Cephalad migration of morphine in CSF following lumbar epidural administration in patients with cancer pain

This study examines the cephalad migration of morphine in CSF following lumbar epidural administration in cancer patients with pain. Fourteen cancer patients were administered 10 mg of morphine in 10 ml of normal saline via an epidural catheter inserted in the lumbar region (usually L2.3) and attached to a subcutaneously implanted portal for drug administration. There was a rapid vascular uptake of morphine from the epidural space with a mean (+/- S.D.) peak blood concentration of 110 +/- 32 ng/ml (range 76-182 ng/ml and the mean time associated with this peak blood concentration was 5.1 +/- 2.3 min (range 2-10 min). A cervical CSF sample was obtained from the C7-T1 interspace in each patient at one of the following times from the completion of the epidural morphine dose: 10, 30, 60, 120, 180, 240 or 360 min. There was a delay of at least 60 min before morphine was detected in significant concentrations (approximately 300 ng/ml) in the cervical CSF samples and peak CSF concentrations occurred after approximately 3 h. The results of this study are compatable with the hypothesis that the delayed onset of respiratory depression sometimes observed following epidural morphine in opioid naive patients results from significant amounts of morphine reaching the respiratory centre in the brain-stem as a consequence of passive CSF flow in a rostral direction from the lumbar region.