En
Búsqueda avanzada
Management of symptoms

Clinical practice guideline on palliative care for adults in the last days of life
Resumida HTML



GENERAL CONSIDERATIONS

Recommendations

  1. To guide decisions on symptom management, assess the main symptoms systematically, to reduce the risk of any being underestimated, and quantify their severity using scales that enable us to assess the results of any measures taken.
  2. Thoroughly review treatment given in the last stage of a patient´s life and adapt it to therapeutic objectives focused on well-being and symptom control.
  3. Stop all treatments that are futile, that is, that do not provide any benefit in the patient´s current condition, discuss the risks and benefits of any medication proposed, and explain that the withdrawal of a medication is due its futility given the patient’s current condition.
  4. Leave clear instructions regarding the treatment in writing, indicating the baseline dosages and alternatives for use at times of crisis.

 

Rationale

The GDG has issued recommendations on good clinical practice focused on the general principles of prescribing in palliative care. Further, a list of key clinical considerations has been drawn up, related to the implementation of the recommendations.

Complete clinical question

For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/gpc_612__atencion_paliativa_sud-2/#question-5

References

19. Díez-Manglano J, Isasi de Isasmendi Pérez S, Rubio Gómez M, Formiga F, Sánchez Muñoz LÁ, Castiella Herrero J, et al. Cuidados en los últimos días de vida en los pacientes hospitalizados en medicina interna. Rev Clin Esp. 2019;219(3):107-15. DOI: 10.1016/j.rce.2018.06.010.

109. Ferris F, Balfour H, Bowen K, Farley J, Hardwick M, Lamontagne C, et al. A Model to Guide Hospice Palliative Care. Ottawa, ON: Canadian Hospice Palliative Care Association, 2002.

110. Carvajal Valcárcel A, Martínez García M, Centeno Cortés C. Versión española del Edmonton Symptom Assessment System (ESAS): un instrumento de referencia para la valoración sintomática del paciente con cáncer avanzado. Medicina Paliativa. 2013;20(4):143-9. DOI: 10.1016/j.medipa.2013.02.001.

111. Delgado-Silveira E, Mateos-Nozal J, Muñoz–García M, Rexach-Canoc L, Vélez-Díaz- Pallarés M, Albeniz-López J, et al. Uso potencialmente inapropiado de fármacos en cuidados paliativos: versión en castellano de los criterios STOPP-Frail (STOPP-Pal). Rev Esp Geriatr Gerontol. 2019;54(3):151–5.

112. Martin-Roselló ML, Fernández-López A, Sanz-Amores R, Gómez-García R, Vidal-España F, Cia-Ramos R. IDC-Pal (Instrumento Diagnóstico de la Complejidad en Cuidados Paliativos) [Internet]. Sevilla: Consejeria de Igualdad, Salud y Politicas sociales. Fundación Cudeca; [accessed 20 Sept 2020]. Available from: http://www.juntadeandalucia.es/salud/IDCPal.

Question

Which medications are most effective for alleviating pain in the last days of life?

Recommendations

  1. Within an overall palliative care approach, encourage appropriate assessment and management of pain in order that patients reach the last days of life with their pain under control, with medication continued and adjusted appropriately. Anticipate patients’ potential needs for analgesia and prescribe medication to provide appropriate pain control in advance, enabling families/close friends and/or the healthcare team to manage the situation as and when necessary.
  2. Do not routinely prescribe analgesic drugs because, though pain is a very common symptom, it is not experienced by everyone in the last days of life.
  3. Consider non-pharmacological ways of managing pain in the last days of life together with pharmacological treatments.
  4. Once reversible causes have been ruled out, the pharmacological treatment of choice for moderate-to-severe pain is opioids. If patients experience mild pain, use “first step” drugs, except when a poor response is expected or there are problems with the route of administration, in which case, consider low-dose opioids.
  5. If opioids are given, fast-acting morphine (oral or parenteral) is the medication of choice in the last days of life.
  6. Do not reduce or stop opioids abruptly, as both such a reduction or withdrawal and poorly controlled pain are known risk factors for disorientation and delirium in patients with advanced chronic conditions.
  7. In patients with neuropathic pain, maintain baseline medication as far as possible, although some may need to be discontinued since the oral route is often not an option in the last days of life, and therefore, take this into account in opioid dosing.

 

Rationale

Given the paucity of scientific evidence on the effectiveness of various drugs for managing pain in patients in the last days of life, the GDG has made recommendations based on the general principles of pain control and management in stages before palliative care and its members’ clinical experience. These recommendations seek to encourage appropriate assessment and control of pain in the last days of life, bearing in mind the major impact of pain.

Complete clinical question

For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/gpc_612__atencion_paliativa_sud-2/#question-5

References

22. National Institute for Health and Care Excellence. Care of dying adults in the last days of life. London: National Institute for Health and Care Excellence; 2015. [accessed 12 Oct 2018]. Available from: https://www.nice.org.uk/guidance/ng31.

113. Supportive PDQ, Palliative Care Editorial B. Last Days of Life (PDQ®): Health Professional Version. PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US); 2019.

114. Coyne P, Mulvenon C, Paice JA. American Society for Pain Management Nursing and Hospice and Palliative Nurses Association Position Statement: Pain Management at the End of Life. Pain management nursing: Official Journal of the American Society of Pain Manage Nurs. 2018;19(1):3-7. DOI: 10.1016/j.pmn.2017.10.019.

115. Prácticas seguras para el uso de opioides en pacientes con dolor crónico. Madrid: Ministerio de Sanidad, Servicios Sociales e Igualdad; 2015

116. Twycross RG. Choice of strong analgesic in terminal cancer: diamorphine or morphine? Pain. 1977;3(2):93-104. DOI: 10.1016/0304-3959(77)90072-0.

117. Sathornviriyapong A, Nagaviroj K, Anothaisintawee T. The association between different opioid doses and the survival of advanced cancer patients receiving palliative care. BMC Palliat Care. 2016;15(1):95-. DOI: 10.1186/s12904-016-0169-5.

118. Bercovitch M, Adunsky A. Patterns of high-dose morphine use in a home-care hospice service: should we be afraid of it? Cancer. 2004;101(6):1473-7. DOI: 10.1002/cncr.20485.

 

Question

Which medications are most effective for alleviating dyspnoea in the last days of life?

Recommendations

  1. Maintain or start specific treatment if the problem that causes dyspnoea (for example, pulmonary oedema, or pleural effusion) is known and the risk-benefit balance is positive.
  2. Use non-pharmacological strategies first, adding pharmacological treatment as and when necessary, to manage dyspnoea in the last days of life.
  3. In the event that the non-pharmacological measures do not alleviate dyspnoea, offer a trial of oxygen therapy regardless of the hypoxemia severity and maintain the therapy if the patient/family perceives a benefit.
 

  1. If dyspnoea is poorly controlled with the aforementioned measures, add symptomatic treatment with morphine, midazolam, or a combination thereof.

 

Rationale

Three good clinical practice recommendations have been made regarding the indications for pharmacological treatment and starting of non-pharmacological measures. Taking into account the quality of the evidence and the risk-benefit balance, we make a weak recommendation in favour of the use of drugs (opioids, benzodiazepines, or a combination of thereof).

Complete clinical question

For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/gpc_612__atencion_paliativa_sud-2/#question-5

References

22. National Institute for Health and Care Excellence. Care of dying adults in the last days of life. London: National Institute for Health and Care Excellence; 2015. [accessed 12 Oct 2018]. Available from: https://www.nice.org.uk/guidance/ng31.

113. Supportive PDQ, Palliative Care Editorial B. Last Days of Life (PDQ®): Health Professional Version. PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US); 2019.

119. Seow H, Barbera L, Sutradhar R, Howell D, Dudgeon D, Atzema C, et al. Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. J Clin Oncol. 2011;29(9):1151-8. DOI: 10.1200/JCO.2010.30.7173.

120. Tishelman C, Petersson L-M, Degner LF, Sprangers MAG. Symptom prevalence, intensity, and distress in patients with inoperable lung cancer in relation to time of death. J Clin Oncol. 2007;25(34):5381-9. DOI: 10.1200/JCO.2006.08.7874.

121. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9ª ed. Boston: Little, Brown & Co; 1994. p. 253-6.

122. Borg G. Simple rating methods for estimation of perceived exertion. Wenner-Gren Center International Symposium. 1976; Series 28:39-47.

123. Campbell ML, Templin T, Walch J. A Respiratory Distress Observation Scale for patients unable to self-report dyspnea. J Palliat Med. 2010 Mar;13(3):285-90. DOI: 10.1089/jpm.2009.0229.

124. Barnes H, McDonald J, Smallwood N, Manser R. Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst 2016;3(3):Cd011008. DOI: 10.1002/14651858.CD011008.pub2.

125. Simon ST, Higginson IJ, Booth S, Harding R, Weingärtner V, Bausewein C. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev. 2016;10(10):Cd007354. DOI: 10.1002/14651858.CD007354. pub3.

126. Navigante AH, Cerchietti LC, Castro MA, Lutteral MA, Cabalar ME. Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer. J Pain Symptom Manage. 2006;31(1):38-47. DOI: 10.1016/j.jpainsymman.2005.06.009.

127. Booth S, Kelly MJ, Cox NP, Adams L, Guz A. Does oxygen help dyspnea in patients with cancer? Am J Respir Crit Care Med. 1996;153(5):1515-8. DOI: 10.1164/ajrccm.153.5.8630595.

128. Clemens KE, Quednau I, Klaschik E. Use of oxygen and opioids in the palliation of dyspnoea in hypoxic and non-hypoxic palliative care patients: a prospective study. Support Care Cancer. 2009;17(4):367-77. DOI: 1007/s00520-008-0479-0.

 

Question

Which drugs are most effective for alleviating nausea and vomiting in the last days of life?

Recommendations

  1. In patients in the last days of life, perform a proportionate assessment of potential causes of nausea and vomiting, which could include:
    • Certain drugs
    • Chemotherapy and/or radiotherapy
    • Psychological factors
    • Biochemical factors, for example, hypercalcemia
    • High intracranial pressure
    • Poor gastrointestinal motility
    • Bowel obstruction.
  2. Consider non-pharmacological measures to treat nausea and vomiting in the last days of life.
  3. In other clinical scenarios, use standard antiemetic medication for palliative care: neuroleptics, antihistamines, prokinetic agents, 5-HT3 receptor antagonists, corticosteroids and benzodiazepines.
 

++++++++

  1. For the treatment of nausea and vomiting in people with bowel obstruction, as well as other pharmacological and non-pharmacological measures, use the following treatments:
    • Hyoscine butylbromide, also known as scopolamine butylbromide, as first-line antisecretory treatment
    • Octreotide if symptoms do not improve within 24 hours after starting treatment with hyoscine butylbromide.

 

Rationale

Two good clinical practice recommendations have been made focusing on assessing the causes of nausea and vomiting and starting of non-pharmacological measures. In the event of bowel obstruction, a weak recommendation has been made in favour of the use of certain medications, taking into account the quality of the evidence; for other clinical scenarios, one good clinical practice recommendation has been made, due to the scarcity of end-of-life research addressing this question.

Complete clinical question

For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/gpc_612__atencion_paliativa_sud-2/#question-5

References

20. Grupo de Trabajo de la Guía de Práctica Clínica sobre Cuidados Paliativos. Guía de Práctica Clínica sobre Cuidados Paliativos. Vitoria: Agencia de Evaluación de Tecnologías Sanitarias del País Vasco; Guías de Práctica Clínica en el SNS: OSTEBA Nº 2006/08.

129. Twycross R, Back I. Nausea and vomiting in advanced cancer. Eur J Palliat Care. 1998;5:39-45.

130. Edmonds P, Karlsen S, Khan S, Addington-Hall J. A comparison of the palliative care needs of patients dying from chronic respiratory diseases and lung cancer. Palliat Med. 2001;15(4):287- 95. DOI: 10.1191/026921601678320278.

131. Klinkenberg M, Willems DL, van der Wal G, Deeg DJ. Symptom burden in the last week of life. J Pain Symptom Manage. 2004;27(1):5-13. DOI: 10.1016/j.jpainsymman.2003.05.008.

132. Mystakidou K, Tsilika E, Kalaidopoulou O, Chondros K, Georgaki S, Papadimitriou L. Comparison of octreotide administration vs conservative treatment in the management of inoperable bowel obstruction in patients with far advanced cancer: a randomized, double-blind, controlled clinical trial. Anticancer Res. 2002;22(2b):1187-92.

133. Ripamonti C, Mercadante S, Groff L, Zecca E, De Conno F, Casuccio A. Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. J Pain Symptom Manage. 2000;19(1):23-34. DOI: 10.1016/s0885-3924(99)00147-5.

134. Mercadante S, Casuccio A, Fulfaro F. The course of symptom frequency and intensity in advanced cancer patients followed at home. J Pain Symptom Manage. 2000;20(2):104-12. DOI: 10.1016/s0885-3924(00)00160-3.

135. Mercadante S, Casuccio A, Agnello A, Serretta R, Calderone L, Barresi L. Morphine versus methadone in the pain treatment of advanced-cancer patients followed up at home. J Clin Oncol. 1998;16(11):3656-61. DOI: 10.1200/jco.1998.16.11.3656.

136. Cox L, Darvill E, Dorman S. Levomepromazine for nausea and vomiting in palliative care. Cochrane Database Syst Rev. 2015;2015(11):Cd009420. DOI: 10.1002/14651858.CD009420.

137. Storrar J, Hitchens M, Platt T, Dorman S. Droperidol for treatment of nausea and vomiting in palliative care patients. Cochrane Database Syst Rev. 2014;2014(11):Cd006938. DOI: 10.1002/14651858.CD006938.pub3.

138. Vayne-Bossert P, Haywood A, Good P, Khan S, Rickett K, Hardy JR. Corticosteroids for adult patients with advanced cancer who have nausea and vomiting (not related to chemotherapy, radiotherapy, or surgery). Cochrane Database Syst Rev. 2017;7(7):Cd012002. DOI: 10.1002/14651858.CD012002.pub2.

139. Sutherland A, Naessens K, Plugge E, Ware L, Head K, Burton MJ, et al. Olanzapine for the prevention and treatment of cancer-related nausea and vomiting in adults. Cochrane Database Syst Rev. 2018;9(9):Cd012555. DOI: 10.1002/14651858.CD012555.pub2.

140. Murray-Brown F, Dorman S. Haloperidol for the treatment of nausea and vomiting in palliative care patients. Cochrane Database Syst Rev. 2015;2015(11):Cd006271. DOI: 10.1002/14651858. CD006271.pub3.

141. Levy M, Smith T, Alvarez-Perez A, Back A, Baker JN, Beck AC, et al. Palliative Care Version 1.2016. J Natl Compr Canc Netw. 2016;14(1):82-113. DOI: 10.6004/jnccn.2016.0009.

142. Guidelines and Protocols Advisory Committee (BC). Part 2: Pain and symptom management. 2017. In: Palliative care for the patient with incurable cancer or advanced disease [report available online]. Victoria: BC; 2017. [accessed 20 Sept 2020]. Available from: https://www2.gov.bc.ca.

 

Question

Which drugs are most effective for alleviating anxiety, delirium and agitation in the last days of life?

Recommendations

  1. Assess all patients in the last days of life for anxiety and delirium (with or without agitation).
  2. Explore and manage potential causes of anxiety and delirium, for example, pain, urinary retention and faecal impaction, in a proportionate manner, in the context of the last days of life and considering the preferences of patients and their families and close friends.
  3. Use non-pharmacological measures for the prevention and management of anxiety and delirium. Give support and training to the family.
  4. Consider using benzodiazepines for managing anxiety.
  5. Consider using traditional antipsychotic medication, and if there is a poor response, its combination with benzodiazepines, for managing delirium.

 

Rationale

Five good clinical practice recommendations have been made focused on improving assessment and the use of non-pharmacological measures. Given that no studies were found assessing the effectiveness and safety of medications for the treatment of anxiety or delirium in the last days of life, the GDG recommend using the medications most widely employed in clinical practice and for which there is considerable experience of their use at this stage.

Complete clinical question

For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/gpc_612__atencion_paliativa_sud-2/#question-5

References

22. National Institute for Health and Care Excellence. Care of dying adults in the last days of life. London: National Institute for Health and Care Excellence; 2015. [accessed 12 Oct 2018]. Available from: https://www.nice.org.uk/guidance/ng31.

110. Carvajal Valcárcel A, Martínez García M, Centeno Cortés C. Versión española del Edmonton Symptom Assessment System (ESAS): un instrumento de referencia para la valoración sintomática del paciente con cáncer avanzado. Medicina Paliativa. 2013;20(4):143-9. DOI: 10.1016/j.medipa.2013.02.001.

143. Kehl KA, Kowalkowski JA. A systematic review of the prevalence of signs of impending death and symptoms in the last 2 weeks of life. Am J Hosp Palliat Care. 2013;30(6):601-16. DOI: 10.1177/1049909112468222.

144. Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review. Palliat Med. 2013;27(6):486-98. DOI: 10.1177/0269216312457214.

145. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361-70. DOI: 10.1111/j.1600-0447.1983.tb09716.x.

146. McCleary E, Cumming P. Improving early recognition of delirium using SQiD (Single Question to identify Delirium): a hospital based quality improvement project. BMJ Qual Improv Rep. 2015;4(1). DOI: 10.1136/bmjquality.u206598.w2653.

147. Tobar E, Romero C, Galleguillos T, Fuentes P, Cornejo R, Lira MT, et al. Método para la evaluación de la confusión en la unidad de cuidados intensivos para el diagnóstico de delírium: adaptación cultural y validación de la versión en idioma español. Med Intensiva. 2010;34(1):4- DOI: 10.1016/j.medin.2009.04.003.

148. Bellelli G, Morandi A, Davis DH, Mazzola P, Turco R, Gentile S, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014 Jul;43(4):496-502. DOI: 10.1093/ageing/afu021.

149. Noguera A, Carvajal A, Alonso-Babarro A, Chisholm G, Bruera E, Centeno C. First Spanish version of the Memorial Delirium Assessment Scale: psychometric properties, responsiveness, and factor loadings. J Pain Symptom Manage. 2014;47(1):189-97. DOI: 10.1016/j.jpainsymman.2013.02.020.

150. Trzepacz PT, Mittal D, Torres R, Kanary K, Norton J, Jimerson N. Validation of the Delirium Rating Scale-Revised-98: comparison with the delirium rating scale and the cognitive test for delirium. J Neuropsychiatry Clin Neurosci. 2001 Spring;13(2):229-42. DOI: 10.1176/ jnp.13.2.229.

151. Finucane AM, Jones L, Leurent B, Sampson EL, Stone P, Tookman A, et al. Drug therapy for delirium in terminally ill adults. Cochrane Database Syst Rev. 2020;1(1):Cd004770. DOI: 10.1002/14651858.CD004770.pub3.

152. Jansen K, Haugen DF, Pont L, Ruths S. Safety and effectiveness of palliative drug treatment in the last days of life – a systematic literature review. J Pain Symptom Manage. 2018;55(2):508-21.e3. DOI: 10.1016/j.jpainsymman.2017.06.010.

153. Salt S, Mulvaney CA, Preston NJ. Drug therapy for symptoms associated with anxiety in adult palliative care patients. Cochrane Database Syst Rev. 2017;5(5): Cd004596. DOI: 10.1002/14651858.CD004596.pub3.

 

Question

Which drugs are most effective for alleviating noisy breathing in the last days of life?

Recommendations

  1. As a person enters the last days of life, be alert to the onset of noisy breathing to consider early initiation of treatment.
  2. Provide information about the causes of noisy breathing and address any concerns, underlining that, although the noise can be distressing, it is unlikely to cause discomfort to the patient due to the low level of consciousness.
  3. Take non-pharmacological measures to alleviate noisy breathing to reduce any potential discomfort in people in the last days of life and their family and friends.
  4. Consider pharmacological treatment of noisy breathing when non-pharmacological measures and communication with the patient and their family prove to be insufficient.

 
  1. Use scopolamine (hyoscine) butylbromide as the first-line treatment, although atropine or scopolamine hydrobromide can be used as alternatives.

 

Rationale

One weak recommendation has been made in favour of the use of drugs for noisy breathing in the last days of life, taking into account the quality of the evidence, which is very low according to the GRADE system, and the risk-benefit balance of the treatments. This recommendation is accompanied by a series of clinical practice recommendations focused on the identification and early management of noisy breathing, improvement of the communication process, and use of non-pharmacological measures.

Complete clinical question

For full information on this question (available in Spanish), see:
http://portal.guiasalud.es/guia-en-capas/gpc_612__atencion_paliativa_sud-2/#question-5

References

154. Lokker ME, van Zuylen L, van der Rijt CCD, van der Heide A. Prevalence, impact, and treatment of death rattle: a systematic review. J Pain Symptom Manage. 2014;47(1):105-22. DOI: 1016/j.jpainsymman.2013.03.011.

155. Clark K, Currow DC, Agar M, Fazekas BS, Abernethy AP. 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(2):131- DOI: 10.1080/15360280801992058.

156. Likar R, Molnar M, Rupacher E, Pipam W, Deutsch J, Mörtl M, et al. A Clinical Study Examining the Efficacy of Scopolamin-Hydrobromide in Patients with Death Rattle (A Randomized, Double-Blind, Placebo-Controlled Study). Palliativmedizin. 2002;3(01):15-9.

157. Likar R, Rupacher E, Kager H, Molnar M, Pipam W, Sittl R. [Efficacy of glycopyrronium bromide and scopolamine hydrobromide in patients with death rattle: a randomized controlled study]. Wien Klin Wochenschr. 2008;120(21-22):679-83. DOI: 10.1007/s00508-008-1094-2.

158. Wildiers H, Dhaenekint C, Demeulenaere P, Clement PM, Desmet M, Van Nuffelen R, 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):124-33. DOI: 10.1016/j. jpainsymman.2008.07.007.

159. Heisler M, Hamilton G, Abbott A, Chengalaram A, Koceja T, Gerkin R. Randomized double- blind trial of sublingual atropine vs. placebo for the management of death rattle. J Pain Symptom Manage. 2013;45(1):14-22. DOI: 10.1016/j.jpainsymman.2012.01.006.

160. 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):329-36. DOI: 10.1191/026921601678320313.

161. 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):279-84. DOI: 10.1089/jpm.2006.9.279.

162. Kåss RM, Ellershaw J. Respiratory tract secretions in the dying patient: a retrospective study. J Pain Symptom Manage. 2003;26(4):897-902. DOI: 10.1016/s0885-3924(03)00292-6.

163. Hughes A, Wilcock A, Corcoran R, Lucas V, King A. Audit of three antimuscarinic drugs for managing retained secretions. Palliat Med. 2000;14(3):221-2.DOI:10.1191/026921600670188257.

164. Star A, Boland JW. Updates in palliative care – recent advancements in the pharmacological management of symptons. Clinical medicine (London, England). 2018;18(1):11-6. DOI: 10.7861/clinmedicine.18-1-11.

165. Mercadante S, Marinangeli F, Masedu F, Valenti M, Russo D, Ursini L, et al. Hyoscine butylbromide for the management of death rattle: sooner rather than later. J Pain Symptom Manage. 2018 Dec;56(6):902-7. DOI: 10.1016/j.jpainsymman.2018.08.018.

166. van Esch HJ, van Zuylen L, Oomen-de Hoop E, van der Heide A, van der Rijt CCD. Scopolaminebutyl given prophylactically for death rattle: study protocol of a randomized double-blind placebo-controlled trial in a frail patient population (the SILENCE study). BMC Palliat Care. 2018;17(1):105. DOI: 10.1186/s12904-018-0359-4.

Hydration
Palliative sedation