Diarrhea is defined as passage of loose or watery stool, typically with at least three episodes in 24 hours.1 It is further classified as acute, lasting 14 days or less; persistent, lasting 15–30 days; and chronic, which continues for more than 30 days.2 In resource-limited settings, the cause is most likely an infectious agent. Antimicrobials are not always warranted but may be necessary, especially in situations such as diarrhea due to Shigella infection or severe cholera.
Common causes of diarrhea include the following:
• Overflow due to impaction from either severe constipation or colorectal tumors
• Side effect of medications or anti-cancer treatment such as chemotherapy and radiotherapy
• Malabsorption due to prior surgeries such as resections or pancreatic insufficiencies
• Neuroendocrine (NE) tumors, for example, Zollinger-Ellison syndrome
In a palliative care context, it is important to rule out constipation and impaction. Clinicians should consider using point-of-care ultrasound (POCUS) for assessment if available. If the diarrhea is due to an obstructive process, then surgical intervention may be necessary for either resection or diversion if this is a viable option. For patients with rectal or other obstructive tumors in whom surgery is not possible, the goal is to produce very soft stools with aggressive laxative use so that they can easily pass around the tumor.
Sanitation and infection control are of paramount importance, especially in situations where people are living in close quarters (e.g., refugee camps). Rehydration is an important component of care in palliation, and guidelines should be followed; however, in terminally ill patients this may lead to volume overload and should be used carefully for comfort when needed, or not at all in certain circumstances, such as with active dying. For all bedbound patients, good perineal skin care is especially important.
Following are guidelines for pharmacological management of gastrointestinal (GI) symptoms (see Chapter 13 for additional dosing guidelines):
• Appropriate antibiotics should be given, if needed, based on local infection patterns. Use antimotility agents with caution in patients with infectious etiology.
• Antisecretory and antimotility agents such as glycopyrrolate, loperamide, or diphenoxylate-atropine are typically used as first-line medications.
• Glycopyrrolate 1–2 mg PO qd–tid PRN; 0.1–0.4 mg IV/SC qd–tid
• Loperamide 4 mg PO followed by 2 mg for each subsequent loose stool up to 16 mg/day
• Diphenoxylate-atropine 5 mg qd–qid up to 20 mg/day
• Somatostatin analog: For refractory diarrhea or diarrhea due to chemotherapy or NE tumors, octreotide can be helpful and effective.
• Octreotide 100–150 mcg SC/IV q8h up to 500 mcg q8h
• Bulking agents (fiber): In certain patients, dietary soluble fibers such as psyllium or methylcellulose can be of help; however, patients must be able to maintain adequate fluid intake.
Constipation is typically characterized by infrequent and difficult defecation, often with painful passage of hard, small stool. This is a very common problem for frail, elderly, critically ill, and terminally ill patients and can have a significant impact on patients’ quality of life. Severe constipation may lead to overflow diarrhea, urinary retention, delirium, nausea, and vomiting.
Common causes of constipation include the following:
• Poor diet in disaster and conflict zones
• Dehydration and immobility
• Disease of the GI tract
• Cancers, strictures, fissures, proctitis
• Metabolic disturbances
• Hypothyroid, hypercalcemia, hypokalemia, diabetes, paraneoplastic syndrome
• Neurological disorders
• Spinal cord injury, malignant spinal cord compression, parkinsonism
• Opioids, antiemetics (e.g., 5HT3 inhibitors, prochlorperazine), anticholinergics, cardiovascular medications, psychiatric medications, supplements (e.g., iron and calcium)
The performance of a rectal examination for rectal tone, fecal impaction, fissures, hemorrhoids, enlarged prostate, tumors, and other issues is critical. Plain film, ultrasound, and other imaging are usually unnecessary. Underlying medical and surgical issues should be addressed. When necessary, manual disimpaction should be performed.
In general, patients should be encouraged to increase mobility whenever possible and to consume a diet conducive to regular bowel movements. It is important to maintain adequate hydration, especially if osmotic agents are being used. Fiber-based bulking agents such as psyllium and cellulose may result in worsening constipation if the patient is unable to consume sufficient water. Docusate, which is a “surfactant/detergent laxative,” has very questionable efficacy with little to no evidence base—in addition, the liquid tastes horrible.
Patients with an ostomy may require a bowel regimen to avoid constipation. Rectal suppositories are generally still effective for patients with a colostomy, since their rectal circulation and innervation are still intact. Rectal stimulation may be required for patients with a spinal cord injury or some other neurogenic cause for constipation. Patients who have minimal or no oral intake will continue to make small amounts of stool from sloughing of intestinal luminal cells and gut bacteria.
Patients typically need both an osmotic agent to provide softening and lubrication and neurostimulation for promotility kinetic effect, commonly referred to as “mush and push.” Neurostimulants act as promotility agents by providing direct stimulation of the lower GI plexus to induce peristalsis and propulsion. Orally administered senna and bisacodyl are activated and absorbed in the colon (lower GI) in 6–12 hours and have little to no stimulant effect on the stomach (gastroparesis) or small intestines. Rectal formulations (suppositories or enemas) act much faster. Suppositories are rapidly converted by rectal flora to their active form in approximately 15–60 minutes. The most common side effect is abdominal cramping.
Osmotic agents play an important role by providing lubrication and softening, and they help trigger stretch receptors in the GI tract. Polyethylene glycol-3350 (PEG-3350) is an iso-osmotic polymer, which makes it very safe to use, especially for maintenance, even for children, the elderly, and the very ill. It easily dissolves into any kind of liquid at any temperature but does require patients to drink 200 mL or more to be effective. As a dose-dependent agent, it can be rapidly acting when given in large volumes.
Sugar-based laxatives include lactulose, sorbitol, and mannitol. They work mainly in the colon by drawing in water and act in about 1–2 days. Lactulose has the additional benefit of being effective in the management of hepatic encephalopathy. Sorbitol and mannitol are cheaper and just as effective for laxation. When these sugars are broken down by GI bacteria, they often cause bloating and flatulence.
bid, twice daily; PO, oral; PR, rectal; qhs, every bedtime; qid, 4 times daily; SC, subcutaneous.
Electrolyte- and saline-based laxatives are typically sodium- and magnesium-based agents (e.g., sodium phosphate, magnesium citrate). They increase secretion and motility and work on the entire gut, including the small intestines. They act quickly, usually within 30 minutes to 2 hours. These are not good agents if patients require regular maintenance laxatives. One must watch for possible electrolyte imbalance, especially in patients with renal problems.
Lubricant laxatives, such as mineral oil and glycerin suppositories, lubricate the stool surface and decrease water absorption. They act slowly in about 1–3 days and are only appropriate for short-term use.
Enemas create a mechanical flushing and lubricating effect. The instilled volume triggers a mechano-stretch receptor response. The addition of pharmacological content may provide an added stimulant or osmotic effect. Enemas should be used with caution in patients at risk for bleeding, such as those with thrombocytopenia.
For opioid-induced constipation, depending on availability, opioid receptor antagonists, such as naloxone, given orally 0.8 mg PO bid to start, may play a role if patients are not responding to traditional laxatives.
Nausea and Vomiting
Vomiting or emesis is the forceful emptying of GI contents through one’s mouth and can be objectively quantified and characterized, whereas nausea is a subjective sensation of the desire to vomit. Nausea and vomiting are often accompanying symptoms, but patients may experience one without the other. It is important to distinguish between nausea and vomiting and to evaluate each separately. Persistent nausea can cause significant distress, discomfort, and decline, even in the absence of vomiting.
Common causes include the following:
• Dysmotility of the upper GI tract
• Medications and treatment-related side effects
• Chemotherapy- and radiotherapy-induced nausea and vomiting (CINV/RINV), digoxin, antibiotics, opioids
• Metabolic disturbances
• Renal failure (uremia), liver failure, electrolyte imbalances
• Obstruction of GI tract (intrinsic vs. extrinsic)
• Tumors (both intra -and extraluminal), constipation, ascites
• Infectious etiology
• Vestibular disturbance
• Often with an anticipatory component
• Severe pain
• Increased intracranial pressure
• Tumors, hemorrhage
Because nausea and vomiting are mediated by multiple receptors, it is helpful to match the underlying process to the most effective treatment.3 One should discontinue or rotate inciting medications whenever possible and avoid or minimize noxious triggers. Adequate hydration and supportive care are essential. Relaxation, distraction techniques, and mindfulness practices can be helpful. Consider treating with stenting, paracentesis, or other interventions and procedures, if appropriate, to address underlying problems.
Following are guidelines for pharmacological management of nausea and vomiting of various etiologies (see Chapter 13 and Box 6.2 for dosing guidelines). Patients often require nonoral routes for medication administration and need continued infusion for optimal symptom management. Many of the medications discussed here can be given subcutaneously and do not require oral or intravenous administration. Note that antidopaminergic agents may cause or exacerbate extrapyramidal symptoms, such as those in patients with Parkinson’s disease. Consider complementary medications that work on multiple receptors and on different parts of the nausea–vomiting pathway. However, do not combine treatments that work against each other, such as metoclopramide with promethazine (procholinergic/promotility with anticholinergic agents).
• Vestibular involvement
• Mediated by cholinergic and histaminic receptors; this is most often associated with motion sickness and dizziness.
• Medications in this group include hyoscine hydrobromide (scopolamine), promethazine, and diphenhydramine
• Chemoreceptor trigger zone (CTZ)
• Mediated by dopamine, 5HT3 (serotonin), and histamine receptors, the CTZ, located at the base of the fourth ventricle, detects and is especially sensitive to changing levels of toxins in the bloodstream, such as with chemotherapy.
• Medications in this group include ondansetron (or other available medications in the -setron family that exert 5HT3 blockade), prochlorperazine (D2 dopamine and H1 histamine blockade), and haloperidol (D2 blockade).
• Gastroparesis can be treated with a prokinetic agent via 5HT4 agonism and procholinergic activity, such as metoclopramide (also provides D2 blockade). Erythromycin can be helpful, but tachyphylaxis is common.
• GI obstruction
• If inflammation and edema are part of the etiology, then steroids like dexamethasone or prednisone may be useful anti-inflammatories (consider a 5-day burst course).
• Prokinetic neurostimulation medications such as senna and bisacodyl may be considered for lower GI involvement. (Please see above section on constipation.)
• Anxiety or anticipatory nausea/vomiting
• Benzodiazepines are not good stand-alone antiemetic agents and may increase risk of aspiration, but they are excellent anxiolytic medications in patients for whom this is an issue.
• CNS irritation and space-occupying lesion
• Initiate steroids if inflammation and edema are present.
• Chlorpromazine (Thorazine)
• This is an older medication but has a broad spectrum of action that is primarily antidopaminergic, with histamine, cholinergic, and serotonin receptor blockade as well.
• (See section on malignant bowel obstruction for further discussion.)
5HT3, 5-hydroxytriptamine receptor; bid, twice daily; CTZ, chemoreceptor trigger zone; D2, dopamine receptor; GABA, gamma-amino butyric acid; GI, gastrointestinal; H1, histamine receptor; IM, intramuscular; IV, intravenous; IVP, intravenous push; PO, oral; PR, rectal; PRN, as needed; qid, 4 times daily; SC, subcutaneous; TD, transdermal; tid, 3 times daily
Malignant Bowel Obstruction (MBO)
MBO may occur as a result of tumor growing from the GI tract itself or from extrinsic compression due to tumor growing outside the GI tract. Most patients autoconvert between varying degrees of partial to complete obstruction as the GI tract moves within the abdominal cavity. Unresolved complete bowel obstruction without a surgical option will often lead to perforation and is fatal within hours to days. Ongoing MBO causes significant and burdensome symptoms related to the swings between hyperactivity of the gut (hypersecretion and hypermotility) resulting in cramps, nausea, and vomiting, and hypoactivity resulting in gastroparesis, GI stasis, and bloating. The goal of treatment is ongoing support.4
Stenting or surgery should be considered, if needed. Decompression via a nasogastric tube or venting gastrostomy can provide some relief but causes discomfort and introduces additional morbidity. IV fluid support should be provided as tolerated for comfort. Management and support of MBO often include monitoring and repletion of electrolytes. Managing symptoms of nausea and vomiting is an essential part of supportive care for MBO. (See section on nausea and vomiting and Chapter 4 on pain management for further discussion.)
Following are guidelines for pharmacological management of MBO (see Chapter 13 for dosing guidelines.)
Octreotide, a somatostatin analog, decreases secretions and decreases motility while allowing the GI tract to maintain reabsorption and other key functions. Its efficacy in MBO is controversial, but for refractory patients it is often trialed when available. It can be given subcutaneously as an injection or as a continuous infusion. Patients may need a few days to see the full effect of this medication. Steroids, like dexamethasone, may often be helpful to decrease inflammation. Promotility agents, such as metoclopramide, may be used in partial bowel obstruction but should be avoided in complete or severe obstruction. These medications may be used in conjunction with each other and provide a synergistic effect.
Anticholinergics, especially those that do not cross the blood–brain barrier (e.g., glycopyrrolate or hyoscine butylbromide), may help decrease GI secretion and motility and thus provide bowel rest. A proton pump inhibitor and H2 blocker may be used to decrease gastric secretion. For patients with complete obstruction or bowel perforation and are not surgical candidates, aggressive symptom management with opioids for pain is essential. Sedation is often a desirable side effect for these patients, and one should choose anticholinergic agents that readily cross the blood–brain barrier, such as hyoscine hydrobromide (scopolamine).
Anorexia and Cachexia
Anorexia is the loss of appetite for food—patients lack the sensation of hunger; it is often an associated symptom in patients with GI symptoms discussed in this chapter. Cachexia is a wasting syndrome of weight loss and muscle atrophy, often characterized by weakness and fatigue.5 With treatment and reversal of the underlying disease process, whenever possible, appetite should return. However, the end stage of many conditions (e.g., cancer, HIV/AIDS) and in actively dying patients anorexia, cachexia, or both are often part of the dying process.
Anorexia must be distinguished from starvation, where hunger is present and patients are being deprived of adequate food intake. Starvation, along with malnutrition, is commonly encountered in humanitarian crises.
It is paramount to provide education and supportive counseling and to address psychosocial and cultural concerns associated with anorexia and cachexia. The eating and sharing of meals is a deeply ingrained human activity that is transcultural. It is often very distressing for family members to witness the process of anorexia and cachexia. Smaller portions and eating for pleasure can be satisfying for many patients. Finding alternate ways of feeding whenever possible may be important for patients, family members, and caregivers. However, clinically, artificial enteral or parenteral nutrition offers no benefit in terminal and end-stage conditions. In end-of-life care, finding alternate ways besides feeding for family members and caregivers to nurture and care for the patient who is anorexic and cachectic is important. Well intended but forced feeding may lead to distress and suffering such as pain, nausea, and vomiting, without the intended benefits. Eating when desired should be for pleasure, adequate caloric/nutritional intake is neither a priority nor a goal in management.
Following are guidelines for pharmacological management of anorexia and cachexia (see Chapter 13 for dosing guidelines).
Treatment of reversible conditions (e.g., oral thrush, constipation) and optimal management of chronic conditions are paramount. Early satiety may be seen in patients with compression of the stomach from ascites, hepatomegaly, or other forms of outlet obstruction and gastroparesis. Metoclopramide, a promotility agent, can be used if the patient has symptoms of early satiety and delayed gastric emptying.
Certain medications have an orexigenic (appetite-stimulating) effect but do not reverse the underlying pathology and do not address the issue of cachexia. However, for the purposes of palliation, glucocorticoid steroids such as dexamethasone can be helpful. Antidepressive and antipsychotic agents such as mirtazapine and olanzapine, when available, may be selected for their profile of desirable side effects, such as appetite stimulation and weight gain. Progestin agents such as megestrol are not usually recommended because of the cost and prothrombotic profile, which is especially problematic for many cancer patients.
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