An international, multi-centre, prospective, observational ICU cohort study of the PROVEnet supported by ESAIC (PRoVENT 2+)
One of the current Research groups was selected in 2022: PRoVENT 2+. Martin Scharffenberg, MD, the task force chair, led this prospective, international, multi-centre, observational cross-sectional study on intensive care units to mainly assess current MV strategies and outcomes in consecutive patients included in a fixed time frame. We aim to significantly increase the number of patients as in the PRoVENT study.
Mechanical ventilation (MV) is an essential and frequent treatment in intensive care units (ICU) but may initiate or aggravate lung injury, especially in the presence of acute respiratory distress syndrome (ARDS) 1. Thus, lung-protective MV, i.e. limited tidal volumes and distending pressures together with an adequate positive end-expiratory pressure (PEEP), is strongly recommended in international guidelines and paramount, especially in critically ill patients requiring long-term MV 2. While not only ARDS patients benefit from pressure- and volume-limited MV strategies, studies suggest that critically ill patients at risk of developing ARDS should also receive protective ventilation to improve outcomes 3. A large observational trial revealed significant differences in respiratory variables between patients at risk for ARDS as compared to those not at risk, while being at risk significantly worsened clinical outcomes 4. However, data were obtained a considerable time ago. Since then, evidence has grown, clinical procedures and routines may have changed in the meanwhile, and awareness for ventilator-induced lung injury (VILI) may have risen over the last years.
Nevertheless, the clinical practice may still be sub-optimal and differ from guidelines and evidence, while geo-economical variations 5,6 and even sex-related differences seven may still exist.
Furthermore, new VILI risk factors and potential mechanisms have been suggested in recent years. The driving pressure eight and mechanical power (MP) 9,10 were shown to be associated with both experimental lung injury and worsened clinical outcomes. However, the normal range of values and their respective association with ARDS development and mortality in non-ARDS patients remains elusive. It should be determined using a broadly pragmatic approach under the current real-world clinical routine. In recent years, mechanical ventilation research has been even more focused on ARDS due to the COVID-19 pandemic. However, we also need to ensure the safety of mechanically ventilated non-ARDS patients to avoid progression to ARDS.
Aim of the study
In invasively ventilated adult ICU patients, we aim to:
- Describe the current practice of mechanical ventilation
- Describe the epidemiological characteristics
- Assess utilisation of adjunctive therapies and diagnostics,
- Determine the likelihood of progression to ARDS, the incidence of non-diagnosed ARDS, and related complications,
- Assess overall mortality rate,
- Identify risk factors associated with the development of ARDS, complications, and mortality,
- Identify potential regional differences in the practice of mechanical ventilation,
- Compare new findings with previous trials (PRoVENT, PRoVENT-iMiC study), and characterise clinical approaches in sub-cohorts (neuro-surgery, thoracic surgery, COVID-19).
Study design, cohort, and protocol overview
PRoVENT 2+ is an investigator-initiated, international, multi-centre, prospective, observational cohort study aiming to collect routine clinical data on intensive care units worldwide. Adult ICU patients for whom invasive MV was initiated within a defined, study centre-selected enrolment window will be included. Patients aged <18 years and patients transferred from another hospital under ongoing ventilation will be excluded from the study. Each study centre can choose the starting point and the length of the enrolment window (1-4 weeks) to allow smaller centres to enrol more patients and large centres to reduce workload. Patient data, including medical history, respiratory and haemodynamic variables, as well as clinical endpoints, will be assessed on the day of initiation of invasive mechanical ventilation (day 0), daily between day 1 and 5 after that, as well as on day 7±1, day 14±2, day 21±2, day 28±2, and day 90±2 (Fig.1). The primary endpoint is the proportion of patients ventilated within protective limits, defined as tidal volume 6-10 ml/kg predicted body weight and PEEP 5-10 cmH2O (both criteria must be met). More endpoints are listed in Fig. 1.
The organisational structure of the PRoVENT 2+ study
The steering committee members of PRoVENT 2+ are listed in Fig.1. We are looking for national coordinating investigators (NCI) who will comply with national regulations and acquire participating centres in their respective countries. One physician at each study centre will be recruited as a local principal investigator and will be responsible for local scientific and structural leadership, data validity and integrity, compliance with local regulations, and their local research group. We will invite and select neuro and cardiac intensive care unit section coordinators.
Transparent authorship rules
We are dedicated to transparent and fair rules for co-authorship. Manuscripts are going to be published under the study group name. However, all active contributors and collaborators will be appropriately acknowledged to reward their efforts.
Please join the global study team!
PRoVENT 2+ shall be a worldwide study to gain representative, solid data from a broad patient cohort. We aim to significantly increase the number of patients compared to previous investigations. By this, PRoVENT 2+ shall be one of the largest prospective observational studies in invasively ventilated ICU patients, where “plus” stands for groups that have not been included before, e.g. cardiothoracic surgery, neurosurgery and COVID-19. However, this ambitious goal can only be achieved through your active participation and valuable contribution. Are you interested in taking an active role in this study and becoming a study centre of PRoVENT 2+? Do you need more details? Please get in touch with the chief investigator via email@example.com!
Further information can be found at https://www.esaic.org/research/research-groups/provent-2/. We are looking forward to fruitful collaborations. Let’s build evidence together!
- Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369(22):2126-2136. doi:10.1056/NEJMra1208707
- Fan E, Del Sorbo L, Goligher EC, et al. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017;195(9):1253-1263. doi:10.1164/rccm.201703-0548ST
- Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308(16):1651-1659. doi:10.1001/jama.2012.13730
- Neto AS, Barbas CSV, Simonis FD, et al. Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multi-centre, prospective study. Lancet Respir Med. 2016;4(11):882-893. doi:10.1016/S2213-2600(16)30305-8
- Pisani L, Algera AG, Neto AS, et al. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies. Lancet Glob Health. 2022;10(2):e227-e235. doi:10.1016/S2214-109X(21)00485-X
- Pisani L, Algera AG, Serpa Neto A, et al. Epidemiological Characteristics, Ventilator Management, and Clinical Outcome in Patients Receiving Invasive Ventilation in Intensive Care Units from 10 Asian Middle-Income Countries (PRoVENT-iMiC): An International, Multicenter, Prospective Study. Am J Trop Med Hyg. 2021;104(3):1022-1033. doi:10.4269/ajtmh.20-1177
- Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med. 2004;32(9):1817-1824. doi:10.1097/01.ccm.0000133019.52531.30
- Amato MBP, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372(8):747-755. doi:10.1056/NEJMsa1410639
- Cressoni M, Gotti M, Chiurazzi C, et al. Mechanical Power and Development of Ventilator-induced Lung Injury. Anesthesiology. 2016;124(5):1100-1108. doi:10.1097/ALN.0000000000001056
- Costa ELV, Slutsky A, Brochard LJ, et al. Ventilatory Variables and Mechanical Power in Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. Published online March 30, 2021. doi:10.1164/rccm.202009-3467OC
Funding: This study is financially supported by the European Society of Anaesthesiology and Intensive Care (ESAIC) in terms of an ESAIC Research Group.Read the Newsletter