Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2018-028601 on 22 May 2019. Downloaded from http://bmjopen.bmj.com/ on February 14, 2022 at Univesity Autonomous of Barcelona. EPISYNC study: predictors of patient- ventilator asynchrony in a prospective cohort of patients under invasive mechanical ventilation - study protocol Mayson Laercio de Araujo Sousa, 1,2 Rudys Magrans,3,4 Fátima K Hayashi,1,2 Lluis Blanch,3,4 R M Kacmarek,5,6 Juliana C Ferreira1 To cite: Sousa MLA, Magrans R, Abstract Hayashi FK, et al. EPISYNC Introduction Patient-ventilator asynchrony is common Strengths and limitations of this study study: predictors of patient- during the entire period of invasive mechanical ventilation ventilator asynchrony in ►► This cohort study will provide important information (MV) and is associated with worse clinical outcomes. a prospective cohort of about the association between respiratory mechan- However, risk factors associated with asynchrony are patients under invasive ics and baseline patient characteristics and the in- mechanical ventilation - not completely understood. The main objectives of this cidence of patient-ventilator asynchrony analysed study protocol. BMJ Open study are to estimate the incidence of asynchrony during during the entire period of mechanical ventilation. 2019;9:e028601. doi:10.1136/ invasive MV and its association with respiratory mechanics ►► Multiple strategies will be put in place to enhance bmjopen-2018-028601 and other baseline patient characteristics. the precision and accuracy of our main predictors Methods and analysis We designed a prospective cohort ►► Prepublication history for and to mitigate the risk of bias. study of patients admitted to the intensive care unit (ICU) this paper is available online. ►► The primary outcome will be automatically mea- Protected by copyright. To view these files, please visit of a university hospital. Inclusion criteria are adult patients sured by a validated software, capable of continu- the journal online (http://​dx.​doi.​ under invasive MV initiated for less than 72 hours, and ously detecting the main types of asynchronies. org/​10.​1136/​bmjopen-​2018-​ with expectation of remaining under MV for more than ►► Limitations include the study location in a single 028601). 24 hours. Exclusion criteria are high flow bronchopleural centre, and the inability of algorithm of asynchrony fistula, inability to measure respiratory mechanics and Received 29 December 2018 to detect flow asynchronies. previous tracheostomy. Baseline assessment includes Revised 12 March 2019 clinical characteristics of patients at ICU admission, Accepted 28 March 2019 including severity of illness, reason for initiation of MV, and measurement of static mechanics of the respiratory programmed delivery of gas from the venti- system. We will capture ventilator waveforms during the lator.1 2 Asynchrony is a frequent event, entire MV period that will be analysed with dedicated present throughout the entire period of software (Better Care, Barcelona, Spain), which mechanical ventilation, although with highly automatically identifies several types of asynchrony and variable frequency, and is associated with calculates the asynchrony index (AI). We will use a linear regression model to identify risk factors associated with worse clinical outcomes, such as prolonged AI. To assess the relationship between survival and AI mechanical ventilation, longer intensive we will use Kaplan-Meier curves, log rank tests and Cox care unit (ICU) and hospital stay, respiratory regression. The calculated sample size is 103 patients. muscle injury, need for tracheostomy and The statistical analysis will be performed by the software R mortality.3–7 Programming (​www.​R-​project.​org) and will be considered Factors that influence the incidence of asyn- statistically significant if the p value is less than 0.05. chrony can be related to the patient, including Ethics and dissemination The study was approved by severity of illness, patient response to medical the Ethics Committee of Instituto do Coração, School of treatments and respiratory mechanics.8 Inves- Medicine, University of São Paulo, Brazil, and informed © Author(s) (or their tigators assessing patient-ventilator inter- employer(s)) 2019. Re-use consent was waived due to the observational nature of the action compared four groups of patients permitted under CC BY-NC. No study. We aim to disseminate the study findings through peer-reviewed publications and national and international with different underling diseases, and commercial re-use. See rights and permissions. Published by conference presentations. found that the incidence of asynchrony was BMJ. Trial registration number NCT02687802; Pre-results. higher in patients with chronic obstructive For numbered affiliations see pulmonary disease (COPD), who already end of article. have elevated airway resistance, especially Introduction in those with abnormal respiratory system Correspondence to Mayson Laercio de Patient-ventilator asynchrony can be static compliance.9 Other studies have also Araujo Sousa; defined as a mismatch between the output shown increased incidence of asynchrony in ​mayson.​laercio@​hc.​fm.u​ sp.​br of a patient’s respiratory centre and the COPD patients, associated with respiratory Sousa MLA, et al. BMJ Open 2019;9:e028601. doi:10.1136/bmjopen-2018-028601 1 Open access BMJ Open: first published as 10.1136/bmjopen-2018-028601 on 22 May 2019. Downloaded from http://bmjopen.bmj.com/ on February 14, 2022 at Univesity Autonomous of Barcelona. system mechanic abnormalities and higher ventilatory Box 1 Participant inclusion and exclusion criteria demand.3 10–12 These findings suggest that the under- lying disease and respiratory mechanics may play a role Inclusion criteriaInclusion criteria in the incidence of asynchrony. Respiratory mechanics ►► Mechanical ventilation initiated within 72 hours. are easy to measure at initiation of mechanical ventilation ►► Expectation of mechanical ventilation for more than 24 hours after and throughout the course of mechanical ventilation, enrolment. allowing the determination of the impact of respiratory ►► Age≥18 years. mechanics on the development of asynchrony. Exclusion criteriaExclusion criteria The most frequently used method to detect asynchrony ►► High flow bronchopleural fistula (pneumothorax with large air leaks is evaluation of ventilator waveforms. However, correct from the chest tube and continuous air bubbling). ►► Thoracic or abdominal deformities that could compromise the accu- identification requires well trained critical care profes- racy of respiratory mechanics measurement. sionals at the bedside at the time the asynchrony occurs, ►► Inability to measure respiratory mechanics (eg, death before respi- and is related with a number of factors, including the ratory mechanics measurement or physician’s decision not to use timing and duration of waveform evaluations.13–15 Hence, sedation and/or neuromuscular blockage). monitoring technologies have been recently developed to ►► Tracheostomy. continuously and automatically detect patient-ventilator asynchrony, especially ineffective effort and double trig- gering. One of those, recently validated by Blanch and colleagues (Better Care, Barcelona, Spain) can automat- (respiratory mechanics) and prevent possible missing ically detect the majority of asynchronies with accuracy data. Tracheostomy will be one of study outcomes, so similar to that of expert intensivists, with good sensitivity patients tracheostomised before ICU admission will be (91.5%) and specificity (96.2%).16 17 excluded. Therefore, we designed an observational cohort study Sampling and screening process to estimate the incidence of patient-ventilator asynchrony The target sample size for EPISYNC is 103 participants during invasive mechanical ventilation and its associa- (see below, statistical analysis), to be recruited in the tion with respiratory mechanics at intubation and others Protected by copyright. Respiratory ICU of School of Medicine, University of São baseline patient characteristics. We hypothesise that Paulo, Brazil, and we will use consecutive sampling. Daily, abnormal baseline respiratory mechanics—increased one of the investigators will screen all patients admitted airway resistance and intrinsic positive end-expiratory in the ICU; patients fulfilling all inclusion criteria and no pressure (PEEP) and decreased static compliance—are exclusion criteria will be included in study. For patients associated with an increase in the patient-ventilator asyn- submitted to more than one episode of mechanical venti- chrony index (AI). The secondary objectives include: lation during their hospital stay, only the first episode will (1) measurement of the level of agreement between be registered. clinical examination and visual inspection of the venti- lator screen at the bedside, with the AI automatically Study measures and data collection calculated by continuous analysis of ventilator waveforms We will describe the data collection in three steps, as and evaluation of the performance of clinical examina- shown in figure 1: baseline, follow-up during mechan- tion in the assessment of asynchrony at the bedside; and ical ventilation and postextubation follow-up. Main study (2) assessment of the relationship between the AI with measures and data collection schedule are shown in ventilator-free days, and ICU and hospital survival. This table 1. paper describes the study design and the EPIdemiology of a SYNChrony (EPISYNC) protocol. Baseline data Baseline respiratory mechanics—static compliance, airway resistance and intrinsic PEEP—will be calculated Methods within 72 hours postintubation, as soon as the patient is Study location and design included in the study. We will measure static properties of We designed a prospective cohort study, including the respiratory system consistent with the ICU’s routine patients under recent invasive mechanical ventilation, protocol for all invasively ventilated patients at admission. aged ≥18 years, and with expectation of mechanical venti- Measurements will be performed 15 min after endotra- lation for more than 24 hours after enrolment. cheal suctioning, using volume-controlled ventilation, Patients will be recruited in the Respiratory ICU of with tidal volume (VT) of 6 mL/kg of predicted body Hospital das Clínicas, School of Medicine, University of weight, square flow waveform and inspiratory flow of 0.5 São Paulo, Brazil. l/s, following the protocol used in our ICU. These stan- dardised ventilator settings will be used only to measure Eligibility criteria respiratory mechanics. After the measurements, the The inclusion and exclusion criteria are enumerated in mode of ventilation and its adjustments will be left to the box 1. Exclusion criteria were designed to ensure preci- ICU team’s discretion. We will calculate predicted body sion and accuracy of the principal predictive variables weight using the following equations (1): 2 Sousa MLA, et al. BMJ Open 2019;9:e028601. doi:10.1136/bmjopen-2018-028601 Open access BMJ Open: first published as 10.1136/bmjopen-2018-028601 on 22 May 2019. Downloaded from http://bmjopen.bmj.com/ on February 14, 2022 at Univesity Autonomous of Barcelona. Figure 1 Overview of EPISYNC protocol. ICU, intensive care unit. { } Trained respiratory therapists will use a checklist to Protected by copyright. 50 + 2.5 [height(cm) { × 0.394] − 60 ,}for male daily access the presence of clinically relevant patient-ven- (1) ‍45.5 + 2.5 [height(cm) × 0.394] − 60 , for female ‍ tilator asynchrony on days when the patient is not We will perform an end-inspiratory pause of 4 s and receiving neuromuscular blocking agents. The evaluation measure peak pressure (Ppeak) and plateau pressure (Pplat); will be done during the morning, with the patient in the then we will perform an end-expiratory pause of 4 s to semirecumbent position, 15 min after airway suctioning. measure total positive end-expiratory pressure (PEEPtotal), The check list includes observation of clinical signs of defined as the airway pressure at the end of the expiratory respiratory distress (box 2) and waveform observation pause. All variables will be measured three times and the on the ventilator screen. The respiratory therapists will mean values will be used. The equations used to calculate be trained to learn to recognise missed efforts, flow asyn- static compliance (Cstat) (2), airway resistance (Raw) (3) chrony, autotriggering, double triggering, short and and intrinsic PEEP (PEEPi) (4) are: prolonged cycling. They will observe the waveforms for VT 5 min, and then make a clinical judgement if asynchro- Cstat = Pplat−PEEPtotal (2) nous events appear to be present in more than 10% of ‍ ‍ Ppeak−Pplat the cycles. ‍Raw = Flow ‍(3) ‍PEEPi = PEEPtotal − PEEPsetting ‍(4) The daily checklist will also include Sequential Organ Failure Assessment, Richmond Agitation and Sedation If the patient continues receiving neuromuscular Scale, Behavioural Pain Scale and the Confusion Assess- blocking agents on the following days, the respiratory ment Method for the ICU. mechanics will be recalculated daily. Follow-up during mechanical ventilation Ventilator parameters The primary outcome measure is the AI, defined as the As mentioned above, we will use a software (Better Care, number of asynchronous events divided by the total Barcelona, Spain) capable of acquiring, analysing and number of ventilator cycles and wasted efforts multiplied recording signals from digital medical devices. Mechan- by 100.3 To estimate AI we will use the validated software ical ventilators and bedside monitors will be connected Better Care (Barcelona, Spain).16 The software will contin- to the acquisition software using a remote access server uously record airflow, airway pressure and tidal volume (ED41000P2-01—Lantronix, Irvine, California, USA). from study inclusion until liberation from the ventilator, To calculate AI, the software continuously captures tracheostomy, death or 28 days of mechanical ventila- the digital output of the mechanical ventilator and asso- tion. Secondary outcomes including ventilator-free days, ciates each acquired waveform with the parameter it tracheostomy and survival will be recoded on all patients. represents (airflow, air pressure and tidal volume). To The ventilators available in our ICU are Servo-i (Maquet) identify asynchronous events, the first step is to identify and Puritan Bennet 840 (Covidien). the mechanical ventilation mode (continuous positive Sousa MLA, et al. BMJ Open 2019;9:e028601. doi:10.1136/bmjopen-2018-028601 3 Open access BMJ Open: first published as 10.1136/bmjopen-2018-028601 on 22 May 2019. Downloaded from http://bmjopen.bmj.com/ on February 14, 2022 at Univesity Autonomous of Barcelona. Table 1 List of measures and data collection schedule Box 2 Clinical signs of respiratory distress/asynchrony Mechanical ventilation Postextubation ►► Tachypnoea. Baseline follow-up follow-up ►► Use of accessories muscles. Demographics X ►► Diaphoresis. Height X ►► Paradoxical diaphragmatic movement. Weight X ►► Subdiaphragmatic retraction. ►► Suprasternal, supraclavicular or intercostal retraction. Cause of ICU admission X ►► Cyanosis. Comorbidities X ►► Tachycardia. Smoking history X ►► Oxygen desaturation. SAPS 3 X ►► Others. Cause of intubation X Adapted from Pierson.23 ARDS criteria at admission X Static compliance X Airway resistance X mechanical ventilation, ventilator-free days, defined as the number of days alive and off the ventilator in the first Intrinsic PEEP X 28 days of ICU stay, the use of postextubation non-invasive PaO2/FiO2 X X ventilation, reintubation, tracheostomy, ICU and hospital Sedation scale (RASS) X X length of stay and mortality. Glasgow Coma Scale X X Delirium X Statistical analysis Behavioural Pain Scale X Analytic plan (BPS) Categorical variables will be presented as proportions and Pneumothorax X continuous variables will be reported as mean and SD or SOFA score X medians and IQR. To evaluate relationship between static compliance, Protected by copyright. Humidification system X Visual perception of X airway resistance and intrinsic PEEP and the AI, all contin- asynchrony on ventilator uous variables, we will use linear regression. To evaluate screen the relationship between AI and other categorical vari- Clinical signs of asynchrony X ables, we will dichotomise AI into AI ≤10% and AI >10%,4 Ventilator settings X and use χ2 test and logistic regression. Duration of mechanical X We will calculate AI for the entire duration of mechan- ventilation ical ventilation, the daily AI, and hourly AI, summing all Use of NIV postextubation X types of asynchrony, and by each type of asynchrony. We Tracheostomy X Mechanical ventilation free X days Table 2 Ventilatory data analysis and processing by Better Length of ICU stay X Care Length of hospital stay X Ineffective Abrupt decreases or increases in expiratory Discharge status (dead or X inspiratory flow by searching for a positive maximum alive) effort value followed by a negative minimum ARDS, acute respiratory distress syndrome; ICU, intensive care unit; value on the first arm of the flow curve and NIV, non-invasive ventilation; PEEP, positive end-expiratory pressure; then evaluating the deviations of these RASS, Richmond Agitation and Sedation Scale; SAPS3, Simplified Acute values against a monoexponential curve Physiology Score 3; SOFA, Sequential Organ Failure Assessment. representing the theoretical mean expiratory flow. (figure 2A) Double Two consecutively effective cycles that are airway pressure; volume control ventilation (VCV); pres- triggering separated by an expiratory time less than sure-controlled ventilation (PCV) and pressure support half the mean Ti (over the last 20 Ti), the first ventilation (PSV)), according to the pattern of inspiratory cycle triggered by the patient. (figure 2B) time (IT), flow, airway pressure and tidal volume. Then, Short cycling In PSV, Ti of the current breath is 50% in each breath, the software investigates the presence shorter than the averaged Ti (over the last 20 of ineffective expiratory effort and double triggering in Ti). (figure 2C) VCV, PCV and PSV; short cycling and prolonged cycling Prolonged In PSV, Ti of the current breath is 200% in PSV, as shown in table 2 and figure 2. cycling larger than the averaged Ti (over the last 20 Ti). (figure 2D) Postextubation follow-up We will follow patients until hospital discharge or death PCV, pressure-controlled ventilation.; PSV, pressure support ventilation; Ti, inspiratory time; VCV, volume control ventilation, within the hospital, and will compute the duration of 4 Sousa MLA, et al. BMJ Open 2019;9:e028601. doi:10.1136/bmjopen-2018-028601 Open access BMJ Open: first published as 10.1136/bmjopen-2018-028601 on 22 May 2019. Downloaded from http://bmjopen.bmj.com/ on February 14, 2022 at Univesity Autonomous of Barcelona. We will collect and manage all study data using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Brazil. REDCap is a secure, web-based application designed to support data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export proce- dures for seamless data downloads to common statis- tical packagesand (4) procedures for importing data from external sources.20 The final database will be cleaned, verified and archived. One official copy of all the study data and master data dictionary will be maintained and updated regularly by study data analysts. One copy of the backups will be saved in an external drive. The files can be shared only by authorised study personnel. Patient and public involvement Patients were not involved in the development of the research question or the design of this study. Ethics and dissemination Because we routinely perform respiratory mechanics Figure 2 Examples of asynchrony events detected by measurements in our ICU for all patients at admission Protected by copyright. Better Care. INSP, inspiratory; PAW, airway pressure; RESP, respiratory; VT, tidal volume. using sedation and neuromuscular blockage if necessary, and the study was non-interventional and did not inter- fere with usual care, informed consent was waived. The will also explore the role of clusters of ineffective effort protocol is registered in the international platform C ​ lin- and double triggering on clinical outcomes.18 19 icalTrials.​gov. To assess the relationship between survival and AI we will We will report study results in accordance to recom- use Kaplan-Meier curves, log rank tests and Cox regression. mended guidelines for reporting observational studies, The statistical analysis will be performed by the software the Strengthening The Reporting of Observational R Programming (R Core Team, Vienna, Austria; URL: Studies in Epidemiology.21 https://www.​R-​project.​org) and will be considered statis- The results of the primary study will be published in tically significant if the p value is less than 0.05. a peer-reviewed journal. Separate manuscripts will be written on secondary objectives and exploratory analysis Sample size and will also be submitted for publication in peer-re- We used G*Power 3.1 to calculate sample size. We esti- viewed journals. mated an effect size of 0.11, based on an expected increase in R² up to 0.10. Using an α of 0.05, a power of Current status 0.8 and testing three main predictors (static compliance, Recruitment of participants started at September 2016, airway resistance and intrinsic PEEP) and up to five more and we expect to complete this study by June 2019. baseline predictors, we calculated a total sample size of 103 patients. Discussion Quality control The EPISYNC study will provide important insights into Data collection and management the association between baseline patient characteristics, To enhance the precision and accuracy of our main including respiratory mechanics, and the incidence of predictors, we will measure baseline respiratory mechanics patient-ventilator asynchrony analysed during the entire three times and use the mean values. Given that this is an period of mechanical ventilation. Also, we aim to provide observational study, the choice of sedatives and neuromus- further insight into the association between asynchrony cular blockage agents and doses used will be at ICU physi- and clinical outcomes, such as ventilator-free days, and cian’s discretion, but we will use train-of-four monitoring ICU and hospital survival. These results will contribute (SunStim Plus, SunMed, Michigan, USA) to determine the to the knowledge base regarding asynchrony and its depth of neuromuscular blockage. Furthermore, we devel- epidemiology, and may influence ventilator guidelines to oped a manual of operations for all study-related activities. improve synchrony in critical ill patients. Sousa MLA, et al. BMJ Open 2019;9:e028601. doi:10.1136/bmjopen-2018-028601 5 Open access BMJ Open: first published as 10.1136/bmjopen-2018-028601 on 22 May 2019. Downloaded from http://bmjopen.bmj.com/ on February 14, 2022 at Univesity Autonomous of Barcelona. Our study has some limitations. First, the study is confined Provenance and peer review Not commissioned; externally peer reviewed. to a single centre, so the incidence of asynchrony will be Open access This is an open access article distributed in accordance with the influenced by the centre’s practice, specific ventilators Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, used and the manner in which ventilator management is and license their derivative works on different terms, provided the original work is provided. In addition, respiratory mechanics measurement properly cited, appropriate credit is given, any changes made indicated, and the use using neuromuscular blocking agents is not a universal stan- is non-commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/. dard and will not always be possible. Second, the algorithm of asynchrony detection has some limitations detecting References short cycling and prolonged cycling, and reverse triggering 1. Sassoon CS, Foster GT. Patient-ventilator asynchrony. Curr Opin Crit Care 2001;7:28–33. will be detected only when it results in double triggering. 2. Thille AW, Brochard L. Promoting Patient-Ventilator Synchrony. Clin Short cycling and prolonged cycling will not be detected Pulm Med 2007;14:350–9. in extreme cases of alternating breaths of very short Ti 3. Chao DC, Scheinhorn DJ, Stearn-Hassenpflug M. Patient-ventilator trigger asynchrony in prolonged mechanical ventilation. Chest with breaths with prolonged Ti. Furthermore, the Better 1997;112:1592–9. Care software is not able to detect flow asynchronies and 4. Thille AW, Rodriguez P, Cabello B, et al. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med auto triggering. However, several studies have shown that 2006;32:1515–22. these types of asynchrony have a very low incidence and 5. de Wit M, Miller KB, Green DA, et al. Ineffective triggering predicts that ineffective effort and double triggering are the most increased duration of mechanical ventilation. Crit Care Med 2009;37:2740–5. important types of asynchrony to calculate AI, and for these 6. Blanch L, Villagra A, Sales B, et al. Asynchronies during mechanical types of asynchrony our methodology is very accurate. And ventilation are associated with mortality. Intensive Care Med 2015;41:633–41. finally, the sample size was calculated based on the primary 7. Ferreira JC, Diniz-Silva F, Moriya HT, et al. Neurally Adjusted outcome variable and predictors, so we may be underpow- Ventilatory Assist (NAVA) or Pressure Support Ventilation (PSV) during spontaneous breathing trials in critically ill patients: a crossover trial. ered to detect differences in mortality. BMC Pulm Med 2017;17:139. Nonetheless, we believe that our results will be generalis- 8. Branson RD, Blakeman TC, Robinson BR. Asynchrony and dyspnea. able to ICUs in low and middle incoming countries, where Respir Care 2013;58:973–89. 9. Nava S, Bruschi C, Fracchia C, et al. Patient-ventilator interaction the burden of critically ill diseases is high and mortality and inspiratory effort during pressure support ventilation in patients rates of patients requiring ventilatory support is elevated.22 with different pathologies. Eur Respir J 1997;10:177–83. Protected by copyright. 10. Leung P, Jubran A, Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Author affiliations Care Med 1997;155:1940–8. 1 Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, 11. Parthasarathy S, Jubran A, Tobin MJ. Cycling of inspiratory and Faculdade de Medicina Universidade de Sao Paulo, Sao Paulo, Brazil expiratory muscle groups with the ventilator in airflow limitation. Am 2 Serviço de Fisioterapia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, J Respir Crit Care Med 1998;158:1471–8. 12. Jolliet P, Tassaux D. Clinical review: patient-ventilator interaction in Faculdade de Medicina Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil 3 chronic obstructive pulmonary disease. Crit Care 2006;10:236. Critical Care Center, Hospital Universitari Parc Taulí, Institut d'Investigació i 13. Colombo D, Cammarota G, Alemani M, et al. Efficacy of ventilator Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain waveforms observation in detecting patient-ventilator asynchrony. 4 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias Crit Care Med 2011;39:2452–7. (CIBERES), Instituto de Salud Carlos III, Sabadell, Spain 14. Chacón E, Estruga A, Murias G, et al. Nurses' detection of ineffective 5 Department of Respiratory Care, Massachusetts General Hospital, Boston, inspiratory efforts during mechanical ventilation. Am J Crit Care 2012;21:e89–93. Massachusetts, USA 15. Ramirez II, Arellano DH, Adasme RS, et al. Ability of ICU Health- 6 Department of Anesthesiology, Massachusetts General Hospital, Boston, Care Professionals to identify patient-ventilator asynchrony using Massachusetts, USA waveform analysis. Respir Care 2017;62:144–9. 16. Blanch L, Sales B, Montanya J, et al. Validation of the Better Care® system to detect ineffective efforts during expiration in Contributors MLdAS and JCF conceived and designed the protocol, drafted mechanically ventilated patients: a pilot study. Intensive Care Med the manuscript and were involved in acquisition of funding. MLdAS organised 2012;38:772–80. and performed the initial analysis of the data. All authors participated in the final 17. Murias G, Montanyà J, Chacón E, et al. Automatic detection of analysis of the data. RMK, LB, RM and FKH participated in the critical revision of the ventilatory modes during invasive mechanical ventilation. Crit Care manuscript for methodological and intellectual content. All authors approved the 2016;20:1–7. final version of the manuscript. 18. Vaporidi K, Babalis D, Chytas A, et al. Clusters of ineffective efforts during mechanical ventilation: impact on outcome. Intensive Care Funding The Episync study is supported by Fundação de Amparo à Pesquisa do Med 2017;43:184–91. Estado de São Paulo (FAPESP), grant number 2015/19122-4. 19. de Haro C, López-Aguilar J, Magrans R, et al. Double cycling during mechanical ventilation. Crit Care Med 2018;46:1385–92. Competing interests RMK reports grants and personal fees from Medtronic, 20. Harris PA, Taylor R, Thielke R, et al. Research electronic data capture personal fees from Orange Medical, grants from Venner Medical, outside the (REDCap)--a metadata-driven methodology and workflow process submitted work. LB is inventor of one Corporació Sanitaria Parc Taulí owned US for providing translational research informatics support. J Biomed patent: ‘Method and system for managed related patient parameters provided by a Inform 2009;42:377–81. monitoring device,’ US Patent No. 12/538,940, founder of BetterCare S.L. which is a 21. von Elm E, Altman DG, Egger M, et al. The Strengthening the research and development company, start up of Corporació Sanitària Parc Taulí. JCF Reporting of Observational Studies in Epidemiology (STROBE) reports grants from FAPESP (Brazilian funding agency), during the conduct of the statement: guidelines for reporting observational studies. J Clin Epidemiol 2008;61:344–9. study; personal fees from Medtronic, outside the submitted work. 22. Azevedo LC, Park M, Salluh JI, et al. Clinical outcomes of patients Patient consent for publication Not required. requiring ventilatory support in Brazilian intensive care units: a multicenter, prospective, cohort study. Crit Care Ethics approval The EPISYNC protocol was approved by the institutional review 2013;17:R63. board of Instituto do Coração, School of Medicine, University of São Paulo, Brazil 23. Pierson DJ. Patient-ventilator interaction. Respir Care (reference number 1.327.840). 2011;56:214–28. 6 Sousa MLA, et al. BMJ Open 2019;9:e028601. doi:10.1136/bmjopen-2018-028601