Diaphragmatic pacing ’harmful’ in amyotrophic lateral sclerosis
medwireNews: Diaphragmatic pacing in conjunction with non-invasive ventilation is detrimental to patients with amyotrophic lateral sclerosis (ALS) and respiratory insufficiency, show findings from a randomised controlled trial.
The combination treatment was associated with significantly shorter survival compared with non-invasive ventilation alone, at 11.0 months versus 22.5 months, report Christopher McDermott (University of Sheffield, UK) and fellow DiPALS Study Group collaborators in The Lancet Neurology.
“Our findings suggest that diaphragm pacing should not be used as a treatment for patients with ALS at the point of respiratory failure”, they say, adding that inserting a diaphragm pacing system could be “harmful”.
This conclusion refutes the findings of a previous multicentre study that showed prolongation of life with the NeuRx 4/4 Diaphragm Pacing System compared with historical controls and led to the device receiving Humanitarian Device Exemption approval from the US Food and Drug Administration, although no data were published and no further randomised controlled trials were conducted.
Between December 2011 and December 2013, McDermott and team randomly assigned 74 individuals with ALS and respiratory insufficiency to receive either non-invasive ventilation plus pacing with the NeuRx 4/4 Diaphragm Pacing System or non-invasive ventilation alone. The patients who were all aged at least 18 years were stabilised on riluzole treatment for at least 30 days prior to randomisation.
Poor overall survival figures led to recruitment being suspended in December 2013 on the advice of the Data Monitoring and Ethics Committee, and by June 2014 pacing was discontinued in all patients.
At the end of follow-up in December 2014, 47 patients had died. Of these, 76% had received pacing while 51% had received ventilation alone. Survival was a significant 11.5 months shorter, on average, for the 37 patients receiving diaphragm pacing and ventilation than the 37 receiving ventilation alone, at a hazard ratio of 2.27, after accounting for age, gender, forced vital capacity and bulbar function.
Pacing was also associated with a greater number of adverse events, at 162 versus 81 with ventilation alone, equivalent to a respective 5.9 and 2.5 events per person–year. Of these, 46 events in the pacing group and 31 in the ventilation-only group were serious.
The negative outcome of pacing on survival was not associated with the level of use of non-invasive ventilation and could not be attributed to surgical complications, although surgery did accelerate ALS disease progression, note the researchers.
They postulate that pacing may be directly harmful to already damaged motor neurons or cause excessive muscle fatigue.
In a related commentary Hiroshi Mitsumoto (Columbia University Medical Center, New York, USA) points out that the possible underlying mechanisms should have been investigated using periodical nocturnal pulse oximetry, for example.
“This information would have helped us learn how to manage non-invasive ventilation in the future”, he says.
By Lucy Piper
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