Background As consciousness decreases in the dying process, patients lose their ability to swallow and clear oral secretions. Air moves over these pooled secretions resulting in noisy ventilation. While there is no evidence that patients find this ‘death/inspiratory rattle/gurgle’ disturbing, evidence from bereaved surveys suggests the noises can be disturbing to visitors and caregivers who may fear the patient is choking. Similar sounds can occur in patients who are not imminently dying, such as brain injuries or amyotrophic lateral sclerosis (ALS) in which increased production of saliva (sialorrhea), or decreased clearance of secretions occurs. Death rattle can be a good predictor of near death in the terminally ill; one study indicated the median time from onset of symptoms to death was 16 hours.
Causes: Two sub-types of the “death rattle” have been proposed, although the significance regarding treatment has not been established: Type 1 = predominantly salivary secretions; Type 2 = predominantly bronchial secretions. More broadly, the following clinical factors likely contribute to the ‘death rattle’:
- Sialorrhea due to neuromuscular dysfunction (common in ALS or brain injuries).
- Medications which increase saliva production (e.g., pilocarpine, clozapine), mucosal irritation (e.g., doxycycline), or dose-dependent drooling as a medication side effect (e.g., clobazam).
- Impaired swallowing from depressed consciousness.
- Other medical illnesses such as gastroesophageal reflux, upper respiratory tract infections, esophageal dysmotility.
Non-pharmacological treatments: Since there is no consensus for pharmacologic recommendations for sialorrhea or the ‘death rattle’, non-pharmacological approaches should be considered first line.
- Discontinue or reduce IV fluid and enteral feeding
- Gentle oropharyngeal suctioning may be used but avoid deep suctioning.
- Reposition the body in a lateral position on either left or right side to facilitate drainage.
- Reposition the body with head down and feet elevated (Trendelenburg position) for a few minutes to move fluid up into the oropharynx for ease of removal. Caution with increased risk aspiration.
- Address family and caregivers with any fears and interpretations associated with the death rattle.
- Counsel caregivers that noisy breathing may not bother the patient even if it bothers them.
Pharmacological treatments Muscarinic receptor blockers (anti-cholinergic drugs) are the most used medication class when pooled oral secretions are refractory to non-pharmacologic measures. They decrease mucous production due to anticholinergic properties. Their effectiveness over placebo has not been consistently established. Patients with noisy breathing from pulmonary disease or infections are less likely to respond to these medications. Examples include scopolamine, hyoscyamine, glycopyrrolate, and atropine. Common adverse effects are blurred vision, sedation, confusion, delirium, restlessness, hallucinations, palpitations, constipation, and urinary retention. The primary difference in these drugs is whether they are tertiary amines which cross the blood-brain barrier (scopolamine, atropine, hyoscyamine) or quaternary amines, which do not (glycopyrrolate). Tertiary amines which cross the blood-brain barrier are more apt to cause more CNS toxicity (sedation, delirium). They are also more likely to affect the heart rate or rhythm and tend to be less expensive.
Drug | Route | Initial Dose | Onset | Duration | Clinical Pearls |
scopolamine (hyoscine) hydrobromide | Transdermal patch | 1.5 mg q72 hrs | ~12 hrs (24 hrs to steady state) | 72 hrs | Place 1-3 patches on hairless skin, typically behind ear. Scopolamine is highly sedating, so its use is limited to patients with a short prognosis (e.g., < 3-4 weeks) |
scopolamine butylbromide | Sub-cutaneous (Sub-Q) | 20 mg QID | 1-2 hrs | 4 hrs | |
hyoscyamine | Oral (PO), sublingual (SL) | 0.125 mg q 6 hrs prn | 30 min | 4-6 hrs | Also, highly sedating. Extended-release formulations available. |
glycopyrrolate | PO | 0.5-1 mg TID prn | 30 min | 2-4 hrs | Poor absorption limits oral use: IV/SC more costly and typically limited to inpatient settings; 5-10 times the cost of tertiary amine alternatives. |
glycopyrrolate | SubQ, IV | 0.2-0.4 mg q 4 hrs prn | 1 min | 7 hrs | |
atropine sulfate | SubQ, IV | 0.1 mg q4 hrs prn | 1 min | 1 hr | Contraindicated in asthma due to excessive drying effect in bronchi. More robust literature to support use. |
atropine sulfate 1% eye drops | SL | 1 drop q4 hrs prn | 30 min | 2 hrs |
Interventional options:
- Botulism injections may be considered for sialorrhea (e.g., ALS) with onset of effect at 1 week and duration of effect of 3-6 months.
- Antibiotics may be considered for respiratory infections such as pneumonia which can contribute to noisy breathing via mucous hypersecretion.
- Aerosolized N-acetylcysteine may reduce sputum viscosity.
- Surgical interventions such as submandibular gland excision, parotid duct ligation or diversion have been described for patients with longer prognoses.
References
- Back IN, Jenkins K, Blower A, Beckhelling J. A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle. Palliat Med. 2001; 15:329-336.
- Ohio Hospice & Palliative Care Organization. Palliative Care Pocket Consultant. Dubuqe, IA: Kendall Hunt Publishing; 2001.
- Twycross R, Wilcock A, eds. Hospice and Palliative Care Formulary USA. Nottingham, UK: Palliativedrugs.com Ltd; 2006.
- Wilders H, Menten J. Death rattle: prevalence, prevention and treatment. J Pain Symptom Manage. 2002; 23:310-317.
- Wee B, Hillier R. Interventions for noisy breathing in patients near to death. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD005177. DOI: 10.1002/14651858.CD005177.pub2.
- Shimizu Y, Miyashita M, et al. Care strategy for death rattle in terminally ill cancer patients and their family members: recommendations from a cross-sectional nationwide survey of bereaved family members’ perceptions. Journal of pain and symptom management 2014; 48: 2-12.
- Lokker ME, van Zuylen L, et al. Prevalence, impact, and treatment of death rattle: a systematic review. Journal of pain and symptom management 2014;47: 105-122.
- Muir J, Smith S, et al. Procalcitonin in special populations: guidance for antimicrobial therapy. American Journal of Health-System Pharmacy 2020;77: 745-758.
- Esch H, Geijteman E, et al. Effect of prophylactic subcutaneous scopolamine butylbromide on death rattle in patients at the end of life. Journal of American Medical Association 2021;326: 1268-1276.
- Cupp M. Giving meds by alternative routes. Pharmacist’s Letter 2020; 360226.
- Protus B, et al. Evaluation of Atropine 1% Ophthalmic Solution Administered Sublingually for the Management of Terminal Respiratory Secretions. American Journal of Hospice and Palliative Medicine 2013; 30: 388-392.
- Merz Pharmaceuticals, LLC. Cuvposa; 1961.
- Heisler M, et al. Randomized Double-Blind Trial of Sublingual Atropine vs. Placebo for the Management of Death Rattle. Journal of Pain and Symptom Management 2013; 45:14-22.
- West-Ward Pharmaceuticals. Atropine sulfate injection. DailyMed 2011.
- McLendon K, et al. Atropine. StatPearls Publishing 2021.
- Merz Pharmaceuticals, LLC. Cuvposa-glycopyrrolate liquid. DailyMed 2021.
- Clark K, et al. A Pilot Phase II Randomized, Cross-Over, Double-Blinded, Controlled Efficacy Study of Octreotide versus Hyoscine Hydrobromide for Control of Noisy Breathing at the End-of-Life. Journal of Pain and Palliative Care Pharmacotherapy 2008; 22:131-138.
- Strickland S, et al. AARC clinical practice guideline: effectiveness of pharmacologic airway clearance therapies in hospitalized patients. Respiratory Care 2015; 60:1071-1077.
- Isaacson S, et al. Safety and Efficacy of RimabotulinumtoxinB for Treatment of Sialorrhea in Adults. Journal of American Medical Association 2020; 77:461-469.
- Chan K, et al. Long-term Safety and Efficacy Data on Botulinum Toxin Type A. Journal of American Medical Association 2013; 139:134-138.
- McGeachan A, et al. Management of oral secretions in neurological disease. Pract Neurol 2017; 17:96-103.
- Bjorn C, et al. Tetracycline induced esophageal ulcers, a clinical and experimental study. Laryngoscope 1983; 93:184-189.
- Dwain T, Larson F. A comprehensive overview of the clinical pharmacokinetics of clobazam. J Clin Pharmacol 2019; 59:7-19.
- Farre M, et al. Salivary secretory disorders, inducing drugs, and clinical management. Int J Med Sci 2015; 12:811-824.
Version History: Originally published in 2004; it has been substantially updated in 2009; 2015; and 2022.
Conflicts of interest: none to report
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know!
Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast Fact is published. Health care providers should always exercise their own independent clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.