Malignant bowel obstruction: Individualized treatment near the end of life
ABSTRACTMalignant bowel obstruction requires a highly individualized approach, tailored to the patient’s medical condition, prognosis, and goals of care. Surgery should not be routinely done. Less-invasive approaches such as gastric and colonic stenting are useful.
KEY POINTS
- Combinations of analgesics, antisecretory drugs, and antiemetics can provide acceptable symptom relief.
- A venting gastrostomy should be considered if drug therapy fails to reduce nausea and vomiting to an acceptable level.
- A nasogastric tube should be used only as a temporizing measure, until symptoms are controlled medically or a venting gastrostomy is placed.
- Total parenteral nutrition is beneficial only in patients with intermediate life expectancy who may otherwise die of starvation rather than the cancer itself.
Contraindications to stenting
Absolute contraindications to stenting are colonic or tumor perforation with peritonitis. A relative contraindication is a rectal tumor within 2 cm of the anal margin. Stenting in this circumstance leads to tenesmus and incontinence.33
Complications of stenting
Death rates during colorectal stent insertion are less than 1%. The hospital stay and incidence of complications are significantly less than with surgery.26,30
Stent migration occurs in 10% of cases and is asymptomatic, but half of patients with this complication require a repeat intervention. The risk of migration is greater if chemotherapy or radiation therapy succeeds in shrinking the tumor.
Bleeding occurs in 5% of cases, usually from the underlying tumor.
Perforation occurs in 4%, but the rate increases to 10% with the use of dilatation before stent placement.
The rate of recurrent obstruction from tumor ingrowth, overgrowth, or fecal impaction is 10%.9,26,29 Recurrent obstruction may be treated with additional stents inserted within the original stent.9
GASTRIC OUTLET OBSTRUCTION: SURGERY VS STENTING
Gastrojejunostomy has in the past been the treatment of choice for gastric outlet obstruction. Certainly, patients with slow-growing tumors and an expected survival of greater than 60 days may be considered for this bypass procedure; those with a short tumor length, a single site of obstruction (preferably in the pylorus or proximal duodenum), a good performance status, and a life expectancy greater than 30 days are good candidates.7 Nevertheless, for patients with advanced cancer and poor performance status, gastroenterostomy carries a significant risk of morbidity and death.28
Endoscopic stenting of gastric outlet obstruction has a greater success rate, a shorter time to oral intake, a lower morbidity rate, a lower incidence of delayed gastric emptying, and a shorter hospital stay compared with gastroenterostomy.28,29 Technical success rates of stenting are 90%, and 75% of patients have resolution of nausea and vomiting.7 Stenting is generally not possible if the obstruction occurs beyond the ligament of Treitz.
Patients who are expected to survive less than 1 month or who have rapidly progressive disease, overt ascites, carcinomatosis, or multiple sites of obstruction should be managed with percutaneous, endoscopically placed gastrostomy tubes.7
Late complications of stenting for gastric outlet obstruction are occlusion with food or ingrowth of tumor through or around the wire mesh.7 This may require laser therapy or placement of a second stent, or both.
DRUG THERAPY
Medical therapy can palliate symptoms of malignant bowel obstruction for most patients.34 Recommendations have been published by the Working Group of the European Association for Palliative Care.24 Symptom management is focused on pain, nausea, and vomiting.
Which drugs can I use for abdominal pain?
Patients experience two types of abdominal pain: continuous and colic. Each type of pain requires different treatment approaches and classes of drugs.
Potent opioids such as morphine, hydromorphone (Dilaudid), and fentanyl (Fentora) are used to relieve continuous abdominal pain.7 The dose is titrated for adequate relief. Subcutaneous, intravenous, sublingual, and transdermal routes can be used if nausea and vomiting prevent oral administration.
However, opioids can aggravate colic by stimulating circular smooth muscle, leading to segmental contractions. Opioid-sparing adjuvant drugs such as ketorolac (Toradol) may improve colic and continuous pain and prevent a partial obstruction from becoming a complete obstruction by sparing opioid doses.35
Colic may persist or worsen with the use of opioids. Drugs that reduce colic include the scopolamine drugs hyoscine butylbromide and hyoscine hydrobromide, glycopyrrolate (Robinul), and octreotide (Sandostatin).7,34–37
Which drugs are appropriate for reducing nausea and vomiting?
Phenothiazines reduce nausea and control vomiting. Chlorpromazine (Thorazine), prochlorperazine (Compro, Compazine), and promethazine (Phenergan) have all been reported to treat nausea successfully.35,37
Haloperidol (Haldol), a butyrophenone selective dopamine D2-receptor antagonist, has negligible anticholinergic activity. At low doses it produces less sedation than phenothiazines and is an ideal agent for patients with nausea and delirium.35 Doses range from 5 to 15 mg/day, given in divided doses or as intermittent or continuous intravenous infusions.
Anticholinergics, with or without somatostatin analogues, reduce gastrointestinal secretions, fluid accumulation, and vomiting. Anticholinergics bind to muscarinic receptors on enteric neurons in the myenteric and the submucosal plexus. Dosages:
- Hyoscine butylbromide 40 to 120 mg/day.
- Hyoscine hydrobromide 0.2 to 0.9 mg/day.7,34
Glycopyrrolate, a quaternary ammonium anticholinergic, has minimal central nervous system penetration and is less likely to cause delirium or cardiac side effects compared with tertiary amine anticholinergics such as atropine and scopolamine.38 The recommended dose is 0.1 to 0.2 mg subcutaneously or intravenously three to four times daily.
Octreotide, an analogue of somatostatin, blocks the release of vasoactive intestinal polypeptide, which is increased in malignant bowel obstruction.14,15 It reduces the excretion of water, sodium, and chloride into the bowel lumen and increases the absorption of electrolytes and water. It also inhibits pancreatic enzyme secretion and splanchnic blood flow. The result of all these effects is reduced luminal content, reduced motility, reduced vascular congestion of the bowel wall, and, in certain circumstances, reduced ascites.39
In small randomized trials, octreotide was more successful than anticholinergics at improving nausea, vomiting, and colic in patients requiring a nasogastric tube and in those whose symptoms were refractory to standard medical treatment.5,34,40–43 A recent case report found octreotide helpful in resolving symptoms of partial bowel obstruction that were unresponsive to standard measures.44
Octreotide is well tolerated and reduces the time patients require a nasogastric tube without significantly worsening xerostomia. High cost limits its use in American hospice care due to the Medicare capitated system of reimbursement for drugs and services, and as a result it is a second-tier drug despite evidence of its efficacy.
Octreotide doses are 100 to 200 mg every 8 hours.
Metoclopramide (Reglan), a dopaminergic antagonist, a 5HT4 receptor agonist, and a 5HT3 receptor blocker at doses greater than 120 mg/day, combines the action of a phenothiazine, which blocks D2 receptors in the central chemoreceptor trigger zone, with promotility actions through serotonin receptors (5HT4).35,37
Metoclopramide should not be used with anticholinergics or in patients with colic or complete obstruction.35,45 In some centers it is the first-line drug for functional or partial bowel obstruction.7 Dosages range from 40 to 240 mg/day.
Olanzapine (Zyprexa), an atypical antipsychotic, blocks multiple neurotransmitter receptors (D2, H1, Ach, 5HT3) responsible for initiating emesis. It is an option in patients whose nausea and vomiting fail to respond to standard antiemetics.46 Dosages range from 2.5 to 20 mg/day.
Dissolvable tablets are given sublingually, which makes olanzapine a versatile antiemetic in cases of intractable nausea. Our unpublished experience is that the sublingual route reduces nausea associated with malignant bowel obstruction and obviates the need for subcutaneous injections or intravenous antiemetic infusions.
Corticosteroids. Although how corticosteroids relieve malignant bowel obstruction is unknown, they are presumed to act centrally.37,45 In addition, they reduce peritumoral edema and luminal salt and water, and they also have antiemetic and analgesic properties.
Evidence from a meta-analysis found that 6 to 16 mg of parenteral dexamethasone per day reduced symptoms and improved bowel function in 60% of patients but did not change the prognosis.11
A trial of 4 or 5 days is adequate to determine response. If there is no response, the corticosteroid should be rapidly tapered. Side effects are minimal when corticosteroids are used short-term.
Combination therapy. Only rarely does a single drug resolve symptoms of malignant bowel obstruction. Antiemetics, analgesics, corticosteroids, antisecretory anticholinergics, and octreotide are often required in combination to achieve acceptable symptom relief.3,5,7,47
In a small prospective case series, the combination of metoclopramide 60 mg/day, octreotide 0.3 mg/day, and dexamethasone 12 mg/day with a single bolus of amidotrizoic acid (a contrast agent) improved intestinal transit within 1 to 5 days and resolved vomiting within 24 hours.45
Compatibility and the route of administration of medications are key considerations when choosing drug combinations.
