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