Intrathecal coadministration of bupivacaine diminshes morphine dose progression during long-term intrathecal infusion in cancer patients

Objective: To determine the difference in intrathecal morphine dose progres sion between a continuous intrathecal infusion of a morphine/bupivacaine mi xture and morphine for pain relief in patients with cancer. Design: Patients were treated with intrathecal drugs in a randomized study and followed prospectively until death. Setting: Institute for Anesthesiology, Department of Pain Treatment, Univer sity Hospital Nijmegen, St Radboud, The Netherlands. Patients: Twenty patients with cancer were selected for intrathecal treatme nt because of either side effects or inadequate relief during conventional pain treatment. Interventions: Intrathecal drug infusion rates and medication were adjusted according to pain relief and side effects. Outcome Measures: Progression of intrathecal morphine dose during a phase o f adequate analgesia in both groups following regression analysis and analy sis of possible treatment related side effects. Results: The combination of intrathecal morphine and bupivacaine resulted i n a diminished progression of the intrathecal morphine dose (slope of regre ssion line = 0.0003 vs. 0.005, p = 0.0001) during a phase of stable analges ia in comparison with the morphine group. No serious side effects presented . Conclusion: The diminished intrathecal morphine dose increase in the combin ation group is considered to be due to a synergistic effect of bupivacaine on the intrathecal morphine-induced antinociception. A dose increment durin g long-term intrathecal infusion in cancer patients appears to be related t o both disease progression and tolerance phenomena.