To the Editor:
With great expectations I awaited publications of the results of the polyanalgesic survey
1
and consensus report 2
after hearing the initial oral presentation at the American Academy of Pain Medicine (AAPM) meeting in New Orleans this year. After carefully reviewing the written report I want to share some thoughts on the topic.There is no doubt that the results of the survey give us an interesting overview of the current status of neuroaxial therapy of chronic pain. At the same time, I categorically disagree with the idea, obviously close to the heart of the authors, that any guidelines can be proposed based on a simple referendum. I want to remind everyone that a poll collected at a certain point of our history would produce the overwhelming conclusion that the Earth is flat. Guidelines, preventing travel to the edge, would have prevented the discovery of America. Only new studies, preferably prospective, randomized and double-blind, will help to formulate rules and laws of medicine. There is a clear indication of the deficit of such research.
1
Nevertheless, the journal offered at least the third survey in 4 years without answers to a majority of questions.1
, 3
, 4
Frankly, it looked a little bit like fortune-telling when the authors predicted a bright future for clonidine, just because one group of physicians liked it more than the other.1
The clinical guidelines suggested by the panel on the basis of the survey results
2
were not infrequently different from the published data in the same issue.1
For example, hydromorphone was clearly a drug of choice to replace morphine in cases of inadequate analgesia or side effects in the survey. The “Expert panel” put this as an equal choice with much less popular mixtures of morphine/clonidine or morphine/bupivacaine. Even more surprising was their suggestion of “usual appropriate/average starting dose of 0.53 mg/day” of intrathecal morphine. Meanwhile, the results of the survey showed that “the mean starting dose for morphine was 1.5 mg/day,” while “the lowest starting dose that respondents would consider averaged 1.0 mg/day.” I wonder where did the strange 0.53 come from?One last point that I want to consider is the shortcoming of the review of the literature in another accompanying article.
5
With 16 expert co-authors and 360 referenced articles one would think that no stone has been left unturned. Nevertheless, quite a few misstatements were made in this article.Besides “one case report of the intrathecal infusion of meperidine” mentioned by the authors, two more were reported by us.
6
This article also discussed the use of hydromorphone. To the authors' “hydromorphone's potency appears to be five times that of morphine.” That statement is not supported by the literature showing that the neuroaxial potency of opioids is in direct correlation with their lipid solubility. While epidural morphine is about 10 time more potent than the intravenous kind, for hydromorphone this ratio equals only 2–4.
7
, 8
That leads to an eventual potency of intrathecal hydromorphone being 2–2.5 times that of morphine.6
This is indirectly confirmed as well by the doses of hydromorphone used in the survey.There are really no randomized, controlled trials of long-term neuroaxial infusion of methadone, but there are numerous short-term randomized and even double-blind studies plus retrospective long-term studies (too multiple to reference here). Contrary to the statement of lack of “studies of any kind of the effects of long-term intrathecal methadone infusions” we have published preliminary report on this subject.
9
Nothing is “trivial” about the activity of the l-isomer of methadone at the NMDA-receptor.
5
Actual activity of the l-isomer at the NMDA-receptor is equal to that of the d-isomer in the spinal cord and twice that in the brain.10
Time and space prevent further additions to this list. To sum it up, I enjoyed reviewing the survey results, but was equally disappointed with the accompanying interpretations and predictions. Real science and not personal preferences will produce many of the answers to today's questions.
References
- Current practices in intraspinal therapy B a survey of clinical trends and decision making.J Pain Symptom Manage. 2000; 20: S4-S11
- Clinical guidelines for intraspinal infusion.J Pain Symptom Manage. 2000; 20: S37-S43
- Intraspinal morphine for chronic pain.J Pain Symptom Manage. 1996; 11: 71-80
- Clinical realities and economic considerations.J Pain Symptom Manage. 1997; 14: S14-S26
- Evidence-based review of the literature on intrathecal delivery of pain medication.J Pain Symptom Manage. 2000; 20: S12-S36
- Experience with alternative solutions in intrathecal treatment of chronic nonmalignant pain.Pain Digest. 1999; 9: 299-302
- Epidural patient-controlled analgesia.Anesth Analg. 1992; 75: 245-251
- Intravenous versus epidural administration of hydromorphone.Anesthesiology. 1995; 82: 682-688
Mironer YE. First experience with methadone in intrathecal treatment of chronic nonmalignant pain [abstract]. AAPM, 16th Annual Meeting Abstracts, New Orleans, February 24–27, 2000:33.
- The d- and l-isomers of methadone bind to non-competitive site on the NMDA receptor in rat forebrain and spinal cord.Neurosci Lett. 1997; 223: 5-8
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© 2001 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc.
