This section describes safety outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
5.1 In a multicentre randomised controlled trial (RCT) of 74 patients with respiratory failure caused by amyotrophic lateral sclerosis (ALS), non-invasive ventilation (NIV) plus diaphragm pacing (n=37) was compared with NIV alone (n=37). In the NIV plus pacing group 76% (26/37) of patients died and in the NIV-alone group 51% (19/37) of patients died. The causes of death were similar across the groups (mainly respiratory failure, chest infection, ALS and hypothermia). In another multicentre triple-blind RCT in 74 patients with probable or definite ALS, active stimulation (n=37) was compared with sham stimulation (n=37). More patients died in the active stimulation group than in the sham stimulation group (49% [18/37] compared with 19% [7/37]) as a result of chest infection, acute respiratory failure and terminal respiratory insufficiency. Six patients died before NIV in the active stimulation group because of acute respiratory failure in 5 and sudden cardiac death in 1. No deaths were related to treatment.
5.2 There were more adverse events reported in the NIV plus pacing group than in the NIV-alone group (162 events [5.9 events per person-year] in 78% [29/37] of patients compared with 81 events [2.5 events per person-year] in 62% [23/37] of patients) in the RCT of 74 patients with respiratory failure caused by ALS. More patients had serious adverse events in the NIV plus pacing group than in the NIV-alone group (73% [27/37] compared with 51% [19/37]; 46 events compared with 31 events). Respiratory events were the most common in both groups (68% [25/37] compared with 38% [14/37]) followed by gastrointestinal events (27% [10/37] compared with 24% [9/37]), symptoms of motor neurone disease (22% [8/37] compared with 8% [3/37]), gastrostomy (percutaneous endoscopic or per-oral image-guided insertion; 14% [5/37] compared with 24% [9/37]), genitourinary events (8% [3/37] in each group), cardiovascular events (11% [4/37] compared with 5% [2/37]) and dermatological problems (8% [3/37] compared with 11% [4/37]).
5.3 Serious adverse events (mainly capnothorax or pneumothorax, acute respiratory failure needing mechanical ventilation, venous thromboembolism and gastrostomy tube placement) were reported in 65% [24/37] of the active stimulation group and in 59% [22/37] of the sham stimulation group in the triple-blind RCT of 74 patients. Some patients had more than 1 adverse event. Other serious adverse events reported include dyspnoea (3 patients), loss of walking ability (3 patients), oesophagitis (1 patient), admission to hospital for any cause (3 patients), accidental removal of gastrostomy tube (1 patient), and reopening of the laparoscopy insertion point needing repair (1 patient). Capnothorax was reported in 13% (5/38) of patients with ALS in a case series of 88 patients. Capnothorax was managed successfully by aspiration, drainage or observation.
5.4 Suture granuloma causing infection at the superficial wire connection site (treated by externalising the electrodes) was reported in 1 patient with ALS in the case series of 88 patients. Infection at the stimulation cable entry point was noted in 22% (8/37) of patients in the active group (3 patients needed antibiotics) and 19% (7/37) of patients in the control group (5 patients needed antibiotics) in the triple-blind RCT of 74 patients. Respiratory infections (needing antibiotics) were reported in 5 patients in a case series of 16 ALS patients with respiratory insufficiency treated by diaphragm pacing. Superficial wound infection (treated with antibiotics) was reported in 1 patient in the same study. Urinary infection (needing admission to hospital) and severe pulmonary infection were reported in 1 patient each in a case series of 11 patients.
5.5 External electrode repairs were needed in 7 patients in the case series of 16 patients with ALS. Wire failure was reported in 14% (5/37) of patients in the NIV plus diaphragm pacing group in the RCT of 74 patients with respiratory failure caused by ALS.
5.6 Pain (needing analgesics) was commonly reported in the active stimulation and sham stimulation groups (92% [34/37] compared with 89% [33/37]) in the triple-blind RCT of 74 patients. Pain needing a reduction in the intensity of diaphragm pacing was noted on day 2 in 54% (20/37) of patients in the active stimulation group and none in the sham stimulation group in the same study.
5.7 In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed the following anecdotal adverse event: excess mortality. They considered that the following were theoretical adverse events: decompensated respiratory failure, breathlessness related to diaphragm pacing and atrophy and progression of diaphragm weakness.