameters at the time of transition to PSV P0.1 during the first 24h of PSV (cmH 2 O) Driving pressure (cmH 2 O) PEEP (cmH 2 O) Respiratory rate (breaths per min) P/F ratio (PSV) Tidal volume (controlled, mL/kg body weight) Tidal volume (PSV, mL/kg body weight) 2.1 (1.3 – 3.5) 11.5 (10 – 12) 12 (10 – 14) 22 (20 – 24) 193 (161 – 222) 4.8 (4.0 – 5.8) 6.7 (5.1 – 7.8) 3.4 (2.1 – 4.5) 12 (10 – 14) 12 (10 – 14) 22 (20 – 24) 174 (155 – 215) 5.1 (4.4 – 5.9) 6.2 (4.9 – 7.4) 1.6 (1.2 – 2.5) 11 (10 – 12) 12 (10 – 14) 24 (20 – 25) 206 (166 – 231) 4.5 (3.8 – 5.6) 6.6 (5.2 – 8.1) <0.001 0.386 0.944 0.284 0.100 0.091 0.235 RASS on the first day of PSV -3 (-4 – -1) -4 (-4 – -3) -2 (-4 – -0.5) <0.001 Failed PSV 36 (46%) 24 (83%) 12 (25%) <0.001 Data are presented as number (%), mean ± standard deviation, or median (interquartile range). Differences between VFDav-28 <14 days and ≥ 14 days were tested by Mann-Whitney U Test for continuous/discrete explanatory variables or Fisher’s Exact Test for dichotomous explanatory variables. Significant values are depicted in bold. ICU = intensive care unit; ARDS = acute respiratory distress syndrome; P/F ratio = the ratio of arterial oxygen partial pressure (PaO 2 in mmHg) to fractional inspired oxygen (FiO 2 expressed as a fraction, not a percentage); VFDav-28 = ventilator-free days and alive 28 days after first attempt of transition to assisted ventilation; PEEP = positive end-expiratory pressure; PSV = pressure support ventilation; P0.1 = negative airway pressure generated during the first 100 msec of an inspiration; RASS = Richmond Agitation-Sedation Scale. The multivariate models revealed that only P0.1 was associated with VFDav-28 < 14 days (OR; 1.43, 95%CI: 1.06–1.93) and ICU mortality (OR: 1.45; 95%CI: 1.08–1.95). Additionally, ROC curves showed a good predictive value of P0.1 for VFDav-28 < 14 days (AUC 0.75) and for ICU mortality (AUC 0.75) (Fig. 1 ). Optimal cut-off values (based on the highest sum of sensitivity and specificity) of P0.1 for predicting VFDav-28 < 14 days and ICU mortality were 2.0 and 3.5, respectively. To evaluate the impact of the chosen cut-off for VFDav-28, we conducted sensitivity analyses using the median cut-off within our patient population (VFDav-28 < 20). These analyses showed similar predictive values for P0.1 (not shown). Discussion This study showed that higher (more negative) P0.1 is associated with less VFDav-28 and a higher ICU mortality. The potential of P0.1 in predicting respiratory deterioration has been shown in another small study in COVID-19 ARDS patients (7). In comparison to this study, exploration of prediction in our cohort revealed lower optimal cut-off values for P0.1. Both cut-off values of 2.0, associated with VFDav-28, and 3.5 for mortality, are within the postulated physiological range, although this range lacks an empirical base (8). Lower P0.1 cut-off values for VFDav-28 compared to mortality could reflect multiple pathophysiological pathways contributing to prolonged weaning comprising both excessively high and low respiratory drive. We acknowledge several limitations. Our study is single-center and included only COVID-19 ARDS patients. We did not account for possible interventions based on high P0.1 values (e.g., adjustments in ventilation and sedation). However, no protocolized interventions in our institution mandate ventilation adjustments based on P0.1, which is in line with a recent study showing that even excessive P0.1 values rarely lead to ventilatory adjustments (8). P0.1 values were derived from the SERVO-U (Maquet) ventilator, which estimates the P0.1. These values are lower than measured P0.1 values, and might explain our lower thresholds for P0.1 and limits generalizability (9). This study does not imply causality between P0.1 and clinical outcomes. A higher P0.1 could reflect a sicker patient. Nevertheless, these measurements and described endpoints should be explored in all-cause ARDS to determine thresholds associated with outcome, and causality. Only then can we study the potential to improve outcomes by modifying patient care based on P0.1 values. In conclusion, this study shows that higher P0.1 values are associated with prolonged duration of invasive ventilation and ICU mortality in patients with COVID-19 ARDS. Declarations Availability of data and materials Data is available upon reasonable request from the corresponding author. Competing interests Not applicable Ethics Declarations and consent to participate The institutional review board of the University Medical Center Groningen approved the study and waived the requirement for written informed consent (METc2023/10410707). Funding Janesh Pillay is supported by a research grant from the Netherlands Organization for Health Research and Development, The Netherlands (ZonMw Clinical Fellowship grant 09032212110044) and has received funding from ‘a Partnership of Siemens and UMCG for building the future of Health’ (PUSH MO24.00027) Author contributions E.A.M.D.t.H.: Study design, data collection and analysis; M.H.R, S.J.R data collection, review and editing; J.P.: Study conceptualization and design; J.M.V: Data analysis; H.W.Z., P.D., W.v.d.B, J.M.D.; review and editing. All authors participated in scientific discussions and manuscript editing. References Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med 2017; 195: 438-442. Cruces P, Retamal J, Hurtado DE, Erranz B, Iturrieta P, Gonzalez C, Diaz F. A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection. Crit Care 2020; 24: 494. Boers NS, Botta M, Tsonas AM, Algera AG, Pillay J, Dongelmans DA, Horn J, Vlaar APJ, Hollmann MW, Bos LDJ, Paulus F, Neto AS, Schultz MJ, investigatorsdagger PR-C. PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands. Ann Transl Med 2020; 8: 1251. Renard Triche L, Futier E, De Carvalho M, Pinol-Domenech N, Bodet-Contentin L, Jabaudon M, Pereira B. Sample size estimation in clinical trials using ventilator-free days as the primary outcome: a systematic review. Crit Care 2023; 27: 303. Botta M, Tsonas AM, Pillay J, Boers LS, Algera AG, Bos LDJ, Dongelmans DA, Hollmann MW, Horn J, Vlaar APJ, Schultz MJ, Neto AS, Paulus F, Group PR-CC. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study. Lancet Respir Med 2021; 9: 139-148. Investigators R-C, Hills TE, Lorenzi E, Berry LR, Shyamsundar M, Al-Beidh F, Annane D, Arabi Y, Aryal D, Au C, Beane A, Bhimani Z, Bonten M, Bradbury CA, Brunkhorst FM, Burrell A, Buxton M, Calfee CS, Cecconi M, Cheng AC, Cove ME, Detry MA, Estcourt LJ, Fitzgerald M, Goligher EC, Goossens H, Green C, Haniffa R, Harrison DA, Hashmi M, Higgins AM, Huang DT, Ichihara N, Jayakumar D, Kruger PS, Lamontagne F, Lampro L, Lawler PR, Marshall JC, Mason AJ, McGlothlin A, McGuinness S, McQuilten ZK, McVerry BJ, Mouncey PR, Murthy S, Neal MD, Nichol AD, O'Kane CM, Parke RL, Parker JC, Rabindrarajan E, Reyes LF, Rowan KM, Saito H, Santos M, Saunders CT, Seymour CW, Shankar-Hari M, Sinha P, Thompson BT, Turgeon AF, Turner AM, van de Veerdonk FV, Weis S, Young IS, Zarychanski R, Lewis RJ, McArthur CJ, Angus DC, Berry SM, Derde LPG, Webb SA, Gordon AC, McAuley DF. Simvastatin in Critically Ill Patients with Covid-19. N Engl J Med 2023. Esnault P, Cardinale M, Hraiech S, Goutorbe P, Baumstrack K, Prud'homme E, Bordes J, Forel JM, Meaudre E, Papazian L, Guervilly C. High Respiratory Drive and Excessive Respiratory Efforts Predict Relapse of Respiratory Failure in Critically Ill Patients with COVID-19. Am J Respir Crit Care Med 2020; 202: 1173-1178. Chow JWY, Al-Bassam W, Yanase F, O'Brien Z, Bassam A, Hadzakis S, Chaba A, Maeda A, Bellomo R, Serpa Neto A, Pressure Support Ventilation Study Group I. P0.1 During Pressure Support Ventilation. Am J Respir Crit Care Med 2023. Telias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L, Ferguson ND, Goligher EC, Brochard L. Airway Occlusion Pressure As an Estimate of Respiratory Drive and Inspiratory Effort during Assisted Ventilation. Am J Respir Crit Care Med 2020; 201: Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4919933","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":342292369,"identity":"be0d5684-7c72-4f16-ae92-73305c6f771e","order_by":0,"name":"Else ter Haar","email":"","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":false,"prefix":"","firstName":"Else","middleName":"ter","lastName":"Haar","suffix":""},{"id":342292370,"identity":"2c8e032d-ff4c-4d31-9f04-ce995bde8a54","order_by":1,"name":"Maurits Renes","email":"","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":false,"prefix":"","firstName":"Maurits","middleName":"","lastName":"Renes","suffix":""},{"id":342292371,"identity":"091ab41c-00ec-44bc-83b9-bcaeaa44df41","order_by":2,"name":"Hendrik Zijlstra","email":"","orcid":"","institution":"Martini Ziekenhuis","correspondingAuthor":false,"prefix":"","firstName":"Hendrik","middleName":"","lastName":"Zijlstra","suffix":""},{"id":342292372,"identity":"21178f7b-ec20-4127-bb11-b0bef50b263b","order_by":3,"name":"Salvador Recinos","email":"","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":false,"prefix":"","firstName":"Salvador","middleName":"","lastName":"Recinos","suffix":""},{"id":342292373,"identity":"96a8ff6f-73cf-4f01-a412-d9d5cec596a0","order_by":4,"name":"Peter Dieperink","email":"","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Dieperink","suffix":""},{"id":342292374,"identity":"646d1d88-6b63-4025-99c1-198c3644b862","order_by":5,"name":"Walter van den Bergh","email":"","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":false,"prefix":"","firstName":"Walter","middleName":"van den","lastName":"Bergh","suffix":""},{"id":342292375,"identity":"16da0c4b-6232-4888-b0fc-4f9240d0a639","order_by":6,"name":"Joep Droogh","email":"","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":false,"prefix":"","firstName":"Joep","middleName":"","lastName":"Droogh","suffix":""},{"id":342292376,"identity":"a4503cc5-e6c7-4d9e-a62b-e320c897fa2a","order_by":7,"name":"Judith Vonk","email":"","orcid":"","institution":"University of Groningen","correspondingAuthor":false,"prefix":"","firstName":"Judith","middleName":"","lastName":"Vonk","suffix":""},{"id":342292377,"identity":"172e2a14-0aae-4166-94c5-9cf88bd1a090","order_by":8,"name":"Janesh Pillay","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYBACxgYGhgMPChgY+KECMsRpSTBgYJBsgAjwEGcVSIvBAWK1MDfwHgTaYpe4+UZ24scvDHcIa2Fs4EsAaklO3HYjd7O0DMMzYrTwGAC1MIO0bGOWYDhMtJb6xM0zSNRyOHGDRO42xg9EaWkG++W48YwzbzdLMxgQocWwvffwhw8V1bL97bkbP/6oOCxHWEszxFjHBiDBzGNAUAMDgzw07uzBrvxBhI5RMApGwSgYeQAAkh4+FRwE4OUAAAAASUVORK5CYII=","orcid":"","institution":"University Medical Center Groningen","correspondingAuthor":true,"prefix":"","firstName":"Janesh","middleName":"","lastName":"Pillay","suffix":""}],"badges":[],"createdAt":"2024-08-15 14:36:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4919933/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4919933/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":64285108,"identity":"2c93c953-ff03-4cc8-91d5-b86b2f6b7b19","added_by":"auto","created_at":"2024-09-11 08:36:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":241491,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver Operating Characteristic (ROC) curves for P0.1 during the first 24 hours after transition to PSV predicting VFDav-28 \u0026lt;14 days and ICU mortality. Areas under the curve (AUC) and the 95% confidence intervals are depicted in the individual graphs.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4919933/v1/5da758dd73fbe2254b08a929.png"},{"id":64286378,"identity":"c4133ca8-5b55-4348-b136-0ace28d15a24","added_by":"auto","created_at":"2024-09-11 08:52:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":684170,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4919933/v1/f58d8c0a-a4ed-43a9-a89a-5e75c1ef2a13.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"P0.1 is associated with duration of ventilation and mortality in patients with COVID-19 ARDS","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOptimal strategies for assisted ventilation in Acute Respiratory Distress Syndrome (ARDS) remain unknown. Notably, the best timing of the transition to pressure support ventilation (PSV) has not been elucidated. Premature transition may inflict injury due to excessive stress and strain on an injured lung caused by excessive inspiratory effort and high respiratory drive. This could lead to patient self-inflicted lung injury (PSILI), which impairs patient outcome (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). One important determinant of the development of PSILI in animal models is respiratory effort (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The airway occlusion pressure at 100ms from the initiation of inspiration (P0.1) is a readily available ventilatory parameter reflecting respiratory effort. In this study, we hypothesized that P0.1 directly after the transition to PSV is associated with clinical outcomes, such as mortality and duration of ventilation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe performed a single-center retrospective study within the University Medical Center Groningen in The Netherlands. The institutional review board waived the requirement for written informed consent (METc2023/10410707).\u003c/p\u003e \u003cp\u003eInvasively ventilated adult patients admitted to our ICU with PCR-confirmed COVID-ARDS who experienced a transition from controlled to PSV between March 2020 and April 2022 were retrospectively identified. In our institution, the timing of transition from controlled to PSV is not protocolized and, therefore, depends on the attending clinician.\u003c/p\u003e \u003cp\u003ePatient characteristics and ventilation parameters were extracted from the patient record (EPIC, Epic Systems Corporation, Verona, WI, USA). Our ICU is equipped with a SERVO-U (Maquet) ventilator, which estimates the P0.1 and exports these values to the electronic patient record every minute. We calculated the mean P0.1 value over the first 24 hours after transition from controlled to PSV or until failure (whichever came first).\u003c/p\u003e \u003cp\u003eThe primary outcome was ventilator-free days and alive in the 28 days following the first transition from controlled to PSV (VFDav-28). This modified endpoint is similar to VFD28 used in many ARDS studies (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). VFDav-28 was dichotomized with a cut-off at 14 days, in line with outcomes in critically ill COVID-19 patients in previous studies (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The secondary outcome was ICU mortality.\u003c/p\u003e \u003cp\u003eMann-Whitney U and Fisher\u0026rsquo;s Exact Test were used to test which variables were associated with VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;14 days and ICU mortality. Two multivariable logistic regression models for both outcomes seperately were created, including the covariates P0.1 and predefined potential confounders (age, sex, and ARDS severity using P/F ratio). ROC curves were generated to assess the predictive value of these models. All analyses were performed using IBM SPSS Statistics version 28.0.1.0 (IBM, New York, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe included 78 patients. Baseline patient characteristics and ventilatory parameters are depicted in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Univariate analyses showed that patients with less ventilator-free days (VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;14 days) had a higher P0.1 compared to patients with VFDav-28\u0026thinsp;\u0026gt;\u0026thinsp;14 days; P0.1 3.4 (IQR 2.1\u0026ndash;4.5) vs 1.6 (IQR 1.2\u0026ndash;2.5), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Counterintuitively, these patients with less VFDav-28 days and higher P0.1 values, had lower RASSscores on the day of transition (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.). Age, gender, BMI, ARDS severity, or other ventilatory parameters on the day of transition were not associated with VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;14 days or ICU mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eBaseline characteristics and ventilatory parameters for the total population and stratified for VFDav-28 \u0026lt;14 days versus\u0026nbsp;\u0026ge;14 days.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal population\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 78)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.54331864904552%\" colspan=\"2\" valign=\"top\" style=\"width: 29.873%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVFDav-28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" rowspan=\"2\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;14 days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 29)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"50%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge;14 days\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at ICU admission\u003c/strong\u003e (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e58\u0026nbsp;\u0026plusmn;\u0026nbsp;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e58\u0026nbsp;\u0026plusmn; 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e58\u0026nbsp;\u0026plusmn; 14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e0.848\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e (male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e53 (68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e22 (76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e31 (63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBody-mass index\u003c/strong\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e30.1\u0026nbsp;\u0026plusmn;\u0026nbsp;6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e29.1\u0026nbsp;\u0026plusmn; 5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e30.7\u0026nbsp;\u0026plusmn; 6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSeverity of ARDS at initiation of invasive mechanical ventilation\u0026nbsp;\u003c/strong\u003e(P/F ratio)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e135 (105 \u0026ndash; 173)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e133 (97\u0026nbsp;\u0026ndash;\u0026nbsp;163)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e139 (111\u0026nbsp;\u0026ndash;\u0026nbsp;180)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e16 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e16 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU length of stay\u003c/strong\u003e (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e14 (9\u0026nbsp;\u0026ndash;\u0026nbsp;27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e28 (18\u0026nbsp;\u0026ndash;\u0026nbsp;43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e12 (8\u0026nbsp;\u0026ndash;\u0026nbsp;15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of invasive mechanical ventilation\u003c/strong\u003e (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e12 (7\u0026nbsp;\u0026ndash;\u0026nbsp;22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e24 (17\u0026nbsp;\u0026ndash;\u0026nbsp;39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e9 (6\u0026nbsp;\u0026ndash;\u0026nbsp;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVFDav-28\u003c/strong\u003e (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e20 (1\u0026nbsp;\u0026ndash;\u0026nbsp;25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e0 (0\u0026nbsp;\u0026ndash;\u0026nbsp;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e24 (21\u0026nbsp;\u0026ndash;\u0026nbsp;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime from intubation to PSV\u003c/strong\u003e (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e5 (3\u0026nbsp;\u0026ndash;\u0026nbsp;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e6 (4\u0026nbsp;\u0026ndash;\u0026nbsp;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e4 (3\u0026nbsp;\u0026ndash;\u0026nbsp;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.043\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProne positioning on the first day of ICU admission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e29 (37%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e16 (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e13 (27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtracorporeal membrane oxygenation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e6 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e3 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e3 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e0.665\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVentilatory parameters at the time of transition to PSV\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eP0.1 during the first 24h of PSV (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\n \u003cp\u003eDriving pressure (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\n \u003cp\u003ePEEP (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\n \u003cp\u003eRespiratory rate (breaths per min)\u003c/p\u003e\n \u003cp\u003eP/F ratio (PSV)\u003c/p\u003e\n \u003cp\u003eTidal volume (controlled, mL/kg body weight)\u003c/p\u003e\n \u003cp\u003eTidal volume (PSV, mL/kg body weight)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.1 (1.3\u0026nbsp;\u0026ndash;\u0026nbsp;3.5)\u003c/p\u003e\n \u003cp\u003e11.5 (10\u0026nbsp;\u0026ndash;\u0026nbsp;12)\u003c/p\u003e\n \u003cp\u003e12 (10\u0026nbsp;\u0026ndash;\u0026nbsp;14)\u003c/p\u003e\n \u003cp\u003e22 (20\u0026nbsp;\u0026ndash;\u0026nbsp;24)\u003c/p\u003e\n \u003cp\u003e193 (161\u0026nbsp;\u0026ndash;\u0026nbsp;222)\u003c/p\u003e\n \u003cp\u003e4.8 (4.0\u0026nbsp;\u0026ndash;\u0026nbsp;5.8)\u003c/p\u003e\n \u003cp\u003e6.7 (5.1\u0026nbsp;\u0026ndash;\u0026nbsp;7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.4 (2.1\u0026nbsp;\u0026ndash;\u0026nbsp;4.5)\u003c/p\u003e\n \u003cp\u003e12 (10\u0026nbsp;\u0026ndash;\u0026nbsp;14)\u003c/p\u003e\n \u003cp\u003e12 (10\u0026nbsp;\u0026ndash;\u0026nbsp;14)\u003c/p\u003e\n \u003cp\u003e22 (20\u0026nbsp;\u0026ndash;\u0026nbsp;24)\u003c/p\u003e\n \u003cp\u003e174 (155\u0026nbsp;\u0026ndash;\u0026nbsp;215)\u003c/p\u003e\n \u003cp\u003e5.1 (4.4\u0026nbsp;\u0026ndash;\u0026nbsp;5.9)\u003c/p\u003e\n \u003cp\u003e6.2 (4.9\u0026nbsp;\u0026ndash;\u0026nbsp;7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.6 (1.2\u0026nbsp;\u0026ndash;\u0026nbsp;2.5)\u003c/p\u003e\n \u003cp\u003e11 (10\u0026nbsp;\u0026ndash;\u0026nbsp;12)\u003c/p\u003e\n \u003cp\u003e12 (10\u0026nbsp;\u0026ndash;\u0026nbsp;14)\u003c/p\u003e\n \u003cp\u003e24 (20\u0026nbsp;\u0026ndash;\u0026nbsp;25)\u003c/p\u003e\n \u003cp\u003e206 (166\u0026nbsp;\u0026ndash;\u0026nbsp;231)\u003c/p\u003e\n \u003cp\u003e4.5 (3.8\u0026nbsp;\u0026ndash;\u0026nbsp;5.6)\u003c/p\u003e\n \u003cp\u003e6.6 (5.2\u0026nbsp;\u0026ndash;\u0026nbsp;8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.386\u003c/p\u003e\n \u003cp\u003e0.944\u003c/p\u003e\n \u003cp\u003e0.284\u003c/p\u003e\n \u003cp\u003e0.100\u003c/p\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003cp\u003e0.235\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRASS on the first day of PSV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e-3 (-4\u0026nbsp;\u0026ndash;\u0026nbsp;-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e-4 (-4\u0026nbsp;\u0026ndash;\u0026nbsp;-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e-2 (-4\u0026nbsp;\u0026ndash;\u0026nbsp;-0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.81497797356828%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFailed PSV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\"\u003e\n \u003cp\u003e36 (46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 13.8235%;\"\u003e\n \u003cp\u003e24 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.27165932452276%\" valign=\"top\" style=\"width: 16.6378%;\"\u003e\n \u003cp\u003e12 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.370044052863436%\" valign=\"top\" style=\"width: 11.1563%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eData are presented as number (%), mean\u0026nbsp;\u003c/em\u003e\u003cem\u003e\u0026plusmn;\u0026nbsp;\u003c/em\u003e\u003cem\u003estandard deviation, or median (interquartile range).\u003c/em\u003e \u003cem\u003eDifferences between VFDav-28 \u0026lt;14 days and\u0026nbsp;\u003c/em\u003e\u003cem\u003e\u0026ge;\u003c/em\u003e\u003cem\u003e14 days were tested by Mann-Whitney U Test for continuous/discrete explanatory variables or Fisher\u0026rsquo;s Exact Test for dichotomous explanatory variables. Significant values are depicted in bold. ICU = intensive care unit; ARDS = acute respiratory distress syndrome; P/F ratio = the ratio of arterial oxygen partial pressure (PaO\u003csub\u003e2\u003c/sub\u003e in mmHg) to fractional inspired oxygen (FiO\u003csub\u003e2\u003c/sub\u003e expressed as a fraction, not a percentage); VFDav-28 = ventilator-free days and alive 28 days after first attempt of transition to assisted ventilation; PEEP = positive end-expiratory pressure; PSV = pressure support ventilation; P0.1 = negative airway pressure generated during the first 100 msec of an inspiration; RASS = Richmond Agitation-Sedation Scale.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;The multivariate models revealed that only P0.1 was associated with VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;14 days (OR; 1.43, 95%CI: 1.06\u0026ndash;1.93) and ICU mortality (OR: 1.45; 95%CI: 1.08\u0026ndash;1.95).\u003c/p\u003e\n\u003cp\u003eAdditionally, ROC curves showed a good predictive value of P0.1 for VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;14 days (AUC 0.75) and for ICU mortality (AUC 0.75) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Optimal cut-off values (based on the highest sum of sensitivity and specificity) of P0.1 for predicting VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;14 days and ICU mortality were 2.0 and 3.5, respectively. To evaluate the impact of the chosen cut-off for VFDav-28, we conducted sensitivity analyses using the median cut-off within our patient population (VFDav-28\u0026thinsp;\u0026lt;\u0026thinsp;20). These analyses showed similar predictive values for P0.1 (not shown).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study showed that higher (more negative) P0.1 is associated with less VFDav-28 and a higher ICU mortality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe potential of P0.1 in predicting respiratory deterioration has been shown in another small study in COVID-19 ARDS patients\u0026nbsp;(7). In comparison to this study, exploration of prediction in our cohort revealed lower optimal cut-off values for P0.1. Both cut-off values of 2.0, associated with VFDav-28, and 3.5 for mortality, are within the postulated physiological range, although this range lacks an empirical base\u0026nbsp;(8). Lower P0.1 cut-off values for VFDav-28 compared to mortality could reflect multiple pathophysiological pathways contributing to prolonged weaning comprising both excessively high and low respiratory drive.\u003c/p\u003e\n\u003cp\u003eWe acknowledge several limitations. Our study is single-center and included only COVID-19 ARDS patients. We did not account for possible interventions based on high P0.1 values (e.g., adjustments in ventilation and sedation). However, no protocolized interventions in our institution mandate ventilation adjustments based on P0.1, which is in line with a recent study showing that even excessive P0.1 values rarely lead to ventilatory adjustments\u0026nbsp;(8). P0.1 values were derived from the SERVO-U (Maquet) ventilator, which estimates the P0.1. These values are lower than measured P0.1 values, and might explain our lower thresholds for P0.1 and limits generalizability\u0026nbsp;(9).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study does not imply causality between P0.1 and clinical outcomes. A higher P0.1 could reflect a sicker patient. Nevertheless, these measurements and described endpoints should be explored in all-cause ARDS to determine thresholds associated with outcome, and causality. Only then can we study the potential to improve outcomes by modifying patient care based on P0.1 values.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study shows that higher P0.1 values are associated with prolonged duration of invasive ventilation and ICU mortality in patients with COVID-19 ARDS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is available upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics Declarations and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe institutional review board of the University Medical Center Groningen approved the study and waived the requirement for written informed consent (METc2023/10410707).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJanesh Pillay is supported by a research grant from the Netherlands Organization for Health Research and Development, The Netherlands (ZonMw Clinical Fellowship grant 09032212110044) and has received funding from \u0026lsquo;a Partnership of Siemens and UMCG for building the future of Health\u0026rsquo; (PUSH MO24.00027)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eE.A.M.D.t.H.: Study design, data collection and analysis; M.H.R, S.J.R data collection, review and editing; J.P.: Study conceptualization and design; J.M.V: Data analysis; H.W.Z., P.D., W.v.d.B, J.M.D.; review and editing. All authors participated in scientific discussions and manuscript editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBrochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. \u003cem\u003eAm J Respir Crit Care Med \u003c/em\u003e2017; 195: 438-442.\u003c/li\u003e\n\u003cli\u003eCruces P, Retamal J, Hurtado DE, Erranz B, Iturrieta P, Gonzalez C, Diaz F. A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection. \u003cem\u003eCrit Care \u003c/em\u003e2020; 24: 494.\u003c/li\u003e\n\u003cli\u003eBoers NS, Botta M, Tsonas AM, Algera AG, Pillay J, Dongelmans DA, Horn J, Vlaar APJ, Hollmann MW, Bos LDJ, Paulus F, Neto AS, Schultz MJ, investigatorsdagger PR-C. PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands. \u003cem\u003eAnn Transl Med \u003c/em\u003e2020; 8: 1251.\u003c/li\u003e\n\u003cli\u003eRenard Triche L, Futier E, De Carvalho M, Pinol-Domenech N, Bodet-Contentin L, Jabaudon M, Pereira B. Sample size estimation in clinical trials using ventilator-free days as the primary outcome: a systematic review. \u003cem\u003eCrit Care \u003c/em\u003e2023; 27: 303.\u003c/li\u003e\n\u003cli\u003eBotta M, Tsonas AM, Pillay J, Boers LS, Algera AG, Bos LDJ, Dongelmans DA, Hollmann MW, Horn J, Vlaar APJ, Schultz MJ, Neto AS, Paulus F, Group PR-CC. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study. \u003cem\u003eLancet Respir Med \u003c/em\u003e2021; 9: 139-148.\u003c/li\u003e\n\u003cli\u003eInvestigators R-C, Hills TE, Lorenzi E, Berry LR, Shyamsundar M, Al-Beidh F, Annane D, Arabi Y, Aryal D, Au C, Beane A, Bhimani Z, Bonten M, Bradbury CA, Brunkhorst FM, Burrell A, Buxton M, Calfee CS, Cecconi M, Cheng AC, Cove ME, Detry MA, Estcourt LJ, Fitzgerald M, Goligher EC, Goossens H, Green C, Haniffa R, Harrison DA, Hashmi M, Higgins AM, Huang DT, Ichihara N, Jayakumar D, Kruger PS, Lamontagne F, Lampro L, Lawler PR, Marshall JC, Mason AJ, McGlothlin A, McGuinness S, McQuilten ZK, McVerry BJ, Mouncey PR, Murthy S, Neal MD, Nichol AD, O\u0026apos;Kane CM, Parke RL, Parker JC, Rabindrarajan E, Reyes LF, Rowan KM, Saito H, Santos M, Saunders CT, Seymour CW, Shankar-Hari M, Sinha P, Thompson BT, Turgeon AF, Turner AM, van de Veerdonk FV, Weis S, Young IS, Zarychanski R, Lewis RJ, McArthur CJ, Angus DC, Berry SM, Derde LPG, Webb SA, Gordon AC, McAuley DF. Simvastatin in Critically Ill Patients with Covid-19. \u003cem\u003eN Engl J Med \u003c/em\u003e2023.\u003c/li\u003e\n\u003cli\u003eEsnault P, Cardinale M, Hraiech S, Goutorbe P, Baumstrack K, Prud\u0026apos;homme E, Bordes J, Forel JM, Meaudre E, Papazian L, Guervilly C. High Respiratory Drive and Excessive Respiratory Efforts Predict Relapse of Respiratory Failure in Critically Ill Patients with COVID-19. \u003cem\u003eAm J Respir Crit Care Med \u003c/em\u003e2020; 202: 1173-1178.\u003c/li\u003e\n\u003cli\u003eChow JWY, Al-Bassam W, Yanase F, O\u0026apos;Brien Z, Bassam A, Hadzakis S, Chaba A, Maeda A, Bellomo R, Serpa Neto A, Pressure Support Ventilation Study Group I. P0.1 During Pressure Support Ventilation. \u003cem\u003eAm J Respir Crit Care Med \u003c/em\u003e2023.\u003c/li\u003e\n\u003cli\u003eTelias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L, Ferguson ND, Goligher EC, Brochard L. Airway Occlusion Pressure As an Estimate of Respiratory Drive and Inspiratory Effort during Assisted Ventilation. \u003cem\u003eAm J Respir Crit Care Med \u003c/em\u003e2020; 201: \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"COVID-19, acute respiratory distress syndrome, pressure support ventilation, patient self-inflicted lung injury, airway occlusion pressure (P0.1)","lastPublishedDoi":"10.21203/rs.3.rs-4919933/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4919933/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eRationale \u003c/strong\u003eIn acute respiratory distress syndrome (ARDS), optimal timing of transition from controlled to assisted ventilation and the ventilatory parameters which define this are unknown. Premature transition may impair recovery of an injured lung through patient self-inflicted lung injury.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives \u003c/strong\u003eTo investigate whether the airway occlusion pressure (P0.1) directly after transition to assisted ventilation is associated with the duration of ventilation and mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eInvasively ventilated patients with COVID-19 ARDS were retrospectively identified. P0.1 was recorded for 24 hours after transition to assisted ventilation. The primary endpoint was the number of ventilator-free days while being alive in the 28 days following the first transition from controlled to assisted ventilation (VFDav-28). Secondary outcome was ICU mortality. Multivariable logistic regression was used to identify variables independently associated with outcome parameters. ROC curves were generated to assess predictive values.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurements and Main Results \u003c/strong\u003e78 patients with COVID-ARDS were included. Higher (more negative) P0.1 was associated with less VFDav-28 and higher ICU mortality. The predictive value of P0.1 for both VFDav-28 and mortality was good (AUC 0.75).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eThis study shows that P0.1 directy after transition to assited ventilation is associated with prolonged duration of invasive ventilation and ICU mortality.\u003c/p\u003e","manuscriptTitle":"P0.1 is associated with duration of ventilation and mortality in patients with COVID-19 ARDS","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-11 08:36:23","doi":"10.21203/rs.3.rs-4919933/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"295d032d-a35b-4076-b719-74ac694831a4","owner":[],"postedDate":"September 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-11T08:36:26+00:00","versionOfRecord":[],"versionCreatedAt":"2024-09-11 08:36:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4919933","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4919933","identity":"rs-4919933","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}