Starting noninvasive ventilation sooner may yield survival benefit
Researchers seek the optimal time to begin ventilation assistance
An earlier start to noninvasive ventilation (NIV) could help to improve respiratory function and prolong survival for people with amyotrophic lateral sclerosis (ALS), according to a small clinical trial in Spain.
While many of the study’s findings failed to reach statistical significance, the researchers believe the data still support the adoption of earlier ventilation assistance to improve ALS outcomes.
In ALS, weakness in muscles needed for breathing can lead to respiratory difficulties for many patients. Respiratory failure is the main cause of death for about 80% of patients.
NIV can help support better breathing for people living with the neurodegenerative disease. With the approach, oxygen is delivered to a person’s airways using a mask or similar device, often initially worn at nighttime.
While it has become recognized that NIV can help to prolong survival and boost life quality, the appropriate time to start a patient on NIV has not been definitively established. Still, it is generally agreed that NIV should be initiated before severe respiratory muscle weakness occurs.
In Spain, where the study was conducted, NIV is typically begun once patients have reached a forced forced vital capacity (FVC) that’s less than 50% of what is predicted for one’s age and sex, according to the researchers.
A standard measure of lung function, FVC assesses the maximum amount of air a person can forcibly exhale from the lungs. A score higher than 80% of predicted is generally considered normal.
Some studies suggest NIV could have greater benefits when initiated at earlier stages of lung function decline, when FVC is at around 65-75% of predicted. But no randomized trials have directly compared the outcomes of ALS patients who started NIV earlier versus later in their disease course.
Randomized, controlled clinical trial
To address that, the scientists conducted a randomized controlled clinical trial (NCT01641965) to evaluate the impacts of earlier NIV initiation on ALS prognosis. The findings from the trial, which was conducted from 2012-2014, were described in the recent publication.
A total of 42 ALS patients were recruited at ALS centers in Spain, all of whom were in the initial phase of respiratory muscle weakness, defined as having an FVC at or less than 75% of expected, but with a previous FVC over 75% recorded in the last six months.
Participants were assigned randomly to an early NIV group, where NIV was initiated immediately, or a standard NIV group, which started NIV when their FVC reached less than 50%, they experienced shortness of breath when lying down, or a daytime buildup of carbon dioxide in the bloodstream.
All participants were using Rilutek (riluzole) throughout the trial, and were followed for a median of 16-18.5 months. Overall disease severity at the start of the study was similar between groups.
Study’s main goal
The study’s main goal was to evaluate differences in survival between the early and standard NIV groups.
Data showed that the median survival time since diagnosis in the early NIV group was longer than in the standard NIV group — 25.2 months compared with 19.4 months. But the differences were not found to be statistically significant, meaning the trial failed to meet its main goal.
Still, a statistically significant association was observed between FVC values throughout the study and death, which “suggests a protective effect of [higher] FVC%,” the researchers wrote.
Overall disease progression was similar between the two groups throughout the study, as were measures of sleep and life quality. Other measures of respiratory function tended to favor the early NIV group, although there were no significant differences.
Rates of NIV-related side effects were similar between groups, the most common of which was dry mouth.
Overall, the researchers believe the findings highlight that the optimal time to start NIV is when FVC values are about 75%, and respiratory muscles are slightly affected.
“This is when NIV can do its job: maintaining muscle strength, slowing the decline in FVC, and preventing nocturnal hypoventilation [nighttime breathlessness] and respiratory complications, and thus prolonging survival,” the scientists wrote.
Some patients hesitant to start NIV earlier
While compliance to treatment was good in the study, the team noted that many patients may be hesitant to start NIV because it implies deterioration. Doctors should thus be mindful of how they approach the topic with their patients and in monitoring compliance.
The researchers believe the failure of the trial to reach its main goal may be that not enough trial participants were recruited (only 42 of the expected 72 participants). This was mostly due to competing clinical trials that were run at the ALS centers at the same time, they said.
“It’s important to highlight the difficulty in conducting studies like this, both now and in the future,” they wrote, noting that few studies like this are likely to be conducted in the future, partly because many centers are already adopting an earlier start to NIV.