Secretions within the respiratory tract causing noisy, gurgling respirations in the last hours of life have been described in 23–92% of deaths in palliative care units [1,2]. A lack of standardized measures and mostly retrospective collection of data have contributed to the wide range of prevalence reported. Often called ‘death rattle’, these respiratory noises can evoke emotional responses in health professionals and carers, leading to a perceived need to intervene. However, a recent systematic review of management strategies of terminal secretions failed to identify effective interventions [3••].
Understanding of the pathophysiology of death rattle remains incomplete, and research is limited by the emotional and logistic difficulties of conducting studies at this stage of life and a lack of objective assessment tools. This paper seeks to review the current definitions, consider the possible mechanisms and causes and to discuss the current interventions for noisy secretions in the dying person.
Defining noisy secretions
‘Death rattle’, so named because of the close association with imminent death, is generally accepted as the noisy respirations heard when dying persons are no longer able to clear the airways. Sometimes perceived as distressing for the dying person and often causing distress in the people close to them, the respirations may be described by relatives as ‘noisy’, ‘rattling’, ‘harsh’ or ‘gurgling’ . Correctly, lay people and professionals alike view these noises as a sign that life is very short, with death likely to occur within 16–60 h following the onset of secretions [1,2,5,6•,7].
Previous attempts to classify death rattle have acknowledged the complexity of this problem. Bennett  proposed two subgroups: type I due to predominantly salivary secretions and type II due to accumulated bronchial secretions. Alternatively, Wildiers and Menten  suggested ‘real’ death rattle to be due to nonexpectorated, nonpathological secretions and ‘pseudo’ death rattle caused by bronchial or other secretions in the presence of pulmonary disease. The latter group is postulated as less likely to respond to anticholinergic medications.
Mechanism of noisy secretions
The literature suggests that death rattle is produced when pooled secretions, that a person can no longer expectorate or swallow, vibrate with respiratory movements. The precise mechanism remains unclear, as does the type of secretions predominantly involved. Saliva and bronchial mucus are considered most likely, but upper gastrointestinal, exudative and transudative respiratory secretions may also result in noisy and gurgling respirations. Although impaired ability to protect the airway is the initial step, it is likely that other reactive changes in the airways and lungs follow, contributing to a process that sometimes culminates in recalcitrant noises.
A three-step mechanism of noisy respirations at the end of life is proposed here. Initially, secretions accumulate due to an inability to swallow or cough. Second, partial airway obstruction occurs as a result of the pooled secretions, as evidenced by gurgling respirations. Third, at the level of obstruction, and in reaction to the obstruction, even more secretions are produced. The ongoing inability to cough and generate adequate expiratory airflow produces a positive feedback loop, leading to increasing intensity of death rattle.
There are precedents that support this proposed stepwise mechanism. Reactive changes of the respiratory tract secondary to pooling of secretions and obstructions are documented in clinical situations separate from terminal care. Although commonly associated with impending death, gurgling respirations may occur as a clinical presentation of partial airway obstruction from any cause. It is recognized that excess respiratory and oral secretions may both cause obstruction and then worsen this obstruction by aggravating the accumulation of more secretions .
It is also recognized that the most effective compensatory mechanism to clear obstructing secretions is a strong cough with expiratory airflow, to force airways open and promote upward movement of retained secretions [8,9]. If forced expiratory flow is limited due to obstruction, dynamic changes in transthoracic pressures lead to more extensive airway compression and secondary pooling of secretions, resulting in even greater airway narrowing .
Causes of secretions
Prospectively collected data on which regression analyses were performed  and other small observational studies suggest that people who die with lung cancer, chest infections, brain tumours or serious head injuries, neuromuscular disorders, especially if associated with dysphagia, or cardiac arrest are likely to develop noisy secretions [10–14]. Although these situations are different, universally, the conditions named are all associated with an absolute or relative increase in oral, bronchial mucus, transudative or exudative secretions, which become clinically prominent when compensatory mechanisms are reduced or lost.
Normally, salivary glands produce 1500–2000 ml of saliva per day . Excessive salivary secretions may be relative when a person is unable to clear saliva by swallowing, or less commonly, due to overproduction. Inability to clear saliva will lead to upper airways becoming narrower, secondary pooling and obstruction as outlined above. People with respiratory weakness due to neuromuscular disorders will already have impaired compensatory mechanisms making death rattle more likely to develop in this group.
Bronchial epithelium secretes mucus as a homeostatic mechanism, providing a defensive barrier and humidification of inhaled air. In nondamaged airways, mucous secretion is at a rate of less than 100 ml per day . However, people with lung cancers, chest infections or inflammatory conditions of the lung may have excessive bronchial secretions either due to the tumour itself or reactive changes in the bronchial epithelium. In some primary lung cancers or cancers metastatic to the lung, severe bronchorrhoea may occur with reports quoting mucous volumes up to 400 ml per day . In the presence of infection and inflammation, cilia are lost, and excessive mucous production occurs , which may also be more viscous and more difficult to clear, again resulting in airway narrowing.
Pulmonary oedema results in alveolar flooding with secondary airway narrowing. Cardiac pulmonary oedema can be the result of numerous insults, but age-related diastolic dysfunction is the most common cause. Neurogenic pulmonary oedema is a poorly understood phenomenon, with the current hypotheses suggesting that thalamic hypoxia may evoke a catecholamine surge resulting in pulmonary oedema. This has been associated with major head trauma, strokes, brain tumours and seizures [17–20]. Obstructive pulmonary oedema has also been reported in up to 11% of paediatric cases of upper airway obstruction and is considered an underrecognized complication of endotracheal intubation for anaesthesia . Diuretics, reduction of preload and positive pressure ventilation are the mainstays of treatment of pulmonary oedema, and anticholinergic medications are very unlikely to be effective.
Assessment of secretions
A clinical assessment of noisy secretions commences with consideration of the person's prognosis in the context of their recent and background history. This will determine whether investigations or interventions may be appropriate. The challenge for a clinician is to differentiate the problem of respiratory tract secretions as a sign of impending death from alternative situations in which a more active approach may be appropriate. Supporting evidence and other signs of dying should be sought including documented progression of an identified life-limiting illness, altered consciousness, inability to verbally respond, changes in peripheral circulation and inability to take any oral substance .
Methods of assessing secretions
There is no standardized assessment tool to classify death rattle or measure the intensity of secretions. In research studies, noise scores, simple numeric or verbal scores of intensity, [6•,23] have been used to report outcomes, including relatives' distress [24,25]. Most studies have relied on single observer scores with the inherent interobserver bias. Interventions remain mostly based on subjective responses to the clinical situation.
Symptom control of noisy secretions
It is not possible to understand the dying person's experience of death rattle, but it is generally accepted that it is unlikely to cause distress for the individual because of their conscious state. The imperative to intervene is largely driven by concern for the dying person's family, friends and carers. Proportionally, more professional carers are bothered by noisy respirations than informal carers [4,26], but their main concerns are for the dying person's relatives and other patients close by.
Typically, nonpharmacological interventions are recommended as the first step. These include re-positioning, oropharyngeal suctioning and decreasing parenteral fluids. In respiratory medicine, re-positioning and suctioning are strongly recommended, but there have been no studies documenting their efficacy at the end of life.
The contribution of parenteral hydration to the development of death rattle remains a contentious matter. There is a striking diversity of practices reported, to continue, reduce or cease parenteral fluid. In other clinical situations, recommended management of respiratory secretions includes increasing hydration to improve upward mucociliary movements and avoid mucous pooling . For frail individuals in the terminal phases of life, the risk of pulmonary oedema worsening respiratory secretions cannot be ignored. Within palliative care, this is an emotional topic with arguments for and against hydration at the end of life. It would seem that the optimal approach is to carefully assess hydration and judiciously use parenteral fluids if necessary. When carefully monitored by specialist palliative care teams, this approach seems to result in few problems .
If conservative measures are ineffective, most palliative care guidelines suggest pharmacological interventions. A recent Cochrane review of interventions for noisy breathing at the end of life highlighted the lack of evidence to support current practices [3••]. It identified that anticholinergic medications, which reduce secretion of saliva and bronchial mucus, remain the most commonly used treatment. This drying effect was first used in the perioperative period to reduce the risk of aspiration and laryngospasm . However, anaesthesia and end-of-life care are not comparable with the most striking difference being the delivery of controlled airflow in anaesthesia.
Preliminary results from a multicentre prospective trial comparing atropine, hyoscine and scopolamine have become available since the publication of the Cochrane review. This study failed to identify any differences in outcome between the subgroups. The intensity of secretions, however, was reduced when anticholinergic treatments were initiated early after onset of clinically audible but still low intensity noises [6•]. This supports previous recommendations for early intervention  and lends weight to our proposed three-step mechanism. The initial problem may be simply pooled secretions, complicated by reactive changes, and secretions that become more difficult to settle.
Other agents have been investigated including parenteral antibiotics  and subcutaneous octreotide , again without producing robust evidence to indicate superior outcomes when the medications were administered to people with established secretions. The lack of efficacy of these trials requires comment, as the underlying rationale for studying each of these agents was sound.
Antibiotics are recommended when pooled mucus becomes purulent, a common scenario in people with chronic obstructive airways diseases such as chronic bronchitis, bronchiectasis, lung abscess or serious infections such as pneumonia . As single dosing seemed to be less effective, other retrospective data examined the quality of deaths in an elderly cohort who all died of pneumonia either receiving or not receiving antibiotics. Although retrospective in nature, the authors concluded that elderly people dying of pneumonia have less discomfort, particularly respiratory, when treated with antibiotics .
The rationale to study octreotide was based on a clinical observation that people pretreated with octreotide seemed not to develop noisy secretions, with the knowledge that the medication blocks receptors in the salivary glands and throughout the lungs. However, unlike the clinical observation, octreotide for death rattle was given only to people with established noisy respirations. Objectively recording outcomes in people pretreated with octreotide would seem the next most logical step.
The use of diuretics or corticosteroids in managing death rattle has not been reported, but there may be a role for these interventions and other novel agents in certain subgroups such as cardiac, neurogenic or obstructive pulmonary oedema.
Care of relatives
There is little doubt that some relatives find the phenomena of death rattle distressing , but this is not true in all situations . To assume that all relatives are bothered will lead clinicians to administer medications that at present are without proven efficacy and that may have adverse effects including delirium, dry mouth, urinary retention and sedation. An alternative approach may be to ensure that people have sufficient information that explains the changes they may observe in the dying person. To do this, clinicians must have the necessary skills as communicators to sensitively approach families. This may be one of the most effective interventions to manage the situation.
Outstanding issues identified around the pathophysiology, assessment and management of death rattle prompt reconsideration of the research agenda.
First, an objective assessment tool needs to be developed. This will help clinicians to better understand which people are likely to require interventions, either pharmacological for the dying person or supportive for those around them, and measure the efficacy of interventions.
Second, better understanding of the mechanisms that underlie noisy secretions in different subgroups is needed and may allow development of a classification system that helps clinicians identify and better manage those most at risk. Objective investigations already in use in other settings may be adapted to the palliative care setting. For example, noninvasive measures of cough strength or the presence of a sawtooth pattern on an expiratory flow curve are used in ICUs to predict people who are likely to develop respiratory distress secondary to impaired cough and respiratory secretions, respectively . These approaches may be easily adaptable and hence allow further exploration of mechanisms in the terminally ill.
Third, preventive strategies need to be considered. This must include early interventions of communication with families and carers of the dying person, nonpharmacological and pharmacological approaches.
Last, more effective rescue interventions or medications for challenging cases must be explored. There are always situations that despite optimal planning may become difficult, and rescue strategies are needed.
The mechanism underlying noisy terminal secretions is more complex than simple pooling secondary to reduced swallow or cough. Interventions are often initiated in response to the distress of relatives and those caring for the dying person. Existing guidelines have been developed from empirical observations, but more work is necessary to better define mechanisms, contributing causes and effective management strategies. Early intervention, both in treating noisy secretions and providing compassionate education and support to relatives, warrants further investigation.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 144).
1 Wildiers H, Menten J. Death rattle: prevalence, prevention and treatment. J Pain Symptom Manage 2002; 23:310–317.
2 Ellershaw JE, Sutcliffe JM, Saunders CM. Dehydration and the dying patient. J Pain Symptom Manage 1995; 10:192–197.
3•• Wee B, Hillier R. Interventions for noisy breathing in patients near to death. Cochrane Database Syst Rev 2008:CD005177. This study provides a succulent summary of the problem and systematically reviews evidence that underpins the use of anticholinergic medications for ‘death rattles’.
4 Wee BL, Coleman PG, Hillier R, Holgate SH. The sound of death rattle II: how do relatives interpret the sound? Palliat Med 2006; 20:177–181.
5 Bennett MI. Death rattle: an audit of hyoscine (scopolamine) use and review of management. J Pain Symptom Manage 1996; 12:229–233.
6• Wildiers H, Demeulenaere P, Clement P, Menten J. Treatment of death rattle in dying patients. Belgian J Med Oncol 2008; 2:275–279. A preliminary report of a large prospective study examining three anticholinergic medications for the ‘death rattle’.
7 Morita T, Tsunoda J, Inoue S, Chihara S. Risk factors for death rattle in terminally ill cancer patients: a prospective exploratory study. Palliat Med 2000; 14:19–23.
8 van der Schans CP. Bronchial mucus transport. Respir Care 2007; 52:1150–1158.
9 Restrepo RD. Inhaled adrenergics and anticholinergics in obstructive lung disease: do they enhance mucociliary clearance? Respir Care 2007; 52:1159–1173, discussion 73–75.
10 Morita T, Hyodo I, Yoshimi T, et al. Incidence and underlying etiologies of bronchial secretion in terminally ill cancer patients: a multicenter, prospective, observational study. J Pain Symptom Manage 2004; 27:533–539.
11 Seah STA, Low JA, Chan YH. Symptoms and care of dying elderly patients in an acute hospital. Singapore Med J 2005; 46:210–214.
12 Glare P, Clark K. Management of a patient with terminal illness: the final stages of life. Med Today 2008; 9:40–48.
13 Elman LB, Dubin RM, Kelley M, McCluskey L. Management of oropharyngeal and tracheobronchial secretions in patients with neurologic disease. J Palliat Med 2005; 8:1150–1159.
14 Sorenson HM. Managing secretions in dying patients. Respir Care 2000; 45:1355–1363, discussion 63–64.
15 Rubin BK. Physiology of airway mucus clearance. Respir Care 2002; 47:761–768.
16 Hidaka N, Nagao K. Bronchioloalveolar carcinoma accompanied by severe bronchorrhea. Chest 1996; 110:281–282.
17 Brambrink AM, Tzanova I. Neurogenic pulmonary oedema after generalized epileptic seizure. Eur J Emerg Med 1998; 5:59–66.
18 Dammers R, van den Bent MJ. Neurogenic pulmonary oedema in a patient with leptomeningeal carcinomatosis. J Neurol Neurosurg Psychiatry 2006; 77:1097.
19 Macmillan CSA, Grant IS, Andrews PJD. Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? Intensive Care Med 2002; 28:1012–1023.
20 Macleod AD. Neurogenic pulmonary edema in palliative care. J Pain Symptom Manage 2002; 23:154–156.
21 Windsor J, Dewdney A, Crooks R, Grocott M. Postobstructive pulmonary oedema. Hosp Med 2004; 65:508.
22 Ellershaw J, Ward C. Care of the dying patient: the last hours or days of life. BMJ 2003; 326:30–34.
23 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.
24 Clark K, Currow D, Agar M, 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. J Pain Palliat Care Pharmacother 2008; 22:131–138.
25 Hughes AC, Wilcock A, Corcoran R. Management of ‘death rattle’. J Pain Symptom Manage 1996; 12:271–272.
26 Wee BL, Coleman PG, Hillier R, Holgate SH. The sound of death rattle I: are relatives distressed by hearing this sound? Palliat Med 2006; 20:171–175.
27 Lanuke K, Fainsinger RL, DeMoissac D. Hydration management at the end of life. J Palliat Med 2004; 7:257–263.
28 Kanto J, Watanabe H, Namiki A. Pharmacological premedication for anaesthesia. Acta Anaesthesiol Scand 1996; 40:982–990.
29 Twycross R, Wilcox A. Symptom management in advanced cancer. 3rd ed. Oxford: Oxford Radcliffe Medical Press; 2001.
30 Spruyt O, Kausae A. Antibiotic use for infective terminal respiratory secretions. J Pain Symptom Manage 1998; 15:263–264.
31 van der Steen JT, Ooms ME, van der Wal G, Ribbe MW. Pneumonia: the demented patient's best friend? Discomfort after starting or withholding antibiotic treatment. J Am Geriatr Soc 2002; 50:1681–1688.
32 Rothaar R, Epstein S. Extubation failure: magnitude of the problem, impact on outcomes, and prevention. Curr Opin Crit Care 2003; 9:59–66.
© 2009 Lippincott Williams & Wilkins, Inc.