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Disease/Disorder

Definition

Respiratory failure (RF) is a syndrome that results from either an impairment of oxygenation or carbon dioxide elimination (inadequate ventilation) or both. Respiratory failure necessitates invasive or noninvasive mechanical ventilation as indicated by a PaCO2 > 50 mm Hg or PaO2 ≤ 50 mm Hg by arterial blood gas (ABG) testing while on room air.

Individuals with spinal cord injuries (SCIs), multiple sclerosis (MS) and neuromuscular disorders (e.g. ALS, Myasthenia Gravis)) are at risk of developing ventilatory failure because of respiratory muscle weakness, reduction of lung and chest wall compliance, reduced vital capacity (VC) and ineffective cough.

Etiology

The ability to sustain alveolar ventilation (volume of fresh air that reaches the alveoli and participates in gas exchange per minute) is determined by neuromuscular competence (respiratory drive, neuromuscular transmission, muscle strength) and load (resistive, elastic and minute ventilation).

Impairments in neuromuscular competence include primary muscle weakness (e.g. myopathies), neuromuscular junction disorders (Myasthenia Gravis (MG)), central or peripheral nervous system disorders (SCI), Guillain-Barre Syndrome (GBS), Amyotrophic Lateral Sclerosis (ALS). These conditions present with weakness of inspiratory and expiratory muscles that lead to a partial or total inability to mechanically ventilate. The inability to mechanically ventilate results in hypoventilation or failure to produce an effective cough.  Respiratory drive (the body’s innate mechanism that controls and regulates breathing) is affected in brain stem lesions (respiratory centers in the medulla and pons), sleep disordered breathing (obstructive sleep apnea, (OSA)) and medication overdose.

Excessive load on the ventilatory system: obesity, pulmonary embolism, atelectasis, lung infections (bacterial and viral, including COVID-19), sepsis, pleural effusion, progressive spinal deformities (e.g., thoracic kyphoscoliosis) and increased intercostal muscle spasticity can decrease chest wall and lung compliance which increases the risk for RF.

Epidemiology including risk factors and primary prevention

Listed below are some common disease processes as epidemiology varies with each.

  • Spinal Cord Injury: Respiratory complications are the most common cause of morbidity and mortality in acute SCI, with an incidence of 36% to 83%. Risk factors include level of injury, aspiration, chronicity of disease, prior lung disease, amongst many others.1
  • Multiple Sclerosis: Advanced respiratory support in MS is highly unusual. A study by Pittock et al. found a total of 22 patients requiring mechanical ventilation over a period of 33 years. The median time to death after the start of ventilation was 22 months.2
  • Amyotrophic Lateral Sclerosis: Respiratory complications are the most common cause of mortality in ALS.  The average survival time after diagnosis is 2-5 years.  Individuals > 65 years old and with severe bulbar involvement have a much poorer respiratory prognosis. The use of invasive ventilation is rarely pursued in the US (2-6%). However, non-invasive ventilation is essential to increasing survival and quality of life outcomes.3
  • Guillain-Barre Syndrome: Overall mortality is as high as 18%, but most fully recover. Respiratory failure is the most common complication, affecting 20–30% of patients. Risk factors include underlying pulmonary health, admission within 7 days of symptom onset, and neck/cranial nerve/bulbar involvement.4
  • Myasthenia Gravis: Mortality is 4% to 8%.  About 15-20% of individuals will require ventilatory support. Predictive factors include neck or bulbar involvement. MuSK positive serology individuals make up 7% of patients requiring ventilatory support. Of note, 85% of MuSK seropositive patients are women.5,6
  • Polymyositis/Dermatomyositis: Pulmonary complication rate is 40%. However, respiratory failure or significant dyspnea is uncommon (about 5%).7

Patho-anatomy/physiology

Respiratory dysfunction can be categorized into the following areas:

  • Muscle weakness which results in decreased ventilatory function
    • The diaphragm and accessory muscles provide insufficient force or become fatigued more easily, as such are unable to ventilate effectively.
    • In addition, the intercostal and abdominal muscles become flaccid. This leads to paradoxical breathing which reduces efficiency of breathing and also reduces vital capacity (VC).
  • Impaired cough and secretion clearance
    • Due to impaired innervation of abdominal and internal intercostal muscles, cough reflex and mobilization of secretions become ineffective
    • Neck, cranial nerve and bulbar involvement reduce the ability for the individual to control secretions once mobilized.
  • Retained secretions and mucus plugging
    • Mucus hypersecretion results from the loss of sympathetic control and unopposed vagal activity. Of note, an increase in secretions is also common with tracheostomy placement.
    • The combination of increased bronchial secretions and ineffective cough leads to mucus plugs, airway obstructions, sudden respiratory distress and potential cardiac arrest.
  • Atelectasis
    • Occurs secondary to impaired expansion of the lungs.
    • Decreased inflation of the alveoli leads to decreased surfactant production.
    • Atelectasis worsens as respiratory muscles fatigue, secretions accumulate and lung compliance decreases.
    • Segments of collapsed lung are unable to participate in gas exchange, leading to ventilation/perfusion (V/Q) mismatch.
  • Bronchospasms
    • Parasympathetic activity is responsible for bronchoconstriction.
    • Loss of sympathetic control and unopposed vagal activity leads to increased airway tone and bronchospasms.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

  • Acute
    • Acute RF is the result of respiratory muscle weakness that leads to impaired cough, decreased VC, atelectasis, decreased lung compliances, increased work of breathing and respiratory fatigue.
    • Focus is on respiratory support and treating any reversible causes (e.g. respiratory infection, GBS). 
  • Subacute
    • In patients with SCI there may be partial recovery of respiratory muscle performance. This recovery can be attributed to spontaneous recovery of diaphragm innervation, reflex activity of intercostal muscles and enhanced performance of accessory muscles of the neck.
    • In patients with more insidious progression of respiratory weakness (e.g. ALS), the recovery of respiratory function depends on the reversal of the inciting cause (e.g. treating pneumonia) and also initiating preventative strategies.
  • Chronic
    • Pulmonary function may be altered by age, time since injury, underlying pulmonary health, obesity, and maximal inspiratory pressure.
    • Some individuals may experience late onset ventilatory failure due to chronic alveolar hypoventilation.
    • Signs and symptoms of progression: tachypnea or dyspnea (especially with decreased workloads), daytime somnolence, fluctuating mental alertness and position-dependent respiratory dysfunction.
    • Possible etiologies: disease progression, cervical myelopathy, post traumatic syringomyelia, progressive scoliosis or kyphosis, sleep apnea, age-related loss of diaphragm motor neurons.
  • End Stage
    • Diseases of the respiratory system are the leading cause of morbidity, mortality, and hospitalization among patients with chronic respiratory dysfunction. This is particularly common in patients with associated bulbar symptoms (e.g. slowed/weak speech, coughing/choking while swallowing, vocal cord spasms).

Specific secondary or associated conditions and complications

  • Pneumonia
    • The risk of developing ventilator associated pneumonia increases by 1% to 3% per day of intubation.1
    • Impaired cough, underlying pulmonary health, aspiration and reduced VC increases the risk when not requiring invasive ventilatory support.
    • In invasive ventilation risk factors include presence of tracheostomy, anterior approach to spinal stabilization and ongoing mechanical ventilation.
  • Sleep-disordered breathing (SDB)
    • Risk factors include increased neck and waist circumference, body mass index above 30 kg/m and use of sedating medications.1
  • Pleural effusions
    • Typically due to presence of atelectasis which further compromises ventilation. This leaves an area of low pressure within the pleural space that is then filled with fluid.
  • Mucus plugging
    • Mucus plugs, caused by increased secretions and impaired cough, can lead to sudden respiratory failure and death.

Essentials of Assessment

History

A comprehensive history of patients at risk or who currently have respiratory failure should include the components listed below. In order to determine patients at risk of respiratory compromise assessing for early signs of respiratory insufficiency is important.  This allows for early initiation of treatment and detection of progressive respiratory failure.

  • Premorbid pulmonary health issues such as chronic obstructive pulmonary disease, cancer, sleep disordered breathing and OSA.
  • A focused social history including drug, alcohol and tobacco use.
  • Any increase in respiratory infection which may point to reduced secretion clearance or dysphagia.
  • Family history neuromuscular diseases.
  • A review of medications to assess for any that put the patient at risk for respiratory failure (e.g. opiates, benzodiazepines, beta blockers)
  • In patients with spinal cord involvement, ASIA classification and level of injury should be established.  High cervical and complete injuries are more likely to require intubation and long-term support.
  • Subjective symptoms such as dyspnea at rest, increasing activity intolerance, functional decline, poor sleep, daytime sleepiness, morning headaches or difficulty concentrating.
  • Bulbar symptoms including but not limited to changes in voice, trouble chewing, difficulty swallowing or excessive drooling.

Physical examination

Physical examination should evaluate for respiratory muscle weakness and bulbar dysfunction. This includes

  • Overall muscle tone and bulk (observation of muscle atrophy/muscle wasting) Alignment of the spine looking for scoliosis or kyphosis.
  • Use of accessory muscles for breathing.
  • Observation of changes in breathing while supine or slight reverse Trendelenburg.
    • Paradoxical abdominal movement with breathing indicates diaphragmatic weakness.
    • If breathing becomes more difficult while lying flat, it could indicate diaphragm weakness in a patient with NMD.
    • In patient who are tetraplegic, breathing may improve due to the diaphragm being in a more mechanically advantageous position, which increases VC.8,9
  • Evaluation and observation of weakness in head control, cranial nerve impairments, speech and vocal clarity, protruding tongue and control of oral secretion to assess neck and bulbar function.
  • Muscle examination should include inspection of muscle atrophy and fasciculations. It should also include a complete strength exam including all major myotomes bilaterally.
  • Sensory testing and deep tendon reflexes (DTRs) can help determine upper motor neuron (UMN) and lower motor neuron (LMN) disorders (hyper-reflexive DTRs in UMN, hypo-reflexive DTRs in LMN)
  • In patients with spinal cord involvement ASIA classification and level of injury should be established: high cervical and complete injuries are more likely to require intubation.
  • A single breath test can be performed at bedside to assess vital capacity. To complete this test, have the patient take a max inspiratory breath.  Then, begin counting and continue to count until the patient has to take another breath. A Normal value is counting up to 50.  Severe impairment of vital capacity is diagnosed when a patient must take another breath before counting to 15.
  • If available a pulmonary function test (PFT) is used to confirm respiratory muscle weakness by a pattern of restriction.
    • Reduced forced expiratory volume in 1 second (FEV1, < 80% of predicted)
    • Reduced forced vital capacity (FVC, < 80% of predicted)
    • Normative FEV1/FVC ratio (>70% of predicted)
    • Reduced total lung capacity (< 80% of predicted)
    • Increased residual volume (RV)
    • Decreased vital capacity (VC, < 10-15 mL/kg of ideal body weight)
    • Negative inspiratory force (NIF) < -20 to -30 cm of water
    • Peak expiratory flow rate or peak cough flow (PCF): < 160 L/min

Functional assessment

Individuals with chronic neurologic disease should be monitored periodically for progression of respiratory function. It is important to determine the need for either invasive or non-invasive ventilation early, in case emergency intubation is necessary.

Mangera et al. proposed a pathway for managing patients with neuromuscular disease who have respiratory failure.9 A summary of tests that assist with the decision for intervention with ventilation is as follows:

  • Functional Vital capacity
    • Test both the seated and supine positions.
    • Vital capacity early on may be reduced only in the supine position indicating weakness of the diaphragm.
    • Non-invasive ventilation should be offered in patients with FVC <50% of predicted values or intermittently > 4 hours with FVC <75%.3
    • In acute decline in respiratory function, serial vital capacities should be obtained. If there is a downward trend and if FVC is < 15 mL/kg mechanical ventilation should be considered.
  • Mouth Pressures
    • Assess both inspiratory and expiratory respiratory muscle strength.
    • Mouth pressures should be assessed with vital capacity to determine respiratory function and need for additional respiratory support.
    • When mouth pressure is reduced to < 60% predicted a patient will need close follow up, serial measurements and an ABG.
  • Sniff nasal inspiratory pressure
    • Assessment of inspiratory muscle strength in a clinic setting.
    • Does not replace formal testing.
    • Low sniff inspiratory pressures indicate inspiratory respiratory muscle weakness.
    • Values of < 60 cm H2O in women and < 70 cm HOH in men are considered the lower limit of normal.10
  • Arterial Blood gases
    • pO2 < 50 mmHg or pCO2 > 50 mmHg is a sign of impending respiratory failure.
  • Electrodiagnosis
    • Assessment of phrenic nerve function is conducted either when a patient is unable to be weaned from the ventilator or   when a patient is having a diaphragmatic pacer placed
    • This is the gold standard for phrenic nerve function. It also often includes evaluation of intercostal function.

Imaging

  • Chest x-ray signs that could indicate a risk for respiratory failure:
    • Kyphoscoliosis
    • Emphysema
    • Respiratory infections
    • Pulmonary edema
    • Atelectasis
    • Raised hemidiaphragm which is commonly caused by a phrenic nerve palsy. If this sign is present, further testing of the phrenic nerve should be done.
  • Diaphragm Fluoroscopy: Should be obtained when VC is lower than expected for neurologic level of injury. Additionally, this imaging is used to assess for diaphragmatic paralysis in patients who have difficulty weaning off the ventilator.
  • Diaphragm ultrasound: Used to assess diaphragmatic excursion. Advantages over diaphragm fluoroscopy include portability, lack of ionizing radiation and ability to quantify diaphragmatic motion.
  • Computed tomography angiography: Preferred choice of imaging to confirm pulmonary embolism.

Supplemental assessment tools

  • Continuous pulse oximetry.
  • Capnography or end-tidal carbon dioxide: once initial arterial blood gas is obtained end-tidal carbon dioxide can be used as an indirect measure of carbon dioxide partial pressure in arterial blood.
  • Phrenic nerve conduction studies and diaphragmatic needle electromyography: used to establish diagnosis, determine severity and follow progression of peripheral respiratory muscle dysfunction.
  • Sleep studies: Patients who suffer from neuromuscular disease and spinal cord disorders suffer from increased frequency of sleep disordered breathing.
  • Formal swallow studies: Used to identify those who have trouble swallowing and those at risk for aspiration and/or nutritional deficiencies.

Early predictions of outcomes

Diaphragmatic innervation and diaphragmatic strength are measured by VC. These can both be used as prognostic indicators for early weaning off ventilation.

Poorer outcomes are associated with

  • Level of injury and complete versus incomplete injury in SCI
  • Bulbar involvement
  • Poor diaphragmatic recovery
  • Poor cognitive function
  • Premorbid pulmonary or respiratory disease
  • Ineffective cough
  • Increased secretions or decreased ability to control secretions
  • Rapid progression of non-respiratory muscular weakness

Professional issues

Regular updated discussions and about a patient’s current medical status. The patient’s goals and care preferences are critical. Patients should be encouraged to speak with their families about the disease’s natural history and their care wishes. An advanced directive should be considered, reviewed and updated regularly.

Rehabilitation Management and Treatments

Available or current treatment guidelines

In 2005, the Consortium for Spinal Cord Medicine developed clinical practice guidelines for respiratory management following SCI.1

In 2014, a review of respiratory failure in ALS which provides good evidence for management in those with progressive RF.3

In 2018, a recent review by Chatwin et al. provides information about airway clearance techniques.11

At different disease stages

The goals of these techniques are to reduce atelectasis and improve ventilation prior to ventilatory support:

  • Deep breathing and voluntary coughing.
  • Intermittent positive pressure breathing.
  • Delivers a positive pressure breath when the patient triggers it.
    • It can increase tidal volume
  • Glossopharyngeal breathing
    • Helps the patient get a deeper breath by gulping rapid mouthfuls of air and forcing it into the lungs.
  • Intrapulmonary percussive ventilation
    • Delivers a deep breath while mobilizing retained secretions
    • The vibrations loosen the retained secretions and deliver aerosol to hydrate viscous mucus plugs.
  • EzPAP
    • Positive expiratory pressure system that can be used with nebulizers to improve atelectasis, secretion clearance, and oxygenation.
    • Continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP)
    • Can be used to provide deep breaths, manage secretions and provide rest periods to non-intubated patients.
    • In ALS this has been shown to improve survival and quality of life measures in > 4 hours per day. 3
  • Patients who are tetraplegic due to SCI are placed in supine or Trendelenburg position.
    • In these patients, the abdominal wall has increased compliance. In the upright position the abdominal contents fall, and the diaphragm flattens.  In the supine or Trendelenburg position the effects of gravity will move the abdominal contents upwards toward the diaphragm and have a resultant increase in vital capacity and FEV1.8
    • Of note, patients with neuromuscular disease may have reduced vital capacity in the supine position, related to diaphragmatic weakness.
  • Abdominal binder
    • In patients with tetraplegia, an abdominal binder may prevent the drop in vital capacity that may occur when transitioning from supine to sitting
  • Respiratory muscle training
    • The goal is to strengthen inspiratory and expiratory musculature that are less affected from neurological injury.

Airway clearance and secretion mobilization

  • Endotracheal suctioning
    • Possible complications include hypoxia, hypotension, infection, tracheal mucosal damage, vagal nerve stimulation, increased bronchial mucus production, anxiety, and fear of suffocation.
  • Mechanical insufflator-exsufflator:
    • Clears retained secretions, reduces the risk of respiratory complications and the need for bronchoscopy.
    • Can be applied via tracheostomy, facemask or mouthpiece.
    • Contraindications include bullous emphysema, susceptibility to pneumothorax or pneumomediastinum and recent barotrauma.
  • Mechanical percussion and vibration
    • Devices include vibration vests and beds with automatic turning and vibration settings.
    • Tapping on different areas of the chest with a cupped hand may help to mobilize secretions.
  • Postural drainage
    • Passive positioning techniques that utilize gravity to help move secretions from the peripheral pulmonary regions to the main airway.
  • Manually assisted coughing
    • Chest compressions that are specifically coordinated to a patient’s’ breathing that results in a significant increase in expiratory peak airflow. It can also help move secretions from the lower lung fields.

Medications to help maintain respiratory function:1

  • Bronchodilators
  • Cromolyn Sodium
  • Steroids
  • Antibiotics
  • Anticoagulation
  • Vaccinations
  • Methylxanthines
  • Anabolic steroids
  • Mucolytics

Once ventilatory support is needed, there are two main types of ventilation to consider

Non-invasive Ventilation

Non-invasive ventilation helps to avoid the need for invasive ventilation. Patients with reduced vital capacity may benefit from nocturnal non-invasive ventilation. It may be offered to patients with decreased oxygen saturation <95% and CO2 > 50 cm H20.

The use of NIV in ALS is well studied due to it being the NMD that has an insidious onset and leads to respiratory failure. The current practices for when to initiate NIV in patients with ALS is when they have one or more subjective signs or symptoms of respiratory decline and an objective measure of reduced function. It is controversial of when to initiate NIV in these patients (FVC <50% versus as high as <75%). Despite this wide range of recommended FVC at which to initiate NIV, benefit has been shown if used for > 4 hours a day and no harm has been shown.3

  • Types: CPAP, BiPAP, APAP
    • CPAP: (Continuous positive airway pressure) provides constant and unchanging airway pressure.
    • BiPAP: (Bi-level positive airway pressure) provides preset variable support during inspiration and expiration. This is better than CPAP because it keeps the alveoli open by administering a smaller PEEP (Positive End-Expiratory Pressure).
  • APAP: (Automatic positive airway pressure) automatically provides a variable positive pressure support during inspiration and expiration, depending on airway resistance.  Tolerance to non-invasive ventilatory support is associated with those who do not have severe bulbar symptoms or facial flaccidity.3

Invasive Ventilation

Indications for intubation include increased respiratory rate, increasing oxygen requirements, decreased breath sounds on auscultation, VC < 15 mL/kg of ideal body weight (IBW) and ABG values of PaCO2 > 50 mm Hg or PaO2 ≤ 50 mm Hg while on room air.

The decision to implement invasive ventilation in patients with chronic neurologic disease should be made carefully after discussion with the patient and after a detailed goals of care discussion. Invasive ventilation has the potential to prolong survival time, 2-5 years in some ALS patients. However, this is only pursued by 2-6% of patients in the US.3

The choice to move to tracheostomy in those who have not been successfully weaned from a ventilator is not uncommon. There are a couple advantage to tracheostomy. First, it provides easier sectioning. Second, it facilitates weaning by allowing less dead space and airway resistance in comparison to intubation. Disadvantages include increased secretion production, infection risk and difficulties with communication.

There are several methods to facilitate communication while on mechanical ventilation. Some examples include lip speaking, mouthing, eye blinks, use of a communication board, use of a Passy-Muir valve, cuff deflation and use of cuff fenestrated tubes.

Ventilator weaning protocols may vary between different centers. In summary ventilator weaning should be initiated once the patient has stable vital signs, normal or improving chest X-ray, VC > 10-15 ml/kg ideal body weight and improved ABG values (PaCO2 of 35-45 mmHg or PaO2 > 75 mmHg, pH 7.35-7.45).  This is often a difficult situation, as such the weaning process should be fully explained to the patient.

In disease processes such as high-cervical SCI discontinued invasive ventilation may not be compatible with survival. In other NMDs such as GBS or MG with respiratory involvement, tracheostomy may be placed during a prolonged recovery period with potential for decannulation.

Emerging/unique interventions

Electrical stimulation of the phrenic nerve or diaphragm by diaphragmatic pacing:

  • Allow patients with SCI an alternative form of long-term respiratory management.
  • Both open and minimally invasive techniques are in use.12
  • Patients should have a backup ventilatory machine at all times in case of device failure.
  • Candidates include:
    • SCI level above C4
    • Functional phrenic nerve and diaphragm
    • Lack of significant airway or pulmonary disease
  • This is currently NOT indicated in ALS. In 2015, a multicentric, open label, randomized controlled trial was stopped due to lack of benefit and increased mortality.12
  • Directed transesophageal phrenic nerve stimulation is a new technique with single stimuli-enabled diaphragm activation currently still being evaluated as a viable option to keep the diaphragm active during artificial ventilation.13

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Follow-up should include regular evaluation of lung function, especially in high-risk individuals (high tetraplegia, ventilator dependent patients, patients with phrenic/diaphragmatic pacers, concomitant COPD, ALS, etc.).
  • Ensure caregivers have education, skills and available support prior to discharge home. Review with patient and caregiver principles on airway management (tracheal/stoma care, suctioning, tracheostomy tube change), safe swallow techniques, assisted cough, medications and early recognition of signs and symptoms of infection. Ideally, a patient will be able to direct his/her care in the presence of a new caregiver.
  • In patients on long term ventilation, review of emergency measures in case of ventilator failure, power failure, equipment malfunction etc. with the patient and caregiver is important. Check that information regarding technical support and community resources is always available. A back-up ventilator should be in good working condition.

Cutting Edge/Emerging and Unique Concepts and Practice

A recent review looking at spinal cord stimulators for cough restoration has shown that the stimulators are able to produce a near maximal cough similar to physiologic performance. Further, subjects with the implantation have reported, “improved sense of well-being, increased ease and independence in removing secretions, reduces stress, and a greater sense of autonomy and mobility.”14

Rehabilitation in the medical or surgical ICU setting (also known as early mobilization) may improve physical function and reduce the duration of delirium, mechanical ventilation and ICU length of stay. A recent Cochrane Review found that there is not currently sufficient research, although several additional studies are currently ongoing.15

Functional electrical stimulation to the abdominal muscles can improve respiratory function in patients with spinal cord injury in both the acute and chronic setting. A review article by McCaughey et al., found that there was a chronic improvement in vital capacity, functional vital capacity and peak expiratory flow. They also found an acute improvement in cough peak flow.16

Gaps in the Evidence-Based Knowledge

The “best” ventilator setting is one of the most controversial topics in respiratory treatment in SCI. Some protocols use a high TV of 20 mL/kg of IBW.  Others use a low TV of 10 mg/kg. A recent randomized controlled trial showed no significant differences in time to wean, incidence of VAP, or occurrence of adverse events among patients with tetraplegia ventilated with a TV of 10 mL/kg versus 20 mL/kg. In addition, ventilation at a high TV was not associated with barotrauma or acute respiratory distress syndrome.17

References

  1. Consortium for Spinal Cord Medicine. Respiratory management following spinal cord injury: a clinical practice guideline for health-care professionals. J Spinal Cord Med. 2005;28(3):259-293.
  2. Pittock SJ, Weinshenker BG, Wijdicks EFM. Mechanical ventilation and tracheostomy in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2004;75(9):1331-1333.
  3. Pinto S, Carvalho M de. Breathing new life into treatment advances for respiratory failure in amyotrophic lateral sclerosis patients. Neurodegener Dis Manag. 2014;4(1):83-102.
  4. Green C, Baker T, Subramaniam A. Predictors of respiratory failure in patients with Guillain–Barré syndrome: a systematic review and meta-analysis. Med J Aust. 2018;208(4):181-188.
  5. Reddel SW, Morsch M, Phillips WD. Clinical and scientific aspects of muscle-specific tyrosine kinase-related myasthenia gravis. Curr Opin Neurol. 2014;27(5):558-565.
  6. Hehir MK, Silvestri NJ. Generalized Myasthenia Gravis: Classification, Clinical Presentation, Natural History, and Epidemiology. Neurol Clin. 2018;36(2):253-260.
  7. Kalluri M, Oddis CV. Pulmonary manifestations of the idiopathic inflammatory myopathies. Clin Chest Med. 2010;31(3):501-512.
  8. Galeiras Vázquez R, Rascado Sedes P, Mourelo Fariña M, Montoto Marqués A, Ferreiro Velasco ME. Respiratory management in the patient with spinal cord injury. Biomed Res Int. 2013;2013:168757.
  9. Mangera Z, Panesar G, Makker H. Practical approach to management of respiratory complications in neurological disorders. Int J Gen Med. 2012;5:255-263.
  10. Caruso P, Albuquerque ALP de, Santana PV, et al. Diagnostic methods to assess inspiratory and expiratory muscle strength. J Bras Pneumol. 2015;41(2):110-123.
  11. Chatwin M, Toussaint M, Gonçalves MR, et al. Airway clearance techniques in neuromuscular disorders: A state of the art review. Respir Med. 2018;136:98-110.
  12. Le Pimpec-Barthes F, Legras A, Arame A, et al. Diaphragm pacing: the state of the art. J Thorac Dis. 2016;8(Suppl 4):S376-S386.
  13. Kaufmann EM, Krause S, Geisshuesler L, Scheidegger O, Haeberlin A, Niederhauser T. Feasibility of transesophageal phrenic nerve stimulation. Biomed Eng Online. 2023 Jan 30;22(1):5. doi: 10.1186/s12938-023-01071-5. PMID: 36717872; PMCID: PMC9885573.
  14. Hachmann JT, Calvert JS, Grahn PJ, Drubach DI, Lee KH, Lavrov IA. Review of Epidural Spinal Cord Stimulation for Augmenting Cough after Spinal Cord Injury. Front Hum Neurosci. 2017;11:144.
  15. Doiron KA, Hoffmann TC, Beller EM. Early intervention (mobilization or active exercise) for critically ill adults in the intensive care unit. Cochrane Database Syst Rev. 2018;3:CD010754.
  16. McCaughey EJ, Borotkanics RJ, Gollee H, Folz RJ, McLachlan AJ. Abdominal functional electrical stimulation to improve respiratory function after spinal cord injury: a systematic review and meta-analysis. Spinal Cord. 2017;55(8):798.
  17. Fenton J, Warner M, Charlifue S, et al. A comparison of high vs. standard tidal volumes in ventilator weaning for individuals with subacute cervical spinal cord injuries: a site-specific randomized clinical trial. Chest. 2011;140(4):403A.

Original Version of the Topic

Kareen A. Velez, MD and Stephen L. McKenna, MD. Pulmonary rehabilitation after ventilatory failure. 12/02/2013.

Previous Revision(s) of the Topic

Philippines Cabahug, MD, Travis Edmiston, MD, and Amira Noles, MD. Pulmonary Rehabilitation after Ventilatory Failure. 9/21/2018

Author Disclosure

Adithi Vemuri, DO
Nothing to Disclose

Anita Kou, MD
Nothing to Disclose