Stability and tolerability of high concentrations of intrathecal bupivacaine and opioid mixtures in chronic noncancer pain: an open-label pilot study.

OBJECTIVE

To evaluate the stability and tolerability of high concentrations of bupivacaine-opioid solutions when used by intrathecal infusion.

DESIGN

Prospective, open label, pilot cohort study.

SETTING

Outpatients at a University medical center.

PATIENTS

Twelve patients with inadequate pain control already receiving intrathecal opioids and low dose bupivacaine.

INTERVENTIONS

Increasing concentrations and doses of bupivacaine between 1 and 5% were prescribed to be added to a stable daily opioid dose. Drug infusate sampling and analysis using high performance liquid chromatography.

OUTCOME MEASURES

Physical examination, assessment of pain and function between (0-60 days) using a linear visual analog scale, and the Oswestry Disability Index.

RESULTS

Final daily doses of bupivacaine were 4-21.4 mg delivered at measured concentrations of 0.4-3.7%. Two patients experienced reversible motor weakness at 6 mg of bupivacaine/day. The in vitro and in vivo sampling of concentrations up to 3.7% of bupivacaine demonstrated that the stability for bupivacaine with morphine (1.2-3%) or hydromorphone (0.4-1%) was >96% of the manufactured concentration. There were no clinically significant changes in the visual analog pain scale or the Oswestry Disability Index.

CONCLUSIONS

This in vivo study demonstrates excellent stability of high concentrations of intrathecal bupivacaine and opioid mixtures. No nonreversible neurological complications were identified in patients receiving daily doses of bupivacaine up to 21.4 mg. Tolerability was variable because of motor weakness. Given that all intrathecal local anesthetics may be neurotoxic, caution must be exercised if high concentrations and daily doses are to be delivered over prolonged periods.