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J Palliat Med. 2004 Aug;7(4):545-50.

Hydromorphone neuroexcitation.

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Community Hospice, Inc., University of California, Davis, Stanislaus Family Practice Residency, Modesto, CA 95350-5443, USA.


Continuous parenteral hydromorphone is used to treat pain in palliative care. Case reports have suggested that neuroexcitatory symptoms, such as agitation, myoclonic activity, and even seizures may occur during administration. However, little information exists on the incidence of these side effects or their relationship to the dose or duration of parenteral hydromorphone. A retrospective chart review was performed on 48 terminally ill hospice patients who received continuous parenteral hydromorphone for pain control. Chart reviews were conducted searching for three neuroexcitatory symptoms: agitation, myoclonus, and seizures; the incidence and relationship of these symptoms were statistically compared to the maximal dose and number of days on continuous parenteral hydromorphone. We found that agitation, myoclonus, and seizures were not associated with the patients gender, age, or diagnosis but found that agitation was associated (p < 0.01) in patients with known metastatic disease. Agitation, myoclonus, and seizures were independently associated with the maximal dose (p < 0.05, p < 0.001, and p < 0.05) and with the duration (p < 0.01, p < 0.05, and p < 0.01) of continuous parenteral hydromorphone A possible mechanism for these findings is hydromorphone-3-glucoronide, a metabolic product of hydromorphone, which has been implicated in neuroexcitatory symptoms in laboratory investigations.

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