End-stage secretions (commonly referred to as “death rattle”) is known to occur in between 12 and 92 percent of patients, with the median time from onset of death rattle until death between 11 and 28 hours. A question around secretions is whether they originate from the throat and salivary glands, or from the lower respiratory tract, possibly due to pneumonia or pulmonary congestion. Discerning the difference may be important in deciding on the treatment approach. For example, the treatment of pneumonia would likely require antibiotics rather than anti-secretory agents, and diuretics may be helpful for lower respiratory congestion.

As most patients are no longer alert at the time of the secretions, most physicians and nurses believe that they are usually not distressed by them. However, studies suggest that a moderately high degree of distress is experienced by the family. Consider discussing the issue with family members so they understand that an unresponsive patient is not aware of the secretions. Family members will often be disturbed by the sound their loved one is making. Reassure them that it is a common part of the dying process and does not cause the patient to suffer.

Nonpharmacological management methods, such as frequent turns, repositioning and minimizing parenteral fluids, seem reasonable and are not harmful. However, these methods have not been evaluated by any specific trials. Deep suctioning is certainly distressing for more alert patients, but even in patients who are no longer alert, suctioning may cause more secretions. Unless secretions are visible in the mouth, suctioning should be avoided.

Two of the most common medications used to treat secretions are both antimuscarinic anticholinergic agents: scopolamine and glycopyrrolate. Various sources quote a range of subcutaneous doses: scopolamine 0.2-0.6 mg q2-6h prn and glycopyrrolate 0.1-0.4mg q4-6h prn. There are no studies looking at the use of both medications together, nor at alternating them. Intuitively, it would seem that this would not be more effective, as they both block the same receptors. One study has suggested that scopolamine may be more effective than glycopyrrolate.

However, these drugs do have different side-effect profiles. Scopolamine crosses the blood-brain barrier, causing more sedation and delirium. Excessive doses of scopolamine will result in more agitation and delirium. Glycopyrrolate does not cross the blood-brain barrier in any significant amount. Therefore, it is thought that glycopyrrolate may be a better medication in patients who are alert and bothered by their own secretions. Further, the literature also suggests that either medication could be used as a continuous infusion if needed (scopolamine 0.6-2.4 mg/24 hours; glycopyrrolate 0.4-1.2 mg/24 hours). Common practice is to start with intermittent PRN dosing, as patients may only require a few doses. Before moving towards higher and more frequent dosing, reconsider the diagnosis (are these actually upper secretions or is the patient developing pneumonia or congestive failure?). Also consider other management options, such as discontinuing parenteral hydration and using an antibiotic or diuretic.

The above recommendations are quite standard, and generally align with common palliative resources[1, 2, 3, 4,]; however, research evidence is not conclusive. One study found no significant differences in effectiveness or survival time among atropine, hyoscine butylbromide, and scopolamine in the treatment of death rattle, but suggested that treatment was more effective when started earlier, at a lower initial rattle intensity, and that effectiveness improved over time.[5] Three studies found no differences in the effectiveness of the different medication regimens, including one regimen that used octreotide.[6,7,8] One randomized controlled trial that looked at atropine (another potential medication, but one which has little benefit over the others), found no differences in results between patients receiving atropine and those receiving placebo.[9] One comparative but uncontrolled study found that scopolamine was significantly more effective than glycopyrrolate in reducing the severity of death rattle 30 minutes after the medication was given, but this effect was no longer present one hour later, or just before death.[10] One retrospective study found that glycopyrrolate was more effective than scopolamine.[11] Two studies found that levels of hydration did not change the prevalence of death rattle.[12,13] There are limitations to all of the studies, and more high-quality studies are required for insight into both pharmacologic and nonpharmacologic interventions.

Suggested guidelines for the use of antimuscarinic drugs for death rattle were published in 2002[14], but, interestingly, a recent systematic published in the Journal of Pain and Symptom Management[15] concludes, similar to a Cochrane publication[16], that current research does not support the standard use of antimuscarinic drugs in the treatment of death rattle. Yet, it seems that for some patients, they may be useful, and they certainly continue to be used.

Communication about secretions with family members and others involved in the care of these patients is extremely important. Understanding the symptom as part of the normal dying process may help reduce family members’ distress.

References

1. Berger AM, Shuster JL, Von Roenn JH. Principles and Practice of Palliative Care and Supportive Oncology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2013.

2. Hanks G, Cherney NI, Christakis NA, Fallon M, Kaasa S, Portenoy RK, eds. Oxford Textbook of Palliative Medicine. 4th ed. New York, NY: Oxford University Press; 2010.

3. Twycross R, Wilcock A, Dean M. Canadian Palliative Care Formulary. 1st Canadian ed. Nottingham, UK: Palliativedrugs.com; 2010.

4. Walsh TD, Caraceni AT, Fainsinger R, et al. Palliative Medicine: Expert Consult. Philadelphia, PA: Saunders Elsevier; 2009.

5. Wildiers H, Dhaenekint C, Demeulenaere P, et al. Atropine, Hyoscine butylbromide, or scopolamine are equally effective for the treatment of death rattle in terminal care. J Pain Symptom Manage. 2009;38(1):124-133.

6. Clark K, Currow DC, Agar M, Fazekas BS, Abernethy AP. A pilot phase II randomized, crossover, 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(2):131-138.

7. Wildiers H, Dhaenekint C, Demeulenaere P, et al. Atropine, hyoscine butylbromide, or scopolamine are equally effective for the treatment of death rattle in terminal care. J Pain Symptom Manage. 2009;38(1):124-133.

8. Hughes A, Wilcock A, Corcoran R, Lucas V, King A. Audit of three antimuscarinic drugs for managing retained secretions. Palliat Med. 2000;14(3):221-222.

9. Heisler M, Hamilton G, Abbott A, et al. Randomized double-blind trial of sublingual atropine vs. placebo for the management of death rattle. J Pain Symptom Manage. 2013;45(1):14-22.

10. 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(4):329-336

11. Hugel H, Ellershaw J, Gambles M. Respiratory tract secretions in the dying patient: a comparison between glycopyrronium and hyoscine hydrobromide. J Palliat Med. 2006;9(2):279-284.

12. Yamaguchi T, Morita T, Shinjo T, et al. Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer. J Pain Symptom Manage. 2012;43(6):1001-1012.

13. Morita T, Hyodo I, Yoshimi T, et al. Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies. Ann Oncol. 2005;16(4):640-647.

14. Bennett M, Lucas V, Brennan M, Hughes A, O'Donnell V, Wee B. Using anti-muscarinic drugs in the management of death rattle: evidence-based guidelines for palliative care. Palliative Medicine. 2002; 16(5): 369-374

15. Lokker ME, van Zuylen L, van der Rijt CC, van der Heide A. Prevalence, impact, and treatment of death rattle: a systematic review. J Pain Symptom Management. 2013. [Epub ahead of print].

16. Interventions to treat noisy breathing, or 'death rattle': the unpleasant, gurgling breathing occurring in many patients who are about to die. In: Cochrane Database of Systematic Reviews; 2012.
Available online: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0013298/