Background: Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the commonest cause of death, usually within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the first update of a review first published in 2009.
Objectives: The primary objective of the review is to examine the efficacy of mechanical ventilation (tracheostomy and non-invasive ventilation) in improving survival in ALS. The secondary objectives are to examine the effect of mechanical ventilation on functional measures of disease progression and quality of life in people with ALS; and assess adverse events related to the intervention.
Search methods: We searched The Cochrane Neuromuscular Disease Group Specialized Register (1 May 2012), CENTRAL (2012, Issue 4), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), CINAHL Plus (January 1937 to April 2012), and AMED (January 1985 to April 2012). We also searched for ongoing studies on ClinicalTrials.gov.
Selection criteria: Randomised and quasi-randomised controlled trials involving non-invasive or tracheostomy assisted ventilation in participants with a clinical diagnosis of amyotrophic lateral sclerosis, independent of the reported outcomes. We planned to include comparisons with no intervention or the best standard care.
Data collection and analysis: For the original review, four authors independently selected studies for assessment and two authors reviewed searches for this update. All authors extracted data independently from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from included studies.
Main results: For the original Cochrane review, the review authors identified and included two randomised controlled trials involving 54 participants with ALS receiving non-invasive ventilation. There were no new randomised or quasi-randomised controlled trials at this first update.Incomplete data were published for one study and we contacted the trial authors who were not able to provide the missing data. Therefore, the results of the review were based on a single study of 41 participants that compared non-invasive ventilation with standard care. It was a well conducted study with low risk of bias.The study showed that the overall median survival was significantly different between the group treated with non-invasive ventilation and the standard care group. The median survival in the non-invasive ventilation group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% CI 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, the survival and quality of life benefit was much more in the subgroup with normal to moderately impaired bulbar function (20 participants); median survival was 205 days longer (216 days in NIV group versus 11 days in the standard care group, P = 0.0059). Non-invasive ventilation did not prolong survival in participants with poor bulbar function (21 participants), although it showed significant improvement in the mean symptoms domain of the Sleep Apnoea Quality of Life Index but not in the Short Form-36 Health Survey Mental Component Summary score. Neither trial reported clinical data on intervention related adverse effects.
Authors' conclusions: Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Future studies should examine the health economics of NIV and factors influencing access to NIV. We need to understand the factors, personal and socioeconomic, that determine access to NIV.