___________________________________________ Palliative Care and Pain Management at the End of Life
prognosis and preferences for care should be factored into a decision to carry out diagnostic testing. As with assessment of all symptoms, constipation should be reassessed frequently; assessment at least every three days is recommended [320]. Management The goal of treatment should be relief of symptoms related to constipation and re-establishment of bowel habits to the patient’s comfort and satisfaction; some recommend a goal of one nonforced bowel movement every one to two days, or at least three times per week [310; 320; 321]. Systematic reviews have demonstrated that data are insufficient to support one laxative or combination of laxatives over others [319; 322; 323; 324]. Many laxatives are FDA approved for occasional constipation, and much of the evidence on their efficacy has come from studies of chronic constipation, not patients with life-limiting disease. In its guidelines for the management of chronic con- stipation, the American College of Gastroenterology notes the following [323]: • Polyethylene glycol (PEG) and lactulose (both osmotic) improve stool frequency and stool consistency. • Data are insufficient to make a recommen-dation about the efficacy of stool softeners (docusate [Colace or Surfak]); stimulant laxatives (senna [Senokot, Ex-Lax] or bisacodyl [Dulcolax, Correctol]); milk of magnesia; herbal supplements (aloe); lubricants (mineral oil); or combination laxatives (psyllium plus senna). The results of a systematic review of studies in the palliative care setting also demonstrated insufficient data for recom- mendations because of a lack of direct comparisons of laxatives [322]. An update to this review includes evidence that subcu- taneous methylnaltrexone is effective in inducing laxation in palliative care in patients with opioid-induced constipation where conventional laxatives have failed [324]. Researchers have concluded that the choice of a laxative should be made on an individual basis, with considerations of patient prefer- ences and the side-effect profile [319; 322]. For all patients, oral formulations are recommended over rectal suppositories [319; 320]. Rectal suppositories and/or enemas should be used with caution in patients receiving chemotherapy due to the increased risk of the rectal route of administration in the setting of cytopenia [310]. European and Canadian consensus groups and the NCCN have developed practice guidelines for constipation in the pal- liative care setting on the basis of the available data and expert opinion ( Figure 11 ) [310; 319; 320]. First-line recommended treatment is a stimulant laxative plus a stool softener (PEG or lactulose) [310; 319; 322]. A small study of senna with and without docusate for hospitalized patients with cancer showed no significant benefit to the addition of docusate; docusate is specifically not recommended in the Canadian consensus recommendations [320; 325]. If constipation persists, other options are bisacodyl, magnesium hydroxide, or sorbitol [310].
Methylnaltrexone (Relistor) was approved by the FDA in 2008 for the treatment of opioid-induced constipation [326]. A sys- tematic review indicated that the subcutaneous drug is effective in the palliative care setting, and is especially useful for patients with constipation refractory to conventional laxatives [324]. In 2014, the FDA approved naloxegol, an oral agent for the man- agement of opioid-associated constipation [327]. However, this drug’s approval is limited to patients with chronic non-cancer pain. Practice recommendations note that methylnaltrexone or naloxegol should be considered for patients taking opioids after failure of other laxatives [310; 319; 320]. Withdrawal of opioids should never be a strategy to manage constipation. Nonpharmacologic interventions are important adjuncts to laxatives, and the interventions used as prophylaxis are recom- mended for ongoing management [319; 320]. NAUSEA AND VOMITING Nausea may occur alone or with vomiting, a neuromuscular reflex. Nausea and vomiting can exacerbate pain and contribute to insomnia, fatigue and weakness, and anorexia. It can also limit activities and cause distress for the patient and family. Nausea is the result of stimulation of one of several pathways: the chemoreceptor trigger zone (located in the medulla), the cortex of the brain, the vestibulocochlear nerve, or the gastro- intestinal tract [67]. Prevalence Nausea alone affects approximately 6% to 68% of adults with life-limiting disease, and vomiting affects 40% [211]. The rate of nausea and vomiting is highest among patients with cancer [211]. Etiology The potential causes of nausea and vomiting near the end of life vary according to life-limiting disease [206; 214; 246; 328; 329]: • Medications (chemotherapy agents, opioids, antidepres- sants, antibiotics) • Radiation therapy (especially to the abdomen or lumbo- sacral spine) • History of peptic ulcer disease or gastroesophageal reflux • Delayed gastric emptying
• Primary or metastatic brain tumor • Gastrointestinal tract obstruction
• Constipation • Renal failure • Hepatic failure • Pancreatitis • Hypercalcemia • High serum levels of dioxin or anticonvulsants
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MDCA1525
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