Evidence Matters - Hospice Pharmacia

to a clinically noticeable volume. 3, 13, 14 Prophylactic treatment with anticholinergic therapy in high-risk patients mayimprove outcomes, but more research is needed to support this theory. 7 Because the use of anticholinergics mayproduce significant side effects, their benefits and burdens should be carefully considered, and for some patients,non-pharmacologic options may be more appropriate.Which anticholinergic should I use and what dose and route are appropriate?The most commonly used anticholinergics to treat excessive secretions include atropine, scopolamine, glycopyrrolate,and hyoscyamine. Currently, management of terminal secretions is largely based upon anecdotal experience; there is noconclusive empirical evidence that one agent is more effective than the others. 3, 6, 13, 14 Therefore, appropriate agent selectionshould be based on the agent’s adverse effect profile, onset of action, duration of action, route of administration,and cost. While higher doses may be observed in practice, the doses provided below are literature-based recommendedstarting doses.Atropine (Atreza, Sal-Tropine®, Isopto-Atropine®, others) is commonly used to manage terminal secretions. It may beadministered by oral (PO), intramuscular (IM), intravenous (IV), or subcutaneous (SC) routes at a starting dose of 0.4mg every 4–6 hours as needed. 15–18 Atropine 1% eye drops can be given orally to the back of the throat or sublinguallyto provide rapid relief of symptoms. 10 The initial recommended dose for the oral administration of eye drops is 1–2drops every 4–6 hours as needed. 16–18 Findings from a single unpublished study indicated that atropine ophthalmicsolution administered sublingually was effective at reducing terminal respiratory secretions. 19 Other studies havereported limited success using atropine drops for other hypersalivary conditions. 20–22Scopolamine (Transderm Scop®, Scopace®, Isopto Hyoscine®) may be administered by PO, IM, IV, and SC routes. Oraltherapy is initiated at a starting dose of 0.4 mg every 8 hours as needed, whereas parenteral dosage forms are initiated ata starting dose of 0.4 mg every 4 hours as needed. 3, 15, 17, 23 Scopolamine is also available as a transdermal patch, which isapplied behind the ear and changed every 72 hours. 9 There is limited evidence to support the application of more thanone patch. One case report and one study showed that two patches were tolerated, 24, 25 but the use of three patches isbased solely upon anecdotal reports. 14, 15 Because the patch may take up to 12 hours for effect, there are limited benefits9, 14for actively dying patients.Glycopyrrolate (Robinul®, Robinul Forte®) may be administered by PO, IM, IV, and SC routes. The recommendedparenteral starting dose is 0.2–0.4 mg three to four times daily as needed. 3, 26 Studies comparing glycopyrrolate andscopolamine found that glycopyrrolate injection had a slower onset and longer duration of action compared toscopolamine injection, but there was no evidence to support the use of one agent over the other. 3, 5, 13, 27 Oralglycopyrrolate, in the form of tablets or liquid, has slow, erratic absorption and usually requires higher starting doses28, 29around 1–2 mg two to three times daily as needed for effect.Hyoscyamine (Levsin®, Levbid®, Levsin SL®, others) is most commonly administered PO or SL. It is available as animmediate-release disintegrating tablet and oral liquid and as a sustained-release tablet/capsule. An injectable formmay also be given IV, IM, or SC. The recommended starting dose for immediate-release oral and parenteral formulationsis 0.125–0.25 mg every 4 hours as needed. 15, 30 Use of hyoscyamine for terminal secretions is purely anecdotal14, 15and based on its anticholinergic mechanism of action.What side effects should I monitor for with anticholinergic therapy?While anticholinergic medications can effectively manage some secretions, it is important to weigh the risks of potentialside effects versus the potential benefits. Elderly patients are particularly sensitive to side effects from anticholinergics.However, during the terminal phase of a patient’s life, the potential benefit of the drugs in reducing secretions andeasing respirations may outweigh the burden of side effects.Atropine and scopolamine are capable of crossing the blood-brain barrier and are, therefore, likely to produceCNS side effects such as drowsiness, confusion, delirium, hallucinations, paradoxical agitation, and restlessness.In comparison, glycopyrrolate and hyoscyamine are far less likely to penetrate this barrier and are relatively free of16, 23, 26, 29, 30central side effects.To cite this article: Gray MY. The Use of Anticholinergics for the Management of Terminal Secretions. Evidence Matters. Summer 2007; 1(3).

Anticholinergics may also cause blurred vision, constipation, dry mouth, urinary retention, and cardiac sideeffects (tachycardia or bradycardia, arrhythmias), 16, 23, 26, 29, 30 although the degree to which these side effects arebothersome in dying patients is not known. Compared to the other agents available, atropine is more likely tocause tachycardia. 2, 28 In addition, although rare, some patients may experience an anaphylactic or serious adversereaction to atropine. Because scopolamine and hyoscyamine are chemically related to atropine, patients prescribedthese medications may experience a cross reaction. However, because of the marked differences in the chemicalstructures, it is unlikely that a patient who reacts to atropine will react to glycopyrrolate in the same manner. Ingeneral, the severity of side effects tends to be dose-related, and side effects are cumulative when patients are takingmore than one medication with anticholinergic activity (e.g., tricyclic antidepressants or antipsychotic agents).HP Partners, please refer to the secretions algorithm on page 80 in the Hospice Pharmacia Medication UseGuidelines, 8th Edition for more information on therapeutic options.Conclusion• Terminal secretions occur in a large number of dying patients and are a strong predictor of impending death.• Terminal respiratory secretions can be, but are not always, a source of distress to relatives. Providing educationand reassurance about the cause and management of secretions may help relieve caregiver distress.• Salivary secretions are more likely to respond to anticholinergic therapy than bronchial secretions.• Anticholinergic agents should be initiated as soon as symptoms appear; although they can inhibit production ofsecretions, they have no effect on secretions that are already present.• There is no conclusive evidence that one anticholinergic agent is more effective than the others, however, the sideeffectprofile among the available agents differ. Further comparative clinical trials and evidence-based guidelinesare needed.• Consider the risk versus benefit before starting anticholinergic therapy, especially in the elderly.References*1. Bennett MI. Death rattle: An audit of hyoscine (scopolamine) use and review of management. J Pain Symptom Manage.Oct 1996;12(4):229–233.2. Wildiers H, Menten J. Death rattle: Prevalence, prevention and treatment. J Pain Symptom Manage. 2002;23(4):310–317.3. Back IN, Jenkins K, Blower A, Beckhelling J. A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of death rattle.Palliat Med. Jul 2001;15(4):329–336.4. Ellershaw JE, Sutcliffe JM, Saunders CM. Dehydration and the dying patient. J Pain Symptom Manage. 1995;10(3):192–197.5. Hugel H, Ellershaw J, Gambles M. Respiratory tract secretions in the dying patient: A comparison between glycopyrronium and hyoscinehydrobromide. J Palliat Med. Apr 2006;9(2):279–284.6. Hughes A, Wilcock A, Corcoran R, Lucas V, King A. Audit of three antimuscarinic drugs for managing retained secretions. Palliat Med. May2000;14(3):221–222.7. Kass RM, Ellershaw J. Respiratory tract secretions in the dying patient: A retrospective study. J Pain Symptom Manage.Oct 2003;26(4):897–902.8. Morita T, Tsunoda J, Inoue S, Chihara S. Risk factors for death rattle in terminally ill cancer patients: a prospective exploratory study. PalliatMed. Jan 2000;14(1):19–23.9. Spiller JA, Fallon M. The use of Scopoderm in palliative care. Hosp Med. 2000;61(11):782–784.10. Sorenson HM. Managing secretions in dying patients. Respir Care. 2000;45(11):1355–1363.13. 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. Palliat Med. 2002;16(5):369–374.14. Owens DA. Management of upper airway secretions at the end of life. J Hosp Palliat Nurs. 2006;8(1):12–14.27. Lawrey H. Hyoscine vs glycopyrronium for drying respiratory secretions in dying patients. Br J Community Nurs. Sep 2005;10(9):421–424, 426.*Reference numbers correspond with those noted in the text. For a complete list of references, please visit ourwebsite, www.hospicepharmacia.com/evidencemattersPlease send comments or ideas for clinical topics to qualityoutcomes@excelleRx.com or give us a call at 215.282.1724

SUMMER 2007Evidence MattersAdditional copies of thisnewsletter can bedownloaded from theQuality Outcomes section ofwww.hospicepharmacia.comDear Clinician,This latest issue of Evidence Matters, the newsletter devoted to sharing clinical informationand promoting an evidence-based approach to palliative medicine, elucidates The Use ofAnticholinergics for the Management of Terminal Secretions.This newsletter is a production of the Quality Outcomes team at excelleRx. Our team isdedicated to building the evidence base and improving outcomes related to chronic illnessand palliative care. We welcome your feedback and questions as well as your suggestions forfuture topics.We hope you find this publication a valuable resource.Sincerely,The Quality Outcomes Team • qualityoutcomes@excelleRx.com • 215.282.17241601 Cherry Street, Suite 1700Philadelphia, PA 19102