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 progression between a continuous intrathecal infusion of a morphine/bupivacaine mixture 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, University Hospital Nijmegen, St Radboud, The Netherlands. PATIENTS: Twenty patients with cancer were selected for intrathecal treatment 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 of adequate analgesia in both groups following regression analysis and analysis of possible treatment related side effects. RESULTS: The combination of intrathecal morphine and bupivacaine resulted in a diminished progression of the intrathecal morphine dose (slope of regression line = 0.0003 vs. 0.005, p = 0.0001) during a phase of stable analgesia in comparison with the morphine group. No serious side effects presented. CONCLUSION: The diminished intrathecal morphine dose increase in the combination group is considered to be due to a synergistic effect of bupivacaine on the intrathecal morphine-induced antinociception. A dose increment during long-term intrathecal infusion in cancer patients appears to be related to both disease progression and tolerance phenomena.