Long-term intrathecal morphine and bupivacaine in patients with refractory cancer pain. Results from a morphine:bupivacaine dose regimen of 0.5:4.75 mg/ml

Abstract

Background: There are no clinical data regarding the ratios and concentrations in which morphine and bupivacaine should be combined, when given intrathecally, to improve analgesia while decreasing adverse effects. This study was undertaken to test the clinical efficacy of a constant infusion of 0.5 mg/ml morphine plus 4.75 mg/ml bupivacaine (morphine: bupivacaine approximately 1:10), given through open intrathecal catheters.

Methods: In 53 patients, the clinical efficacy was estimated from: pain relief (visual analog scale scores 0-10); daily dosages (intrathecal and total opioid and intrathecal bupivacaine); scores (0-5) of nonopioid analgesic and sedative consumption, gait and daily activity, and amount of sleep; and rates of adverse effects.

Results: During the intrathecal period (7-334, median 29 days), all 53 patients obtained acceptable pain relief (visual analog scale scores 0-2 vs. 6-10 in the pre-intrathecal stage). The total opioid daily consumption decreased (median 10 vs. 120 mg), the sleep was about two times longer, the nonopioid analgesic and sedative consumption about two times lower, and the gait ability pattern was unchanged. The daily dose of intrathecal morphine (median 6 mg) and the daily intrathecal volumes (median 10 ml) were low, whereas the daily dose of intrathecal bupivacaine was relatively high (median 50 mg). Side effects potentially related to intrathecal morphine (seizures, cerebral, and spinal clonus) were not recorded. Side effects attributable to intrathecal bupivacaine (in patients not having these complications before the intrathecal treatment) occurred in the forms of late urinary retention (9 of 27), paresthesias (11 of 27), paresis/gait impairment (9 of 27), and occasional episodes of orthostatic arterial hypotension (1 of 53 patients).

Conclusions: A constant intrathecal infusion with a morphine:bupivacaine ratio of approximately 1:10 and concentrations of morphine of 0.5 mg/ml and bupivacaine of 4.75 mg/ml may significantly improve the relief of refractory cancer pain with a certain risk of adverse effects (which should be balanced against pain by the patient) from the relatively high intrathecal bupivacaine doses and concentration.