Evidence About the Pharmacological Management of CONSTIPATION PART 2: IMPLICATIONS FOR PALLIATIVE CARE Constipation remains a challenging problem for patients and caregivers in home healthcare. Part 1 of this two-part series discussed the scope, physiology, and evidence-based prac- tice for nonpharmacological interventions for constipation. This second article will focus on evidence-based pharmacological prevention and management of constipation, medication cost, and implications for palliative care. Matthew Pitlick, PharmD, BCPS, and Deborah Fritz, PhD, RN vol. 31 • no. 4 • April 2013 Home Healthcare Nurse 207 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. While eliminating causative factors and increasing fluid/fiber intake should be attempted when possible, these are often inappropriate or unreasonable options in palliative care. Many medications are available and differ in efficacy, safety, adverse effect profile, overall tolerability, and cost. Case Study Introduction focuses on pharmacologic treatment of constipa- Mr. M. is a 66-year-old African American man who tion and implications for palliative care patients. was diagnosed with multiple myeloma 3 months ago after complaints of bone pain and fatigue. His Pharmacological Therapy problem list includes anemia, hypercalcemia, Bulk-Forming Laxatives and well-controlled diabetes mellitus on oral These agents’ bulk-forming laxatives, including medications. He is receiving lenalidomide, dexa- methylcellulose, polycarbophil, and psyllium, bulk methasone, and melphalan to treat his cancer. He stool contents, increase retention of water, and in- is not eligible for an autologous stem cell trans- crease the rate of stool transit through the intes- plantation. Ms. M. states that her husband has tine (Powell & Fleming, 2011). These actions result less energy to do the activities he has enjoyed in increased stool frequency. Bulk-forming laxa- since retirement. Although his bone pain is now tives may take 3 to 5 days for effect but can take well controlled, she is concerned that his chronic longer. Adequate fluid intake (1.5–2 L) is required constipation is affecting his quality of life. for use. Abdominal distention and flatulence are Mr. M.’s current medications are: common adverse effects but can resolve with contin- ued use. In general, these laxatives should not be • lenalidomide orally 25 mg daily, used in palliative care situations, as they can cause • dexamethasone orally 40 mg in the morning, obstructions of the esophagus, stomach, small intes- • melphalan orally 6 mg daily, tine, and colon, especially with inadequate fluid • zoledronic acid 4 mg IV every 4 weeks, intake (Powell & Fleming, 2011; Spinzi et al., 2009). • metformin orally 1,000 mg twice daily (BID), Psyllium has been associated with anaphylactic • morphine sulfate ER orally 30 mg BID, reactions, as well (Ho et al., 2008). The palliative • morphine sulfate IR orally 10 mg every 2 to 3 care patient, generally, cannot tolerate or intake hours as needed for breakthrough pain, and the amount of fluid needed for bulk-forming laxa- • docusate sodium orally 200 mg BID. tives to work properly and safely. Background Emollients The goal of patient management for home health- Commonly known as stool softeners, these agents care providers, in particular for palliative care work by increased wetting and softening fecal patients, is the improvement of quality of life mass, which allows for easier passage of stool. issues that affect the physical and psychological Softening of stools generally occurs in 1 to 3 days well-being of their patients. These issues may in- (Powell & Fleming, 2011). Docusate is the most clude pain, fatigue, reduced mobility, and, com- commonly used stool softener and should be used monly, constipation. Constipation continues to to prevent painful defecation and straining in situ- challenge home healthcare providers, especially ations when this should be avoided such as se- in palliative care. For a detailed definition of con- vere hypertension, cardiovascular disease, and stipation, please refer to Part 1 of this article recent surgery or myocardial infarction. Docusate (Fritz & Pitlick, 2012). In an effort to improve may increase fecal soiling, otherwise there are symptoms of constipation, pharmacologic mea- very few side effects associated with these agents sures may be necessary. This second part article (Powell & Fleming, 2011). Stool softeners are 208 Home Healthcare Nurse www.homehealthcarenurseonline.com Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. ineffective in treating constipation and should not an abundance of evidence showing efficacy and be used as monotherapy for treatment of constipa- safety with PEG over placebo (Locke, et al., 2000; tion (Gallegos-Orozco et al., 2012). However, they Powell & Fleming, 2011; Ramkumar & Rao, 2005; work well when combined with stimulant laxa- Weitzel & Goode, 2012). Unlike other laxatives, tives and lead to a softer, easier stool to pass as PEG has been shown safe when used up to 6 to the stimulant causes laxation (Locke et al., 2000; 12 months (Powell & Fleming, 2011; Singh & Rao, Powell & Fleming, 2011; Weitzel & Goode, 2012). 2010). PEG has been shown superior to lactulose as well (Ramkumar & Rao, 2005). Lubricant Lactulose and sorbitol are hyperosmotic laxa- Mineral oil can soften stool and prevent strain- tives that work in a similar way. In addition to ing, similar to emollients. It typically works in 2 altering fluid activity, these agents decrease pH in to 3 days. However, safety concerns severely the colon, which increases colonic peristalsis. limit its use. Lipid pneumonia can result from This increases stool frequency and consistency. aspiration, especially in the very ill and elderly. Adverse effects include flatulence, nausea, In addition, absorption of Vitamins A, D, E, and K abdominal discomfort or bloating, diarrhea, and can be disrupted. Other adverse effects such as electrolyte imbalances. Lactulose has been shown pruritus and soiling can occur as well (Leung et to be superior to placebo for chronic constipa- al., 2011; Powell & Fleming, 2011). Given these tion and effective in opioid-induced constipation issues, mineral oil should not be recommended in (Liu, 2011). Sorbitol is similar to lactulose, is more palliative care situations (Locke et al., 2000; cost-effective, and causes less nausea. However, Powell & Fleming, 2011; Weitzel & Goode, 2012). hyperglycemia may occur with sorbitol, so it is important to monitor patients with diabetes. Osmotic Laxatives Lactulose and sorbitol could be useful in palliative These agents include glycerin, polyethylene glycol care situations; however, there are not enough stud- (PEG, brand name: Miralax), lactulose, sorbitol, ies in this patient population and more frequent use and saline laxatives such as magnesium hydrox- of the laxative is needed. See Box 1 for evidence- ide, citrate, phosphate, and sodium phosphate. based practice regarding lactulose and PEG. These agents draw water into the colon through Saline laxatives include magnesium hydrox- osmosis, leading to a softer stool, and induce a ide, citrate, sulfate, phosphate, and sodium phos- bowel movement. Adverse effects are common phates. These agents act primarily by osmosis in among these laxatives (except glycerin and PEG) the small and large intestines (oral) or colon and elderly patients tend to be more susceptible. (rectal). They increase the intraluminal pressure Glycerin is a very safe and effective laxative for acute evacuation. It is available in suppository form and induces bowel movement in 30 minutes. Box 1. Evidence-Based Practice: Adverse effects are rare but may include mild Lactulose Versus Polyethylene Glycol rectal irritation. Lactulose versus polyethylene glycol for chronic PEG is an osmotic laxative with adequate effi- constipation (Lee-Robichaud et al., 2010). cacy and a favorable adverse effect profile. PEG Research Problem: To determine if lactulose possesses fewer adverse effects than other os- or polyethylene glycol is more effective to treat motic laxatives because it is not absorbed sys- chronic constipation. temically or metabolized by colonic bacteria. For Methods: Comprehensive literature review with constipation during palliative care, PEG is an ex- meta-analysis of randomized controlled trials cellent choice because of its wetting and stimula- comparing lactulose to polyethylene glycol. tion effects with low incidence of adverse effects. Results: Ten randomized controlled trials were in- Possible adverse effects include abdominal pain, cluded. Polyethylene glycol was found to be better than lactulose in outcomes of stool frequency and electrolyte disturbances, and dehydration; how- form of stool. ever, incidence is lower than that for other laxa- Implications for home healthcare practice: tives (Clemens & Klaschik, 2008). Additionally, Polyethylene glycol should be considered over PEG must be dissolved in a glass of water (8 oz), lactulose for treatment of chronic constipation. which can be an issue if the patient is fluid re- SORT LEVEL: B stricted or cannot tolerate excess fluids. There is vol. 31 • no. 4 • April 2013 Home Healthcare Nurse 209 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. less effective drug (Locke et al., 2000; Powell & A very common Fleming, 2011; Weitzel & Goode, 2012). In the past, clinicians have hesitated