Treatment with midazolam for nocturnal sedation of terminal cancer patients in a hospice setting

ABSTRACT

Sleep disturbance often leads to physical and psychological distress and contributes to poor quality of life in terminal cancer patients. Midazolam is administered by continuous intravenous infusion in many Japanese palliative care units for the purpose of nocturnal sedation when patients cannot take oral medications or do not sufficiently respond to oral or per-rectal medication. However, there is insufficient data to assess optimal doses and other parameters for administration. In addition, the possibility of tolerance to midazolam reported in several studies is a further limitation. The present study retrospectively surveyed inpatient hospice experience in 19 patients who were prescribed midazolam in an attempt to induce nocturnal sedation. The midazolam infusion rate used for the longest period each day to maintain appropriate sleep without oversadation and with clear arousal on the following morning was defined as the "maintenance dose". Midazolam maintenance doses of 2 patients were greatly increased during their treatment period. Statistical analysis was then conducted in the other 17 patients using NONMEM software to analyze time-dependent changes in maintenance doses and possible associated factors. However, in the other 17 patients no significant time-dependent changes were observed during midazolam treatment. It would suggest that torerance may not be induced by intermittent administration of midazolam. Midazolam maintenance doses were significantly greater in patients treated with haloperidol.