Abstract
Only in recent years have there been systematic evaluations of the concentration-response pharmacodynamics for epidural and intrathecal local anaesthetic agents. Whilst these have been determined for inhalation and intravenous anaesthetic agents using the clinical models of minimum alveolar concentration (MAC) and minimum infusion rate (MIR) respectively, the same standards had not been applied to regional analgesic techniques. The majority of research into local anaesthetic dose requirements and the effect on them of other analgesics such as opioids, have generally been in the style of recipe designs with comparisons of fixed combinations of drugs. It is now clear that many of these studies have involved concentrations above the 95th centile for efficacy (EC95), at the top of the concentration-response curve where subtle differences will be missed or apparently similar efficacies misinterpreted. Study designs involving dose-varying regimens such as predetermined multiple dose testing, isobolographic methods and up-down sequential allocation are more informative than fixed recipe designs and allow quantification of effect.
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Columb, M.O. (2000). Clinical trials: up-down sequential allocation. In: Reynolds, F. (eds) Regional Analgesia in Obstetrics. Springer, London. https://doi.org/10.1007/978-1-4471-0435-3_15
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DOI: https://doi.org/10.1007/978-1-4471-0435-3_15
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