https://www.selleckchem.com/products/blu-285.html Reverse triggering (RT) occurs when respiratory effort begins after a mandatory breath is initiated by the ventilator. RT may exacerbate ventilator-induced lung injury and lead to breath stacking. We sought to describe the frequency and risk factors for RT amongst ARDS patients and identify risk factors for breath-stacking. Secondary analysis of physiologic data from children on Synchronized Intermittent Mandatory pressure control ventilation enrolled in a single center RCT for ARDS. When children had a spontaneous effort on esophageal manometry, waveforms were recorded and independently analyzed by two investigators to identify RT. We included 81,990 breaths from 100 patient-days and 36 patients. Overall, 2.46% of breaths were RTs, occurring in 15/36 patients (41.6%). Higher tidal volume and a minimal difference between neural respiratory rate and set ventilator rate were independently associated with RT (p=0.001) in multivariable modeling. Breath stacking occurred in 534 (26.5%) of 2017 RT breaths, and 14 (93.3%) of 15 RT patients. In multivariable modeling, breath stacking was more likely to occur when total airway delta pressure (Peak Inspiratory Pressure-PEEP) at the time patient effort began, Peak Inspiratory Pressure, PEEP, and Delta Pressure were lower, and when patient effort started well after the ventilator initiated breath (higher phase angle) (all p<0.05). Together these parameters were highly predictive of breath stacking (AUC 0.979). Patients with higher tidal volume and who have a set ventilator rate close to their spontaneous respiratory rate are more likely to have RT, which results in breath stacking over 25% of the time. Clinical trial registered with ClinicalTrials.gov (NCT03266016). Patients with higher tidal volume and who have a set ventilator rate close to their spontaneous respiratory rate are more likely to have RT, which results in breath stacking over 25% of the time. Clinical trial regis