Elsevier

The Lancet Neurology

Volume 5, Issue 2, February 2006, Pages 140-147
The Lancet Neurology

Fast track — Articles
Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial

https://doi.org/10.1016/S1474-4422(05)70326-4Get rights and content

Summary

Background

Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial.

Methods

92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (TiMCS and Tisym) and mean improvement (μMCS and μsym) were measured.

Findings

NIV improved TiMCS, Tisym, μMCS, μsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0·006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including μsym (p=0·018), but conferred no survival benefit.

Interpretation

In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.

Introduction

Amyotrophic lateral sclerosis, also known as motor neuron disease, is one of the commonest neurodegenerative conditions of adult life. Progressive weakness of limb, axial, bulbar, and respiratory muscles due to motor neuron injury and eventual cell death results in disability and ultimately death, usually within 3 years of onset. Respiratory muscle function is a strong predictor of quality of life1 and survival.2, 3 Although death is usually due to respiratory failure, most patients in Europe and the USA do not receive non-invasive ventilation (NIV),4, 5, 6 reflecting clinical uncertainty about its role in this condition. NIV has not been shown to improve quality of life or survival in a randomised controlled trial, but people with amyotrophic lateral sclerosis who use NIV survive longer than those who are intolerant of or decline treatment7, 8 or non-randomised controls.9 Small prospective studies of NIV have established improvement in various domains of quality of life,10, 11, 12, 13 but none included a contemporaneous and well-matched control group, and only a few people had bulbar weakness, suggesting that only selected patients with amyotrophic lateral sclerosis were included. In our uncontrolled pilot study,13 NIV was associated with improved quality of life as assessed by several instruments. The mental component summary of the short form 36 (SF36) and the symptoms domain of the sleep apnoea quality-of-life index (SAQLI) were the most responsive to intervention with NIV.13 Of five different criteria for initiation of NIV, orthopnoea was the best predictor of quality-of-life benefit and adherence to treatment.13

In this randomised controlled trial, we aimed to determine the effect of NIV on quality of life and survival in a typical population of patients attending a single regional centre. The study was designed to assess the general applicability of NIV across the clinical spectrum of patients with amyotrophic lateral sclerosis.

Section snippets

Trial design and participants

We obtained ethical approval for the study from the local research ethics committee and informed consent from all participants. The only exclusion criteria were current or previous use of NIV, life-threatening comorbidity, age older than 75 years, or inability to complete the quality-of-life assessment because of cognitive impairment or inability to communicate by speech or lightwriter. Patients who indicated that they did not wish their lives to be prolonged by medical intervention were still

Results

Of 121 patients attending the centre and potentially available for the study, 19 did not meet inclusion criteria and ten eligible patients declined enrolment (figure 1). Of the 92 people enrolled, 41 met one or both criteria for randomisation during the period of surveillance, from September, 2000, to December, 2003, (22 NIV, 19 standard care). Follow up continued for a further 12 months. 38 randomised patients had orthopnoea, and 20 of these had a normal PaCO2 (12 NIV, eight standard care) and

Discussion

This randomised trial shows that NIV improves both quality of life and survival in patients with amyotrophic lateral sclerosis. In some amyotrophic lateral sclerosis centres NIV is applied so enthusiastically that this trial might be considered controversial for ethical reasons. However, the possible benefits of NIV have not been proved in a randomised controlled trial and any benefits might be outweighed by the associated inconvenience and discomfort from the use of NIV, especially for

References (41)

  • JC Desport et al.

    Nutritional status is a prognostic factor for survival in ALS patients

    Neurology

    (1999)
  • ES Louwerse et al.

    Amyotrophic lateral sclerosis: mortality risk during the course of the disease and prognostic factors. The Netherlands ALS Consortium

    J Neurol Sci

    (1997)
  • GD Borasio et al.

    Standards of palliative care for patients with amyotrophic lateral sclerosis: results of a European survey

    Amyotroph Lateral Scler Other Motor Neuron Disord

    (2001)
  • SC Bourke et al.

    Non-invasive ventilation in motor neuron disease: current UK practice

    Amyotroph Lateral Scler Other Motor Neuron Disord

    (2002)
  • WG Bradley et al.

    Current management of ALS: comparison of the ALS CARE Database and the AAN Practice Parameter. The American Academy of Neurology

    Neurology

    (2001)
  • LS Aboussouan et al.

    Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis

    Ann Intern Med

    (1997)
  • H Hein et al.

    Intermittent assisted ventilation in neuromuscular diseases: course and quality of life

    Pneumologie

    (1999)
  • RA Lyall et al.

    A prospective study of quality of life in ALS patients treated with noninvasive ventilation

    Neurology

    (2001)
  • LS Aboussouan et al.

    Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis

    Muscle Nerve

    (2001)
  • SC Bourke et al.

    Non invasive ventilation in ALS: indications and effect on quality of life

    Neurology

    (2003)
  • Cited by (865)

    • Supporting patients with hypercapnia

      2024, Clinical Medicine, Journal of the Royal College of Physicians of London
    • Palliative Care in Amyotrophic Lateral Sclerosis

      2023, Journal of Pain and Symptom Management
    View all citing articles on Scopus
    View full text