Intrathecal (IT) Morphine and Ziconotide combined with Levobupivacaine: a winning triangle?

This prospective trial investigates the effects of intrathecal Ziconotide combined with Morphine and Levobupivacaine in malignant pain. Methods Adult patients with malignant pain refractory to high doses of oral opioids were enrolled. Mean VASPI scores and mean doses of 3 drugs were recorded at 48 hours and every week until 2 months of treatment. Adverse events were also recorded. Results 56 patients were recruited (age 63 + 12, F/M 18/38). 16 patients had lung, 14 had gastro-intestinal, and 9 had urologic cancer. At T0 the mean VASPI score was 88±6, and the mean doses of Morphine, Ziconotide and Levobupicaine were 0.8±0.3 mg/day, 1.6±0.8 mcg/day and 2.9±0.9 mg/day, respectively. At 48 hours the mean VASPI score was significantly reduced to 48.5±17 (p<0.05). This significant re- duction persisted over 2 months of follow-up. At 1 month, mean doses of Morphine, Ziconotide and Levobupicaine were 1.4±0.9 mg/day, 2.5±1.3 mcg/day and 3.9±2.1 mg/day, respectively. At 2 month, mean doses of Morphine, Ziconotide and Levobupicaine were 2.0±1.2 mg/day, 2.8±1.1 mcg/day and 3.8±2.0 mg/day, respectively. The mean VASPI score at that time was 43.7±21. Adverse events were con- fusion (9%), dizziness (10%), nausea (10%), vomiting (5%), urinary retention (16%), hallucination (3%). There was one infection related to the infusion system, and it occurred in a HIV patient. Conclusions The present trial suggests that the combination of IT Morphine and Ziconotide plus Levobupicaine could be a rationale choice to achieve a rapid control of refractory malignant pain: the decrease of VASPI score is significant as soon as 2 days and persists during the 2 months of study. The addition of Levobupivacaine seems to potentiate the effects of the other 2 drugs, allowing a reduction in cumulative doses of both Morphine and Ziconotide over time, compared to those reported in similar populations (1,2). The low doses of the 3 drugs could also explain the reduced incidence of adverse events in these difficult to treat patients, compared with recent reports (2,3). However, uri- nary retention can be emphasized by the addiction of Levobupivacaine in patients with pelvic cancer. Other trials are needed to confirm the safe, rapid and effective synergistic action of IT combination of Morphine, Ziconotide and Levobupivacaine.