# Identifying and preventing ventilator induced diaphragm weakness in children

> **NIH NIH R01** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2021 · $432,945

## Abstract

Project Summary
Nearly half of mechanically ventilated (MV), critically ill adults develop ventilator-induced respiratory muscle
weakness (particularly of the diaphragm), which impairs successful weaning from MV, often leads to re-
intubation, and is associated with higher post-ICU mortality. We have recently shown that respiratory muscle
weakness is associated with extubation failure in critically ill children, but we still lack crucial information on
the mechanisms and timing of this weakness, its importance for ventilator weaning, and its potential
prevention through promoting more physiologic levels of patient effort of breathing during MV.
Diaphragm weakness is most common in patients exposed to high levels of controlled ventilation. In children,
we have shown that usual care ventilator management is frequently associated with minimal patient effort of
breathing. To enhance patient effort, we developed a novel computer-based approach (Real-time Effort Driven
ventilator management (REDvent)), which offers systematic recommendations to reduce controlled ventilation
during the acute phase of MV, and uses real-time measures to adjust supported ventilator pressures such that
patient effort of breathing remains in a normal range during the ventilator weaning phase. Through a Phase I
clinical trial, we demonstrated that patients managed with REDvent spent fewer days on MV than historical
controls, and bedside providers could easily implement REDvent. Our central hypothesis is that REDvent use
will reduce ventilator-induced respiratory muscle weakness, leading to shorter time on MV by enhancing the
patient’s capacity for effective, unsupported ventilation and by facilitating MV weaning.
This application proposes a Phase II controlled clinical trial that will obtain comprehensive, serial assessments
of respiratory muscle strength and architecture to understand the evolution of ventilator-induced respiratory
muscle weakness in critically ill children, and test whether REDvent can preserve respiratory muscle strength
and reduce time on MV. Three integrated yet independent Specific Aims are proposed: SA 1 will determine
the clinical impact of REDvent by examining whether REDvent use for either acute or weaning phase ventilator
management results in shorter MV weaning times compared to usual care; SA 2 will use a sophisticated,
multi-modal approach to obtain a comprehensive view of respiratory muscle capacity, effort, load, and
architecture to quantify the importance of respiratory muscle weakness on weaning outcomes in children, and
identify when this weakness develops; SA 3 seeks to determine the independent effect of patient effort of
breathing on the development of respiratory muscle weakness, after controlling for known or suspected risk
factors for respiratory muscle weakness. Upon completion, this study will provide important information on
the pathogenesis and timing of respiratory muscle weakness during MV in children, whether this weakness can
...

## Key facts

- **NIH application ID:** 10178072
- **Project number:** 5R01HL134666-05
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Robinder Khemani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,945
- **Award type:** 5
- **Project period:** 2017-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178072

## Citation

> US National Institutes of Health, RePORTER application 10178072, Identifying and preventing ventilator induced diaphragm weakness in children (5R01HL134666-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178072. Licensed CC0.

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