Background     Respiratory failure is the most common cause of death from amyotrophic lateral sclerosis (ALS). In most cases, respiratory muscle weakness from ALS develops insidiously as the disease progresses.  This allows most patients, families, and clinicians time to carefully discuss the options for ventilatory support before such decisions need to be made. Options for ventilatory support should be discussed long before the development of respiratory insufficiency. In addition, patients should be encouraged to identify a power of attorney for health care/healthcare proxy and to discuss their preferences about ventilatory support early in the course of the illness.

Assessment of respiratory insufficiency     Early signs and symptoms of respiratory muscle weakness are subtle: dyspnea with mild exertion, supine dyspnea, insomnia, morning headache, reduced appetite, weight loss, dizziness, depression, anxiety and marked fatigue.  There are no standard protocols to detect early respiratory failure. With time, dyspnea will become more obvious and eventually will be present even at rest.  Forced vital capacity (FVC) is the most common pulmonary test for tracking respiratory insufficiency in ALS, though early respiratory insufficiency may be better detected by nocturnal oximetry or maximal inspiratory pressure (MIP).  An FVC less than 1L or less than 30% of predicted value indicates significant risk of respiratory failure and death.  Serial respiratory testing is useful in identifying and tracking respiratory failure over time and assists in identifying the optimal timing for initiating respiratory interventions, as well as the safety of other procedures such as GTube placement which become riskier as respiratory capacity diminishes.

Choices for respiratory management 

• Bi-level Positive Airway Pressure (BiPAP or bilevel support), a type of non-invasive ventilation, can improve symptoms of hypoventilation, quality of life, and survival by several months.  Inability to safely clear secretions, which is common in those with bulbar involvement, is a relative contraindication to bilevel support.  In fact, inability to clear secretions secondary to progressive ALS is often used as a clinical sign to indicate that bilevel support should be discontinued. The use of oxygen at night without ventilatory assistance may not be sufficient for many patients with advanced ALS with life prolonging goals of care, as oxygen desaturation and chronic hypercapnia may lead to suppression of respiratory drive during sleep.  During the day bilevel support can be used to alleviate respiratory muscle fatigue. The use of ‘intermittent positive pressure’ breathing machines has been reported to expand the lungs and reduce atelectasis.
• Portable ventilator support: examples include the brand names Trilogy or Astral.  These machines have internal and external batteries and typically have a unique feature called mouthpiece ventilation (MPV) to provide volume-targeted ventilatory support.  They are typically more expensive than BiPAP support.  While there are not well-controlled studies to establish their superiority over BiPAP, the on-demand support that these machines can provide via their open-circuit MPV can make eating and speaking less challenging.
• Full-time invasive ventilatory support is considered when non-invasive ventilation is no longer effective or tolerable. Most patients who select invasive ventilatory support are dependent on it and unable to communicate verbally. While invasive ventilation supports respiration and can prolong survival by years, neurologic progression of the ALS will continue, and many reach a state in which they are alert but entirely unable to communicate (much like a locked-in state). The decision to pursue invasive ventilation should include a broader discussion in which the patient and their caregivers define the acceptable quality of life they want to prolong, and specifically whether they will want to discontinue invasive ventilation if they reach a locked-in state.

Supportive care     Regardless of assisted ventilatory choices, compassionate and effective palliative care must be implemented. A calm environment, the reassuring presence of relatives, trunk elevation and chest physiotherapy may all provide relief.  The sensation of shortness of breathing can be reduced by morphine (2.5-10 mg by mouth or 1-2 mg IV/subcutaneous every 1-4 hours). Titration of the morphine dose against the clinical effect almost never leads to a life-threatening respiratory depression (see Fast Fact #27). Anxiety due to respiratory insufficiency can be treated with lorazepam (0.5-1.0 mg sublingually).   When co-morbid medical complications develop, or patient determined quality of life deteriorates, ventilator support can be withdrawn, and symptom control provided to allow for a comfortable death.  See Fast Fact #33, Fast Fact #34, and Fast Fact #35 about ventilator withdrawal. See Fast Fact #299, Fast Fact #300, and Fast Fact #301 regarding management of sialorrhea and other common symptoms in ALS.

References: 

1. Bosario GD, Voltz R, Miller RG.  Palliative care in amyotrophic lateral sclerosis.  Neurologic Clinics. 2001; 19(4):801-827.
2. Bradley WG, Daroff RB, et al.  Neurology in Clinical Practice.  Woburn, MA: Butterworth-Heinemann; 2000:  pp2005-2014.
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8. Lechtzin N, Cudkowicz ME, de Carvalho M, et al. Respiratory measures in amyotrophic lateral sclerosis [published correction appears in Amyotroph Lateral Scler Frontotemporal Degener. 2018 Aug;19(5-6):478. doi: 10.1080/21678421.2018.1464641]. Amyotroph Lateral Scler Frontotemporal Degener. 2018;19(5-6):321-330.
9. Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology [published correction appears in Neurology. 2009 Dec 15;73(24):2134] [published correction appears in Neurology. 2010 Mar 2;74(9):781]. Neurology. 2009;73(15):1218-1226.
10. Everett EA, Pedowitz E, Maiser S, et al. Top Ten Tips Palliative Care Clinicians Should Know About Amyotrophic Lateral Sclerosis. J Palliat Med. 2020;23(6):842-847.
11. Niedermeyer S, Murn M, Choi PJ.  Respiratory failure in amyotrophic lateral sclerosis.  Chest 2019; 155(2):401-8.

Version History:  This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published July 2006; 3rd Edition May 2015; 4th Edition in April 2025 after being reviewed and updated by Jessica Besbris MD.
Conflicts of Interests: None to report.