Domiciliary non-invasive ventilation in stable COPD?

Chronic obstructive pulmonary disease (COPD) is the commonest indication for domiciliary non-invasive ventilation (NIV) in Europe. However, there is a paucity of evidence to support its use. A number of short-term randomised controlled trials (RCTs) failed to show any consistent benefit from NIV. In a crossover study comparing 3 months of bilevel ventilation plus long term oxygen therapy (LTOT) with LTOT alone, there were small improvements in arterial blood gas tensions during spontaneous breathing by day and in health-related quality of life (QOL) with NIV. In a longer term RCT, 20 patients randomised to NIV were compared with 24 controls; there was a reduction in the need for hospitalisation in the first 3 months in the NIV group but this effect disappeared by 1 year. One-year survival (78%) was similar in both groups. Dyspnoea, measured using the Borg scale, was reduced in the NIV group. In a larger RCT from Italy, 90 stable patients on oxygen for more than 6 months were randomly assigned to continuing oxygen alone or oxygen and bilevel ventilation. There was no change in survival, lung or inspiratory muscle function, exercise tolerance or sleep quality score in either group. By contrast, the arterial carbon dioxide tension (PaCO2) measured on usual oxygen and resting dyspnoea scores improved. Health-related QOL, as assessed by the Maugeri Foundation Respiratory Failure Questionnaire (MRF 28), improved in the NIV plus oxygen group, but there was no difference in St George’s Respiratory Questionnaire (SGRQ) scores. NIV has also been used as an adjunct to pulmonary rehabilitation with two RCTs showing greater improvements in exercise capacity and QOL when NIV, used overnight, was added to a pulmonary rehabilitation programme. 10 In this issue of Thorax McEvoy et al report the results of an RCT of NIV in patients with chronic stable hypercapnic ventilatory failure due to COPD (see page 561). The study was powered for survival. The patients had severe airflow limitation with a forced expiratory volume in 1 s (FEV1) approximately 25% predicted and severely impaired QOL. The sleep-related increase in transcutaneous carbon dioxide tension (TcCO2) was reduced in the NIV + LTOT group compared with the group receiving LTOT alone (12.6 vs 18.8 mm Hg). Over the course of the study there were 40 deaths in the NIV group compared with 46 in the LTOT group. At 24 months, 47% of the LTOT-treated patients had died compared with 32% of the NIVtreated patients. By 3.5 years the survival curves had come together. At follow-up at 1 year there was no change in PaCO2 during spontaneous breathing by day on oxygen at the same flow rate in either group or in the FEV1. QOL as measured by the SGRQ was unchanged, but statistically significant differences were observed in several subscales of the SF36 and the profile of mood questionnaires, suggesting that patients treated with NIV had poorer general and mental health, and reported less vigour and more confusion and bewilderment. It is interesting to compare these data with those previously published (table 1). The rationale behind the use of NIV and the way that it was applied in these studies is different. An understanding of how NIV ‘‘works’’ is critical in determining the therapeutic end point of NIV, but this remains unresolved. Competing theories include resting of chronically fatigued respiratory muscles, reducing the load against which the respiratory muscle pump must work or restoring the central drive to breathe. There is evidence that restoration of central chemosensitivity and a reduction in load are important, and the ventilator needs to be set to have an effect upon these parameters. In negative studies, if important physiological parameters are not affected, it cannot be concluded that NIV really had no effect. A major problem with previous studies is that there has either been no clear physiological target behind the choice of ventilator mode and settings or the evidence that an effect has been achieved is weak. Casanova et al adjusted pressures to decrease accessory muscle use, reduce the sensation of dyspnoea and reduce respiratory rate by 20%. Oxygen was titrated to maintain saturations of .90%. No measurements were made of carbon dioxide tensions or data provided confirming the degree to which accessory muscle use or respiratory rate were reduced. No evidence therefore is provided to confirm a physiological effect. Clini et al used pressure support ventilation delivered by a spontaneous/timed bilevel ventilator through a nasal mask. Oxygen was added to achieve a target saturation of .90%. All patients underwent a 10-night NIV trial in hospital before randomisation. Patients were deemed to be compliant when they used the ventilator for 5 h/night and, among the compliant patients, the average was high at 9.2 h/night. No data were provided as to the proportion of ‘‘compliant’’ patients or the average compliance overall. The effectiveness of NIV had to be proven by a 5% decrease in PaCO2 after 1 h of continuous support and by night time oximetry. NIV was considered effective when the patient spent .90% of the recording time with saturations .90% during NIV. However, oximetry cannot be used to assess the adequacy of ventilation when patients are receiving supplemental oxygen. Again, the evidence of a physiological effect from NIV when it was administered (ie, during sleep) is not convincing. In the study by McEvoy et al, patients assigned to NIV were admitted for 3–4 days to hospital for education and familiarisation with a patient-triggered bilevel positive pressure device. Bilevel positive airway pressure was gradually increased during daytime and night time trials to the maximum tolerated with a target difference between inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) of >10 cm H2O. The level of EPAP was determined during a polysomnographic study, with the level being increased to abolish snoring and obstructive events. NIV was considered successfully established when at least 3 h of sleep was confirmed on NIV at an IPAP–EPAP difference of at least 5 cm H2O. There was no requirement to change oxygen saturation or TcCO2, although NIV did reduce the maximum sleep-related rise in TcCO2 from 16.5 to 12.6 mm Hg. If restoration of central drive is important, the patient needs to spend the night, on average, with a respiratory alkalosis. This Correspondence to: Dr M W Elliott, Department of Respiratory Medicine, St James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK; mwelliott@ doctors.org.uk Editorial