Changes

April 2025 — minor update. QOF indicators removed in line with NHS England's 2025 Quality and Outcomes Framework.

Update

Goals

To support primary healthcare professionals to:

• Assess the likely causes of noisy respiratory secretions in people at the end of life.
• Alleviate distress to the person caused by accumulated respiratory secretions at the end of life.
• Alleviate distress to the family and carers caused by noisy respiratory secretions at the end of life.

Outcome measures

Audit criteria

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

NICE quality standards

NICE have defined Quality Standards relevant to end of life care for adults [NICE, 2013]. 

What is it?

• During the terminal phase of a person's illness, secretions may accumulate in the airway and result in gurgling and rattling noises during inspiration and expiration (sometimes described as a 'death rattle') [Twycross, 2016].

Why do secretions accumulate?

• Secretions are produced from the salivary glands (most common) and the bronchial mucosa and pool in the hypopharynx [Chan, 2015; Twycross, 2016]. These secretions can accumulate because:
  • Of poor clearance [Chan, 2015; Twycross, 2016]. For example:
    • Swallowing and/or coughing are decreased or absent (for example because of weakness or reduced consciousness, which may be due to the illness, or to the use of sedative, hypnotic, or opioid drugs).
    • There is increased stickiness of mucus (due to dehydration).
    • The cilia do not function properly to move mucus up the respiratory tract (for example because of smoking).
    • The person is supine or semi-recumbent (which causes secretions to pool in the hypopharynx).
  • Secretions are excessive or abnormal. For example increased mucus production due to [Twycross, 2016]:
    • Chest infection, which is common in advanced cancer.
    • Pulmonary oedema, which may be difficult to diagnose because investigations (for example radiologic examination) are often not appropriate or practical in the last days of life.
    • Bronchorrhoea (rare) is defined as the production of 100 mL or more per day of watery mucus. Up to 9 litres of mucus production per day has been reported. Bronchorrhoea most commonly occurs with bronchoalveolar carcinoma but may also arise from pulmonary metastases from other tumours. The tumour cells cover the bronchiolar surfaces and cause inflammation of the mucosa, which triggers copious mucus production [Chan, 2015].
• Gastric reflux may also cause pooling of fluid in the hypopharynx [Twycross, 2016].
• Oropharyngeal or gastric contents may be aspirated into the larynx and lower respiratory tract. Factors predisposing to aspiration include impaired consciousness, old age, impaired cough or gag reflex, and structural diseases of the airway and upper gastrointestinal tract. People who aspirate may have recurrent episodes of choking, coughing, or pneumonia.

How common is it?

• The prevalence of noisy respiratory tract secretions in people who are dying ranges from 23–92%, and typically occurs 17–57 hours before death [Wee, 2008].
• A definitive prevalence is difficult to establish because most available studies include non-comparable samples (for example people with different underlying conditions), have studied few people (n = less than 100), or are methodologically flawed.

What is the prognosis?

• The presence of audible respiratory secretions ('death rattle') is a strong predictor of death.
  • A study from a palliative care unit in Belgium found that of 25 people with different cancers who developed noisy respiratory secretions, 12 died within 24 hours and 19 died within 48 hours [Wildiers, 2002].

How do I know my patient has it?

• Pooling of secretions such as saliva in the hypopharynx is likely if a gurgling, rattling, or bubbling noise can be heard persistently from the person's airway during the terminal phase of life.

Scenario: Assessment

From age 16 years onwards.

Scenario: Noisy respiratory secretions at the end of life

From age 16 years onwards.

Which antimuscarinic should I prescribe?

• Drug choice should be guided by the adverse effect profiles of the different drugs and local palliative care guidelines and drug availability.
• Consider changing or stopping medicines if noisy respiratory secretions continue and are still causing distress after 12 hours (medicines may take up to 12 hours to become effective).
• Consider changing or stopping medicines if unacceptable side effects, such as dry mouth, urinary retention, delirium, agitation, and unwanted levels of sedation, persist.

[Wilcock, 2020]

What dose of antimuscarinic should I use?

• Initially give a subcutaneous bolus injection of an antimuscarinic drug to treat noisy respiratory secretions, and if there is a positive response, continue administering the drug by subcutaneous infusion using a syringe driver.
• Antimuscarinics can also be administered by repeated subcutaneous bolus injections at appropriate intervals, but use of regular injections is generally not practical or optimal for the patient. When given in this way, the dose and frequency of antimuscarinic drug administration varies according to the severity of respiratory secretions and patient response. They are usually given every 4 hours as required. 
• For antimuscarinic drug doses, see Table 2.

Table 2. Typical antimuscarinic drug doses for people with noisy respiratory tract secretions.

[Back, 2021; BNF, 2021]

Adverse effects of antimuscarinics

• Common adverse effects of antimuscarinic drugs include dry mouth, constipation, urinary retention, agitation, drowsiness, and blurred vision. There is no evidence as to what extent these occur in people in the terminal phase of illness.
• The adverse effect profile of antimuscarinic drugs can be used to advantage in some people to help provide more comfort in the terminal stage of life. Hyoscine hydrobromide crosses the blood-brain barrier and can cause central nervous system effects, especially in elderly people. Possible desirable effects are its sedative and anti-emetic activity, whereas undesirable effects include confusion and delirium.
• Hyoscine butylbromide and glycopyrronium bromide do not readily cross the blood-brain barrier and therefore do not produce central nervous system adverse effects.

[Twycross, 2014; ABPI Medicines Compendium, 2015; ABPI, 2019; ABPI, 2020]

How do I administer anti-emetic drugs via a syringe driver?

• Drug delivery via syringe drivers is an option if the person cannot take medicines by mouth.
• Only drugs that are known to be safe and effective when administered subcutaneously should be used. Use water for injection as the diluent when mixing drugs in a syringe driver (except for levomepromazine, dexamethasone, octreotide, and ketorolac).
• Before mixing drugs, check their compatibility.
  • Always follow local palliative care guidelines or seek advice from local palliative care services or hospital pharmacy drug information services before mixing drugs in a syringe driver.
  • Data are most often available on combinations of two drugs in a syringe driver, although some combinations of three or four drugs are compatible.
  • The following combinations of three drugs may be incompatible:
    • Cyclizine + haloperidol + hyoscine butylbromide: generally regarded as incompatible.
    • Cyclizine + hyoscine butylbromide + midazolam: observational reports of incompatibility.
    • Cyclizine 8.82 mg/mL + dexamethasone sodium phosphate 0.71 mg/mL + hyoscine butylbromide 2.35 mg/mL reported compatible: incompatibility may occur at higher doses.
  • If you cannot contact the appropriate authorities for further guidance, see the Syringe Driver Survey Database within the website palliativedrugs.com. This site requires registration. In addition, Table 3 provides a brief guide to two drug combination compatibilities.
• Do not use solutions that are discoloured or have precipitated.

Table 3. Compatibility for two drugs commonly given by syringe driver.

[Regnard, 2022; Wilcock, 2020; BNF, 2021]

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of palliative care - secretions.

Search dates

October 2016 - March 2021

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp Palliative Care/, exp Terminal Care/, exp Terminally Ill/, palliat$.tw., (terminal adj care).tw., palliative.tw., cancer.tw., terminal.tw., end of life.tw.
• (respiratory adj2 secretion$).tw., (respiratory adj2 congestion$).tw., rattl$.tw., (retained adj secretion$).tw., (airway ADJ secretion$).tw., (noisy ADJ2 secretion$).tw., (bronchial ADJ secretion$).tw., (death ADJ ratt$).tw.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.