Thursday, March 12, 2009
Pallimed Case Conferences (cases.pallimed.org) is closed to comments and new posts as of April 25, 2013.
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By Tamara Sacks, MD
Originally posted at the Institute to Enhance Palliative Care, University of Pittsburgh Medical Center
Vol 9, No. 2 - February 2009
CH is a 56-year-old woman with metastatic breast cancer to bone, liver and brain. She is admitted to the hospital with increasing lethargy and a marked decrease in her oral intake. She has also not had a bowel movement for 10 days. Further interview reveals that she has been on a fentanyl patch 75 mcg for months, senna and colace, and hydrochlorothiazide. Her diuretic is stopped and she is placed on intravenous fluids. Except for dehydration, a metabolic work up is unremarkable. Her exam reveals hypoactive bowel sounds, a scaphoid abdomen with palpable mobile masses, and soft stool in the rectal vault. She is disimpacted. No active bowel movement follows despite suppositories. She is also not able to retain enemas. She has increasing nausea and anorexia. Given her inadequate response to a bowel regimen from below and inability to tolerate an oral regimen, she is dosed with methylnaltrexone subcutaneously x1. She has a large formed bowel movement 2 hours later.
Constipation is a well recognized side effect from opioids. Tolerance does not occur. In fact, the dose that can cause constipation is ¼ of an analgesic dose. Opioids exert their constipating effects by decreasing GI motility, gastric emptying, increasing ileocecal valve tone, increasing fluid resorbtion, and decreasing the reflex to defecate.
Methylnaltrexone (MNTX) is a mu receptor antagonist that unlike naloxone does not cross the blood brain barrier as it is a quaternary amine. Naloxone has been used in the past for opioid induced constipation. However, this use has also been associated with opioid withdrawal and decreased pain relief. MNTX was approved for the treatment of opioid induced constipation by the FDA last year. Given its expense, many institutions have tried to limit its use. Our institution has made a Palliative Care consult one of three consultation services that can approve dosing.
The phase three clinical trials that led to approval of MNTX involved patients either enrolled in hospice or as part of a palliative care program, and opioids were thought to be the primary cause of the constipation. They must have been receiving opioids for two weeks and on a stable opioid and laxative regimen for three days.
Enrolled patients had had no bowel movement in greater than 48 hours or had had less than 3 bowel movements the week prior. Bowel obstruction, fecal impaction or other acute abdominal processes were ruled out. In addition, patients with peritoneal dialysis catheters and fecal ostomy bags were excluded. While 80 percent of the patient population had cancer, patients with cardiovascular disease, AIDS, dementia, and COPD were also included. MNTX is administered subcutaneously based on the patient’s weight. After administration of MNTX, greater than or equal to 50% of the study group had a bowel movement within 4 hours. Most patients had a bowel movement within 30-70 minutes. As compared to placebo, the most frequent side effects were abdominal cramping, nausea, dizziness, increased body temperature and flatulence. However, the number of patients who discontinued therapy secondary to side effects was similar to that in the placebo group. No decrease in pain control or signs of opioid withdrawal were noted as compared to the placebo group.
There are many medications and dosage forms that are available for opioid induced constipation. Previously, routes of administration have been oral and rectal. Dysphagia, nausea or decreased mental status can greatly hinder an adequate regimen by mouth. Rectal routes of suppositories and enemas can also be tried. Inability of the patient to participate can limit effectiveness of enemas. In properly selected patients, MNTX may be able to aid in relief of opioid constipation without adversely affecting pain control
1. Thomas, Jay et. al. Methylnaltrexone for Opioid Induced Constipation in Advanced Illness. 2008. NEJM 358 (22): 2332-2343.
2. Yuan, Chun-Su. Methylnaltrexone Mechanisms of Action and Effects on Opioid Bowel Dysfuction and Other Opioid Adverse Side Effects. The Annals of Pharmacotherapy, 2007. 41: 984- 993
Thursday, March 12, 2009 by Christian Sinclair ·
Monday, March 9, 2009
SURVEY CLOSED WED MARCH 18, 2009
Results posted on Pallimed Main blog in April(re-posted from the main Pallimed blog)
Dear Pallimed Readers,
Thanks so much for joining us here at Pallimed. Last January we had our first annual survey to get some more structured feedback from the readers. (Here are the results from the 2008 Pallimed Readers Survey.) This year we ask you for a few minutes to complete this year's survey. (Last year the survey took less then 6 minutes on average.)
It is even shorter then last year's, since we took out some questions! Blame it on the economy, we cannot even afford more questions this year. Drew, Amber, Amy, Tom and I appreciate your feedback very much.
The survey is open for just one week. Please complete it only once. It is the same survey regardless of which blog (Main, Arts, Cases) you access it from.
We will not sell your information. We pledge not to bombard you with survey pop-ups, or separate emails asking you to finish this. It is a voluntary survey.
We are expecting to provide our readers with some feedback from the survey by the end of March.
Christian Sinclair (on behalf of Drew, Amber, Amy, Tom and Pallimed)
Monday, March 9, 2009 by Christian Sinclair ·