Characteristics of Distribution of Morphine and Metabolites in Cerebrospinal Fluid and Plasma With Chronic Intrathecal Morphine Infusion in Humans

Abstract

Background-Despite widespread use of chronic intrathecal (IT) infusions of morphine, there is little systematic human work evaluating the steady-state morphine concentrations or cerebrospinal (CSF) chemistry after long-term IT morphine delivery. We sought to address these issues in patients receiving chronic IT morphine infusion.

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

“…Many animal studies have shown a rostral-caudal gradient from the catheter tip (20,81,91), and the recent work of Wallace and Yaksh confirms this in a human study (170). In patients receiving IT morphine, CSF morphine concentrations decreased by distance from the catheter tip with a gradient that correlated with the infusion dose, and over a range of infusion rates of 0.1-1.0 mL/day.…”

“…Many factors have been proposed and evaluated as contributing to differential drug distribution in the CSF. For instance, anatomic variation, postural changes, drug solution density, binding characteristics of drugs at the dorsal horn, CSF volume and variations in CSF pulsatile flow with heart rate, stroke volume, and respiratory cycle have been examined (20,156,170,281,283). Additionally, it has been suggested that the rate of dispersion in the CSF cannot be explained by diffusion alone (156,283).…”

“…With regard to rostral-caudal spread of hydrophilic medications such as morphine, it has been demonstrated that a rather steep concentration gradient exists as samples are taken at points further removed from the catheter tip. The authors of this finding suggested that drug dilution over distance and drug concentration at the site of action may be important in providing analgesic efficacy (170). Given these data, simplistic views of CSF dynamics do not provide insight into the possible clinical implications of decisions made surrounding drug-infusion rate and drug dispersal within the CSF.…”

Primary Hydromorphone-Related Intrathecal Catheter Tip Granulomas: Is There a Role for Dose and Concentration?

“…Since North et al reported the first granuloma formation in 1991 , there have been many articles describing inflammatory mass lesions at the tips of intrathecal catheters, mostly in the form of case reports or case series . Intrathecal catheter tip granulomas have been reported to occur at a rate of 0.5–3% of cases, though these numbers are believed to be conservative estimates of the actual prevalence .…”