Initial Intrathecal Dose Titration and Predictors of Early Dose Escalation in Patients With Cancer Using a 100:1 Oral to Intrathecal Morphine Conversion Ratio

Abstract

Pain is common in patients with advanced cancer, and intrathecal drug delivery (IDD) has been successfully used for recalcitrant pain. We report on our experience using a 100:1 oral-to-intrathecal morphine conversion ratio for initial dosing and factors predictive of early dose escalation. Retrospective review of an intrathecal drug delivery system (IDDS) data base at the Huntsman Cancer Institute-University of Utah in cancer patients initiated on IDD with morphine or hydromorphone. Demographic characteristics, preoperative opioid use, and initial and hospital discharge IDD settings were collected. A total of 275 patients were identified between June 2014 and May 2020. The median oral-to-intrathecal morphine conversion ratio for initial IDD dosing was 105.5:1 (interquartile range [IQR] 90-120, range 75-150). No serious adverse effects including respiratory depression or sedation were noted and the median length of stay was one night (IQR 1-2, range 1-22). Ninety-six percent of patients discontinued opioids immediately following IDDS implant. Initial IDD dosing was adequate in 42% of patients. Dose reduction was required in 4% prior to discharge due to nausea, patient request, weakness, pruritus, or urinary retention. Dose escalation was required in 54%, with a median dose increase of 66.7% (IQR 33-150%, range 5-1150%). Patients in the highest quartile of dose escalation, ≥70% between IDD initiation and discharge, had associations with younger age, higher preoperative opioid use, and inpatient status. No significant associations were found in patients who required dose reduction as compared to other patients. An oral-to-intrathecal morphine conversion ratio of approximately 100:1 for initiation of IDD in patients with cancer pain was safe and well tolerated and may facilitate rapid elimination of systemic opioids. Dose reduction was rare, while a majority of patients required further dose escalation prior to discharge.