Interventional procedure overview of intramuscular diaphragm stimulation for ventilator-dependent chronic respiratory failure from high spinal cord injuries
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Evidence summary
Population and studies description
This interventional procedures overview is based on approximately 500 patients from 1 prospective single-arm trial with a meta-analysis of 5 studies (Onders 2022), 3 retrospective case series (Onders 2018, Monden 2022, Wijkstra 2022), 1 systematic review (Garara 2016) and 1 case report (Dong 2021). There was some patient overlap between studies. This is a rapid review of the literature, and a flow chart of the complete selection procedure is shown in figure 1. This overview presents 6 studies as the key evidence in table 2 and table 3, and lists 23 other relevant studies in table 5.
The 6 studies included patients from the US, Canada, Iceland, Spain, Italy, the Netherlands and Brazil. In the studies that reported the recruitment period, it ranged from 2000 to 2019. The systematic review included studies published between January 2000 and June 2015. One primary study also included a meta-analysis of 4 additional studies (Onders 2022).
In the systematic review, the mean delay of insertion ranged from 40 days to 9.7 years. In the other 4 studies, the median time from injury to DPS surgery or the phrenic nerve test ranged from 10 to 28 months. The follow up period was not reported for all studies. In the systematic review, 2 studies had follow up periods of 6 months and 2 years. Of the other 4 studies, 1 had a mean follow up of 12 months, 1 was 3 years and 1 was 'long term' (the actual period was not reported but the overall median survival was 22 years).
The systematic review only included adult patients. Onders et al. (2018) reported that 14 paediatric patients were included in the study population and the age range in Wijkstra et al. (2022) was 2 to 65 years.
Table 2 presents study details.
Study no. | First author, date country | Patients (male: female) | Age | Study design | Inclusion criteria | Intervention | Follow up |
|---|---|---|---|---|---|---|---|
1 | Onders 2022 US, Canada, Iceland | a) n=53 (41:12) b) n=192 | a) Mean 36 years | Prospective multicentre single-arm trial (a) and meta-analysis of trial results with 4 additional studies (b) | a) Clinically stable, cervical spinal cord injury with dependence on mechanical ventilation; age >18 years; clinically acceptable bilateral phrenic nerve continuity; diaphragm movement with stimulation visible under fluoroscopy and >90% oxygen saturation. | Device: NeuRx DPS (Synapse Biomedical, US) | Not reported |
2 | Onders 2018 US | n=92 (74:18) [including 39 patients also in study 1] | Mean age at time of injury 27 years | Retrospective case series | Patients with traumatic spinal cord injury, with stimulable diaphragms. | Device: NeuRx DPS, (Synapse Biomedical, US) | 'long term' |
3 | Monden 2022 US | n=28 (24:2; 2 unknown) | Mean 34 years | Retrospective case series | Patients with ventilator-dependent high tetraplegia who had a DPS implanted. | No details described | Mean 3.1 years |
4 | Wijkstra 2022 Spain, Italy, the Netherlands | n=33 (24:9) | Mean 33 years (range 2 to 65) | Retrospective case series | At least 1 year old, with a cervical spinal cord injury that resulted in a complete or partial dependency on mechanical ventilation. | Device: NeuRx DPS (Synapse Biomedical, USA) | 12 months |
5 | Garara 2016 US, Brazil | n=186 | Mean 22 to 39 years (range 16 to 74 where stated) | Systematic review (including 2 multicentre retrospective studies, 8 case series and 2 case reports) | Adult patients with traumatic high cervical injury who were ventilator-dependant. | Intramuscular diaphragmatic stimulation | 6 months and 2 years (only reported for 2 studies) |
6 | Dong 2021, US | n=1 male | 22 years | Case report | The patient had rapidly progressive quadriplegia, with an acute spinal cord infarction secondary to fibrocartilaginous emboli from disc material, complicated by respiratory failure needing chronic mechanical ventilation. | Intramuscular diaphragmatic stimulation | 1 month |
Efficacy outcomes | Safety outcomes | |
|---|---|---|
Proportion of patients using DPS to breathe without ventilator assistance for at least 4 hours a day:
Proportion of patients using DPS to breathe without ventilator assistance for 24 hours a day: 58.5% (31/53); 95% CI 44.1% to 71.9% Overall, patients in the primary study were able to achieve 4 hours of continuous use in a mean of 2.6 months (95% CI 1.9 to 3.2 months) and 24 hours of continuous use in a mean of 7.6 months (95% CI 3.6 to 11.7 months). Percentage of tidal volume over basal requirements: for all patients 48.4% (95% CI 37.0 to 59.9%), males 42.1% (95% CI 29.0 to 55.1) and females 70.1% (95% CI 47.7 to 92.5); p<0.001 tidal volume versus basal requirements | Primary study
There were no serious device-related adverse events reported during the course of the study. Additional studies used in meta-analysis Device-related adverse effects:
| |
Onders 2018 | Proportion of patients using DPS to breathe without ventilator assistance for at least 4 hours a day: 88.0% (81/92) Proportion of patients using DPS to breathe without ventilator assistance for 24 hours a day: 60.9% (56/92) This was higher in patients who had the procedure within 1 year of injury (72.7% [24/33]) compared with those who had the procedure after 2 years (51.2% [22/43]). Full recovery of breathing with subsequent diaphragm pacing removal: 5.4% (5/92); all 5 patients had the procedure within 6 months of injury. Unsuccessful weaning off mechanical ventilation: 5.4% (5/92); 1 patient had been on the ventilator for 25 years and had significant scoliosis. Overall median survival: 22.2 years |
Cause of death was unknown in 14 patients. For the remaining 17 patients, cause of death included myocardial infarction (n=2), homicide (n=1), systemic mastocytosis (n=1), pulmonary embolism (n=2), overdose (n=1), Guillain-Barre syndrome (n=1), ventilator disconnect (was not pacing at the time; n=1), seizures (n=1), heat stroke (n=1), osteomyelitis sepsis (n=1), stroke (n=1), pneumonia (n=1), malignant hyperthermia (n=1), and withdrawal of care (n=2). |
Monden 2022 | Median time spent using the DPS per day: 15.0 hours (IQR 6.0 to 23.5 hours). 14.3% (4/28) of patients had returned to independent breathing, without diaphragmatic pacing and mechanical ventilation, at the time of the interview, spending a median time of 5.5 hours (IQR 1.0 to 14.5 hours) breathing independently per day. Most patients still used mechanical ventilation when not using their DPS. Effect of DPS on participation and quality of life:
When patients were asked to report what they disliked about the DPS, 5 patients described its negative effect on speech (limiting the number of words a patient could speak without pausing, poor voice quality, not being able to speak). Most patients (96%) were happy that they had the DPS implanted and 86% reported that they were satisfied with it (some patients had since returned to mechanical ventilation but appreciated the opportunity to try DPS). |
Frequency of aspiration episodes was lower in 2 patients, higher in 1 patient and the same in 24 patients. Frequency of infection or pneumonia was lower in 4 patients, higher in 3 patients and the same in 20 patients. |
Wijkstra 2022 | Median time spent using the DPS per day:
Proportion of patients using DPS for at least 4 hours a day:
Proportion of patients using DPS for at least 15 hours a day:
Proportion of patients using DPS for 24 hours a day, with complete liberation from mechanical ventilation:
Proportion of patients using DPS for night-time stimulation:
| Adverse events
|
Garara 2016 | Technical success:
Complete liberation from mechanical ventilation:
|
|
Dong 2021 | The device was successfully implanted with no complications. | Two months after DPS implantation, the patient developed frequent premature ventricular contractions followed by ventricular fibrillation and cardiac arrest. Return of spontaneous circulation was achieved after prolonged cardiopulmonary resuscitation by advanced cardiac life support algorithm including numerous shocks. A single chamber implantable cardiac defibrillator was implanted and the voltage for DPS was reduced. |
Procedure technique
Of the 6 studies, 3 reported that the NeuRx DPS (Synapse Biomedical, US) device was used.
Efficacy
Proportion of patients using DPS to breathe without ventilator assistance for at least 4 hours a day
The proportion of patients using DPS to breathe without ventilator assistance for at least 4 hours a day was reported by 3 studies and ranged from 77% to 96% (Onders 2022, Onders 2018, Wijkstra 2022). In 1 study, this was compared to a predefined objective performance goal of 45% (Onders 2022).
Proportion of patients using DPS to breathe without ventilator assistance for 24 hours a day
The proportion of patients using DPS to breathe without ventilator assistance for 24 hours a day was reported by 3 studies and ranged from 36% to 61% (Onders 2022, Onders 2018, Wijkstra 2022). In 1 study, it was reported that this was higher in patients who had the procedure within 1 year of injury (73% [24/33]) compared with those who had the procedure after 2 years (51% [22/43]; Onders 2018). In a systematic review of 12 studies, between 40% and 73% of patients were completely free of ventilator support after conditioning (Garara 2016).
Median time spent using DPS per day
In 2 studies, the median time spent using DPS per day was 15 hours (IQR 6 to 24 hours) and 14 hours (IQR 4 to 24 hours; Monden 2022, Wijkstra 2022).
Full recovery of breathing
In 1 study, 5% (5/92) of patients had full recovery of breathing with subsequent diaphragm pacing removal. All 5 patients had the procedure within 6 months of their spinal cord injury (Onders 2018). In 1 study, 14% (4/28) of patients had returned to independent breathing, without diaphragmatic pacing and mechanical ventilation, at the time of the interview, spending a median time of 5.5 hours (IQR 1.0 to 14.5 hours) breathing independently (Monden 2022).
Quality of life and patient satisfaction
The effect of DPS on participation and quality of life was reported in 1 study. Of the 28 patients, 17 (61%) reported that activities were improved by DPS, 11 (41%) reported that it was easier to travel, 2 (7%) reported that it was harder to travel, 10 (36%) reported that employment or productivity was easier and 18 (64%) reported no change in employment or productivity. Most patients (96%) were happy that they had the DPS implanted and 86% reported that they were satisfied with it (Monden 2022).
Safety
Capnothorax or pneumothorax
Capnothorax or pneumothorax was reported in up to 42% of patients after the procedure, in the systematic review of 12 studies (Garara 2016). All reported cases were treated successfully with observation, simple aspiration, or a chest drain. In the study by Monden (2022), pneumothorax needing additional surgery was reported in 1 patient within 2 weeks of the DPS implantation procedure. In the study by Wijkstra (2022), pneumothorax was reported in 9% (3/33) of patients, 1 of which was reported to be related to the device or procedure and was treated by thoracocentesis. In the same study, 6% (2/33) of patients had device or procedure-related capnothorax.
Pneumonia
Four studies reported pneumonia, although this was not necessarily related to the procedure. In the study by Onders (2022), pneumonia was reported in 8% (4/53) of patients and pacing was resumed after the pneumonia cleared. In the study by Monden (2022), pneumonia or aspiration was reported as an ongoing complication (beyond 2 weeks of the procedure) in 21% (6/28) of patients. In the study by Wijkstra (2022), there were 2 deaths attributed to pneumonia and 3 patients were hospitalised for it. A further 27% (9/33) of patients had pneumonia but it was reported not to be related to the procedure or device. In the study by Onders (2018), the cause of death was reported to be pneumonia in 1 patient.
Infection
Infection was reported in 4 studies. Infection at the wire sites was reported in 14% (4/28) and 4% (2/53) of patients in 2 studies (Monden 2022, Onders 2022). In the meta-analysis reported in Onders (2022), infection issues at the electrode wire site were reported in 17% of patients. In the systematic review by Garara (2016), 2 patients had a postoperative wound infection, both of which were treated by adjusting the electrode wires. In the study by Wijkstra (2022), 1 patient had pleural drainage for infection.
Pain
In the meta-analysis reported in Onders (2022), pain with pacing was reported in 14% of patients. Ongoing pain (beyond 2 weeks of the procedure) was reported in 14% (4/28) of patients in the study by Monden (2022).
Device complications
In the meta-analysis reported in Onders (2022), electrode wire issues involving hospitalisation was reported in 13% of patients. In the study by Monden (2022), broken or wrong lead placement was reported in 7% (2/28) of patients and repairs or repositioning of wires was reported in 18% (5/28) of patients. In the study by Wijkstra (2022), 1 patient needed hospitalisation for revision of DPS and 1 patient had a DPS wire eruption.
Cardiac complications
In the systematic review by Garara (2016), the DPS interacted with a pre-existing internal cardiac pacemaker in 1 patient.
Ventricular tachycardia leading to cardiac arrest was described in 1 patient who had DPS in a case report. A single chamber implantable cardiac defibrillator was implanted and DPS was continued at a lower voltage (Dong 2021).
Other
In the systematic review by Garara (2016), intermittent aspiration of food during meals was reported in 1 patient. Co-contraction of abdominal muscles and access site haemorrhage were reported in 1 patient each in the study by Wijkstra (2022). In the study by Monden (2022), spasticity was reported in 18% (5/28) of patients. In the same study, 1 patient had an adverse reaction to DPS within 2 weeks of the procedure.
Anecdotal and theoretical adverse events
Expert advice was sought from consultants who have been nominated or ratified by their professional Society or Royal College. They were asked if they knew of any other adverse events for this procedure that they had heard about (anecdotal), which were not reported in the literature. They were also asked if they thought there were other adverse events that might possibly occur, even if they have never happened (theoretical).
They did not describe any anecdotal or theoretical adverse events.
Two professional expert questionnaires for this procedure were submitted. Find full details of what the professional experts said about the procedure in the specialist advice questionnaires for this procedure.
Validity and generalisability
No comparative studies were identified.
Most of the studies had a small sample size.
Only 1 prospective study was included (Onders 2022).
The study by Monden et al. (2022) was a self-report questionnaire about experiences over the previous year and may be subject to recall bias.
Of the 5 studies, 2 specifically stated that only adults were within the inclusion criteria (Onders 2022, Garara 2016).
Follow up periods were not reported for all studies. One study had a mean follow up of 3 years (Monden 2022) and 1 had 'long term' follow up. The study that reported outcomes at 6 and 12 months showed that the success rate was higher after 12 months (Wijkstra 2022).
Evidence was only included on patients with chronic respiratory failure, but the length of time on mechanical ventilation varied between and within studies. Almost all the included articles in the systematic review reported implantation several years after injury. There was some evidence to suggest that patients who had the procedure sooner after their spinal cord injury may have better outcomes.
The mechanism of spinal cord injury varied and this is likely to affect the outcome of the procedure. One paper noted that the procedure had a lower success rate for patients who had a violent injury, such as a gunshot wound (Onders 2018).
Post operative weaning programmes varied between studies.
Many patients were on home ventilation, and the weaning process was done by family members and caregivers. Other patients were weaned in hospital.
A potential conflict of interest was declared by authors of 2 papers (Onders 2018 and Onders 2022) and 2 studies reported funding from Synapse Biomedical, the company that makes the device (Onders 2022 and Wijkstra 2022).
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