Effect of Noninvasive Positive- Pressure Ventilation on Survival in Amyotrophic Lateral Sclerosis Loutfl Sami Aboussouan, MD; Saeed U. Khan, MD; David P. Meeker, MD; Kay Stelmach, RRT; and Hiroshi Mitsumoto, MD Background: Noninvasive positive-pressure ventilation may benefit patients with amyotrophic lateral sclerosis and respiratory insufficiency. Objective: To determine 1) whether patients tolerant of noninvasive positive-pressure ventilation have better sur- vival than intolerant patients and 2) whether bulbar symp- toms account for intolerance of noninvasive positive- pressure ventilation. Design: Observational cohort study. Setting: Tertiary care referral center. Patients: 39 patients with amyotrophic lateral sclerosis who were treated with noninvasive positive-pressure ven- tilation. Intervention: Noninvasive positive-pressure ventilation was started for patients with new orthopnea, new hyper- capnia, or both. Patients were divided into two groups: those tolerant of and those intolerant of noninvasive pos- itive-pressure ventilation. Results: The risk for death from onset of respiratory in- sufficiency was higher for intolerant patients than for tolerant patients (relative risk, 3.1 [95% CI, 1.8 to 9.6]). Moderate or severe bulbar symptoms were more prevalent among intolerant patients than among tolerant patients (67% compared with 33%; P = 0.04). Conclusions: Among patients with amyotrophic lateral sclerosis, those who are tolerant of noninvasive positive- pressure ventilation have better survival than do those who are intolerant. Bulbar symptoms partially account for intolerance of noninvasive positive-pressure ventilation. R espiratory failure is the most common cause of death in patients with amyotrophic lateral scle- rosis (1). Nocturnal noninvasive positive-pressure ventilation is the treatment of choice for patients with chronic respiratory insufficiency secondary to slowly progressive neuromuscular diseases (2). How- ever, the optimal use of noninvasive positive-pres- sure ventilation in amyotrophic lateral sclerosis re- mains undefined, and use of this intervention has raised several concerns. For instance, the course of amyotrophic lateral sclerosis varies, and some patients have a rapid decline in lung function (3). In addition, approxi- mately 50% of patients with neuromuscular diseases or sleep apnea are intolerant of positive-pressure devices (4, 5). Some investigators have discouraged use of this ventilation in patients with amyotrophic lateral sclerosis and bulbar symptoms (2, 6, 7). Fur- ther concern was raised by the finding of a survival disadvantage, relative to controls, in patients with Duchenne neuromuscular dystrophy who began re- ceiving noninvasive positive-pressure ventilation (8). Ethical considerations may preclude placebo- controlled trials in patients with amyotrophic lateral sclerosis because of the putative benefits of nonin- vasive positive-pressure ventilation (2) and the rap- idly fatal nature of the disease (9). We therefore sought to determine 1) whether patients with amyo- trophic lateral sclerosis and respiratory insufficiency who are tolerant of noninvasive positive-pressure ventilation have a survival advantage compared with those who are intolerant and 2) whether bulbar symptoms account for intolerance of noninvasive positive-pressure ventilation. Ann Intern Med. 1997;127:450-453. From Wayne State University School of Medicine, Detroit, Michigan; and the Cleveland Clinic Foundation, Cleveland, Ohio. For current author addresses, see end of text. Methods Study Sample Our study was done at the Cleveland Clinic Foundation between March 1993 and February 1996. The diagnosis of amyotrophic lateral sclerosis was based on the El Escorial World Federation of Neurology criteria (10). Follow-up evaluation at the neuromuscular clinic, including spirometry, was done every 3 to 6 months and as necessary. All patients who had dyspnea on exertion, hypercapnia, orthopnea, or an FVC less than 60% of the pre- dicted value were referred to the pulmonary clinic, where a clinical evaluation, pulmonary function tests, and tests for daytime arterial blood gases were done every 1 to 2 months. Bulbar symptoms were assessed by using the speech and swallow compo- nents of the amyotrophic lateral sclerosis severity scale and were graded as "absent to mild" or "mod- 450 15 September 1997 • Annals of Internal Medicine • Volume 127 • Number 6 Downloaded From: http://annals.org/ by a Penn State University Hershey User on 08/02/2013