Associative increases in amyotrophic lateral sclerosis survival duration with non-invasive ventilation initiation and usage protocols

• Authors: Nishad Khamankar, Emory University; Grant Coan, University of Texas; Barry Weaver, Emory University; Cassie Mitchell, Emory University
• Journal Title: Frontiers in Neurology
• Volume: Volume 9, Number JUL
• Publisher: Frontiers Media | 2018-07-12
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3389/fneur.2018.00578
• Subjects: Health Sciences, Pathology; Engineering, Biomedical
• Keywords: non-invasive ventilation; palliative care; neuromuscular disease; respiratory intervention; survival duration

Abstract

Objective: It is hypothesized earlier non-invasive (NIV) ventilation benefits Amyotrophic Lateral Sclerosis (ALS) patients. NIV typically consists of the removable bi-level positive airway pressure (Bi-PAP) for adjunctive respiratory support and/or the cough assist intervention for secretion clearance. Historical international standards and current USA insurance standards often delay NIV until percent predicted forced vital capacity (FVC %predict) is < 50. We identify the optimal point for Bi-PAP initiation and the synergistic benefit of daily Bi-PAP and cough assist on associative increases in survival duration. Methods: Study population consisted of a retrospective ALS cohort (Emory University, Atlanta, GA, USA). Primary analysis included 474 patients (403 Bi-PAP users, 71 non-users). Survival duration (time elapsed from baseline onset until death) is compared on the basis of Bi-PAP initiation threshold (FVC %predict); daily Bi-PAP usage protocol (hours/day); daily cough assist usage (users or non-users); ALS onset type; ALSFRS-R score; and time elapsed from baseline onset until Bi-PAP initiation, using Kruskal-Wallis one-way analysis of variance and Kaplan Meier. Results: Bi-PAP users' median survival (21.03 months, IQR = 23.97, N = 403) is significantly longer (p < 0.001) than non-users (13.84 months, IQR = 11.97, N = 71). Survival consistently increases (p < 0.01) with FVC %predict Bi-PAP initiation threshold: < 50% (20.3 months); ≥50% (23.60 months); ≥80% (25.36 months). Bi-PAP usage > 8 hours/day (23.20 months) or any daily Bi-PAP usage with cough assist (25.73 months) significantly (p < 0.001) extends survival compared to Bi-PAP alone (15.0 months). Cough assist without Bi-PAP has insignificant impact (14.17 months) over no intervention (13.68 months). Except for bulbar onset Bi-PAP users, higher ALSFRS-R total scores at Bi-PAP initiation significantly correlate with higher initiation FVC %predict and longer survival duration. Time elapsed since ALS onset is not a good predictor of when NIV should be initiated. Conclusions: The "optimized" NIV protocol (Bi-PAP initiation while FVC %predict ≥80, Bi-PAP usage > 8 h/day, daily cough assist usage) has a 30. 8 month survival median, which is double that of a "standard" NIV protocol (initiation FVC %predict < 50, usage > 4 h/day, no cough assist). Earlier access to Bi-PAP and cough assist, prior to precipitous respiratory decline, is needed to maximize NIV synergy and associative survival benefit.