Cerebral and lung kinetics of morphine in conscious sheep after short intravenous infusions

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dc.contributor.authorUpton, R.
dc.contributor.authorLudbrook, G.
dc.contributor.authorMartinez, A.
dc.contributor.authorGrant, C.
dc.contributor.authorMilne, R.
dc.date.issued2003
dc.description© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia
dc.description.abstractBackground. The analgesic effects of morphine are delayed relative to its concentration in blood. The rate of equilibration of morphine between blood and brain may contribute to this delay, but the kinetics of this process have not been modelled. This was determined in conscious instrumented sheep. The lung kinetics of morphine were also determined given their importance in defining systemic kinetics after i.v. bolus administration. Methods. Sheep were given short i.v. infusions of morphine (30 mg over 4 min). Cerebral kinetics were inferred from arterio–sagittal sinus concentration gradients and cerebral blood flow, and lung kinetics from the pulmonary artery–aortic gradient and cardiac output. These data were fitted to flow- and membrane-limited models of the kinetics in each organ. Results. Morphine had minimal cardiovascular effects, did not alter cerebral blood flow and caused insignificant respiratory depression. Lung kinetics were best described by a single distribution volume (2036 ml) with a first-order loss (1370 ml min–1), which was attributed to deep distribution. The cerebral kinetics of morphine were characterized by a significant permeability barrier. Permeability across the barrier (7.44 ml min–1) was estimated with good precision, and was approximately one-fifth of the nominal cerebral blood flow. The distribution volume of morphine in the brain was estimated with less precision, but was described by a brain:blood partition coefficient of approximately 1.4. The time required for 50% equilibration between brain and blood concentrations was approximately 10.3 min. Conclusion. The cerebral equilibration of morphine was relatively slow, and was characterized by significant membrane limitation.
dc.description.statementofresponsibilityR. N. Upton, G. L. Ludbrook, A. M. Martinez, C. Grant and R. W. Milne
dc.identifier.citationBritish Journal of Anaesthesia, 2003; 90(6):750-758
dc.identifier.doi10.1093/bja/aeg131
dc.identifier.issn0007-0912
dc.identifier.issn1471-6771
dc.identifier.orcidUpton, R. [0000-0001-9996-4886]
dc.identifier.orcidLudbrook, G. [0000-0001-6925-4277]
dc.identifier.urihttp://hdl.handle.net/2440/5946
dc.language.isoen
dc.publisherProf Sci Publ
dc.source.urihttps://doi.org/10.1093/bja/aeg131
dc.subjectLung
dc.subjectBrain
dc.subjectAnimals
dc.subjectSheep
dc.subjectMorphine
dc.subjectAnalgesics, Opioid
dc.subjectCardiac Output
dc.subjectInfusions, Intravenous
dc.subjectCerebrovascular Circulation
dc.subjectFemale
dc.titleCerebral and lung kinetics of morphine in conscious sheep after short intravenous infusions
dc.typeJournal article
pubs.publication-statusPublished

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