Frequency of Screening and SBT Technique Trial - North American Weaning Collaboration (FAST-NAWC): a protocol for a multicenter, factorial randomized trial

Weaning from invasive mechanical ventilation (MV) is the process during which the work of breathing is transferred from the ventilator back to the patient. Nearly 40% of the time spent on invasive MV is dedicated to weaning [1, 2]. Although invasive MV is effective in managing respiratory failure, its use is associated with the development of numerous complications including ventilator-associated pneumonia (VAP) and respiratory muscle weakness [3]. The risk for VAP increases after the fifth day of invasive MV, is associated with substantial morbidity, and may increase mortality [4]. Conversely, premature or failed attempts at extubation necessitating reintubation are also associated with greater risk of VAP [5], prolonged intensive care unit (ICU) stay, and increased mortality [6, 7]. Consequently, in their efforts to minimize patient’s exposure to invasive MV, clinicians are challenged by a “trade-off” between the complications associated with protracted ventilation and the risks associated with failed attempts at extubation [8].

More than two decades of research support the use of specific strategies to limit invasive MV including: (1) the use of multidisciplinary screening protocols to identify appropriate candidates for a spontaneous breathing trial (SBT) [9, 10]; (2) the conduct of SBTs [6, 7, 11, 12] in patients who pass screening criteria; and (3) the use of specific modes and techniques (reductions in Pressure Support [PS]) and once daily (OD) SBTs (PS ± positive end expiratory pressure [PEEP] or T-piece) [12‐14] to discontinue ventilator support in patients who fail an initial SBT. In a 2014 Cochrane review of 17 RCTs (n = 2434), use of an SBT screening protocol compared to usual care was associated with significant reductions in weaning time, duration of MV, and ICU stay [9]. However, the strength of the conclusions that could be made from this meta-analysis were limited by heterogeneous populations, individual study risk of bias, and comparison of OD screening (intervention arm) to usual care (control arm) in most included trials. Importantly, no trial in this review compared more frequent screening to daily screening. Only one trial (n = 385) compared twice daily screening to usual care and noted a significantly shorter duration of MV and a trend toward a lower VAP with twice daily screening [15]. In national and international weaning surveys, daily SBT screening is the current standard of care [16, 17]. Notwithstanding, daily screening may be poorly aligned with the continuous care provided in most ICUs because it is not patient-centered and disregards the impact that treatment interventions, initiated after morning patient care rounds (e.g. reducing sedation), may have on SBT screening efforts later in the day.

The preferred technique to conduct an SBT remains unclear. Although PS SBTs are more commonly used in North America, significant inter-institutional variability exists in how SBTs are conducted [18]. Two meta-analyses of randomized controlled trials (RCTs) compared PS and T-piece weaning, including, but not limited to, the conduct of SBTs, found beneficial effects of PS weaning [19, 20]. Similarly, a meta-analysis that directly compared alternative SBT techniques [11] and two guidance documents [12, 21] support use of PS SBTs. Conversely, a physiologic meta-analysis favored use of T-piece SBTs [22].

Although a large body of evidence regarding weaning and SBT conduct exists, it remains insufficient to guide care regarding how frequent SBT screening should occur and the SBT technique that should be used. The around-the-clock availability of respiratory therapists (RTs) in most North American ICUs presents a unique opportunity to identify the optimal SBT screening frequency and SBT technique. In the Frequency of Screening and SBT Technique – North American Weaning Collaborative (FAST-NAWC) Trial, we will compare the effect of different screening frequencies (OD vs at least twice daily [ALTD]) and SBT techniques (PS + PEEP vs T-piece) in critically ill adults on time to successful extubation [23].

The FAST-NAWC Trial is novel in several ways. First, the FAST-NAWC Trial will be the largest weaning trial conducted in the North America where weaning involves close collaboration between RTs and physicians. Second, the FAST-NAWC seeks to identify the optimal SBT screening frequency and SBT technique to minimize patients’ exposure to invasive ventilation and ventilator-related complications. Third, this trial is being implemented with novel collaborations between Canadian and American research networks and respiratory care and critical care societies. Finally, the FAST-NAWC Trial is being conducted with the input of ICU survivors and family members. They will ensure that the trial is implemented in a manner that is sensitive to patient’s and families’ needs.

To address the concerns that elderly, critically ill patients may experience more AEs with more frequent SBT screening and be less likely to be enrolled in this trial due to concomitant treatment limitations and co-morbidities, we conducted two parallel, multicenter, pilot screening frequency trials [25]. Both trials compared OD with ALTD screening in elderly patients aged ≥ 65 years (SENIOR Trial; ClinicalTrials.gov NCT02243449; 11 ICUs) and non-elderly patients aged < 65 years (RELEASE Trial; NCT02001220; 10 ICUs) [25]. Recognizing the need to change screening culture, we prioritized the evaluation of SBT screening frequency and permitted centers to use their preferred SBT technique in both pilot trials. We demonstrated similar recruitment and consent rates, few AEs, and comparable outcomes in younger and older patients [25]. Conduct of the pilot trials enabled us to refine several exclusion criteria and enhance the generalizability of our findings. Subsequently, we conducted a factorial design, FAST pilot trial (n = 110) comparing both screening frequency and SBT technique [48]. With this trial, we refined recruitment estimates, identified barriers to recruitment, and assessed potential co-interventions. Patients enrolled in the FAST pilot trial will be included in the FAST-NAWC trial.

Careful consideration has been given to important aspects of the FAST-NAWC study design to limit selection, identification, treatment, and performance bias in this necessarily unblinded weaning trial. To limit selection bias, we will use a central randomization process with full allocation concealment. To limit identification bias, RTs will conduct SBT screening assessments and SBTs. To limit delays in identifying SBT candidates, we avoided use of subjective assessments in selecting our SBT screening criteria (e.g. level of consciousness, no sedation, no vasopressors, hemoglobin > 100 g/L). Conversely, we included an objective test, the rapid shallow breathing index (f/VT) [26], measured on standardized settings, in all SBT screening assessments. We will record practices before SBT screening that have the potential to influence SBT performance including pain, sedation, and delirium management and whether patients are being mobilized. To enhance the generalizability of our findings, we will permit SBTs to be 30–120 min in duration at clinician’s discretion. Finally, to limit treatment bias, we provided guidance on: (1) titration of ventilator settings, PEEP, and FiO₂; (2) use of NIV after extubation; (3) reintubation; and (4) tracheostomy.

Establishing the optimal screening frequency and SBT technique is appealing to ICU clinicians because these interventions are sensible, low-risk, and represent an efficient use of current resources. Findings from this trial have the potential to change clinical practice, enhance the care delivered to critically ill adults, and improve outcomes.