Systematic review
Effect of long-term mechanical ventilation (LTMV) part 1 – neuromuscular disease or central respiratory failure
Systematic review
|Updated
The Norwegian Directorate of Health recently prepared new guidelines for the use of LTMV outside hospitals. The Norwegian Knowledge Centre for Health Services was commissioned to prepare a systematic review on the efficacy of LTMV. This is the first of three reviews, and here we summarize evidence on the effectiveness of LTMV for patients with neuromuscular disorders and for patients with central respiratory failure.
Key message
Background
Patients who fail to maintain adequate respiration may need long-term mechanical ventilation (LTMV) in shorter or longer periods. Patients using LTMV constitute a heterogeneous group with respect to age, diagnoses and disease progression. Norwegian data suggests considerable regional differences in the use of LTMV.
Commission
The Norwegian Directorate of Health recently prepared new guidelines for the use of LTMV outside hospitals. The Norwegian Knowledge Centre for Health Services was commissioned to prepare a systematic review on the efficacy of LTMV. This is the first of three reviews, and here we summarize evidence on the effectiveness of LTMV for patients with neuromuscular disorders and for patients with central respiratory failure.
Main results
- LTMV may be associated with some degree of life extension and improved quality of life for patients with amyotrophic lateral sclerosis, at least for patients with good bulbar function. The quality of evidence is low, and it is not possible to draw firm conclusions about the real effect.
- LTMV can be associated with life extension among hypoventilated patients with Duchenne muscular dystrophy, but the quality of evidence is low, and it is not possible to draw firm conclusions about the real effect.
- Across patients with various neuromuscular diagnoses, it seems that LTMV may be associated with fewer hospital admissions, and that invasive LTMV is associated with greater risk of complications and hospitalization than non-invasive LTMV. The quality of evidence is low, and we can not draw firm conclusions about the real effect.
- For some diagnoses, for example central respiratory failure, we were not able to identify any research fulfilling our inclusion criteria.
Summary
Background
Patients with a variety of disorders may require long-term mechanical ventilation (LTMV). The potential users are heterogeneous in terms of diagnoses (pathophysiology), age, and prognosis. Norwegian data show that children with 40 different diagnoses are currently registered as LTMV-users, with spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) as the most common. Among adult LTMV-users, the most frequent diagnoses are stable chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), amyotrophic lateral sclerosis (ALS) and sequelae of poliomyelitis.
The need for LTMV is in some cases obvious. For example, a comprehensive spinal cord injury located in the upper part of the neck will affect central respiratory center as well as respiratory muscles, and round-the-clock use of respirator is necessary to maintain breathing. In other cases, patients are only in need for ventilator support some hours each day, for example during the night. The medical indications underlying initiation of LTMV are unclear, and recent Norwegian data shows substantial regional variations in when LTMV is recommended.
We have summarized the existing scientific evidence about the effect of LTMV for patients with neuromuscular disease, central respiratory failure, chest wall disorders, obesity hypoventilation syndrome and chronic obstructive pulmonary disease (COPD). We worked with all the material in parallel processes, but we find it appropriate to publish the result in a series of three reports. The current report comprises evidence for effectiveness of LTMV for patients with neuromuscular disease and for patients with central respiratory failure.
Methods
We have systematically reviewed research about the effectiveness of LTMV for patients with neuromuscular disease and for patients with central respiratory failure. We searched for systematic reviews and primary studies in relevant bibliographic databases. Independently, two people assessed all titles and abstracts and selected articles for inclusion. We assessed the quality of relevant systematic reviews using checklists, and we assessed the risk of bias of included primary studies.
Articles that were considered relevant for inclusion were classified based on the diagnoses of the participants. For each diagnostic group we assessed the overall quality of evidence for each of the primary outcomes (life prolongation, quality of life, hospitalization, and sleep) using GRADE. Whenever it was possible and appropriate, we combined the result of primary studies in meta-analyses.
Results
We included 34 publications. One of the included studies was a systematic review about the effect of LTMV for patients with ALS, summarizing data from 12 primary studies and 625 participants. Furthermore, we included three randomized controlled trials concerning patients with Duchenne muscle dystrophy (70 participants), post-polio (8 participants) and various neuromuscular diagnoses (26 participants) respectively. The remaining 30 studies are observational studies and involve 1500 to 2000 participants with various neuromuscular disorders.
The quality of the evidence is in general low or very low, implying that it is not possible to conclude firmly. However, there are some vague evidence suggesting that non-invasive LTMV (mask treatment) may lead to life extension and improved quality of life among patients with ALS. The increase in median survival was limited to 48 days (219 vs. 171 days), and benefits are probably greater among patients with good bulbar function (i.e. throat, chewing, speech features).
LTMV may have positive effects on survival for patients with Ducennes muscle dystrophy and hypoventilation, but data from one randomized controlled trial suggest that it is unfavourable to start treatment with LTMV too early (i.e., before clinical signs of hypoventilation occurs). The mortality does not seem to differ between patients who are invasively (tracheostomy) and non-invasively (mask) ventilated, respectively.
Across LTMV-users with various neuromuscular diseases, it seems like invasive LTMV is associated with a higher risk of complications and hospitalizations compared with non-invasive LTMV. However, the quality of the evidence is very low, mainly because the association is based on observational studies in which groups that are ventilated by means of invasive and non-invasive methods are likely to be prognostic imbalanced.
For patients with spinal cord injury and tetraplegia, we see that LTMV-dependent patients score similar on quality of life scores as patients who are not LTMV-dependent.
Discussion
Despite a large number of neuromuscular disorders for which long-term mechanical ventilation (LTMV) may be beneficial, the available research evidence is seemingly sparse. This lack of evidence is not surprising, and can be explained by several factors. First, many neuromuscular diagnoses are rare, and it is therefore challenging to collect adequate sample size and conduct robust studies. Second, in some instances the indication for treatment is sometimes obvious, as is the case for patients with spinal cord injuries located in the upper part of the neck who dependent on LTMV to maintain respiration. However, many patients fall into another category: The issue is not necessarily whether they need LTMV or not, but whether one strategy is more effective than the other (e.g. when is it appropriate to start LTMV in patients with a progressive disease). These questions can be addressed through research, for example in trials where the participants are allocated to different active treatment strategies. In this review, we present results from a randomized study suggesting that the timing of LTMV-initiation can be crucial for the overall effect. We also noted some studies comparing the effectiveness of different ventilators or ventilator setting, but it fell beyond the scope of the current report to review these comparisons.
Conclusion
- LTMV may be associated with some degree of life extension and improved quality of life for patients with ALS, at least for patients with good bulbar function. The quality of evidence is low, and it is therefore difficult to draw firm conclusions about the real effect.
- LTMV may be associated with life extension in hypoventilated patients with Duchenne muscle dystrophy, but the quality of the evidence is low. Very low quality evidence from a single randomized controlled study, suggests that it is not beneficial to start LTMV too early.
- For patients with various neuromuscular diagnoses it seems like:
- Initiation of LTMV may be associated with a decrease in the need for hospital admissions.
- Invasive LTMV is probably associated with greater risk of complications and hospitalizations than non-invasive LTMV.
- The quality of evidence is very low, and it is therefore not possible to draw firm conclusions about the real effect.
For some diagnoses, including central respiratory failure, we were not able to identify any research fulfilling our inclusion criteria.