Bipap improves survival and rate of pulmonary function decline in patients with ALS

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Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor neuron disease that frequently causes death within five years of diagnosis. The majority of deaths are due to pulmonary complications resulting from respiratory muscle weakness and bulbar involvement. A promising respiratory intervention is the recently introduced bi-level intermittent positive pressure (Bipap), which is a noninvasive ventilator modality shown to reduce the work of breathing and improve not only gas exchange, but also exercise tolerance and sleep quality. The aim of this study was to assess the utility of Bipap in prolonging survival in ALS. We retrospectively analyzed the results of Bipap use in 122 patients followed at Hahnemann University. All patients in this study were offered Bipap when their forced vital capacity (FVC) dropped below 50% of predicted value. Group 1 (n=38) accepted Bipap and used it more than 4 h/day. Group 2 (n=32) did not tolerate Bipap well and used it less than 4 h/day. Group 3 (n=52) refused to try Bipap. There was a statistically significant improvement in survival from initiation of Bipap in Group 1 (14.2 months) compared to Group 2 (7.0 months, P=0.002) or 3 (4.6 months, P<0.001) respectively. Furthermore, when the slope of vital capacity decline was examined, the group that used Bipap more than 4 h/day had slower decline in vital capacity (−3.5% change/month) compared to Group 2 (−5.9% change/month, P=0.02) and Group 3 (−8.3% change/month, P<0.001). We conclude that Bipap can significantly prolong survival and slow the decline of FVC in ALS. Our results suggest that all patients with ALS be offered Bipap when their FVC drops below 50%, at the onset of dyspnea, or when a rapid drop in %FVC is noted.

Introduction

Amyotrophic Lateral Sclerosis (ALS) is a steadily progressive and usually lethal disease resulting from loss of motor neurons in the brain, brainstem and spinal cord [1], [2], [3]. Patients typically die within 3–5 years of onset due to respiratory failure [1], [4], however cases with much shorter or longer survival are well documented [3]. No significant differences in rate of disease progression depending on area of onset (bulbar or limb), age, or gender have been found in these earlier studies. However, a recent analysis of prognostic indicators from the ALS CNTF Treatment Study Group showed that shorter survival was associated with greater age, shorter interval from symptom onset to diagnosis, lower serum chloride due to respiratory acidosis, and lower percent-predicted forced vital capacity (%FVC) [5].

The rate of decline in respiratory function has been related to mortality regardless of the pulmonary function parameters at the time of the initial assessment [6]. This rate was found to be linear for each patient with significant interpatient variability. The average drop of predicted vital capacity was −3.5% per month [7]. Nearer death the forced vital capacity (FVC) decreased more rapidly [8]. From the pulmonary function studies, %FVC was found to be the most specific and sensitive indicator of disease progression and a better predictor of death than the neuromuscular score [3], [6]. Furthermore, forced vital capacity was the factor best correlated to respiratory symptoms [7].

A variety of non-invasive nasal ventilators have been developed and utilized in an attempt to avoid the complications and difficulties associated with invasive mechanical ventilation in late stages of respiratory insufficiency [9], [10], [11], [12]. Noninvasive ventilation can preserve oral feeding and speech, reduce risk of respiratory infections as well as reduce burden for care givers and costs [13]. The most recent and closest to physiologic respiratory function is the bi-level intermittent positive air pressure (Bipap). It is triggered by the patient’s own respiratory efforts and has been shown to reduce the work of breathing and to improve gas exchange, sleep quality and compliance [14], [15], [16]. Although recent small studies have shown improved survival with Bipap [17], [18], [19], discouraging findings in other neuromuscular disorders [20] have led to limited use of this modality in ALS. We studied 122 patients with ALS in order to further evaluate the effects of Bipap on survival and serial pulmonary function.

Section snippets

Patients and methods

A retrospective chart review to evaluate the effects of Bipap on survival and progression of pulmonary function in patients with advanced ALS was undertaken. Patients diagnosed with ALS according to the El Escorial criteria [21], who were followed in the ALS Clinical Center at Hahnemann University Hospital between 1993 and 1997 were included in the study. Patients were seen routinely every three months and pulmonary function testing was performed during most visits. Those with a diagnosis of

Demographic data (Table 1)

A total of 122 patients were included in the study (52 men and 70 women, average age 62.2±11.8 years at study entry). In 35.2% of patients the onset of the disease was bulbar and in the remaining 64.8% onset was in a limb. During the course of the disease, PEG tube was placed in 43.4% of the patients for an average of 8.4 months. There was no significant difference in the percentage of patients with PEG tube in each group. However, the patients with longer survival after Bipap also used PEG

Discussion

Our data show that Bipap can prolong survival and slow the decline in pulmonary function in patients with advanced ALS. This is the first large scale study to clearly demonstrate a positive effect of this mode of noninvasive ventilatory support in patients with ALS, and supports our previous results and other smaller studies that showed benefits from Bipap [17], [18], [19]. Furthermore, this study demonstrates for the first time that Bipap can improve slopes of FVC decline when followed with

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