A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management)

Abstract

Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO 2 , inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28day ventilator free days. Clinical Trials Registration: NCT03266016

Real-Time Effort Driven Ventilator Management: A Pilot Study*

“…Together, these findings justify using this tool in a larger, randomized clinical trial, which is currently ongoing (NCT03266016). [24] The physiological principles of lung protective ventilation have been advocated for the last 20 years. A variety of consensus and evidence based recommendations for both adults and children with ARDS specifically focus on limiting tidal volume and driving or plateau pressure, embracing permissive hypercapnia, using PEEP to prevent atelectotrauma, and minimizing FiO 2 exposure.…”

Extubation Readiness Practices and Barriers to Extubation in Pediatric Subjects

“…Because many subjects were extubated despite a breathing frequency above the target or a tidal volume below the target, it may be worth considering adjusting the protocol to tolerate slightly higher breathing frequencies and lower tidal volumes. 5,26 The rapid shallow breathing index combines both breathing frequency and tidal volume (the rapid shallow breathing index equals breathing frequency divided by tidal volume) and has been used to predict extubation success in adults, but only a few pediatric studies. [26][27][28] There is a lack of strong predictive rapid shallow breathing index values that account for different acceptable breathing frequencies in different age groups in the pediatric population.…”

Continuous Noninvasive Blood Gas Estimation in Critically Ill Pediatric Patients With Respiratory Failure

“…The main application of the model is likely to be when patients are in a relatively stable clinical state. Hopefully, it will be a viable tool for avoiding blood draws and facilitating continuous BG monitoring leading to more lung protective practices as we currently understand ventilation and oxygenation management 24 . Ventilator decision support protocols based on measurements of arterial BG have proven useful in the management of adult respiratory failure 20 .…”