Monday, November 27, 2006

Morphine side effects

For those of you who celebrated it, I hope you had a fine Thanksgiving last week.

I'm trying to slowly dig through my backlog of un-blogged articles I had flagged and thought I'd mention an interesting article from the American Journal of Hospice & Palliative Medicine. It's a prospective study of morphine related side effects in (mostly advanced) cancer patients chronically on morphine, who were cared for by the Cleveland Clinic palliative medicine team (median age 64 years, half had ECOG's of 3 or 4 at the start of the study, median daily oral morphine dose was 144mg, most were also receiving non-morphine analgesics/adjuvants). The subjects answered a 32 item questionnaire about their symptoms once weekly for 4 weeks (42 patients answered at least one questionnaire; 30 answered all 4). The prevalence of symptoms at the time of the first interview had some surprises: 90% had dry mouth, 69% sedation, 64% myoclonus, 60% constipation, 48% flushing, 38% urinary hesitancy, 36% dysphoria, 26% nausea, 24% nausea, 21% nightmares. The symptoms that were present for an entire month in those who answered all 4 questionnaires were dry mouth (77%, although only 20% moderate to severe), 23% had constipation (3% mod-severe), 13% sedation (10% mod-severe), 43% myoclonus (0% mod-severe), 23% had urinary hesitancy (3% severe), 10% nausea (0% severe), 10% itching (0% severe).

A couple things about this. First, the authors noted this was the first prospective study of morphine related side effects in this patient population which was initially shocking to me, but on further reflection seemed congruent with the general poor state of symptom research in the cancer patient (outside of Epo/fatigue & 5HT3 inhibitors/chemo-nausea studies). The other point is that these are symptoms of advanced cancer patients who are chronically on morphine, not necessarily symptoms due to morphine (this was a straight-forward descriptive study without a control or comparison group, and clearly much of this symptom burden is from other drugs/processes). That aside, what surprised me (and the authors too) was that certain symtpoms such as dry mouth and myoclonus were pretty common (and 20% reported moderate to severe dry mouth for the entire month!), as were urinary retention symptoms--these were reported much more than I am noticing in my practice. On the other hand nausea was not very common and thankfully persistent moderate to severe nausea was absent from this group. This supports the idea that patients quickly become tolerant to morphine's nauseating effects. On the other hand sedation was quite common and 10% complained of persistent moderate to severe sedation for the entire month. Again, how much of this is due to morphine is unclear, but it is consistent with observations that a certain percentage of patients never get fully tolerant to the CNS toxicity associated with opioids. Personally, this study has raised for me the need to more aggressively look for these maybe-more-frequent-than-previously-suspected side effects such as myoclonus, xerostomia, and urinary hesitancy.

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