A new optimized protocol for the use of a noninvasive ventilation technique called bi-level positive airway pressure (Bi-PAP) allows patients with amyotrophic lateral sclerosis (ALS) to live twice as long as they normally would if they received the standard protocol, according to researchers.
Their findings were reported in the study, “Associative Increases in Amyotrophic Lateral Sclerosis Survival Duration With Non-invasive Ventilation Initiation and Usage Protocols,” published in Frontiers in Neurology.
ALS is a progressive neurodegenerative disorder caused by the gradual destruction of motor neurons — nerve cells responsible for voluntary muscle control — in the spinal cord and in the brain.
As the disease worsens, patients eventually lose control of the muscles that run between the ribs and allow the chest to move, causing severe respiratory complications, the most common cause of death for ALS patients.
For this reason, assistive breathing interventions, including noninvasive ventilation (NIV) techniques such as bi-level positive airway pressure (Bi-PAP), are often prescribed for ALS patients.
Bi-PAP is a machine that delivers pressurized air directly to the patients’ upper airways through a mask that is placed over the mouth. The positive air pressure prevents throat muscles from collapsing, minimizing the risks of obstructions and allowing patients to breathe more easily.
Unlike other invasive techniques, Bi-PAP does not affect swallowing and, because it is removable, it interferes less with patients’ daily activities while providing a better quality of life without increasing the risk of pneumonia, one of the biggest drawbacks of invasive procedures.
However, currently there is no consensus in clinical practice regarding Bi-PAP usage protocols, and its impact on the survival of ALS patients has never been addressed in large studies.
International and U.S. insurance standards often delay NIV initiation until the percent predicted forced vital capacity (FVC %predict) — a standard respiratory measure of ALS patients’ respiratory function — is less than 50, or half of the expected FVC value.
It has already been hypothesized that starting NIV before FVC %predict is below 50 could be beneficial for patients, but this has never been addressed in a large-scale study.
To address this hypothesis, researchers from the Emory University School of Medicine and the University of Texas Health Science Center at San Antonio conducted a retrospective study of 474 ALS patients (403 Bi-PAP users and 71 nonusers).
Survival duration — time elapsed from the first clinic visit until patients’ death — was assessed taking into account Bi-PAP initiation threshold (FVC %predict); Bi-PAP usage protocol (hours per day); daily cough assist usage (users or nonusers); ALS onset and type; ALSFRS-R score; and time elapsed from ALS onset until Bi-PAP initiation.
Investigators found that Bi-PAP users lived much longer than nonusers, with a median survival of 21.03 months compared to 13.84 months, respectively.
They also found that survival duration increased consistently with earlier Bi-PAP initiation, ranging from 20.3 months at FVC %predict less than 50, to 25.36 months at FVC %predict higher than 80.
Survival duration also increased with longer Bi-PAP usage, increasing from 15.07 months (less than four hours a day) to 23.20 months (with more than eight hours a day of usage).
Cough assist together with Bi-PAP also had a positive effect on patients’ survival (25.73 months) compared to Bi-PAP alone (15.0 months). Overall, higher ALSFRS-R scores were associated with higher Bi-PAP initiation thresholds and longer patient survival.
There was no significant correlation between the time elapsed from ALS onset until Bi-PAP initiation, suggesting that the time elapsed since disease onset does not seem to be a good predictor of when these patients should start NIV.
These findings demonstrate there is an optimal time window to initiate Bi-PAP treatment (with FVC %predict higher than 80), at a specific Bi-PAP usage (more than eight hours a day), together with daily cough assist.
Although more studies are needed to consolidate these conclusions, authors are convinced these findings highlight the reason why “standard” NIV (with FVC %predict less than 50, a Bi-PAP usage of less than fours a day, and without cough assist) clearly loses ground to the new optimized protocol version.
“Additional studies are needed to better ascertain why optimized Bi-PAP protocols, which are typically considered as palliative only, are associated with such stark increases in survival duration,” researchers wrote.
“Interestingly, while we did see significant associative increases in survival duration, the use of NIV did not change the slope of respiratory disease decline (data not shown), which was also highlighted in a recent smaller NIV study,” they added.