Background and objectiveNo studies have evaluated the impact of different settings of non-invasive ventilation (NIV) in patients affected by amyotrophic lateral sclerosis (ALS). We explored consequences of positive end-expiratory pressure (PEEP) application on effectiveness of ventilation, sleep architecture and heart rate variability (HRV) in patients with ALS naive to ventilatory treatment. MethodsIn two consecutive nights, 25 patients received in random order 0 or 4cmH(2)0 of PEEP during nocturnal NIV administration (Idea Ultra ResMed) with the same level of total positive inspiratory pressure. Polysomnographies were performed to evaluate sleep and NIV quality, as well as HRV. HRV was analyzed on 4-h periods and on 5-min segments of stable NREM sleep. ResultsWe did not observe differences in gas exchanges during NIV with and without PEEP. Conversely, during PEEP application increases in leaks (41.429.3% vs 31.025.7%, P=0.0007) and in autotriggerings (4.2 (IQR 1.3-10.0) vs 0.9 (IQR 0.0-3.0) events/h, P<0.001, PEEP vs no PEEP, respectively) occurred. Besides, N3 sleep stage duration decreased (2.5% (IQR 0.0-18.0) vs 0.0% (IQR0.0-12.1), P=0.001) and arousal/awakening index increased (16.9 +/- 7.4 vs 13.4 +/- 5.0 events/h, P=0.01). Data on HRV were available in 15 patients. A higher low/high frequency ratio, either in the 4-h (3.8 +/- 2.6 vs 2.9 +/- 1.7, P=0.04, PEEP vs no PEEP, respectively) or in the 5-min segments (2.6 +/- 1.8 vs 1.45 +/- 0.9 P=0.01) was found during PEEP administration. ConclusionIn ALS patients, PEEP application during NIV was associated with worse NIV and sleep quality and with higher sympathetic activity. In patients affected by amyotrophic lateral sclerosis, the administration of 4cmH(2)0 of positive end expiratory pressure during non-invasive ventilation increased unintentional leaks, patient-ventilator asynchronies and sleep fragmentation. Additionally it increased nocturnal sympathetic activity.