Monday, December 3, 2007
(Editor's note: Tom posted this on Saturday but it never got distributed by Feedblitz, our email updater, so I'm re-posting it on 12/3/7 in order for it be sent out for those of you who read the blog only via email.)
A Sebastiano Mercadante review is something that always catches my eye. He tends to be thorough and to look at the evidence critically. His recent article in Drugs and Aging on pain management in elderly cancer patients continues the trend. Edoardo Arcuri, a frequent collaborator, is co-author. Another Mercadante characteristic is a willingness to criticize other clinicians. The article cites, among the barriers to adequate management of pain in elders, a study finding that hospice nurses caring for the elderly "are almost twice as likely to incorrectly leave pain off a problem list than to incorrectly ascribe pain to a patient not reporting it." Even more pointed is a zinger at physician "unwillingness" to monitor opioid-related adverse effects.
The article also asks some important questions related to common assumptions about pain and elders: Do older patients feel less pain? Are they more sensitive to analgesics? In general, the answer to both questions is: the evidence is lacking, is unclear, or is contradicatory. The clinical bottom line, then, is: begin at lower doses than one would for younger adults, but be prepared to titrate to patient response. Unfortunately, they do not specify what "lower" means, but most clinicians start at 50% of the "usual" starting dose for opioids. They also say, however, that a cautious approach should not become one of "wasting time" when pain is acute. Pain can be aggressively managed and doses tritrated upward as needed as long as monitoring is frequent and appropriate to the patient's condition.
They particularly counsel caution with traditional (nonselective) NSAIDs because of the higher incidence of severe adverse effects as age increases. "NSAID renal toxicity may appear at lower doses in the elderly with subclinical renal insufficiency."
In the section on opioid elimination they point out that due to decreased muscle mass, serum creatinine is a less reliable predictor of glomerular filtration than in younger patients. Excretion may therefore be slower than predicted by serum creatine values.
Required skills for successful pharmacologic management of pain:
- objectively assess functional age
- understand the impact of coexisting conditions
- carefully manage the number and type of medications taken concurrently
- adequately communicate with patients and relatives
- pain assessments and use of analgesics tends to decline as patients get older: those over 85 are at greater risk than those at 65, but there is no evidence that pain is experienced less
- there is great variability in physiologic and functional aging--the rate of decline is variable
- "the hypothesis that elders have a higher threshold for pain has not been supported"
- "no physiologic changes in pain perception in the elderly have been demonstrated"
- in general, elders require lower doses of opioids, but "only careful titration based on individual response can ensure that patients receive the level of analgesia that they require"
- elders do not have a greater incidence of side offects with opioids, but when they occur they tend to be more severe
- "the rate of drug delivery rather than the absolute dose over time was seen to influence both analgesia and side effects" (translation: increased dosing interval for immediate release opioids may be necessary)
- renal function is more important than hepatic function in the development of toxicity from morphine (glucoronidation can occur even in fairly advanced hepatic dysfunction)
It seems to be a common rule of thumb in this country (at least in the academic medical centers of my acquaintence) that hydromorphone is the preferred "first choice" opioid for elders or the first alternative should toxicities to morphine develop. This point is not even addressed in the article. Except for potency, they seem to indicate that morphine and hydromorphone are about the same. Oxycodone is recommended as a good alternative because the "pharmacokinetics of oxycodone are mostly independent of age, renal function, and serum albumin." Of course, parenteral oxycodone is available in Europe, but not in North America. Transdermal fentanyl is also said to be worthy of consideration for patients with chronic pain and reduced renal clearance, because it "might be better tolerated than morphine because of lack of accumulation of important metabolites." They caution, however, that the decreased lean body mass to fat ratio may may "facilitate fentanyl accumulation once fat and muscle stores are saturated."This may be one of those articles to consider for Drew's famous Teaching File. It requires a close read, but provides an excellent "if you only have time to read one article" resource.
December 1 is World AIDS Day.
A research team at the Mayo Clinic presented findings this week at the meeting of the Radiological Society of North America on its study of cryoablation for pain resulting from metastatic bone tumors. 34 patients with 10 different tumor types were treated. 80% reported "clinically significant" pain reducation that persisted at 24 weeks after the procedure. Next up: a multi-institutional study that compares cryoablation head to head with radiation therapy.
A study (secondary analysis of a bisphosphnate study) published online ahead of print in Cancer this week again highlights the disparity between Caucasian and non-Caucasion patients in pain from advanced cancer. This study found that in a large international (19 countries!) cohort of women with metastatic breast cancer non-Causasian women (82% of whom were from the US) reached a pain level of 7 or higher (Brief Pain Inventory) significantly earlier than white women. They suggest that race be considered a risk factor for pain and that clinicians be prepared for aggressive and earlier intervention for pain in non-Caucasian women.
An article in the October issue of the Fordham Law Review uses the recent trial of a doctor accused of murdering/euthanizing her patients during the Katrina disaster to launch a discussion of intent and the use of "risky pain medication" at the end of life. It's pretty dense & legalistic (oh yeah, its the Fordham Law Review) but essentially defends judicious use of pain medication at the end of life (for pain) and "terminal sedation" [there are plenty of other terms that can be used; this one is particularly loaded] for intractable symptoms. Many people, of course, have raised the ethical issue that intent is difficult for a 3rd party to determine. In a criminal trial, a prosecutor has to convince a jury that the intent was to hasten death. My own opinion: since there is no evidence that appropriately titrated analgesics and sedatives hasten death--and evidence is accumulating (examples here and here) that they don't--double effect is not usually necessary as an ethical basis for defending the use of either class of drug in patients near death and experiencing severe symptoms.