5 tips for using drugs to manage non-pain symptoms in palliative care

Ayesha Hassan, pharmacist, Royal Inland Hospital, Interior HealthPatients may incur many symptoms during their palliative journey. This article focuses on three non-pain-related symptoms that pharmacists may be consulted about: constipation, cough and hiccups. This article is not intended to provide an in-depth review, but rather to offer a condensed approach with five helpful tips to manage these symptoms.Constipation Constipation can cause much discomfort, with physical symptoms such as nausea, vomiting, abdominal pain and anorexia.(1,2) Halitosis and fecal leakage can be demoralizing and affect socialization. Constipation is experienced by 30%–50% of the palliative population, increasing to 90% in those using opioids.(3-5) Left unresolved, it can lead to agitation and delirium, adding to psychological distress.(1,2) If inadequately treated, constipation can progress to fecal impaction, resulting in urinary retention, painful fissures, ulceration, bleeding and anemia.(6-9)Pharmacists should systematically assess diet, hydration status and mobility, compare usual and current bowel routines, and then correct any modifiable risk factors (e.g., discontinue bulk-forming laxatives in patients with limited mobility or those who cannot maintain adequate hydration).(10-12) They should also review the dosage and ongoing need for medications that often contribute to constipation (e.g., opioids, antacids, diuretics, iron, ondansetron, anticholinergic agents).(13) One in three patients attempt to modify their opioid regime to avoid constipation, rendering their pain management suboptimal.(14-16)The goal in managing constipation in palliative patients is to achieve comfortable passage of soft stool every two to three days, to prevent fecal impaction.(2,17) Be mindful that even with minimal intake, the body continues to produce 30–60 g of stool per day, so a laxative may still be warranted.(10)1. Limited evidence supports probiotic use to help manage constipation in palliative patients.Studies often used specific bacterial cultures; results cannot be generalized to other probiotic products. The potential benefits of probiotics (possible improved stool frequency and consistency) versus the risk of bacterial overgrowth must be carefully considered, especially in acutely ill or severely immunocompromised patients (e.g., post-chemotherapy).(10,18)2. In opioid-induced constipation, try routine use of a stimulant (e.g., sennosides) plus an osmotic laxative (e.g., lactulose or polyethylene glycol [PEG]).(1,10,19-21).Osmotic agents provide moisture to soften stool, making expulsion easier.(20,22) Increase the osmotic laxative dose to soften hard stool, but reduce the dose if fecal leakage occurs. Divide the stimulant dose if the patient becomes colicky.(3,21) Individualize therapy; a separate stool softener (e.g., docusate) used in conjunction with a stimulant offers flexible titration, whereas a combination product (e.g., docusate/sennosides) reduces pill burden. In refractory cases, methylnaltrexone or naloxegol may be options under advisement of palliative care experts.(23)Chronic dry coughPersistent chronic dry cough can be distressing. Besides throat and chest irritation, it can worsen pain and cause rib fractures.(24-26) Other symptoms include dyspnea, nausea, vomiting, poor appetite, incontinence and sleep deprivation.(10,24,25) Conversation becomes difficult, and the repetitive noise can disturb others.(10,26)Cough occurs in 86% of those dying from advanced diseases.(10,27,28) Tobacco users, and those with lung cancer, head and neck cancers, chronic obstructive pulmonary disease or end organ failure are particularly susceptible.(10,28) Chronic cough lasts longer than eight weeks, but many will seek treatment much earlier.(2,10,24,29,30) Pharmacists can advise on smoking cessation and nonpharmacologic strategies (e.g., ensure good ventilation, breathing and relaxation exercises) to minimize anxiety.(2,7,31,32)Nebulized saline (2.5–5 mL) or cold air humidification is effective in reducing dryness and airway irritation.(2,29,30,33-36) Simple syrup (10 mL q2–4h) and anesthetic lozenges can help soothe irritation, provided that the sugar content is acceptable and the patient has no swallowing issues.(10,25,33,37,38) Dextromethorphan has variable benefit.(27,28,33,37,38) In severe cases, morphine immediate-release [IR] is now standard therapy, starting with low doses (see Tip 3).(2,10,25,28,34,39)3. Morphine is preferred over codeine to treat chronic dry cough.(28,39)Once the gold standard for cough, codeine has been shown to be inconsistently effective or no more effective than placebo.(10,40-42) Comparatively, morphine acts more potently on mu-receptors and is unaffected by CYP2D6 metabolism.(38,42) Other opioids have not demonstrated superiority over morphine.(10,32) In opioid-naïve patients, start with a low dose of morphine IR (2.5–5 mg po q4–6h) on a scheduled basis and assess patient response in five days. If needed, recommend upward titration by 20%–50%, or the addition of smaller prn doses in between regularly scheduled doses.(28,29,39) For patients already established on opioids, first optimize breakthrough doses by an increase of at least 20%, then titrate the regularly scheduled base opioid and adjust the prn opioid doses depending on patient response.(28,29)Persistent hiccupsPersistent hiccups may seem minor, occurring in only 1%–9% of palliative care patients; yet, they can have a profound impact on quality of life.(43-48) The cause may be multifactorial, although gastric stasis is probably the most common cause in patients with advanced diseases. Hiccups lasting longer than two days can cause a reduction in food intake and sleep.(49-51) Prolonged hiccups (> 4 weeks) can lead to fatigue, exhaustion, weight loss and mental distress, and strain social functioning.(49,51-53) Severe hiccups can cause reflux and vomiting, leading to dehydration, electrolyte imbalance, aspiration pneumonia and arrhythmias.(10,54) Inquire about hiccups, especially in patients with gastrointestinal, thoracic or central nervous system (CNS) pathologies.(44,49,50,55)4. Baclofen is now a first-line agent for hiccups.This is based on case reports of efficacy and two small randomized controlled trials showing hiccup control within 30 minutes to three hours.(56-60) Table 1 summarizes first- and second-line agents for hiccups, although no drugs or natural remedies have been approved for this indication in Canada.(60) Pharmacists should review the ongoing need for medications known to cause hiccups (e.g., opioids, benzodiazepines, dexamethasone, chemotherapeutic agents).(43,51) Dexamethasone can induce hiccups in 25% of susceptible patients in doses above 10 mg.(10,51)TABLE 1: Treatments for Persistent Hiccups(9,10,56-64)First-line drugsBaclofen: 5–20 mg po q6–12h (max. 40 mg/day)Gabapentin: 100 mg po tid-qid & titrate (max. 1200 mg/day)Second-line drugsPantoprazole: 40 mg once daily or bidMetoclopramide: 10 mg po/subcutaneous/intravenous tid-qidDomperidone: 10 mg po tid-qidAntacid with simethicone: 10 mL po qid5. Gabapentin may be preferred in hiccups associated with CNS diseases.(61-63)Gabapentin can also help patients with co-existing neuropathic pain. If a patient with hiccups also suffers from reflux, an antacid, simethicone, H2-blocker or proton pump inhibitor can be tried alone or in addition to gabapentin.(9,10,62,64)SummaryPharmacists can play an integral role in supporting patients with life-limiting illnesses. It is important to manage not only pain, but all distressing symptoms. With systematic assessment and insight into patient experience, pharmacists can advise on both modifiable risk factors and management options.Ayesha Hassan (ayeshahassan918@gmail.com) received her Master of Palliative Care at the University of Newcastle, UK. She is currently a clinical pharmacist in hospital practice in Kamloops, B.C.References on next page ...References:1. Candy B, Jones L, Larkin PJ, et al. Laxatives for the management of constipation in people receiving palliative care. 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5 tips for using drugs to manage non-pain symptoms in palliative care

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