Respiratory muscle weakness due to neuromuscular disease: Management

INTRODUCTION — Respiratory muscle weakness due to neuromuscular disease can lead to acute and/or chronic ventilatory failure as well as recurrent aspiration and pneumonia. Management, which is largely supportive, can provide symptomatic relief, improve quality of life, and in some instances, prolong life.

The management of respiratory muscle weakness due to neuromuscular disease will be reviewed here. The clinical manifestations and evaluation of patients with respiratory muscle weakness are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

The approach outlined in this topic is in keeping for the most-part with guidelines [1].

TREATMENT OF THE UNDERLYING DISORDER — Respiratory muscle weakness is common among patients who have several types of neuromuscular disorders (table 1) [2,3]. In all cases, treatment of the underlying neuromuscular disorder is indicated, if feasible.

The response of respiratory muscle weakness to specific treatments may vary depending on the specific disease entity. For example, respiratory failure due to conditions such as Guillain-Barré syndrome, myasthenia gravis, polymyositis, and multiple sclerosis may be responsive to disease-specific therapy such that respiratory failure resolves as the underlying disease improves in response to therapy; in such cases ventilatory assistance may only be temporary. In contrast, other neuromuscular disorders are not reversible or may progress despite therapy (eg, amyotrophic lateral sclerosis [ALS], Duchenne muscular dystrophy [DMD]), thereby necessitating full-time ventilatory support and adjunctive aids. (See 'Chronic ventilatory support' below.)

Specific treatments are found in individual topics:

●ALS (see "Disease-modifying treatment of amyotrophic lateral sclerosis" and "Symptom-based management of amyotrophic lateral sclerosis")

●Myasthenia gravis (see "Overview of the treatment of myasthenia gravis" and "Myasthenic crisis")

●Guillain-Barré syndrome (see "Guillain-Barré syndrome in adults: Treatment and prognosis")

●Multiple sclerosis (see "Initial disease-modifying therapy for relapsing-remitting multiple sclerosis in adults" and "Treatment of acute exacerbations of multiple sclerosis in adults" and "Symptom management of multiple sclerosis in adults")

●DMD (see "Duchenne and Becker muscular dystrophy: Management and prognosis")

●Polymyositis (see "Initial treatment of dermatomyositis and polymyositis in adults")

●Diaphragmatic or phrenic nerve injury (see "Surgical treatment of phrenic nerve injury" and "Recognition and management of diaphragmatic injury in adults")

●Myotonic dystrophy (see "Myotonic dystrophy: Treatment and prognosis")

●Mitochondrial myopathy (see "Mitochondrial disorders: Treatment")

ACUTE VENTILATORY SUPPORT

Initial assessment — Patients with respiratory muscle weakness may present with acute respiratory failure due to their underlying neuromuscular disease itself (eg, Guillain-Barré syndrome), a complication of their disease (eg, aspiration pneumonia), or another intercurrent illness (eg, acute congestive heart failure).

Patients typically present with dyspnea and cough. Patients may also complain of a sense of "suffocation." Respiratory distress may not be as apparent as in patients who do not have respiratory muscle weakness. This is because many patients cannot increase their respiratory rate or tidal volume to meet ventilatory demand and additionally may not be able to expectorate large volumes of sputum, particularly if they are dehydrated. These features may mislead the clinician into believing that the patient is comfortable and does not need intubation. Thus, clinicians should look for subtle signs, such as thoracoabdominal paradox, and have a low threshold to perform arterial blood gas analysis for the early detection of acute hypercapnia.

The need for noninvasive versus invasive ventilation should be evaluated. Indications for either form of ventilation in the acute setting are similar to those in the general population and are discussed separately. Aspects that are particular to patients with respiratory muscle weakness are discussed in this section. (See "Approach to the adult with dyspnea in the emergency department" and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "The decision to intubate".)

A surrogate marker of lung function has been studied as a tool to help clinicians decide who to intubate. As an example, a single breath count test (SBC) is performed by the patient taking full inhalation and then counting, for as long as possible, at a rate of two counts per second. Studies have shown a correlation between SBC testing and vital capacity with lower counts indicating more severe respiratory dysfunction. In a study of 68 Guillain-Barré patients admitted to neurocritical care unit, 75 percent with SBC <19 required mechanical ventilation. A strong correlation between SBC and vital capacity was found [4]. In a study of 94 patients with Guillain-Barré Syndrome, 32 of 44 patients with a single breath count <7 required intubation compared to 0 of 50 patients with counts >7 [5]. Studies in patients with myasthenia gravis suggest that counts below 20 to 25 indicate abnormal respiratory function [6]. Studies specifically examining the role of SBC in predicting the need for noninvasive ventilation (NIV) are not yet available. Nevertheless, it seems reasonable to consider NIV in acute settings when the SBC is <20. There are insufficient data to make a recommendation in patients with stable chronic disease.

Noninvasive ventilation — The indications, contraindications (table 2), and technical aspects of initiating NIV (table 3) in patients with acute respiratory failure from respiratory muscle weakness, are similar to those in patients without respiratory muscle weakness. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation".)

In brief, we suggest the following as a guide:

●We consider most patients with neuromuscular weakness and acute respiratory failure as candidates for NIV unless contraindications such as the need for immediate intubation or severe bulbar dysfunction are present (table 2). Patients with significant bulbar dysfunction are poor candidates for NIV since they are unable to protect their lower airway and are at high risk of aspiration with NIV.

●In general, we initiate NIV using an oronasal mask to minimize leaks and ensure adequate ventilation. Bilevel positive airway pressure (BPAP) is the most common mode used. BPAP requires inspiratory and expiratory PAP (IPAP, EPAP) to be set with the difference between the two representing the degree of pressure support. The bigger the difference the greater the tidal volume that is delivered. We make sure that patients are not overventilated relative to their baseline gas exchange parameters and target baseline values for arterial oxygen and carbon dioxide parameters.

●Patients with respiratory muscle weakness (regardless of whether bulbar dysfunction is present) may experience upper airway obstruction with NIV. IPAP delivered via an oronasal mask may cause intermittent posterior displacement of the tongue resulting in inspiratory narrowing of the upper airway. An adequate EPAP level can help prevent this, especially if pharyngeal collapse caused by the abrupt reduction from inspiratory to expiratory pressure contributes to upper airway obstruction. Alternatively, the patient can be switched to a nasal mask with a chin strap (to prevent air leak from the mouth) [7].

●For patients already on chronic NIV due to chronic respiratory failure from respiratory muscle weakness, settings and duration of use may need to be increased to accommodate increased ventilatory needs. For example, the IPAP may need to be increased to increase the tidal volume delivered and the support may need to be extended from nocturnal support only to 24 hour support.

●For patients with upper extremity weakness, there is a relative contraindication to NIV since they cannot grasp the mask to remove it if needed (eg, in the event of unexpected vomiting).

In patients with acute respiratory failure from respiratory muscle weakness, small observational studies suggest that NIV may decrease the need for invasive mechanical ventilation, shorten intensive care unit (ICU) length of stay, and improve mortality [8-10]:

●In a prospective cohort study of 17 patients with neuromuscular disease who received NIV for acute respiratory failure (24 episodes), 79 percent did not progress to invasive mechanical ventilation [9]. A smaller retrospective study demonstrated similar findings [10].

●An observational study compared 14 patients with neuromuscular disease who received NIV for acute respiratory failure to 14 historical controls who received invasive mechanical ventilation [8]. The NIV group had lower mortality, a shorter length of ICU stay, and lower need for invasive mechanical ventilation. However, half of those on NIV also received a percutaneously placed small-bore tube providing tracheal access for secretion removal (ie, "mini-tracheostomy").

Select features in patients with acute respiratory failure from respiratory muscle weakness may predict the need for NIV. In a study of 32 patients with amyotrophic lateral sclerosis (ALS) who had acute respiratory infection, predictors of the need for NIV included a forced vital capacity (FVC) <55 percent predicted and a reduced peak cough flow <2.9 L/sec [11]. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Diagnostic evaluation'.)

Invasive mechanical ventilation

Indications — Patients who need immediate invasive mechanical ventilation include those who present with cardiorespiratory arrest, severe respiratory distress, marked blood gas abnormalities, or impaired consciousness, and patients who have contraindications to NIV (eg, severe bulbar dysfunction with aspiration) (table 2). Invasive mechanical ventilation should be initiated “early” (ie, before it is needed emergently), especially in patients with acutely progressive neuromuscular weakness, since early intubation may decrease the risk of early-onset pneumonia [12]. (See "The decision to intubate" and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure".)

Intubation with select induction agents should be considered. Agents including ketamine, etomidate, combined ketamine with propofol, or reduced dose propofol may be preferred since they may decrease the risk of prolonged hypotension that frequently follows intubation in patients with neuromuscular weakness who are hypovolemic and debilitated. Patients with dysautonomia (especially with Guillain-Barré syndrome) may also experience profound hypotension if the patient is positioned head up or have a pronounced vagal response to intubation, especially if the dose of induction agent is inadequate. Succinylcholine should be avoided since it can trigger malignant hyperthermia in patients with some conditions that cause muscle weakness (table 4), life threatening hyperkalemia in patients with denervating conditions, anesthesia-induced rhabdomyolysis (eg, in patients with Duchenne or Becker muscular dystrophy), and result in an unpredictable response in patients with select muscle disorders (eg, patients with myasthenia are typically resistant to succinylcholine). Similarly, the response to nondepolarizing neuromuscular blocking agents (NMBAs; eg, rocuronium, vecuronium, cisatracurium) is unpredictable in patients with some muscle diseases (eg, multiple sclerosis, amyotrophic lateral sclerosis) while patients with myasthenia gravis are exquisitely sensitive to nondepolarizing NMBAs. (See "Rapid sequence intubation in adults for emergency medicine and critical care".)

General ICU supportive measures — Several supportive measures that are typically used during the care of mechanically ventilated patients are similar to those used in all critically ill patients. These issues are discussed separately:

●Ventilator care (see "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit")

●Sedation and analgesia (see "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal")

●Venous thromboembolism prophylaxis (see "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients")

●Stress ulcer prophylaxis (see "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention")

●Prevention of ventilator-associated pneumonia (see "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults")

Specific issues in managing ventilated patients with neuromuscular disorders include the following:

●Avoidance of overventilation – We make sure that patients are not overventilated relative to their baseline gas exchange parameters and target baseline values for arterial oxygen and carbon dioxide parameters.

●Physical therapy – Critically ill patients with neuromuscular disease are particularly at increased risk for developing superimposed critical illness myopathy or polyneuropathy. Measures to reduce this risk and prevent post intensive care unit syndrome should be undertaken. (See "Neuromuscular weakness related to critical illness" and "Post-intensive care syndrome (PICS) in adults: Clinical features and diagnostic evaluation".)

●Fluid and electrolytes – Particular care should be taken to correct electrolyte abnormalities (eg, hypophosphatemia, hypokalemia) and avoid factors that may further compromise respiratory muscle function, including neuromuscular blocking agents, aminoglycosides, and glucocorticoids.

●Nutrition – Overfeeding must be avoided as the associated increase in carbon dioxide production can worsen hypercapnia [13]. Nutrition in patients requiring continuous chronic ventilatory support is discussed separately. (See "Malnutrition in advanced lung disease" and "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription" and "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction", section on 'Nutrition'.)

Discontinuing invasive mechanical ventilation — Discontinuation of mechanical ventilation follows a three-step process of readiness testing followed by a period of ventilatory support reduction, typically a spontaneous breathing trial (SBT), and extubation (or decannulation for those with a tracheostomy). However, when determining whether invasive mechanical ventilation can be discontinued in a patient with respiratory muscle weakness, extra caution is warranted because weaning failure is common (27 to 48 percent). While the optimal approach is unknown, the principles of readiness testing and SBTs are similar to patients who do not have neuromuscular disorders. However, we typically require that the patient tolerate an SBT of more than two hours (rather than 30 minutes) before considering extubation.

Our rationale for this approach is that patients referred to chronic weaning units are a group of patients who classically have diaphragmatic weakness and in whom half fail weaning trials of a duration longer than two hours; we make the assumption that this likely applies to patients with neuromuscular disease.

Although not routine, we also have a low threshold to extubate to NIV. In a case control study, 10 patients with neuromuscular disease who were extubated directly to NIV and received assisted coughing aids after extubation, were less likely to require reintubation and tracheostomy compared with 10 historic controls [14]. (See "Weaning from mechanical ventilation: Readiness testing" and "Initial weaning strategy in mechanically ventilated adults" and "Management of the difficult-to-wean adult patient in the intensive care unit" and "Management and prognosis of patients requiring prolonged mechanical ventilation", section on 'Weaning'.)

Rates of weaning failure are high, ranging from 27 to 48 percent, and are largely supported by several small observational studies [15-18]. As examples:

●In a retrospective study of 44 patients with Guillain-Barré syndrome, 24 were extubated and 20 underwent tracheostomy without attempted extubation [15]; 42 percent of the extubations failed. This rate is significantly higher than the average rate of extubation failure in the ICU, which is approximately 10 to 15 percent.

●In a similar study of patients with myasthenic crisis, 27 percent of extubations failed [16]. Advanced age and pulmonary complications (pneumonia, atelectasis) were associated with extubation failure.

Aggressive secretion clearance may decrease the duration of mechanical ventilation. In a retrospective cohort study of 18 patients with 24 episodes of acute respiratory failure due to myasthenia gravis, an aggressive approach to airway care (combining intermittent positive pressure breathing, bronchodilators, suctioning, sighs and chest physiotherapy) was associated with less atelectasis, less pneumonia, and a shorter duration of mechanical ventilation than seen in historical controls [19].

Predictors of successful extubation include a MIP more negative than -50 cm H₂O (eg, -60 cm H₂O) and improvement of the VC by 4 mL/kg or more from pre-intubation to pre-extubation [15].

Predictors of failure may include age >50 years, VC of less than 25 mL/kg during days one to six of intubation, evidence of chronic hypercapnia, dysautonomia, and poor baseline lung function [15,20,21]. Failure rates are higher if more than one predictor is present. For example, in one case-control study of 53 patients admitted for 73 episodes of myasthenic crisis, the likelihood of requiring intubation beyond two weeks was 88 percent if three risk factors were present [20].

In another study of 37 patients with Guillain-Barré syndrome, a pulmonary function score (PFS) was calculated immediately prior to intubation and on the twelfth day of mechanical ventilation [21]:

The PFS ratio between the two values of <1 was associated with the need for more than three weeks of mechanical ventilation with a sensitivity and specificity of 100 and 70 percent, respectively. Validation of this index has not been undertaken. (See "Tracheostomy: Rationale, indications, and contraindications", section on 'Optimal timing in mechanically ventilated patients'.)

For patients who fail weaning or fail extubation with no identifiable reversible cause, tracheostomy is commonly considered beginning at 7 to 10 days, provided this is consistent with the patient’s wishes [22]. However, some patients with chronic neuromuscular disease may be successfully extubated to NIV without an intervening need for tracheostomy (eg, those who have been NIV-dependent prior to the acute event and in whom the reason for ventilation was fully reversible). (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction", section on 'Extubation to CNVS and MIE' and 'Tracheostomy' below and 'Patient values and preferences' below.)

Following extubation, most patients should have a formal swallowing evaluation since swallowing dysfunction is typically more common in this population than in patients without respiratory muscle weakness. (See "Extubation management in the adult intensive care unit", section on 'Refeeding'.)

Outcomes — Even with timely intubation, patients with respiratory muscle weakness from neuromuscular disease tend to have relatively poor outcomes [20,23-26]. These data are derived from small observational studies. For example, in studies of intubated patients with Guillain-Barré syndrome, mortality was reported to be 12 to 20 percent and the median duration of mechanical ventilation was 18 to 29 days [24,25,27]. Among intubated patients with myasthenia gravis, mortality was 4 to 8 percent and the median duration of mechanical ventilation was 14 days, one week longer than patients without neuromuscular disease [20,23].

CHRONIC VENTILATORY SUPPORT — All patients with respiratory muscle weakness from a neuromuscular disorder (NMD) should be evaluated for the need for chronic ventilatory assistance, typically with noninvasive ventilation (NIV). Patients with progressive disease should also be monitored clinically with pulmonary function tests (eg, every three to six months) and gas exchange parameters (eg, every six months) to determine the optimal time for ventilatory support. Most of the clinical data used to make the decision regarding NIV are already obtained during the clinical evaluation of patients with neuromuscular weakness. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

Noninvasive ventilation

Indications — Chronic respiratory failure in the context of a NMD known to cause respiratory muscle weakness (table 1), clinical symptoms, objective physiologic testing, and evidence of hypoventilation or sleep disordered breathing are collectively used to determine if or when NIV is initiated (table 5) [28,29].

In patients with symptomatic chronic respiratory failure from respiratory muscle weakness who have evidence of nocturnal and/or daytime hypoventilation, we suggest evaluation for chronic ventilatory assistance with NIV.

Evaluation for NIV is also appropriate inpatients with progressive neuromuscular disorders who have early physiologic evidence of respiratory muscle weakness, even in the absence of symptoms or frank hypoventilation and in those who have symptoms suggestive of sleep disordered breathing in association with their underlying NMD.

Mask NIV administered at night with supplementary use of mouthpiece ventilation is typically employed as an initial strategy. Practical applications of NIV are discussed separately.  (See "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support".)

Symptomatic chronic respiratory failure — Several neuromuscular disorders are associated with the development of symptomatic chronic respiratory failure from respiratory muscle weakness (table 1).

Symptoms — Symptoms suggestive of respiratory muscle weakness are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Clinical manifestations'.)

Physiologic evidence of respiratory muscle weakness — Optimal parameters for chronic ventilatory support with NIV are unknown. Data indicate that no single measure at any one point in time is best for assessing the need for NIV. In our practice, we make clinical decisions after serial measurement of the maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced vital capacity (FVC), vital capacity (VC), and sniff nasal pressure (SNIP). (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Clinical manifestations' and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Noninvasive positive pressure ventilation'.)

NIV is typically indicated when any one or more of the following is present [30-35]:

●FVC <50 percent predicted

●VC <15 to 20 mL/kg, <60 percent of predicted, or <1 liter

●MIP <-60 cm H₂O (eg, -50 cm H₂O; indicates a high risk for hypercapnia)

●MEP <40 cm H₂O (indicates inadequate cough strength and risk for secretion retention)

●SNIP <40 cm H₂O

These thresholds may vary depending upon the underlying neuromuscular disorder or institution. As an example, the threshold for VC was derived from studies of patients with Guillain-Barré syndrome. It is uncertain whether the VC is similarly helpful in patients with acute respiratory muscle weakness due to other peripheral neuromuscular diseases, such as myasthenia gravis [35]. The threshold value for MIP also varies depending upon the institution and country (eg, in Europe a cutoff <40 cm H₂O is used).

A "20-30-40 rule" has been proposed [23,30]. The rule advocates the initiation of ventilatory support when the VC is less than 20 mL/kg, the MIP is less negative than -30 cm H₂O (eg, -20 cm H₂O), or the MEP is less than 40 cm H₂O. Prospective studies are needed to determine if this rule decreases the need for emergent intubation and improves overall outcome.

Chronic hypoventilation — In the chronic setting, the presence of nocturnal or daytime hypoventilation is an indication for NIV. We typically document evidence of nocturnal hypoventilation from capnography studies performed during sleep while daytime hypercapnia is usually detected on an awake arterial blood gas. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Inadequate ventilation'.)

Asymptomatic patients with progressive disease — In patients with progressive neuromuscular disorders, starting chronic ventilatory support before frank symptoms or hypoventilation develops may have a survival benefit (eg, FVC <80 percent predicted, although the cutoff of FVC <50 percent predicted is more commonly used) [36]. Further details on monitoring respiratory function in patients with progressive neuromuscular disease are provided separately. (See "Symptom-based management of amyotrophic lateral sclerosis", section on 'Respiratory function management' and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support", section on 'Patient selection'.)

Sleep disturbance — In patients with NMD, symptoms suggestive of sleep disordered breathing such as obstructive sleep apnea may prompt evaluation for nocturnal NIV in the sleep laboratory with polysomnography [37]. However, polysomnography is not necessary in the absence of symptoms suggestive of an underlying sleep disorder. (See "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders" and "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Diagnostic evaluation'.)

Contraindications — Contraindications to NIV include severe bulbar dysfunction, upper airway obstruction, retention of respiratory secretions, inability to achieve a satisfactory interface, poor cooperation, and/or inadequate cough (table 2). Patient selection for NIV in patients with chronic neuromuscular disorders are discussed in detail separately. (See "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support", section on 'Patient selection'.)

Efficacy — Limited data in patients with chronic respiratory failure due to neuromuscular disorders suggest that nocturnal NIV improves daytime gas exchange, sleep, quality of life, and in some patients, survival [38-53]. Best studied is amyotrophic lateral sclerosis (ALS):

●In a randomized trial of 92 patients with ALS who had orthopnea (with MIP <60 percent of predicted) and/or symptomatic daytime hypercapnia, NIV plus standard care was compared with standard care alone [47]. NIV improved survival by 205 days in patients without bulbar involvement, while no survival benefit was noted in those with bulbar disease. Patients with bulbar dysfunction who received NIV had some quality of life improvement, but without a survival benefit.

●In a series of 71 patients with ALS treated with NIV for chronic respiratory failure, independent predictors of improved survival were tolerance of nocturnal NIV (risk ratio 0.32, 95% CI, 0.13-0.78) and a slower rate of decline of FVC [48]. Patients with mild or no bulbar symptoms were more likely to be tolerant of NIV.

●Diaphragmatic pacing (in addition to NIV) does not augment survival in patients with ALS [54,55]. These data are discussed separately. (See "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications".)

Limited data in patients with respiratory muscle weakness from thoracic cage disease suggest a similar benefit:

●A prospective study of 244 patients with chronic respiratory failure due to kyphoscoliosis reported improved survival with home NIV compared with long-term oxygen therapy (hazard ratio 0.30, 95% CI 0.18-0.51) [56].

●Small observational studies of patients with restrictive thoracic cage disease show improved sleep efficiency, stage N3 and/or rapid eye movement (REM) sleep during NIV [57-59].

The exact mechanism by which nocturnal NIV can correct daytime hypoventilation in patients with neuromuscular and chest wall disease has not been fully elucidated. It is hypothesized that central chemoreceptor sensitivity may be restored by correction of profound nocturnal hypercapnia, or that the quality of sleep is changed when nocturnal NIV is employed [60,61]. Observational studies also suggest that nocturnal mechanical ventilation at least partially improves lung mechanics, respiratory muscle strength, or reduces ventilation‐perfusion mismatch, by day as well as night [41]. (See "Control of ventilation".)

Outcomes — Patients with respiratory muscle weakness from neuromuscular disease can survive for years on NIV. Most require nocturnal support and some also require NIV for limited periods during the day. A small proportion of patients may benefit from continuous NIV (almost 24/7). (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction".)

Patients with nonprogressive myopathic or lower motor neuron lesions can be managed with NIV indefinitely. In contrast, patients with progressive upper motor neuron lesions, such as those with bulbar ALS or Duchenne muscular dystrophy (DMD), develop stridor and spastic upper airway collapse that can render NIV less effective and necessitate tracheostomy for continued survival. (See 'Tracheostomy' below.)

Technical aspects of initiating NIV in patients with neuromuscular disease who have nocturnal hypoventilation or early chronic respiratory failure are discussed separately. (See "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support" and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Practical aspects of initiation" and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Adaptation and follow-up after initiation".)

Tracheostomy — In patients with respiratory muscle weakness due to neuromuscular disease, tracheostomy should be considered in the chronic setting or following an acute event.

●Indications – Indications include the following:

•Patients who have difficulty clearing their secretions despite adjunctive therapies. (See 'Respiratory adjunctive therapy' below.)

•Patients who require intermittent long-term mechanical ventilation, but in whom NIV is contraindicated (eg, severe bulbar dysfunction) or declined (table 2).

•Patients whose chronic respiratory failure has worsened and intermittent long-term NIV with respiratory adjunctive therapy is no longer sufficient.

•Patients who fail to wean from mechanical ventilation following an acute event.

In the chronic setting, the purpose of tracheostomy is chronic ventilation and/or secretion management as well ventilation for acute intercurrent illnesses. In the acute setting, the focus is also weaning to the point of decannulation and spontaneous breathing with or without NIV, although complete liberation from mechanical ventilation is not always achievable.

●Making the decision – While the decision to proceed with tracheostomy is best made prior to any acute event that might prompt invasive mechanical ventilation with an endotracheal tube, this may not always be feasible for patients who present unexpectedly with acute disease (eg, spinal trauma, Guillain-Barré syndrome, myasthenic crisis). In addition, some patients change their mind over time or when faced with death in the near or immediate future. Thus, revisiting this decision is important during chronic care of these patients. (See "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support", section on 'Patient preferences' and "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction", section on 'Indications for tracheostomy' and "Advance care planning and advance directives".)

●Outcomes (liberation and life expectancy) – Data describing outcome in tracheostomized patients with respiratory muscle weakness are limited. While patients with acute reversible etiologies, such as Guillain-Barré syndrome have a high likelihood of being liberated from mechanical ventilation, others with progressive neuromuscular disorders may not be as successful in weaning and end up partially or completely ventilator-dependent. In our experience, patients can survive for many years with a tracheostomy, although life-expectancy is likely limited when compared with spontaneously breathing patients who do not have a neuromuscular disorder.

Predicting who will be successfully liberated and who will not is poorly studied and may be dependent upon factors including age, nature of the underlying illness, and presence of other comorbidities. In one retrospective study of 60 patients with ALS who underwent tracheostomy for failure to wean from mechanical ventilation, on discharge from the acute care facility, 70 percent were completely ventilator-dependent, 28 percent were partially ventilator-dependent and 1.6 percent were liberated from mechanical ventilation [62]. Liberation rates thereafter were not described, but survival rates were 65 percent at one year and 45 percent at two years after tracheostomy. Survival was significantly shorter in patients older than 60 years at the time tracheostomy was performed. Details regarding transitioning from tracheostomy to NIV are discussed separately. (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction" and "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction", section on 'Tracheostomy to noninvasive ventilatory support'.)

●Nutrition – Swallowing dysfunction is common after intubation and when a tracheostomy is present, even among patients without pre-existing neuromuscular disease. Many patients who require a tracheostomy long term for ventilation, also require enteral feeding via a gastrostomy or jejunostomy tube, although some patients may be able to swallow safely with a tracheostomy in place within a stable chronic setting [63]. For patients with neuromuscular disorders who are successfully decannulated, an evaluation of bulbar function and swallowing should be undertaken before allowing them to eat [64]. (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction".)

●Disposition of service – Patients with respiratory muscle weakness who have a tracheostomy do not necessarily need a long term care facility indefinitely. Some patients can be chronically ventilated at home, provided appropriate support is available. (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction".)

Technical details regarding tracheostomy placement are provided separately. (See "Tracheostomy: Rationale, indications, and contraindications".)

Respiratory adjunctive therapy — In patients with respiratory muscle weakness who have ineffective cough, we suggest the routine use of adjuncts to assist coughing for secretion clearance. Benefits to support their routine use outside of this indication are unclear, although other physiologic benefits such as transiently improved respiratory compliance may exist. Such adjuncts can be used in the chronic setting as well as during and/or recovering from acute respiratory tract illnesses.

Interventions include mechanical insufflation-exsufflation (MIE), manually assisted coughing, hyperinflation maneuvers for lung volume recruitment (LVR), and secretion clearance techniques. We generally prefer MIE, although it has not been directly compared to the other interventions and in many cases we use a combination of such therapies depending on the patient’s preference, muscle weakness group, (inspiratory and/or expiratory), cough and glottis strength, volume of secretions, and level of expertise [38,65].

When prescribed, most are applied daily or twice daily. In the chronic setting, acceptance or adherence to these maneuvers is likely an issue that affects efficacy [66].

Techniques to augment cough — Maneuvers that improve inspiratory and/or expiratory flow can augment cough. However, the efficacy of such maneuvers, may be more limited in patients who cannot obtain effective glottic closure, which is required to generate high intrathoracic pressure during cough (eg, bulbar dysfunction in patients with ALS and DMD). The physiology of cough is described separately. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Muscles of respiration and cough' and 'Lung volume recruitment (assisted inflation maneuvers)' below and 'Manual-assisted cough (abdominal thrust)' below and 'Mechanical insufflation-exsufflation' below.)

Adequacy of cough can be determined by regularly measuring cough peak flow (PCF). Values >160 L/min are necessary for an effective cough to clear respiratory secretions. It has been suggested that a “baseline” PCF >270 L/min, when the patient is well, is required to maintain a PCF >160 L/min when the patient is unwell [67]. Assessing cough strength is mostly done as part of the diagnostic evaluation of respiratory muscle weakness but may also need to be monitored in those with progressive disease. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Assessing cough strength'.)

Mechanical insufflation-exsufflation — Insufflation-exsufflation can be delivered via a mechanical device to patients who are spontaneously breathing (ie, MIE) (figure 1). Both phases, insufflation and exsufflation, are active (ie, device assisted). During insufflation, positive pressure is applied (usually +40 cm H₂O), which results in an inspired tidal volume. Exsufflation rapidly follows over 0.02 seconds. Pressure becomes negative (usually -40 cm H₂O) and is sufficient to generate about 10 L per second of exsufflation (ie, expiratory) flow. Note, these expiratory flows are higher than that which would be achieved with passive expiration. The goal is to fully inflate then fully empty the lungs in four to six seconds to clear airway debris. Treatments are typically administered once or a twice a day but frequency can be increased in the setting of active respiratory infection or after extubation or decannulation.

Using the same device, MIE can also be applied through an endotracheal or tracheostomy tube when patients are on a mechanical ventilator. However, higher insufflation pressures are generally used (eg, 60 to 70 cm H₂O) to compensate for a drop in pressure across the endotracheal or tracheostomy tube.

MIE can be used alone or in combination with manually assisted coughing (see 'Manual-assisted cough (abdominal thrust)' below). However, when MIE is administered at sufficiently high pressures (eg, 50 to 60 cm H₂O), the concomitant abdominal thrusts from the manual assist maneuver usually do not further increase the exsufflation flow, and so, are probably not necessary.

MIE is generally well tolerated with complications infrequently reported and can be used in the home [68]. Gastric distension and chest wall discomfort can occasionally occur. There are rare reports of pneumothorax [69].

MIE may be less effective in patients who have expiratory airflow limitation (eg, chronic obstructive pulmonary disease) because it is associated with worsening expiratory airway collapse and a decrease in the PCF [70,71]. In addition, with disease progression and/or bulbar dysfunction, laryngeal dysfunction can result from MIE when higher inflation pressures are used (eg, laryngeal adduction during insufflation and hypopharyngeal collapse during exsufflation) [72]. With any of these circumstances, we lower MIE pressures, and if this is not effective, we use alternative cough augmentation maneuvers such as manually assisted coughing. (See 'Manual-assisted cough (abdominal thrust)' below.)

Data to support the routine use of MIE, either during stable disease or during acute respiratory tract infections are limited to observation studies with minimal data describing its effect on clinically important outcomes such as disease progression, need for invasive mechanical ventilation, or survival [73-79]:

●MIE plus chest physical therapy reduces treatment failure in patients with neuromuscular disease who have a respiratory tract infection, compared with historical controls managed with chest physical therapy alone [76].

●MIE via a tracheostomy tube is more effective at clearing respiratory secretions than tracheal suctioning in patients with ALS [77].

●MIE produces a greater increase in PCF than a manually assisted cough in some, but not all, studies [74,78].

●MIE improves physiologic parameters including vital capacity, peripheral oxygenation, exhaled tidal volume, and peak expiratory flow in patients with neuromuscular disease [79-81].

●Use of a protocol that included MIE (or other lung-assist devices) and manual assisted coughing lowered the hospitalization rate among patients with DMD [73].

●MIE has been shown to eliminate the need for deep airway suctioning and can return ambient air oxyhemoglobin saturation to normal when preparing patients for successful extubation or decannulation [82,83].

The insufflation component of MIE can also be used for passive lung volume recruitment (LVR) which is discussed below. (See 'Lung volume recruitment (assisted inflation maneuvers)' below.)

Manual-assisted cough (abdominal thrust) — The manual-assisted cough (also called "quad cough") is an abdominal thrust that is provided by a caregiver and timed to occur at the same time as the patient's voluntary cough effort. It has variable efficacy in different populations.

●In patients who have expiratory muscle weakness, manual-assisted cough is effective as an isolated maneuver, and can be augmented when combined with insufflation techniques [84].

●In patients who have inspiratory muscle weakness (eg, when the vital capacity is 1.5 L or less), manual-assisted cough is insufficient as an isolated maneuver and should be combined with insufflation or recruitment maneuvers.

●Similarly, manual-assisted coughing may also not be sufficiently effective in the presence of severe scoliosis or severely impaired bulbar-innervated muscles.

●In addition, it should be avoided following meals due to the risk of aspiration and cannot be used in patients with abdominal trauma.

Lung volume recruitment (assisted inflation maneuvers) — Assisted lung inflation maneuvers are LVR maneuvers that increase inspiratory tidal volume. LVR is designed to improve lung compliance, reduce restriction, decrease the work of breathing, and improve cough flow.

LVR maneuvers can be device-assisted (active) or spontaneously performed (passive), none of which has been proven superior. With the exception of glossopharyngeal breathing, a manual resuscitator (eg, Ambu bag) or volume-cycled ventilator is typically used to deliver preset volumes for inflation; pressure-cycled ventilators cannot be used for LVR [85,86]. Delivered volumes are typically higher than a normal tidal volume and generally approach maximum lung insufflation capacity (ie, until the glottis can hold no additional air). This provides a greater volume of gas to be forced out during a cough, thereby also improving cough effectiveness. In LVR, exhalation is passive unless combined with manual-assisted coughing or exsufflation. Spontaneous LVR maneuvers such as glossopharyngeal breathing, require intact bulbar function for the patient to be able to retain the delivered tidal volume [87]. However, this is not an issue for LVR maneuvers delivered by a device through an endotracheal tube or tracheotomy tube.

There are several ways to deliver LVR maneuvers, which include the following:

●Mechanical inspiration using a mechanical insufflator or a volume cycled ventilator – These device-assisted LVR maneuvers are especially useful for patients unable to stack breaths such as patients with poor bulbar dysfunction when glottis strength is inadequate to hold consecutively delivered air volumes [75].

The insufflation component of MIE may be used for LVR. Alternatively, a volume-cycled ventilator (invasive or noninvasive) may be used to deliver a preset inspiratory tidal volume. Exhalation can be passive or assisted (eg, manual-assisted cough, exsufflation). Intermittent positive pressure breathing (IPPB) devices have also been used to deliver a set pressure to expand the lungs (and can also be used to deliver aerosolized medications); however, IPPB devices have largely been supplanted by NIV.

●Stacked breaths – Stacked breathing is initiation of inspiration before the completion of expiration. Glossopharyngeal (GPB) or "frog breathing" is a breath-stacking technique learned spontaneously by or taught to patients with respiratory muscle weakness [88]. To perform effective GPB, the upper airway and tongue musculature must be intact. Thus, the main users of GPB are a rapidly diminishing population of patients with post-polio syndrome, those with high cervical cord lesions, and others with neuromuscular diseases that spare the upper airway musculature. Some patients use GPB to become independent from mechanical ventilation for up to several hours at a time while awake. Others with progressive neuromuscular disease use it for prolonged periods to delay the eventual need for mechanical ventilation [89].

During GPB, the patient performs gulping maneuvers that inject 50 to 60 mL boluses of air into the lungs. Each "gulp" takes 0.5 seconds and is repeated 10 to 12 times to achieve a normal tidal volume or maximal tolerated inspiratory capacity. The intake of tidal volume is repeated 10 times per minute for a total volume of 5 to 6 L/min.

Delivery of stacked breaths can be also achieved using a manual resuscitation bag (eg, Ambu bag). Compression of the manual resuscitation bag transmits inspiratory pressure to the airways through an airtight oronasal mask or mouthpiece. Exhalation is prevented by either the one-way valve or the patient controlling their glottis. Once the maximum tolerated assisted inspiratory capacity is reached, passive exhalation to functional residual capacity or a spontaneous or assisted forced expiratory maneuver (eg, cough) follows. Breath-stacking can also be performed using a volume-cycled NIV device.

Data to support the use of LVR are limited to observational series that mostly describe efficacy on surrogate outcomes such as inspiratory capacity and PCF with limited data to support an effect on concrete clinical outcomes (eg, pneumonia rate, hospitalizations, mortality). In reality, the efficacy likely varies, being effective for some and less effective for others [90]. However, identifying who benefits and who does not is unclear.

●In patients with DMD, two observational cohorts suggested slower rates of decline in forced vital capacity (FVC) following the initiation of daily LVR (-4.5 versus -0.5 percent predicted per year) [86,91]. The PCF was unaffected by LVR. Similar results were seen in patients with multiple sclerosis treated with twice daily LVR [92].

●In a small randomized controlled trial of patients with ALS, no difference was found in the number of episodes of chest infection, duration of symptoms during each episode of infection, need for hospitalization, quality of life, or median survival when breath-stacking using a lung volume recruitment bag was compared to the mechanical insufflator-exsufflator [66].

●In 52 adult patients with DMD receiving NIV, no difference in cough effectiveness was seen when breath stacking from a home ventilator was compared with that generated from a lung volume recruitment bag [93].

●In 18 patients with severe respiratory muscle dysfunction from neuromuscular disease, PCFs were highest using a combination of LVR using a volume-cycled ventilator and manually assisted cough compared with either MIE or MIE combined with manually assisted cough [94].

Managing secretions — Managing oral and pulmonary secretions can be an issue in patients with respiratory muscle weakness, especially in patients with bulbar dysfunction and those with acute respiratory infections. We typically use one or more techniques to mobilize secretions and reduce secretion volume, which are discussed in the sections below.

Secretion mobilization techniques — High frequency chest-wall oscillation (HFCWO), intrapulmonary percussive ventilation, and MIE are techniques that can mobilize secretions from the airways [87]. Data describing efficacy are limited. A 12 week, controlled trial of HFCWO in 46 patients with ALS showed reduced dyspnea, but no slowing of deterioration in pulmonary function [95]. Data also suggest that MIE may be effective for secretion clearance during respiratory tract infections [96] and may reduce the rate of intubation or bronchoscopy when compared to those treated without MIE [76].

HFCWO is an external chest wall device that delivers oscillations to the chest using an inflatable vest that wraps around the chest. The device produces vibrations at variable frequencies and intensities, to facilitate expectoration. An intrapulmonary percussive ventilation device is a pneumatic device that can be connected to a face mask, mouthpiece, endotracheal tube or tracheostomy that intermittently delivers small tidal volumes at high frequencies (100 to 300 cycles per minute) creating percussions inside the lung. MIE is described above. (See 'Mechanical insufflation-exsufflation' above.)

Reducing secretion volume — Oral secretions can be reduced using anticholinergic agents (transdermal scopolamine, nebulized or subcutaneous glycopyrrolate, topical atropine, oral amitriptyline, oral hyoscyamine sulfate), injection of botulinum toxin into the submandibular or parotid glands, or external beam radiation to the salivary glands. Approximately two-thirds of patients respond to these interventions [97]. However, anticholinergics must be used carefully because of associated side effects (eg, constipation, dry mouth). Salivary gland botulinum toxin injection can provide benefit for three to four months, but laryngeal dysfunction can occur as an adverse effect [98,99]. The medication should be discontinued if the patient does not experience symptomatic improvement.

PATIENT VALUES AND PREFERENCES — For patients with respiratory failure due to neuromuscular disease, clinicians should understand the patients’ values and goals for medical care both in the acute and chronic care setting (eg, restoring health, extending life, or relieving pain and suffering). Palliative care teams can help to facilitate discussions regarding patients’ goals and preferences and can provide ongoing care if the goals are to focus on palliation. (See "Ethical issues in palliative care" and "Benefits, services, and models of subspecialty palliative care".)

Some patients with neuromuscular disease can expect continued progression of their underlying disease process even with long term respiratory support (eg, amyotrophic lateral sclerosis, Duchenne muscular dystrophy [DMD]), although the rate of disease progression varies. In this population, some patients may not choose permanent assisted ventilation with tracheostomy, based on issues related to quality of life and expectations of worsening disability, while others find it acceptable.

Progressive neuromuscular diseases of childhood, such as spinal muscular atrophy and milder variants of DMD present different challenges. In these diseases, long-term ventilatory support is more common and often associated with good quality of life, and decisions are often made during childhood by parents. For these patients, as with adult patients, a clear understanding of the decision-maker’s expectations is essential.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Noninvasive ventilation in adults".)

SUMMARY AND RECOMMENDATIONS

●Respiratory muscle weakness can be commonly encountered among patients who have neuromuscular disease due to a variety of etiologies (table 1). Supportive management of respiratory muscle weakness due to neuromuscular disease can provide symptomatic relief, improve quality of life, and in some cases, prolong life. In all cases, treatment of the underlying neuromuscular disorder is indicated, if feasible, although the response may vary depending on the specific disease entity. (See 'Introduction' above and 'Treatment of the underlying disorder' above.)

●Acute respiratory failure – Patients with respiratory muscle weakness may present with acute respiratory failure due to the underlying neuromuscular disease itself, a complication of their disease, or another intercurrent illness. Initial evaluation involves deciding whether the patient is suitable for noninvasive (NIV) or invasive ventilation. Indications for either form of ventilation in the acute setting are similar to those in the general population. However, the features of respiratory distress may be subtle such that the threshold for obtaining an arterial blood gas should be low. (See "Approach to the adult with dyspnea in the emergency department" and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure" and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "The decision to intubate".)

•The indications, contraindications (table 2), and technical aspects of initiating NIV (table 3) are similar to those in patients without respiratory muscle weakness. Notably, patients with significant bulbar dysfunction are poor candidates for NIV since they are unable to protect their lower airway and are at high risk of aspiration with NIV and upper airway collapse. (See 'Noninvasive ventilation' above and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation".)

•Similarly, indications for immediate intubation and invasive mechanical ventilation, ventilation strategies, and supportive care are similar to those who have acute respiratory failure without respiratory muscle weakness. However, select issues should be taken into consideration (see 'Invasive mechanical ventilation' above):

-Suitable induction agents (table 4) that may avoid prolonged hypotension in susceptible patients include ketamine, etomidate, combined ketamine with propofol, or reduced-dose propofol (eg, hypovolemic and debilitated). While neuromuscular blocking agents are not contraindicated, the response can be variable. Succinylcholine is generally avoided due to the increased risk of malignant hyperthermia, hyperkalemia, and rhabdomyolysis in some patients with select neuromuscular disorders. (See 'Indications' above and "Induction agents for rapid sequence intubation in adults for emergency medicine and critical care".)

-We avoid electrolyte abnormalities (eg, hypophosphatemia, hypokalemia) and other factors that may further compromise respiratory muscle function, including neuromuscular blocking agents, aminoglycosides, and glucocorticoids. (See 'General ICU supportive measures' above.)

-Extra caution is warranted when deciding whether to discontinue mechanical ventilation because the likelihood of weaning failure is high among patients with respiratory muscle weakness (27 to 48 percent). (See 'Discontinuing invasive mechanical ventilation' above.)

●Chronic respiratory failure – All patients with chronic respiratory insufficiency due to respiratory muscle weakness from neuromuscular disease should be evaluated for the need for ventilatory support, typically with NIV. Patients with progressive disease should be monitored clinically with pulmonary function tests (eg, every three to six months) and gas exchange parameters (eg, every six months) to determine the optimal time for initiating chronic ventilatory support. (See 'Chronic ventilatory support' above.)

•In the context of an appropriate diagnosis (table 1), subjective clinical findings, objective physiologic tests, and evidence of hypoventilation or sleep disordered breathing are used to determine when NIV is indicated (table 5). (See 'Noninvasive ventilation' above and 'Indications' above.)

•Symptomatic respiratory failure with evidence of hypoventilation – For patients with symptomatic chronic respiratory failure due to neuromuscular weakness with evidence of nocturnal and/or daytime hypoventilation, we suggest evaluation for chronic ventilatory assistance with NIV (Grade 2C). (See 'Symptomatic chronic respiratory failure' above.)

•Progressive neuromuscular disorder – Evaluation for NIV is also appropriate in patients with progressive neuromuscular disorders who have early physiologic evidence of respiratory muscle weakness even in the absence of frank hypoventilation or symptoms. These parameters include (see "Symptom-based management of amyotrophic lateral sclerosis", section on 'Noninvasive positive pressure ventilation' and 'Physiologic evidence of respiratory muscle weakness' above):

-Forced vital capacity <50 percent predicted

-Vital capacity (VC) <15 to 20 mL/kg, 60 percent of predicted, or <1 L

-Maximal inspiratory pressure <-60 cm H₂O (eg, -50 cm H₂O)

-Maximal expiratory pressure <40 cm H₂O

-Sniff nasal inspiratory pressure <40 cm H₂O

•Sleep disordered breathing – We also evaluate for NIV during polysomnography when co-existing sleep disordered breathing is suspected in patients with neuromuscular disorder. (See "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders" and 'Sleep disturbance' above.)

•Contraindications – Contraindications to NIV include severe bulbar dysfunction, upper airway obstruction, retention of respiratory secretions, inability to achieve a satisfactory interface, poor cooperation, and/or inadequate cough (table 2). (See 'Contraindications' above.)

•Tracheostomy – Tracheostomy is indicated for patients with neuromuscular disease who have difficulty clearing their secretions, require intermittent long-term mechanical ventilation but in whom NIV is contraindicated, patients who have worsening chronic respiratory failure and in whom intermittent long-term NIV is no longer sufficient, or patients who fail to wean from invasive mechanical ventilation. (See 'Tracheostomy' above.)

●In patients with respiratory muscle weakness who have ineffective cough, we suggest the routine use of adjuncts to assist coughing for secretion clearance (Grade 2C). Benefits to support their routine use outside of this indication are unclear. Such adjuncts can be used in the chronic setting as well as during acute respiratory tract illnesses. They can also be used in spontaneously breathing or ventilated patients. (See 'Respiratory adjunctive therapy' above.)

•Interventions include mechanical insufflation-exsufflation (MIE), manual-assisted coughing, hyperinflation maneuvers, and secretion clearance techniques. We typically prefer MIE, although it has not been directly compared with other interventions and in many cases we use a combination of therapies (eg, mechanical insufflation and manual-assisted cough). (See 'Techniques to augment cough' above.)

•We typically use one or more techniques to mobilize secretions and reduce secretion volume. (See 'Reducing secretion volume' above.)

●For patients with respiratory failure due to respiratory muscle weakness from neuromuscular disease, it is particularly important for clinicians to understand the patients' values and goals for medical care (eg, restoring health, extending life, or relieving pain and suffering). We believe that discussions about patients’ desires regarding long-term care decisions are an integral part of the care of such patients. Palliative care teams can help to facilitate discussions regarding patients' goals and preferences and can provide ongoing care if the goals are to focus on palliation. (See 'Patient values and preferences' above.)