A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

People with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who require noninvasive ventilation in later disease stages use significantly higher opioid doses and for more extended periods than do patients who never need mechanical ventilation, according to a new study in Japan.
The opioids were started for these individuals mostly to help minimize shortness of breath and ease pain. But several patients included in the single-center study never reached a stable dose, and most also needed anxiolytics and antidepressants to aid in symptom control.
These findings suggest &#8220;that there are limits to the relief of distress with opioids alone,&#8221; the researchers wrote, noting that patients whose respiration is managed with noninvasive ventilation may have other issues causing distress.
“Symptom control with opioids alone may be difficult, and the development of multifaceted evaluation and care is desirable,” the team wrote.
The study, “<a href="https://link.springer.com/article/10.1007/s13760-023-02344-5">High doses of opioids usage for amyotrophic lateral sclerosis patients with non‑invasive ventilation</a>,” was published in the journal <a href="https://www.springer.com/journal/13760">Acta Neurologica Belgica</a>.
[recommended-reading id=84549]
<h3>Opioid use started for most patients for breathing difficulties</h3>
ALS is caused by damage and death of motor neurons, the nerve cells that control voluntary movement. With the loss of these cells, the brain can no longer control muscle movements, and patients progressively lose their ability to perform everyday tasks.
In the later stages of the disease, paralysis usually occurs, leading to pain, and a vast number of patients also experience difficulty breathing. These symptoms contribute to a great degree of distress in about 40%-70% of people with ALS, according to researchers.
The use of a ventilator to support breathing can extend survival in patients, studies have shown. But the distress associated with breathing problems is still difficult to treat, the researchers say.
&#8220;The [noninvasive ventilation] group needed psychotropic drugs more frequently than the no-[mechanical ventilation] group,&#8221; the team wrote. Such mental health treatments include antidepressants and antianxiety medications, as well as stimulants, antipsychotics, and mood stabilizers.
Morphine, a type of opioid mainly used to treat pain, may be helpful for some patients in easing the pain and distress caused by labored breathing in ALS. Still, “only a few studies have addressed morphine dosing in ALS patients, with a limited number of cases,” the researchers wrote.
[quote=&#8221;center&#8221;]There are limits to the relief of distress with opioids alone.[/quote]
To clarify how opioids are use to treat symptoms of ALS, researchers in Tokyo examined data from 84 patients treated with morphine at their hospital. All of the patients were followed up until their death. Each received the opioids between January 2010 and December 2018 and died in that period, mainly due to respiratory failure.
Among these patients, 57 (67.9%) did not use mechanical ventilation, 21 (25%) used noninvasive ventilation (NIV) — the delivery of oxygen using a face mask — and four (4.8%) underwent tracheostomy invasive ventilation (TIV), an opening in the trachea to insert a tube that delivers oxygen to the lungs. Two patients only underwent tracheostomy.
&#8220;All the deceased patients were eventually given some form of oxygen,&#8221; the researchers wrote.
[recommended-reading id=22396]
<h3>Opioid use for most patients on noninvasive ventilation spanned 13 months</h3>
Patients received morphine mainly orally or directly to the stomach via a tube inserted in the abdomen, but there were some for whom morphine was delivered by intravenous or in-the-vein administration or via skin patches.
Results showed that patients in the NIV group lived about 10 more months after their diagnosis, on average, than those who used no mechanical ventilation. But the NIV group required a significantly higher opioid dose — 65.7 mg versus 31.7 mg — and used these drugs for significantly longer periods, specifically 13.3 months versus 1.7 months.
“This result indicates that the no-[mechanical ventilation] group received opioids only for a short time before death,” the researchers wrote.
This was supported by the fact that 34.5% of the patients in the no-mechanical ventilation group were started on opioids one month before their death, compared with 10% of the individuals in the NIV group.
The researchers noted that a larger proportion of patients given NIV (33%) never reached a stable opioid dose, compared with 21% of the patients without mechanical ventilation. But when only patients on stable doses were included, those in the NIV group continued to use significantly higher doses than those who did not use mechanical ventilation (29.2 vs. 19 mg).
The most common symptom leading to opioids use was shortness of breath in both groups, although it was more predominant in the no-mechanical ventilation group than in the NIV group (91% vs. 57%). Other reasons included pain, anxiety, and restlessness.
Finally, patients in the NIV group needed psychotropic medications more frequently than the no-mechanical ventilation group, and the most commonly used medications were benzodiazepines, used to ease anxiety and insomnia, and antidepressants.
Although opioid and psychotropic drug use was low in the TIV group, or those given an opening in the trachea, the results do not indicate that these patients require less opioid treatment because they are less distressed, the researchers noted. Still, analyses in this group were hampered by a reduced number of patients with TIV, mostly because patients on TIV usually survive longer.
“What happens in this group of long-term survivors and what kind of care is needed is not yet fully understood, and needs further study,” the researchers wrote.

Opioid use greater for ALS patients on noninvasive ventilation: Study

An earlier start to noninvasive ventilation (NIV) could help to improve respiratory function and prolong survival for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to a small clinical trial in Spain.
While many of the study&#8217;s findings failed to reach statistical significance, the researchers believe the data still support the adoption of earlier ventilation assistance to improve ALS outcomes.
The study, &#8220;<a href="https://content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd221658">Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial</a>,&#8221; was published in the <a href="https://content.iospress.com/journals/journal-of-neuromuscular-diseases/Pre-press/Pre-press">Journal of Neuromuscular Diseases</a>.
[recommended-reading id=85375]
In ALS, weakness in muscles needed for breathing can lead to <a href="https://alsnewstoday.com/symptoms-of-als/#Breathing_difficulties">respiratory difficulties</a> 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&#8217;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&#8217;s less than 50% of what is predicted for one&#8217;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.
<h3>Randomized, controlled clinical trial</h3>
To address that, the scientists conducted a <a href="https://classic.clinicaltrials.gov/ct2/show/NCT01641965">randomized controlled clinical trial (NCT01641965)</a> 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 <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a> (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.
<h3>Study&#8217;s main goal</h3>
The study&#8217;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 &#8220;suggests a protective effect of [higher] FVC%,&#8221; 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.
&#8220;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,&#8221; the scientists wrote.
<h3>Some patients hesitant to start NIV earlier</h3>
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.
&#8220;It’s important to highlight the difficulty in conducting studies like this, both now and in the future,&#8221; 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.

Tag: noninvasive ventilation

Opioid use greater for ALS patients on noninvasive ventilation: Study

Starting noninvasive ventilation sooner may yield survival benefit