Biomaterial Database

CSF and plasma morphine concentrations in cancer patients during chronic epidural morphine therapy and its relation to pain relief. 1987

Håkan Samuelsson, and Gunnar Nordberg, and Thomas Hedner, and Jan Lindqvist

Department of Anesthesia, Central Hospital, S-501 15 BoråsSweden Department of Anesthesia, Sahlgren's University Hospital, S-413 45 GöteborgSweden Department of Clinical Pharmacology, Sahlgren's University Hospital, S-413 45 GöteborgSweden.

Seventeen patients with advanced cancer pain, treated with chronic epidural morphine, were studied. Minimum plasma and CSF morphine concentrations (CSSmin) were determined at pharmacokinetic steady state. A linear relationship was found between epidural morphine dose and concentrations obtained in plasma (r = 0.92) as well as CSF (r = 0.90). The line for best fit was much steeper for CSF than for plasma. The CSF/plasma concentration gradient of morphine at CSSmin was 132 +/- 31 (mean +/- S.E.M.). Large interindividual variations of morphine concentrations in CSF were found. It is suggested that the variations are due to substantial differences in transdural morphine diffusion between individuals. No correlation was found between pain relief, evaluated with a visual analog scale, and CSF morphine concentrations at pharmacokinetic steady state, when calculated in 9 patients. Mean duration of treatment was 104 days (range 14-366) and the daily dose was increased from 18 +/- 2 to 87 +/- 31 mg/day (mean +/- S.E.M.). A total of 39 epidural catheters were inserted in 14 patients. The catheters were patent for 2-223 days with a mean of 38 days. When re-examined later during treatment, 2 out of 8 patients demonstrated decreased CSF morphine concentrations in spite of increased doses given. One patient with extremely high dose demand is reported on separately and data supporting the concept of a combined spinal and systemic brain morphine effect in such cases are presented. Side effects were not a major problem but the possibility of infectious complications should be considered during chronic epidural morphine therapy.

UI	MeSH Term	Description	Entries
D007268	Injections, Epidural	The injection of drugs, most often analgesics, into the spinal canal without puncturing the dura mater.	Epidural Injections,Extradural Injections,Peridural Injections,Injections, Extradural,Injections, Peridural,Epidural Injection,Extradural Injection,Injection, Epidural,Injection, Extradural,Injection, Peridural,Peridural Injection
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009020	Morphine	The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.	Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D010148	Pain, Intractable	Persistent pain that is refractory to some or all forms of treatment.	Refractory Pain,Intractable Pain,Intractable Pains,Pain, Refractory,Pains, Intractable,Pains, Refractory,Refractory Pains
D004058	Diffusion	The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT.	Diffusions
D004361	Drug Tolerance	Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.	Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man