Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation

Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation | 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 Research Article Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation Maria Teresa Passarelli, Matthieu Petit, Roberta Garberi, Guillaume Lebreton, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3990147/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 Objectives: To describe clinical characteristics, mechanical ventilation strategies, and outcomes in patients with severe acute respiratory distress syndrome (ARDS) during weaning from venovenous extracorporeal membrane oxygenation (VV ECMO). Design: Retrospective, multicenter cohort study over 7 years. Settings: Two tertiary ICUs, high-volume ECMO centers in France and Italy. Patients: Patients with ARDS on ECMO and successfully weaned from VV ECMO. Measurements and main results: Patients were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning. Among 393 adult patients with severe ARDS successfully weaned from ECMO, 292 were on controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95%CI], 1.23[0.84-1.82]). However, spontaneous breathing during SGOT was associated with a shorter duration of mechanical ventilation and ICU length of stay after ECMO discontinuation, without an increase of ECMO-related complications, such as severe bleeding or pneumothorax, compared to controlled ventilation. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning. Contrarily, mechanical ventilation modalities during SGOT did not demonstrate an independent association with the likelihood of successful weaning. Conclusions: A weaning ECMO strategy incorporating spontaneous breathing during SGOT appears safe and is associated with favorable outcomes. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes. acute respiratory distress syndrome extracorporeal membrane oxygenation weaning mechanical ventilation spontaneous breathing Figures Figure 1 Figure 2 Figure 3 Take home message A weaning venovenous ECMO strategy incorporating spontaneous breathing during sweep-gas off trial appears safe and is associated with favorable outcomes. INTRODUCTION The rationale for venovenous extracorporeal membrane oxygenation (V-V ECMO) utilization is to ensure adequate gas exchange while allowing ventilator settings that enhance ventilator-induced lung Injury (VILI) prevention, a key contributor to morbidity and mortality in acute respiratory distress syndrome (ARDS) [ 1 ]. The evidence supporting the use of ECMO is becoming more robust, as demonstrated in multicenter clinical trials [ 2 , 3 ], bayesian analysis [ 4 ], and meta-analyses [ 5 – 7 ]. On these bases, the latest European guidelines on ARDS strongly recommend V-V ECMO utilization [ 8 ]. However, there are still pending research questions in that field, especially on the timing and the modalities of ECMO weaning. Once the lung function has sufficiently recovered [ 2 , 9 ], the sweep gas flow is turned off, and the patient’s oxygenation and decarboxylation are both closely monitored for 6 to 24 hours to assess the ability to be decannulated and liberated from V-V ECMO [ 9 ]. However, the optimal timing of this weaning trial and its modalities have not been well standardized and are mainly based on clinician preferences and expert opinion [ 10 – 13 ]. Indeed, two specific periods for ECMO weaning could be identified. Early weaning from V-V ECMO, when the patient is still on controlled ventilation with deep sedation, could reduce the risks of ECMO-related complications and costs. However, this approach may jeopardize the prevention of VILI and expose the patients to the need for a new ECMO run [ 13 , 14 ]. On the other hand, waiting for an awake patient capable of breathing spontaneously on V-V ECMO may necessitate time.[ 15 ] This strategy could theoretically prolong the duration of ECMO, thereby increasing the patient's vulnerability to ECMO-related complications. To date, the impact of different ventilation strategies during ECMO weaning on outcomes has been poorly investigated, although some authors have recently outlined ventilatory and clinical parameters that can predict unfavorable outcomes [ 14 , 16 ]. Furthermore, the decision to discontinue ECMO or mechanical ventilation first is still a matter of debate [ 17 , 18 ]. The objectives of this multicenter, retrospective study were 1) to describe the mechanical ventilation settings used at the time of V-V ECMO weaning in two experienced ECMO centers; 2) to compare two different approaches during the weaning process, namely controlled mechanical ventilation versus spontaneous assisted breathing, in terms of mechanical ventilation duration, ICU and hospital lengths of stay, and mortality after ECMO weaning. MATERIALS AND METHODS Study design and patients . This study retrospectively included patients with severe ARDS (according to the Berlin Definition [ 19 ]) treated with ECMO in two university tertiary medical centers between January 2015 and December 2022. The medical ICUs from Pitié-Salpêtrière Hospital, Paris, and IRCCS San Gerardo dei Tintori Hospital, Monza, are among the largest and the most experienced ECMO centers in France and Italy, respectively. All consecutive patients with ARDS who received V-V ECMO or other ECMO settings (i.e., veno-arterial, V-A, or veno-arteriovenous, V-AV) during the study period were screened. Only patients weaned alive from V-V ECMO were included in this study. The exclusion criteria were: no intubation on ECMO, bridge to lung transplant, or extubated before ECMO weaning. Following ethical standards of local Institutional Review, no informed consent was required for this retrospective, observational study. The National Commission for Informatics and Liberties (no. 2217028v0) and the Comitato Etico Brianza (ref. NP3369) approved the data collection for this study. Sweep gas-off trial (SGOT). The ventilatory and blood gas parameters at the end of the sweep gas-off trial (SGOT) that preceded the liberation from ECMO were recorded. The SGOT trial consisted of turning off the sweep gas flow while maintaining ECMO blood flow > 3L/min, to avoid clotting [ 9 ]. The test duration ranges from 6–12 hours (i.e. Monza, Italy) to 24 hours (i.e. Paris, France) and aims to emulate gas exchanges with mechanical ventilation only. Based on lung function improvement, respiratory mechanics, and gas exchanges [ 9 ], the clinician in charge of the patient decided to perform an SGOT on controlled mechanical ventilation or spontaneous breathing with pressure support. Based on these mechanical ventilation modalities at the time of SGOT, patients were classified as Controlled Ventilation Group (i.e. patients who underwent the trial either on Volume-Control Ventilation, Pressure-Control Ventilation, Airway Pressure Release Ventilation, or Pressure-Control Bi-Level Positive Airway Pressure) or Spontaneous Breathing Group (i.e. patients on pressure support ventilation during the SGOT). Successful weaning criteria, including lung mechanics and gas exchanges, according to mechanical ventilation modalities during SGOT have been described elsewhere [ 20 , 21 ] and are reported in Table s1 (Supplementary Information). Data collection . We collected data before ECMO implantation and at the time of ECMO weaning. Pre-ECMO ventilation settings and blood gas, Sepsis-related Organ Failure Assessment (SOFA) score, need for renal replacement therapy (RRT), cause of ARDS (i.e., viral pneumonia, bacterial pneumonia, autoimmune cause, or others), adjunct therapies before ECMO start, and ECMO management were also reported. Outcome variables . The primary outcome was the time to successful weaning from mechanical ventilation within 90 days following ECMO discontinuation. Successful weaning from mechanical ventilation was defined as the removal of the endotracheal tube or tracheostomy cannula (for tracheostomized patients) without the need for reintubation in the following 72 hours. Death or new ECMO run within 90 days after ECMO weaning were considered as competing events. Secondary outcomes were ventilator-associated pneumonia (VAP), ICU and hospital length of stay and mortality. Statistical analyses . Baseline characteristics are reported as proportions (%) for categorical variables and as median [interquartile range, IQR] for continuous variables. The primary endpoint was the time to successful mechanical ventilation weaning within the 90 days following ECMO weaning, in the presence of the competing risks of death and second ECMO run according to the two mechanical ventilation groups. The cumulative incidence curves for these competing events were drawn for each group. The cumulative incidence of successful mechanical ventilation weaning was compared between groups using a Gray test. The subdistribution hazard ratios (sHR) were estimated (with their 95% confidence interval, CI) for the competing events using a Fine and Gray competing risk regression. Baseline variables (i.e., obtained at the time of ECMO start) and ECMO weaning variables (i.e., obtained at the time of ECMO weaning) included in the multivariable model were defined a priori based on the available literature. Baseline variables included age, body mass index, COVID-19-related ARDS (yes/no), pre-ECMO PaO 2 /FiO 2 , and pre-ECMO SOFA. ECMO weaning variables were ventilation mode and compliance of the respiratory system at the time of the SGOT, ECMO duration, prone positioning on ECMO, VAP, pneumothorax, and renal replacement therapy before the SGOT. Additionally, one sensitivity analysis was conducted stratified on COVID-19. Categorical outcomes were compared with chi-square or Fisher’s exact tests, and continuous outcomes with Student’s t-test or Wilcoxon’s test, as appropriate. All analyses were conducted at the two-sided α risk of 5%. All analyses were performed using R software (R Foundation for Statistical Computing, Vienna, Austria), version 4.1.3. RESULTS Study population . This study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations for reporting cohort studies [ 22 ]. The study flowchart is presented in Fig. 1 . Of 603 patients receiving VV ECMO primarily for ARDS during the 7-year study period, 390 (median age 50 (IQR 41;57) years) underwent a successful ECMO weaning and were included in our study. Two hundred and ninety-two (75%) patients had an SGOT on Controlled Ventilation whereas 98 (25%) were on Spontaneous Breathing. The baseline and pre-ECMO characteristics of these two study groups are reported in Table 1 . Briefly, patients in the controlled ventilation group were significantly younger, had a higher body mass index, and were more frequently retrieved on ECMO to the two referral centers. The most frequent comorbidities were hypertension, diabetes, and chronic respiratory disease. Notably, 27 (7%) patients were immunocompromised at cannulation. The main cause of ARDS was COVID-19 in both groups, followed by bacterial pneumonia and viral non-COVID pneumonia. Patients in the controlled ventilation group had a significantly longer time between mechanical ventilation and ECMO than those in the spontaneous breathing group (3[1 − 6] vs 1[1 − 5] days, respectively, p = 0.004) and showed a lower Pre-ECMO PaO 2 /FiO 2 ratio and a higher PaCO 2 . Pre-ECMO lung mechanics were more severe in the controlled ventilation group, with a significantly lower PEEP, a higher plateau pressure and respiratory rate, and a lower tidal volume. In this subgroup, before ECMO implementation, nitric oxide, and prone positioning were used more frequently. Table 1 Baseline characteristics according to the ventilation modalities during sweep gas-off trial All patients Controlled ventilation Spontaneous breathing p-value N = 390 N = 292 N = 98 Female sex 136 (35) 97 (33) 39 (40) 0.289 Age, yr 50 [41;57] 49 [39;56] 52 [44;59] 0.009 BMI, kg/m 2 31.2 [27.5;37.5] 31.7 [27.8;38.5] 30.5 [26.2;35.2] 0.038 Pregnancy 16 (4) 14 (5) 2 (2) 0.269 Comorbidities Hypertension 144 (37) 111 (38) 33 (34) 0.401 Diabetes 93 (24) 79 (27) 14 (14) 0.011 Chronic respiratory disease a 69 (18) 60 (20) 9 (9) 0.012 Chronic heart failure 31 (8) 24 (8) 7 (7) 0.900 Chronic renal disease 15 (4) 13 (4) 2 (2) 0.392 Immunocompromised status 27 (7) 15 (5) 12 (12) 0.030 ARDS etiology 0.091 COVID-19 184 (47) 151 (52) 33 (34) Bacterial 97 (25) 66 (23) 31 (32) Viral Other 55 (14) 34 (12) 21 (21) Autoimmune 14 (4) 7 (2) 7 (7) Other 12 (3) 9 (3) 3 (3) Unknown 18 (5) 15 (5) 3 (3) MV-to-ECMO interval, d 3 [1;6] 3 [1;6] 1 [1;5] 0.004 Retrieved on ECMO 310 (79) 253 (87) 57 (58) <0.001 Pre-ECMO blood gas PaO 2 /FiO 2, mmHg 65 [54;75] 61 [51;70] 71 [57;88] <0.001 PaCO 2 , mmHg 56 [49;65] 57 [49;67] 54 [47;62] 0.026 pH 7.33 [7.24;7.39] 7.32 [7.22;7.39] 7.35 [7.28;7.39] 0.097 Pre-ECMO ventilation : PEEP, cmH 2 O 12 [10;15] 12 [10;14] 14 [12;15] 0.005 Plateau Pressure, cmH 2 O 30 [28;32] 30 [30;32] 28 [25;30] <0.001 Tidal Volume, ml/kg ibw 5.9 [4.5;6.5] 5.8 [2.8;6.2] 6.4 [5.6;7.3] <0.001 Respiratory Rate, cycles/min 28 [25;30] 30 [26;32] 26 [22;29] <0.001 Pre-ECMO SOFA score 11 [8;13] 12 [8;14] 8 [5;11] <0.001 Pre-ECMO adjunct therapies NMB 382 (98) 286 (98) 96 (98) 1.000 Prone Positioning 293 (75) 232 (79) 61 (62) 0.001 iNO 156 (40) 128 (44) 28 (29) 0.017 High dose corticosteroids 47 (12) 32 (11) 15 (15) 0.335 Pre-ECMO RRT 32 (8) 23 (8) 9 (9) 0.845 MV on ECMO 393 (100) 292 (100) 98 (100) . ECMO configuration <0.001 VV Fem-Jug 289 (74) 266 (91) 23 (23) VV Fem-Fem 92 (24) 18 (6) 74 (75) Other 9 (2) 8 (3) 1(1) Values are expressed as median (interquartile range) or n (%). a Chronic respiratory disease includes asthma, chronic obstructive pulmonary disease, or restrictive lung disease. BMI body mass index, MV = mechanical ventilation, iNO = inhaled nitric oxide, NMBA = neuromuscular blocking agents, RRT = renal replacement therapy. Characteristics during the SGOT. The characteristics and lung mechanics at the time of SGOT are presented in Table 2 . At the time of SGOT, patients were on ECMO for 13 [ 7 – 29 ] and 12 [ 9 – 18 ] days (p = 0.398) in the controlled ventilation and the spontaneous breathing groups, respectively. When compared to patients in the spontaneous breathing group, patients in the controlled ventilation group had a significantly lower tidal volume, PEEP, and higher respiratory rate. Similarly, lower static respiratory system compliance and higher plateau pressure and driving pressure were reported in the controlled ventilation group. Table 2 Characteristics during sweep gas-off trial according to the ventilation modalities. All patients (N = 390) Controlled ventilation (N = 292) Spontaneous breathing (N = 98) p-value ECMO duration, days 13 [7;27] 13 [7;29] 12 [9;18] 0.398 Ventilation during SGOT : <0.001 Controlled ventilation VCV 237 (60) 237 (81) 0 (0) PC-APRV 40 (10) 40 (14) 0 (0) PC-BiPAP 13 (3) 13 (4) 0 (0) PCV 2 (0.5) 2 (1) 0 (0) Spontaneous Breathing PSV 26 (7) 0 (0) 26 (27) PSV + sigh 72 (18) 0 (0) 72 (73) Ventilatory parameters Tidal Volume, ml/kg ibw 6.1 [5.7;7.1] 6 [5.6;6.4] 7.6 [6.7;9] <0.001 Respiratory rate, cycles/min 26 [20;29] 28 [25;30] 15 [14;19] <0.001 PEEP, cmH 2 O 12 [8;14] 10 [8;14] 12 [10;14] <0.001 Plateau Pressure, cmH 2 O 26 [23;28] 27 [24;29] 22 [21;25] <0.001 Driving Pressure, cmH 2 O 14 [11;18] 15 [13;19] 11 [9;13] <0.001 Compliance, ml/cmH 2 O 29 [21;40] 25 [19;33] 46 [36;59] <0.001 Pressure Support level, cmH 2 O 10 [8;10] - 10 [8;10] . FiO 2 , % 40 [40;50] 40 [40;50] 40 [40;50] 0.161 Blood gas parameters PaO 2 , mmHg 89 [79;110] 88 [77;108] 96 [83;115] 0.003 PaCO 2 , mmHg 43 [38;48] 41 [38;46] 47 [43;51] <0.001 pH 7.43 [7.39;7.46] 7.43 [7.38;7.47] 7.43 [7.40;7.46] 0.812 Lactates, mmol/L 1 [0.7;1.3] 1 [0.7;1.3] 1 [0.8;1.4] 0.210 Bicarbonates, mmol/L 28.6 [24.7;31.6] 28.0 [23.9;31.0] 30.5 [28.0;33.2] <0.001 Values are expressed as median (interquartile range) or n (%). VCV volume control ventilation, PC-APRV pressure control-airway pressure release ventilation, PC-BiPAP pressure control-bilevel positive airway pressure, PCV pressure control ventilation, PSV pressure support ventilation, PEEP Positive End Expiratory Pressure, PaO2 partial pressure of arterial oxygen, PaCO2 p artial pressure of arterial carbon dioxide, RRT renal replacement therapy, VAP ventilator-associated pneumonia Primary and secondary outcomes. The probability of successful weaning from mechanical ventilation within 90 days of ECMO discontinuation was not significantly different between the two groups (sHR, 1.23 [95%CI, 0.84–1.82], p = 0.301) (Fig. 2 ). Death or a second ECMO run, the competing component of the primary outcome, was not significantly different between groups (sHR, 1.13 [95%CI [0.33–3.88]), p = 0.802 (Fig. 2 ). However, the duration of mechanical ventilation after ECMO weaning was shorter in the spontaneous breathing group (8 [4;19] vs 14 [7;28] days, p = 0.002) (Table 3 ). Similarly, patients in the spontaneous breathing group had a lower unadjusted length of stay in the ICU and the hospital and lower hospital mortality after ECMO weaning. ECMO-related complications, such as severe bleeding or ischemic stroke were not different between the two groups. Ventilator-associated pneumonia was more frequently recorded in the controlled ventilation group (Table 3 ). Table 3 ECMO management, complications, and outcomes according to the mechanical ventilation modalities during sweep gas-off trial All patients N = 390 Controlled ventilation N = 292 Spontaneous breathing N = 98 P overall Prone Positioning on ECMO 244 (62) 187 (64) 57 (56) 0.215 Tracheostomy 163 (42) 124 (42) 39 (40) 0.730 RRT 169 (43) 114 (39) 55 (54) 0.010 At least one VAP 268 (68) 210 (72) 58 (57) 0.010 Any severe bleeding 89 (23) 69 (24) 20 (20) 0.604 Hemothorax 9 (2) 6 (2) 3 (3) 0.702 Gastrointestinal bleeding 25 (6) 22 (8) 3 (3) 0.183 Other bleeding 55 (14) 44 (15) 11 (11) 0.430 Ischemic stroke 5 (1) 5 (2) 0 (0) 0.344 Pneumothorax 47 (12) 34 (12) 13 (13) 0.805 MV duration post ECMO weaning, d 13 [6;28] 14 [7;28] 8 [4;19] 0.002 Total ICU LOS, d 44 [24;64] 48 [28;67] 26 [21;49] <0.001 ICU LOS post-ECMO weaning, d 16 [9;31] 19 [11;34] 10 [7;21] <0.001 Total hospital LOS, d 68 [41;92] 72 [46;95] 48 [35;73] <0.001 Hospital LOS post-ECMO weaning, d 35 [23;57] 39 [24;62] 28 [18;48] 0.001 ICU mortality post ECMO weaning 36 (9) 32 (11) 4 (4) 0.091 Hospital mortality post ECMO weaning 42 (11) 38 (13) 4 (5) 0.041 Values are expressed as median (interquartile range) or n (%). d days, MV mechanical ventilation, ICU intensive care unit, LOS length of stay After adjustment to the patient’s characteristics and events occurring during the ECMO run, being on spontaneous ventilation during SGOT was not associated with a greater probability of successful mechanical ventilation weaning. Conversely, older age, ventilator-associated pneumonia on ECMO, pneumothorax, and RRT in ICU were significantly associated with a lower probability of successful weaning from mechanical ventilation at 90 days. A shorter ECMO duration and greater static compliance during SGOT were associated with a significant increase in the probability of weaning from mechanical ventilation (Fig. 3 ). Moreover, similar risk factors for successful weaning from mechanical ventilation at 90 days were found when the model was stratified on COVID-19 (Table S2 , Supplementary Information). DISCUSSION This study investigated ventilatory modalities and subsequent outcomes in 390 patients weaned from V-V ECMO. The analysis revealed no significant difference in the rate of successful mechanical ventilation weaning after SGOT, accounting for death and the need for a second ECMO run as competing events. Despite similar ECMO duration, patients on spontaneous breathing during SGOT had a shorter post-ECMO weaning mechanical ventilation duration and ICU and hospital length of stay, when compared to patients on controlled mechanical ventilation. However, after adjusting for covariates, spontaneous breathing during SGOT was not independently associated with a higher probability of being weaned from mechanical ventilation, as compared to controlled ventilation. Noticeably, spontaneous breathing during ECMO weaning was not associated with a higher incidence of ECMO-related complications. Strong evidence to guide mechanical ventilation settings during V-V ECMO is still lacking. Current recommendations rely on experts’ opinions and ventilatory settings used in the ECMO groups in two recent RCTs [ 2 , 3 , 9 ]. Ultra-protective lung ventilation settings could enhance VILI prevention on ECMO [ 23 ], as suggested in the LIFEGARDS study [ 24 ] and several reviews [ 21 , 25 , 26 ]. Nonetheless, the association between ventilatory parameters while on ECMO and outcomes has not been well established, with studies showing conflicting results [ 24 , 27 ]. Literature regarding mechanical ventilation settings during ECMO weaning is even more scarce since this topic has received very little attention. Limited data offer guidance about when and how to perform an SGOT [ 10 – 12 , 21 , 28 ]. Al-Fares et al . demonstrated that patients exhibiting higher tidal volumes, heart rate, ventilatory ratio, and esophageal pressure swings during SGOT have a decreased likelihood of achieving a safe liberation from VV ECMO [ 14 ]. Similarly, Gerhardinger et al. recently identified higher respiratory rate and PaCO 2 before SGOT as independent risk factors for ECMO weaning failure while, during the trial, impaired oxygenation was the most relevant risk factor of ECMO weaning failure [ 29 ]. A higher PaCO 2 and respiratory rate at the time of ECMO decannulation were also associated with prolonged mechanical ventilation and ICU length of stay following decannulation, whereas high PEEP seemed protective [ 16 ]. Our multivariate analysis showed that pneumothorax, ventilation-associated pneumonia, and renal replacement therapy during ECMO, all surrogates of patient severity, were independently associated with a lower likelihood of being successfully weaned from mechanical ventilation at day 90. The ECMO duration until SGOT was unexpectedly found to be not different between the two groups in our study. One could argue that waiting for patients to be able to undergo spontaneous breathing ventilation could expose them to a longer ECMO run and therefore greater likelihood of ECMO-related complications. Interestingly, severe bleeding and pneumothorax incidence were similar between the two groups. These findings are reassuring, suggesting that maintaining V-V ECMO support until being on spontaneous ventilation appears to be a safe strategy. This strategy did not increase the likelihood of successful mechanical ventilation weaning but was associated with a shorter duration of post-ECMO ventilation, hospital length of stay, and in-hospital mortality. A weaning ECMO strategy waiting for spontaneous breathing during SGOT may also reduce the cost and resource consumption following decannulation. However, a lower pre-ECMO severity, which allowed a more rapid improvement of lung functions in the spontaneous breathing group, could also partially explain these findings. Identifying the most relevant time for an SGOT still warrants further investigation. Although it is to date the largest study on mechanical ventilation modalities during SGOT, we acknowledge that our study has several limitations. First, given its retrospective design, it is not possible to establish direct causal relationships, but only associations. Second, there might be a bias due to the inclusion of patients from two distinct ECMO centers, with possibly different practices in ECMO management. Third, we did not collect data regarding the use of adjunct therapies for ARDS post-ECMO weaning in both groups, which may also have an important impact on economic and human resources. Lastly, our follow-up was limited to 90 days after ECMO weaning. Exploring the impact of these ventilation strategies on long-term lung function or psychological status could be valuable. CONCLUSION A strategy comprising spontaneous breathing during SGOT was not associated with a higher incidence of successful weaning from mechanical ventilation, compared to controlled mechanical ventilation. However, spontaneous breathing during SGOT was associated with a shorter duration of mechanical ventilation and ICU length of stay after ECMO discontinuation, without exposure to more frequent ECMO-related complications. Further research is needed to assess the optimal ventilation strategy during weaning off V-V ECMO and its impact on short- and long-term outcomes. Declarations Author Contributions: Concept and design: Passarelli, Petit, Giani, Schmidt. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Passarelli, Petit, Giani, Schmidt. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Passarelli, Petit, Schmidt. Conflict of Interest Disclosures: Dr. Matthieu Schmidt reports lecture fees from Getinge, Dräger, Baxter, and Fresenius Medical Care outside the submitted work. 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JAMA 307:. https://doi.org/10.1001/jama.2012.5669 Combes A, Hajage D, Capellier G et al (2018) Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med 378:1965–1975. https://doi.org/10/gdk7tn Combes A, Schmidt M, Hodgson CL et al (2020) Extracorporeal life support for adults with acute respiratory distress syndrome. Intensive Care Med 46:2464–2476. https://doi.org/10.1007/s00134-020-06290-1 Von Elm E, Altman DG, Egger M et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370:1453–1457. https://doi.org/10.1016/S0140-6736(07)61602-X Rozencwajg S, Guihot A, Franchineau G et al (2019) Ultra-Protective Ventilation Reduces Biotrauma in Patients on Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome*. Crit Care Med 47:1505–1512. https://doi.org/10.1097/CCM.0000000000003894 Schmidt M, Pham T, Arcadipane A et al (2019) Mechanical Ventilation Management during Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome. An International Multicenter Prospective Cohort. Am J Respir Crit Care Med 200:1002–1012. https://doi.org/10.1164/rccm.201806-1094OC Schmidt M, Pellegrino V, Combes A et al (2014) Mechanical ventilation during extracorporeal membrane oxygenation. Crit Care 18:203. https://doi.org/10.1186/cc13702 Assouline B, Combes A, Schmidt M (2023) Setting and Monitoring of Mechanical Ventilation During Venovenous ECMO. Crit Care 27:95. https://doi.org/10.1186/s13054-023-04372-2 The ReVA Research Network and the PROVE Network, Investigators S, Neto A, Schmidt M et al (2016) Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis: Mechanical ventilation during ECMO. Intensive Care Med 42:1672–1684. https://doi.org/10.1007/s00134-016-4507-0 Gannon WD, Stokes JW, Bloom S et al (2021) Safety and Feasibility of a Protocolized Daily Assessment of Readiness for Liberation From Venovenous Extracorporeal Membrane Oxygenation. Chest 160:1693–1703. https://doi.org/10.1016/j.chest.2021.05.066 Gerhardinger F, Fisser C, Malfertheiner MV et al (2023) Prevalence and Risk Factors for Weaning Failure From Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Insufficiency. Crit Care Med. https://doi.org/10.1097/CCM.0000000000006041 Supplementary Files STROBECHECKLISTECMOWean.docx SupplementaryInformationWeanECMO5.0.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-3990147","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276959208,"identity":"e1fa497a-39ea-4578-96f9-cc77f2e0ec7a","order_by":0,"name":"Maria Teresa Passarelli","email":"","orcid":"","institution":"Policlinico di Monza SpA","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Teresa","lastName":"Passarelli","suffix":""},{"id":276959209,"identity":"22bb514c-b6b0-44a2-b0bd-5cb0eb90119f","order_by":1,"name":"Matthieu Petit","email":"","orcid":"","institution":"APHP: Assistance Publique - Hopitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Matthieu","middleName":"","lastName":"Petit","suffix":""},{"id":276959210,"identity":"3b03ddfb-59a5-4e5a-a91c-b6cba7a847cd","order_by":2,"name":"Roberta Garberi","email":"","orcid":"","institution":"Monza Polyclinic Group: Policlinico di Monza SpA","correspondingAuthor":false,"prefix":"","firstName":"Roberta","middleName":"","lastName":"Garberi","suffix":""},{"id":276959211,"identity":"d5f00947-017d-4bf9-b0ba-26777705ee71","order_by":3,"name":"Guillaume Lebreton","email":"","orcid":"","institution":"APHP: Assistance Publique - Hopitaux de Paris","correspondingAuthor":false,"prefix":"","firstName":"Guillaume","middleName":"","lastName":"Lebreton","suffix":""},{"id":276959212,"identity":"2128c284-b82e-465d-b6f6-046004870104","order_by":4,"name":"Charles Edouard Luyt","email":"","orcid":"","institution":"APHP: Assistance Publique - Hopitaux de 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Schmidt","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIie3PsWoCMRjA8U8KTsG5IGpfQPhCICCIz3LhQJerdRLHA8F7hSsd7hXyCCeluJzNmm4HtzoILh0O2os6FEo83ATzH/J9Q36EALhcN9oDoBkEwGtC97iAmXbQWP4hyM6E1RA4E2iiCOtIP1KbYjYbiiTafsh8Xk7kZrvO94AvNsIzv7GMcSxkNh1r7xOfq8WnMeAgtJG0IgTfhXwkXItVRdKAtwmUaH1FFYb8iCQ+kQmqnSFoJ/r4SipCfSIe6qCOFPSNoM9kFvDqL4y+6h2jMV4gSuQHUo46SZTxr+95t9dSAc33Czv531NqzisAQC+85rbL5XLdQ7/UeFpXPAloogAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-2931-4412","institution":"Hopital Universitaire Pitie Salpetriere","correspondingAuthor":true,"prefix":"","firstName":"Matthieu","middleName":"","lastName":"Schmidt","suffix":""}],"badges":[],"createdAt":"2024-02-26 06:22:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3990147/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3990147/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52451626,"identity":"3a2f9432-d737-46ad-9a16-10f62647a3f5","added_by":"auto","created_at":"2024-03-11 19:14:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":611912,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy Flowchart\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eARDS \u003c/em\u003eacute respiratory distress syndrome\u003cem\u003e, V-A ECMO \u003c/em\u003eveno-arterial extracorporeal membrane oxygenation\u003cem\u003e,\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eV-V ECMO \u003c/em\u003evenovenous extracorporeal membrane oxygenation\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3990147/v1/bf73a5797d7a65ec400d8dba.png"},{"id":52451628,"identity":"5554b0d9-ed87-4cc7-83c5-98156cd6c517","added_by":"auto","created_at":"2024-03-11 19:14:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":14118,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCumulative incidence function for the events of mechanical ventilation successful weaning and death or second run of ECMO, according to mechanical ventilation modalities during sweep gas-off trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003esHR \u003c/em\u003esubdistribution hazard ratio\u003cem\u003e, MV \u003c/em\u003emechanical ventilation\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3990147/v1/3ccc664cffc70d810d76d7ea.png"},{"id":52451627,"identity":"d02d01a8-0fa7-4314-9873-ac843f4f4aa5","added_by":"auto","created_at":"2024-03-11 19:14:11","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":325154,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssociation of covariates with the 90-day adjusted probability of successful weaning from mechanical ventilation after ECMO decannulation in the multivariable model, expressed using sHR (points) with their 95% CI (error bars)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003esHR \u003c/em\u003esubdistribution hazard ratio\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3990147/v1/f81729dac825f1ae5f8a7c13.jpeg"},{"id":53641051,"identity":"f7783600-56f3-468c-ba31-47d940069aeb","added_by":"auto","created_at":"2024-03-28 12:13:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":812587,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3990147/v1/8b5b0be5-faef-436b-a70b-e83667b491b8.pdf"},{"id":52451629,"identity":"334f03a3-f52f-4573-a437-47521d0c0625","added_by":"auto","created_at":"2024-03-11 19:14:11","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":34454,"visible":true,"origin":"","legend":"","description":"","filename":"STROBECHECKLISTECMOWean.docx","url":"https://assets-eu.researchsquare.com/files/rs-3990147/v1/1d0bad60d45a779f4885d095.docx"},{"id":52451630,"identity":"77fa5984-e0c6-417f-82eb-1ac221f9bfe0","added_by":"auto","created_at":"2024-03-11 19:14:11","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":40630,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformationWeanECMO5.0.docx","url":"https://assets-eu.researchsquare.com/files/rs-3990147/v1/5e22ebc3c6c7d89fc0151375.docx"}],"financialInterests":"","formattedTitle":"Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation","fulltext":[{"header":"Take home message","content":"\u003cp\u003eA weaning venovenous ECMO strategy incorporating spontaneous breathing during sweep-gas off trial appears safe and is associated with favorable outcomes.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eThe rationale for venovenous extracorporeal membrane oxygenation (V-V ECMO) utilization is to ensure adequate gas exchange while allowing ventilator settings that enhance ventilator-induced lung Injury (VILI) prevention, a key contributor to morbidity and mortality in acute respiratory distress syndrome (ARDS) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The evidence supporting the use of ECMO is becoming more robust, as demonstrated in multicenter clinical trials [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], bayesian analysis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and meta-analyses [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. On these bases, the latest European guidelines on ARDS strongly recommend V-V ECMO utilization [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, there are still pending research questions in that field, especially on the timing and the modalities of ECMO weaning. Once the lung function has sufficiently recovered [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], the sweep gas flow is turned off, and the patient\u0026rsquo;s oxygenation and decarboxylation are both closely monitored for 6 to 24 hours to assess the ability to be decannulated and liberated from V-V ECMO [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the optimal timing of this weaning trial and its modalities have not been well standardized and are mainly based on clinician preferences and expert opinion [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Indeed, two specific periods for ECMO weaning could be identified. Early weaning from V-V ECMO, when the patient is still on controlled ventilation with deep sedation, could reduce the risks of ECMO-related complications and costs. However, this approach may jeopardize the prevention of VILI and expose the patients to the need for a new ECMO run [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. On the other hand, waiting for an awake patient capable of breathing spontaneously on V-V ECMO may necessitate time.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] This strategy could theoretically prolong the duration of ECMO, thereby increasing the patient's vulnerability to ECMO-related complications. To date, the impact of different ventilation strategies during ECMO weaning on outcomes has been poorly investigated, although some authors have recently outlined ventilatory and clinical parameters that can predict unfavorable outcomes [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, the decision to discontinue ECMO or mechanical ventilation first is still a matter of debate [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe objectives of this multicenter, retrospective study were 1) to describe the mechanical ventilation settings used at the time of V-V ECMO weaning in two experienced ECMO centers; 2) to compare two different approaches during the weaning process, namely controlled mechanical ventilation versus spontaneous assisted breathing, in terms of mechanical ventilation duration, ICU and hospital lengths of stay, and mortality after ECMO weaning.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e \u003cb\u003eStudy design and patients\u003c/b\u003e. This study retrospectively included patients with severe ARDS (according to the Berlin Definition [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]) treated with ECMO in two university tertiary medical centers between January 2015 and December 2022. The medical ICUs from Piti\u0026eacute;-Salp\u0026ecirc;tri\u0026egrave;re Hospital, Paris, and IRCCS San Gerardo dei Tintori Hospital, Monza, are among the largest and the most experienced ECMO centers in France and Italy, respectively. All consecutive patients with ARDS who received V-V ECMO or other ECMO settings (i.e., veno-arterial, V-A, or veno-arteriovenous, V-AV) during the study period were screened. Only patients weaned alive from V-V ECMO were included in this study. The exclusion criteria were: no intubation on ECMO, bridge to lung transplant, or extubated before ECMO weaning.\u003c/p\u003e \u003cp\u003e Following ethical standards of local Institutional Review, no informed consent was required for this retrospective, observational study. The National Commission for Informatics and Liberties (no. 2217028v0) and the Comitato Etico Brianza (ref. NP3369) approved the data collection for this study.\u003c/p\u003e \u003cp\u003e\u003cb\u003eSweep gas-off trial (SGOT).\u003c/b\u003e The ventilatory and blood gas parameters at the end of the sweep gas-off trial (SGOT) that preceded the liberation from ECMO were recorded. The SGOT trial consisted of turning off the sweep gas flow while maintaining ECMO blood flow\u0026thinsp;\u0026gt;\u0026thinsp;3L/min, to avoid clotting [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The test duration ranges from 6\u0026ndash;12 hours (i.e. Monza, Italy) to 24 hours (i.e. Paris, France) and aims to emulate gas exchanges with mechanical ventilation only. Based on lung function improvement, respiratory mechanics, and gas exchanges [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], the clinician in charge of the patient decided to perform an SGOT on controlled mechanical ventilation or spontaneous breathing with pressure support. Based on these mechanical ventilation modalities at the time of SGOT, patients were classified as \u003cem\u003eControlled Ventilation Group\u003c/em\u003e (i.e. patients who underwent the trial either on Volume-Control Ventilation, Pressure-Control Ventilation, Airway Pressure Release Ventilation, or Pressure-Control Bi-Level Positive Airway Pressure) or \u003cem\u003eSpontaneous Breathing Group\u003c/em\u003e (i.e. patients on pressure support ventilation during the SGOT). Successful weaning criteria, including lung mechanics and gas exchanges, according to mechanical ventilation modalities during SGOT have been described elsewhere [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and are reported in Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003es1\u003c/span\u003e (Supplementary Information).\u003c/p\u003e \u003cp\u003e \u003cb\u003eData collection\u003c/b\u003e. We collected data before ECMO implantation and at the time of ECMO weaning. Pre-ECMO ventilation settings and blood gas, Sepsis-related Organ Failure Assessment (SOFA) score, need for renal replacement therapy (RRT), cause of ARDS (i.e., viral pneumonia, bacterial pneumonia, autoimmune cause, or others), adjunct therapies before ECMO start, and ECMO management were also reported.\u003c/p\u003e \u003cp\u003e \u003cb\u003eOutcome variables\u003c/b\u003e. The primary outcome was the time to successful weaning from mechanical ventilation within 90 days following ECMO discontinuation. Successful weaning from mechanical ventilation was defined as the removal of the endotracheal tube or tracheostomy cannula (for tracheostomized patients) without the need for reintubation in the following 72 hours. Death or new ECMO run within 90 days after ECMO weaning were considered as competing events. Secondary outcomes were ventilator-associated pneumonia (VAP), ICU and hospital length of stay and mortality.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analyses\u003c/b\u003e. Baseline characteristics are reported as proportions (%) for categorical variables and as median [interquartile range, IQR] for continuous variables.\u003c/p\u003e \u003cp\u003eThe primary endpoint was the time to successful mechanical ventilation weaning within the 90 days following ECMO weaning, in the presence of the competing risks of death and second ECMO run according to the two mechanical ventilation groups. The cumulative incidence curves for these competing events were drawn for each group. The cumulative incidence of successful mechanical ventilation weaning was compared between groups using a Gray test. The subdistribution hazard ratios (sHR) were estimated (with their 95% confidence interval, CI) for the competing events using a Fine and Gray competing risk regression. Baseline variables (i.e., obtained at the time of ECMO start) and ECMO weaning variables (i.e., obtained at the time of ECMO weaning) included in the multivariable model were defined \u003cem\u003ea priori based\u003c/em\u003e on the available literature. Baseline variables included age, body mass index, COVID-19-related ARDS (yes/no), pre-ECMO PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e, and pre-ECMO SOFA. ECMO weaning variables were ventilation mode and compliance of the respiratory system at the time of the SGOT, ECMO duration, prone positioning on ECMO, VAP, pneumothorax, and renal replacement therapy before the SGOT. Additionally, one sensitivity analysis was conducted stratified on COVID-19.\u003c/p\u003e \u003cp\u003eCategorical outcomes were compared with chi-square or Fisher\u0026rsquo;s exact tests, and continuous outcomes with Student\u0026rsquo;s t-test or Wilcoxon\u0026rsquo;s test, as appropriate. All analyses were conducted at the two-sided α risk of 5%. All analyses were performed using R software (R Foundation for Statistical Computing, Vienna, Austria), version 4.1.3.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cb\u003eStudy population\u003c/b\u003e. This study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations for reporting cohort studies [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The study flowchart is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Of 603 patients receiving VV ECMO primarily for ARDS during the 7-year study period, 390 (median age 50 (IQR 41;57) years) underwent a successful ECMO weaning and were included in our study. Two hundred and ninety-two (75%) patients had an SGOT on Controlled Ventilation whereas 98 (25%) were on Spontaneous Breathing. The baseline and pre-ECMO characteristics of these two study groups are reported in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Briefly, patients in the controlled ventilation group were significantly younger, had a higher body mass index, and were more frequently retrieved on ECMO to the two referral centers. The most frequent comorbidities were hypertension, diabetes, and chronic respiratory disease. Notably, 27 (7%) patients were immunocompromised at cannulation. The main cause of ARDS was COVID-19 in both groups, followed by bacterial pneumonia and viral non-COVID pneumonia. Patients in the controlled ventilation group had a significantly longer time between mechanical ventilation and ECMO than those in the spontaneous breathing group (3[1\u0026thinsp;\u0026minus;\u0026thinsp;6] vs 1[1\u0026thinsp;\u0026minus;\u0026thinsp;5] days, respectively, p\u0026thinsp;=\u0026thinsp;0.004) and showed a lower Pre-ECMO PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e ratio and a higher PaCO\u003csub\u003e2\u003c/sub\u003e. Pre-ECMO lung mechanics were more severe in the controlled ventilation group, with a significantly lower PEEP, a higher plateau pressure and respiratory rate, and a lower tidal volume. In this subgroup, before ECMO implementation, nitric oxide, and prone positioning were used more frequently.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics according to the ventilation modalities during sweep gas-off trial\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControlled ventilation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSpontaneous breathing\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;390\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;292\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;98\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.289\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, yr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 [41;57]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 [39;56]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52 [44;59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.2 [27.5;37.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.7 [27.8;38.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.5 [26.2;35.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.269\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eComorbidities\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic respiratory disease \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic renal disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunocompromised status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eARDS etiology\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e184 (47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151 (52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eViral Other\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMV-to-ECMO interval, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 [1;6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 [1;6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 [1;5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetrieved on ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e310 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e253 (87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57 (58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePre-ECMO blood gas\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2,\u003c/sub\u003e mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 [54;75]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 [51;70]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71 [57;88]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaCO\u003csub\u003e2\u003c/sub\u003e, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 [49;65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 [49;67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54 [47;62]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.33 [7.24;7.39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.32 [7.22;7.39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.35 [7.28;7.39]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePre-ECMO ventilation\u003c/span\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePEEP, cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [10;15]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 [10;14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 [12;15]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlateau Pressure, cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 [28;32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 [30;32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 [25;30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTidal Volume, ml/kg ibw\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9 [4.5;6.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.8 [2.8;6.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.4 [5.6;7.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory Rate, cycles/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 [25;30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 [26;32]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 [22;29]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-ECMO SOFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 [8;13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 [8;14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 [5;11]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePre-ECMO adjunct therapies\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNMB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e382 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e286 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 (98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProne Positioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e293 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e232 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eiNO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh dose corticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.335\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-ECMO RRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.845\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMV on ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e393 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e292 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eECMO configuration\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVV Fem-Jug\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e289 (74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e266 (91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVV Fem-Fem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eValues are expressed as median (interquartile range) or n (%).\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e \u003cem\u003eChronic respiratory disease includes asthma, chronic obstructive pulmonary disease, or restrictive lung disease.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eBMI body mass index, MV\u0026thinsp;=\u0026thinsp;mechanical ventilation, iNO\u0026thinsp;=\u0026thinsp;inhaled nitric oxide, NMBA\u0026thinsp;=\u0026thinsp;neuromuscular blocking agents, RRT\u0026thinsp;=\u0026thinsp;renal replacement therapy.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eCharacteristics during the SGOT.\u003c/b\u003e The characteristics and lung mechanics at the time of SGOT are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. At the time of SGOT, patients were on ECMO for 13 [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and 12 [\u003cspan additionalcitationids=\"CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] days (p\u0026thinsp;=\u0026thinsp;0.398) in the controlled ventilation and the spontaneous breathing groups, respectively. When compared to patients in the spontaneous breathing group, patients in the controlled ventilation group had a significantly lower tidal volume, PEEP, and higher respiratory rate. Similarly, lower static respiratory system compliance and higher plateau pressure and driving pressure were reported in the controlled ventilation group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics during sweep gas-off trial according to the ventilation modalities.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003cp\u003e\u003cem\u003e(N\u0026thinsp;=\u0026thinsp;390)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControlled ventilation\u003c/p\u003e \u003cp\u003e\u003cem\u003e(N\u0026thinsp;=\u0026thinsp;292)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSpontaneous breathing\u003c/p\u003e \u003cp\u003e\u003cem\u003e(N\u0026thinsp;=\u0026thinsp;98)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECMO duration, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 [7;27]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 [7;29]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 [9;18]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.398\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eVentilation during SGOT\u003c/span\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eControlled ventilation\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e237 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e237 (81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePC-APRV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePC-BiPAP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSpontaneous Breathing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSV\u0026thinsp;+\u0026thinsp;sigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eVentilatory parameters\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTidal Volume, ml/kg ibw\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1 [5.7;7.1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 [5.6;6.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.6 [6.7;9]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory rate, cycles/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 [20;29]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 [25;30]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 [14;19]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePEEP, cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 [8;14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 [8;14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 [10;14]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlateau Pressure, cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 [23;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 [24;29]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 [21;25]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDriving Pressure, cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 [11;18]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 [13;19]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 [9;13]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompliance, ml/cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 [21;40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 [19;33]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 [36;59]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePressure Support level, cmH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 [8;10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 [8;10]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFiO\u003csub\u003e2\u003c/sub\u003e, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 [40;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 [40;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 [40;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBlood gas parameters\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 [79;110]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 [77;108]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96 [83;115]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaCO\u003csub\u003e2\u003c/sub\u003e, mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 [38;48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 [38;46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 [43;51]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.43 [7.39;7.46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.43 [7.38;7.47]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.43 [7.40;7.46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.812\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactates, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 [0.7;1.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 [0.7;1.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 [0.8;1.4]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.210\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBicarbonates, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.6 [24.7;31.6]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.0 [23.9;31.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.5 [28.0;33.2]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are expressed as median (interquartile range) or n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eVCV\u003c/em\u003e volume control ventilation, \u003cem\u003ePC-APRV\u003c/em\u003e pressure control-airway pressure release ventilation, \u003cem\u003ePC-BiPAP\u003c/em\u003e pressure control-bilevel positive airway pressure, \u003cem\u003ePCV\u003c/em\u003e pressure control ventilation, \u003cem\u003ePSV\u003c/em\u003e pressure support ventilation, \u003cem\u003ePEEP\u003c/em\u003e Positive End Expiratory Pressure, \u003cem\u003ePaO2\u003c/em\u003e partial pressure of arterial oxygen, \u003cem\u003ePaCO2 p\u003c/em\u003eartial pressure of arterial carbon dioxide, \u003cem\u003eRRT\u003c/em\u003e renal replacement therapy, \u003cem\u003eVAP\u003c/em\u003e ventilator-associated pneumonia\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePrimary and secondary outcomes.\u003c/b\u003e The probability of successful weaning from mechanical ventilation within 90 days of ECMO discontinuation was not significantly different between the two groups (sHR, 1.23 [95%CI, 0.84\u0026ndash;1.82], p\u0026thinsp;=\u0026thinsp;0.301) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Death or a second ECMO run, the competing component of the primary outcome, was not significantly different between groups (sHR, 1.13 [95%CI [0.33\u0026ndash;3.88]), p\u0026thinsp;=\u0026thinsp;0.802 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHowever, the duration of mechanical ventilation after ECMO weaning was shorter in the spontaneous breathing group (8 [4;19] vs 14 [7;28] days, p\u0026thinsp;=\u0026thinsp;0.002) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Similarly, patients in the spontaneous breathing group had a lower unadjusted length of stay in the ICU and the hospital and lower hospital mortality after ECMO weaning. ECMO-related complications, such as severe bleeding or ischemic stroke were not different between the two groups. Ventilator-associated pneumonia was more frequently recorded in the controlled ventilation group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eECMO management, complications, and outcomes according to the mechanical ventilation modalities during sweep gas-off trial\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll patients \u003cem\u003eN\u0026thinsp;=\u0026thinsp;390\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControlled ventilation \u003cem\u003eN\u0026thinsp;=\u0026thinsp;292\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSpontaneous breathing\u003c/p\u003e \u003cp\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;98\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP overall\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProne Positioning on ECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187 (64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTracheostomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e163 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.730\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e169 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114 (39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAt least one VAP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e268 (68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e210 (72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny severe bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.604\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemothorax\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.430\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIschemic stroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumothorax\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.805\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMV duration post ECMO weaning, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 [6;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 [7;28]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 [4;19]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal ICU LOS, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 [24;64]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 [28;67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 [21;49]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU LOS post-ECMO weaning, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 [9;31]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 [11;34]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 [7;21]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal hospital LOS, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 [41;92]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 [46;95]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 [35;73]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital LOS post-ECMO weaning, d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 [23;57]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 [24;62]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 [18;48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU mortality post ECMO weaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital mortality post ECMO weaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are expressed as median (interquartile range) or n (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003ed\u003c/em\u003e days, \u003cem\u003eMV\u003c/em\u003e mechanical ventilation, \u003cem\u003eICU\u003c/em\u003e intensive care unit, \u003cem\u003eLOS\u003c/em\u003e length of stay\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter adjustment to the patient\u0026rsquo;s characteristics and events occurring during the ECMO run, being on spontaneous ventilation during SGOT was not associated with a greater probability of successful mechanical ventilation weaning. Conversely, older age, ventilator-associated pneumonia on ECMO, pneumothorax, and RRT in ICU were significantly associated with a lower probability of successful weaning from mechanical ventilation at 90 days. A shorter ECMO duration and greater static compliance during SGOT were associated with a significant increase in the probability of weaning from mechanical ventilation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Moreover, similar risk factors for successful weaning from mechanical ventilation at 90 days were found when the model was stratified on COVID-19 (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e, Supplementary Information).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study investigated ventilatory modalities and subsequent outcomes in 390 patients weaned from V-V ECMO. The analysis revealed no significant difference in the rate of successful mechanical ventilation weaning after SGOT, accounting for death and the need for a second ECMO run as competing events. Despite similar ECMO duration, patients on spontaneous breathing during SGOT had a shorter post-ECMO weaning mechanical ventilation duration and ICU and hospital length of stay, when compared to patients on controlled mechanical ventilation. However, after adjusting for covariates, spontaneous breathing during SGOT was not independently associated with a higher probability of being weaned from mechanical ventilation, as compared to controlled ventilation. Noticeably, spontaneous breathing during ECMO weaning was not associated with a higher incidence of ECMO-related complications.\u003c/p\u003e \u003cp\u003eStrong evidence to guide mechanical ventilation settings during V-V ECMO is still lacking. Current recommendations rely on experts\u0026rsquo; opinions and ventilatory settings used in the ECMO groups in two recent RCTs [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Ultra-protective lung ventilation settings could enhance VILI prevention on ECMO [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], as suggested in the LIFEGARDS study [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and several reviews [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Nonetheless, the association between ventilatory parameters while on ECMO and outcomes has not been well established, with studies showing conflicting results [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Literature regarding mechanical ventilation settings during ECMO weaning is even more scarce since this topic has received very little attention. Limited data offer guidance about when and how to perform an SGOT [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Al-Fares \u003cem\u003eet al\u003c/em\u003e. demonstrated that patients exhibiting higher tidal volumes, heart rate, ventilatory ratio, and esophageal pressure swings during SGOT have a decreased likelihood of achieving a safe liberation from VV ECMO [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Similarly, Gerhardinger \u003cem\u003eet al.\u003c/em\u003e recently identified higher respiratory rate and PaCO\u003csub\u003e2\u003c/sub\u003e before SGOT as independent risk factors for ECMO weaning failure while, during the trial, impaired oxygenation was the most relevant risk factor of ECMO weaning failure [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A higher PaCO\u003csub\u003e2\u003c/sub\u003e and respiratory rate at the time of ECMO decannulation were also associated with prolonged mechanical ventilation and ICU length of stay following decannulation, whereas high PEEP seemed protective [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our multivariate analysis showed that pneumothorax, ventilation-associated pneumonia, and renal replacement therapy during ECMO, all surrogates of patient severity, were independently associated with a lower likelihood of being successfully weaned from mechanical ventilation at day 90.\u003c/p\u003e \u003cp\u003eThe ECMO duration until SGOT was unexpectedly found to be not different between the two groups in our study. One could argue that waiting for patients to be able to undergo spontaneous breathing ventilation could expose them to a longer ECMO run and therefore greater likelihood of ECMO-related complications. Interestingly, severe bleeding and pneumothorax incidence were similar between the two groups. These findings are reassuring, suggesting that maintaining V-V ECMO support until being on spontaneous ventilation appears to be a safe strategy. This strategy did not increase the likelihood of successful mechanical ventilation weaning but was associated with a shorter duration of post-ECMO ventilation, hospital length of stay, and in-hospital mortality. A weaning ECMO strategy waiting for spontaneous breathing during SGOT may also reduce the cost and resource consumption following decannulation. However, a lower pre-ECMO severity, which allowed a more rapid improvement of lung functions in the spontaneous breathing group, could also partially explain these findings. Identifying the most relevant time for an SGOT still warrants further investigation.\u003c/p\u003e \u003cp\u003eAlthough it is to date the largest study on mechanical ventilation modalities during SGOT, we acknowledge that our study has several limitations. First, given its retrospective design, it is not possible to establish direct causal relationships, but only associations. Second, there might be a bias due to the inclusion of patients from two distinct ECMO centers, with possibly different practices in ECMO management. Third, we did not collect data regarding the use of adjunct therapies for ARDS post-ECMO weaning in both groups, which may also have an important impact on economic and human resources. Lastly, our follow-up was limited to 90 days after ECMO weaning. Exploring the impact of these ventilation strategies on long-term lung function or psychological status could be valuable.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eA strategy comprising spontaneous breathing during SGOT was not associated with a higher incidence of successful weaning from mechanical ventilation, compared to controlled mechanical ventilation. However, spontaneous breathing during SGOT was associated with a shorter duration of mechanical ventilation and ICU length of stay after ECMO discontinuation, without exposure to more frequent ECMO-related complications. Further research is needed to assess the optimal ventilation strategy during weaning off V-V ECMO and its impact on short- and long-term outcomes.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConcept and design:\u003c/em\u003e Passarelli, Petit, Giani, Schmidt.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcquisition, analysis, or interpretation of data:\u003c/em\u003e All authors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDrafting of the manuscript:\u003c/em\u003e Passarelli, Petit, Giani, Schmidt.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCritical revision of the manuscript for important intellectual content:\u003c/em\u003e All authors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis:\u003c/em\u003e Passarelli, Petit, Schmidt.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures:\u003c/strong\u003e Dr. Matthieu Schmidt reports lecture fees from Getinge, Dr\u0026auml;ger, Baxter, and Fresenius Medical Care outside the submitted work. Dr. Alain Combes reports grants from Getinge, and personal fees from Getinge, Baxter, and Xenios outside the submitted work. No other disclosures were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u003c/strong\u003e None\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSlutsky AS, Ranieri VM (2013) Ventilator-Induced Lung Injury. N Engl J Med 369:2126\u0026ndash;2136. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMra1208707\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1208707\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCombes A, Hajage D, Capellier G et al (2018) Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. 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Crit Care Med. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/CCM.0000000000006041\u003c/span\u003e\u003cspan address=\"10.1097/CCM.0000000000006041\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"acute respiratory distress syndrome, extracorporeal membrane oxygenation, weaning, mechanical ventilation, spontaneous breathing","lastPublishedDoi":"10.21203/rs.3.rs-3990147/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3990147/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives: \u003c/strong\u003eTo describe clinical characteristics, mechanical ventilation strategies, and outcomes in patients with severe acute respiratory distress syndrome (ARDS) during\u003cstrong\u003e \u003c/strong\u003eweaning from venovenous extracorporeal membrane oxygenation (VV ECMO).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign: \u003c/strong\u003eRetrospective, multicenter cohort study over 7 years.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSettings: \u003c/strong\u003eTwo tertiary ICUs, high-volume ECMO centers in France and Italy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients: \u003c/strong\u003ePatients with ARDS on ECMO and successfully weaned from VV ECMO.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurements and main results: \u003c/strong\u003ePatients were classified based on their mechanical ventilation modality during the sweep gas-off trial (SGOT) with either controlled mechanical ventilation or spontaneous breathing (i.e. pressure support ventilation). The primary endpoint was the time to successful weaning from mechanical ventilation within 90 days post-ECMO weaning. Among 393 adult patients with severe ARDS successfully weaned from ECMO, 292 were on controlled ventilation, and 101 were on spontaneous breathing during SGOT. The 90-day probability of successful weaning from mechanical ventilation was not significantly different between the two groups (sHR [95%CI], 1.23[0.84-1.82]). However, spontaneous breathing during SGOT was associated with a shorter duration of mechanical ventilation and ICU length of stay after ECMO discontinuation, without an increase of ECMO-related complications, such as severe bleeding or pneumothorax, compared to controlled ventilation. After adjusting for covariates, older age, higher pre-ECMO sequential organ failure assessment score, pneumothorax, ventilator-associated pneumonia, and renal replacement therapy were independently associated with a lower probability of successful weaning from mechanical ventilation after ECMO weaning. Contrarily, mechanical ventilation modalities during SGOT did not demonstrate an independent association with the likelihood of successful weaning.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eA weaning ECMO strategy incorporating spontaneous breathing during SGOT appears safe and is associated with favorable outcomes. Further research is needed to assess the optimal ventilation strategy during weaning off VV ECMO and its impact on short- and long-term outcomes.\u003c/p\u003e","manuscriptTitle":"Mechanical ventilation settings during weaning from venovenous extracorporeal membrane oxygenation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-11 19:14:06","doi":"10.21203/rs.3.rs-3990147/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":"4e70ce0f-c3fd-48c6-a3da-a73ec979d301","owner":[],"postedDate":"March 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-28T12:04:52+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-11 19:14:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3990147","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3990147","identity":"rs-3990147","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}