Innovative ventilation technologies used in the intensive care unit for adults and children: a scoping review

Patient and public involvement

This review is part of a larger programme of work which aims to map current evidence underpinning innovative ventilation technologies across adults and children, and to appraise evidence on clinical and cost-effectiveness of promising technologies prioritised by key stakeholders.

We convened an expert reference group to inform the project design, delivery, and dissemination. The expert reference group included service commissioners (represented through NHS England), clinicians, and patients and carers with personal experience of invasive ventilation. We invited professional organisations (e.g., Intensive Care Society, Paediatric Intensive Care Society) to nominate clinician representatives. We identified and invited patient contributors through our local patient and public involvement research group, which helped design this study, and our other existing networks, such as the NIHR Applied Research Collaboration West Midlands PPI Network. The group met to agree terms of reference of the group and support the study team in identifying and mapping a list of innovative technologies to be included in our scoping review. To support the process of classifying interventions, we presented and discussed our early ideas on how best to characterise the ventilation care pathway using a conceptual model/ taxonomy. The project PPI co-applicant (MT) worked closely with the research team to provide day-to-day project support, ensuring that the project remains focussed on the interests of patients and members of the public.

Identification of innovative ventilation technologies

Our initial list of innovative ventilation technologies was developed through collaborator group knowledge and review of key clinical guidelines focussed on the care of invasively ventilated adults and children, including those developed by the European Society of Intensive Care Medicine, American Thoracic Society, Society of Critical Care Medicine and the UK Intensive Care Society^17–24. We worked in partnership with an expert advisory group comprised of clinicians, patient representatives, researchers, and service commissioners with expertise across adult and paediatric intensive care to refine our list of technologies and identify additional technologies. Our final list comprised 22 innovative ventilation technologies (Table 1).

Population, concept, context framework

We identified our review framework as:

Search strategy

We searched MEDLINE (Ovid), Embase (Ovid), Science Citation Index and Conference Proceedings – Science (WoS), Cochrane Library (Wiley), CEA Registry and ACM Digital Library in October 2023 and ran update searches in May 2024 using a combination of free-text and MeSH terms. We limited our search to studies published since 2010 to avoid including historical interventions which proved either ineffective or impractical to implement in practice. No language restrictions were applied. Our search strategy was iteratively developed by an information specialist (RC), in collaboration with clinical experts.

For emerging technologies and technologies under-represented in the included studies, we searched the following grey literature sources: internet (Google) searches, ProQuest Dissertations & Theses Global database, proceedings of selected conferences of interest (published 2021 onwards) and websites of relevant organisations. Our detailed search strategy is available in Appendix 1 (Extended data).

Study selection

We included studies that described the use of an innovative ventilation technology in adults and children at risk of requiring, or currently receiving, invasive mechanical ventilation. Our comparator of interest was standard care or another innovative ventilation technology. For innovative ventilation technologies used in patients receiving invasive mechanical ventilation, we included only intensive care unit studies. For innovative ventilation technologies used in patients at risk of requiring invasive mechanical ventilation, we included studies undertaken either on the intensive care unit or in the wider acute hospital. To be eligible, studies were required to report at least one outcome of interest, namely a patient-reported outcomes (e.g. quality of life), a clinical effectiveness outcome (e.g. mortality), a cost-effectiveness outcome, or a surrogate outcome that provides information about intervention efficacy (e.g. oxygenation).

Eligible study designs were randomised controlled trials, non-randomised comparative studies with a control group, systematic reviews, and economic evaluations. We excluded non-randomised studies with a repeated measure design as these were deemed to not include a comparator group. We excluded studies of neonates, defined as pre-term birth and/or those cared for exclusively in neonatal intensive care units. We excluded animal studies as, whilst they can be helpful in identifying therapeutic targets for clinical testing, the generalisability of findings from animal models of invasive mechanical ventilation to humans is limited²⁵. A detailed overview of study eligibility criteria is available in Appendix 2.

Titles and abstracts were screened by a single review team member. For each review team member, a 10% sample of records was independently screened by another reviewer to ensure consistency in decision-making. An agreement level of 90% was deemed to represent an adequate level of agreement. Following title and abstract screening, two reviewers independently screened the full texts of potentially eligible studies, and recorded reasons for exclusion of ineligible studies. We resolved any disagreement through discussion or, if required, consultation with a third reviewer.

Study classification and data charting

Eligible studies were coded/charted based on key features, namely: innovative ventilation technology type, patient population, stage of ventilation care pathway, study design, sample size, outcome measures, setting, and sources of funding. To support our mapping, we developed a taxonomy to define stage in the ventilation care pathway, based on previous studies²⁶. Our taxonomy, as shown in Figure 1, comprised four stages, namely: innovative technologies to reduce the risk of requiring invasive mechanical ventilation (stage one); innovative technologies used during invasive mechanical ventilation to support treatment of acute respiratory failure, including optimisation of oxygenation, and to minimize ventilator induced lung injury (stage two); innovative technologies to support the process of weaning from invasive mechanical ventilation (stage three); and innovative technologies to reduce risk of re-intubation following extubation (stage four).

Figure 1. Ventilator care pathway overview.

An individual reviewer extracted data from each study. The extraction in 20% of studies was checked by a second reviewer and disagreements resolved by discussion. No quality assessment was undertaken for included studies, in line with commonly adopted approaches to undertaking scoping reviews¹⁶.

Data synthesis and output

We synthesised and summarised data in two complementary ways.

Narrative summaries: We presented a series of summary tables to show the volume and nature of evidence for each innovative ventilation strategy across all patients and for key sub-groups (e.g. population type (adults/ children), and stage of the invasive ventilation care pathway). These were accompanied by brief texts highlighting key features of the evidence base.

Evidence maps: These provide visual representation of all evidence across all patients and innovative technologies²⁷. The evidence maps were created in two formats: first we created a Sankey diagram using the online SankeyMATIC to illustrate the complex relationships between key features of included studies; second we produced detailed cross-tabulation of the number of studies for individual innovative ventilation strategies broken down by key study features, separately for adults and children.

Search results

Our search identified a total of 22,274 records after de‐duplication and removal of some publication types. After screening of titles and abstracts and removal of 20,937 irrelevant records, we retrieved 1337 potentially relevant reports for detailed assessment. After assessment of the full‐text papers, we included 851 studies. A summary of the search results and study selection process is displayed in the study selection flow diagram (Figure 2). A list of all the included studies is provided in Appendix 3.

Figure 2. Study selection flow chart.

Overall volume and nature of evidence

The included studies were mapped onto 22 innovative ventilation strategies (Table 2). Most studies focused on the use of non-invasive respiratory support strategies to either prevent the initial need for invasive mechanical ventilation (n=319, 37%) or prevent the need for re-intubation following tracheal extubation (n=130, 15%). Other areas with a high number of studies included closed-loop ventilation modes (n=78, 9%), extracorporeal membrane oxygenation for acute hypoxaemic respiratory failure (n=79, 9%), neurally-adjusted ventilatory assist (n=63, 7%) and airway pressure release ventilation (n=36, 4%). Technologies where few eligible studies were identified included driving pressure/ mechanical pressure limited ventilation (n=13, 1%), mechanical insufflation-exsufflation (n=12, 1%), phrenic nerve stimulation (n=2, <1%) and lung and diaphragm protective ventilation (n=1, <1%). Figure 3 illustrates the volume and key features of evidence across the four stages of the ventilation care pathway.

Figure 3. Sankey diagram summarising studies by design, population, stage of the ventilation care pathway, technology and outcome.

ECMO- Extracorporeal membrane oxygenation; APRV- Airway pressure release ventilation; ECCO₂R- Extracorporeal carbon dioxide removal; HFOV- high-frequency oscillatory ventilation; NAVA- neurally adjusted ventilatory assist; SBT- spontaneous breathing trial

Geographically, primary research studies (n=564) spanned six continents, with 206 (36%) based in Europe, 198 (34%) in Asia, 90 (16%) in North America and 79 (14%) in other geographical areas. There were few studies that recruited across multiple continents (n=18, 3%). Figure 4 highlights the distribution of primary studies across countries.

Figure 4. Map showing number or primary research studies by country of origin.

Most of the included studies assessed outcomes of innovative ventilation technologies on adult patients (n=706, 83%) while only 15% of studies were conducted on children (n=128). The remaining studies (n=17, 2%) covered both adults and children.

The included studies evaluated technologies spanning across the four stages of the ventilation care pathway. Most of the included studies (n=343, 40%) evaluated the effectiveness of innovative technologies in reducing the risk of needing invasive ventilation. Many studies (n=289, 34%) assessed innovative technologies to support treatment of acute respiratory failure and minimise ventilator induced lung injury. A relatively smaller number of studies targeted interventions aimed at supporting the process of weaning from invasive ventilation (n=161, 19%) or reducing the risk of re-intubation (n=147, 17%).

We identified a large number of systematic reviews (n=277, 33%), with most of these reviews evaluating the effectiveness of non-invasive respiratory support strategies to either prevent the initial need for tracheal intubation (n=125, 45%) or prevent the need for re-intubation following tracheal extubation (n=40, 14%). Our scoping review included 564 (66%) primary studies; of which 327 (58%) were randomised controlled trials and 237 (42%) were observational studies. We identified only ten (1%) economic evaluations. The review identified more single-centre primary studies (405, 71%) than multi-centre studies (166, 29%). Industry funding was reported in 3% of the included studies (n=25), while 43% (n=365) were non-commercially funded. However, many studies (461, 54%) reported no receipt of external funding or provided no information about funding.

Most of the included studies used clinical (e.g., mortality and intubation rate, n=787, 92%) and surrogate outcomes (e.g., oxygenation parameters, n=517, 61%) to measure the effectiveness of innovative ventilation strategies. A limited number of studies reported the use of patient-reported outcomes (n=19, 2%) and cost-effectiveness outcomes (n=28, 3%).

Evidence in adults and children

Table 2 provides a breakdown of evidence by adults and children, and a detailed overview of evidence for each technology in adults and children is included in Appendix 4 and 5 (Extended data). For children, we identified 11 technologies where there was no primary research study. We also identified no economic evaluations or any study of COVID-19 respiratory failure. In general, the proportion of studies by funding type, reported outcomes and study type were similar across studies in adults and children. However, there tended to be more single-centre studies and North American studies in children. Sankey diagrams depicting the volume and type of evidence in adults and children can be found in Appendix 6 and 7 (Extended data).