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Altered brain exposure of morphine in experimental meningitis studied with microdialysis
Author(s) -
Tunblad K.,
Ederoth P.,
Gärdenfors A.,
HammarlundUdenaes M.,
Nordström C.H.
Publication year - 2004
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.0001-5172.2003.0311.x
Subject(s) - medicine , microdialysis , morphine , meningitis , anesthesia , pharmacokinetics , cisterna magna , area under the curve , pharmacology , central nervous system , cerebrospinal fluid , surgery
Background: During pathologic conditions such as meningitis and traumatic brain injury the function of the blood–brain barrier (BBB) is disturbed. In the present study we examined the cerebral pharmacokinetic pattern of morphine in the intact brain and during experimentally induced meningitis using a pig model. Secondly, the use of intracerebral microdialysis as a potential tool for monitoring damage in the BBB by studying the pharmacokinetics of morphine is addressed. Methods: Six pigs were studied under general anaesthesia. One occipital and two frontal microdialysis probes and one pressure transducer were inserted into the brain tissue. Another probe was placed into the jugularis interna. Morphine 1 mg kg −1 was administered as a 10‐min infusion, and morphine concentrations were then measured for 3 h. Meningitis was subsequently induced by injecting lipopoly‐saccharide into the cisterna magna. When meningitis was established, the morphine experiment was repeated. Results: The unbound area under the concentration‐time curve (AUC u ) ratio of morphine in brain to blood was 0.47 (0.19) during the control period, and 0.95 (0.20) ( P < 0.001) during meningitis. The increase in the brain/blood AUC u ratio during meningitis implies decreased active efflux and increased passive diffusion of morphine over the BBB. The half‐life of morphine in brain was longer than in blood during both periods, and was unaffected by meningitis. Conclusion: This study demonstrates that the morphine exposure to the brain is significantly increased during meningitis as compared with the control situation.