It is generally believed that IV "morphine" administration in dialysis patients is acceptable as
opposed to other analgesics especially "demerol" (meperidine) or its European counterpart
"biperidine" which are apparently stricly contraindicated in this population of patients. In my
experience, some ESRD patients given morphine sulfate intravenously (10 - 15 mg over 24 hrs) for
pain control, develop respiratory depression along with mental obtundation, sometimes requiring
eventual intubation and ventilation for a brief period of time, followed by a gradual recovery.
In some of these cases, although morphine overdose is suspected, naloxone (narcan) administration
is not apprently effective . Is IV morphine realtively or completely contra-indicated in ESRD
patients? Are there any published or conventional guidelines for morphine dose adjustment? Can
naloxone contribute to worsening of morphine sulfate overdose symptoms? Are there safer but
equally efficient options for pain contol e.g. post-operatively in ESRD patients?
Kamyar Kalantar-Zadeh, MD
UCSF Division of Nephrology
Answer by George R. Aronoff, M.D., FACP and Michael E. Brier, Ph.D. (University of Louisville Kidney Disease Program)<
The major pathway for morphine elimination is hepatic conjugation with glucuronic acid. Little
morphine is excreted unchanged in the urine. Consequently, renal insufficiency does not effect the
elimination rate of morphine. However, the kidneys mostly excrete the polar glucuronide metabolites
of morphine and these may substantially accumulate in patients with renal failure. The most active
of the
morphine metabolites is morphine-6-glucuronide, and may even be more potent than morphine (1). The
elimination half-life of the polar metabolites of morphine may be increased 10-fold in patients with
renal failure from a mean of four hours in patients with normal renal function to more than 40
hours (2).
Because of the accumulation of active morphine metabolites, increased sedation has been reported in
renal failure patients receiving morphine (3). This effect might be particularly expected after
prolonged treatment with repeated doses. Although the extent of extra corporeal removal of morphine
and its glucuronide metabolites by hemodialysis, peritoneal dialysis and continuous filtration is
not known, the compounds are relatively small molecules and are not known to be highly protein
bound. Consequently, we might expect some elimination by these techniques.
Our current recommendations for morphine are to reduce the dose to about 75% of the usual dose in
patients with creatinine clearances between 10 and 50 mL/min and to about 50% of the usual dose in
patients with creatinine clearances less than 10 mL/min (4). Morphine should be used with caution,
particularly when given in repeated doses.
We suggest that meperidine be avoided in patients with renal failure because of the potential
accumulation of nor-meperidine. Nor-meperidine is a polar metabolite, normally excreted by the
kidneys, which has been reported to lower the seizure threshold.
George R. Aronoff, M.D., FACP
Michael E. Brier, Ph.D.
University of Louisville Kidney Disease Program
References
1. The Pharmacological Basis of Therapeutics. Gilman, et al., eds. 1990. Pergamon Press. New
York
2. Drug Dosage in Renal Insufficiency. Gunter Seyfert, ed. 1991. Kluwer Academic Publishers.
Norwell, MA.