British journal of anaesthesia
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The concept of 'personalized medicine' in which a knowledge of genetic factors guides prescribing tailored to the individual is popularly considered to be an inevitable consequence of completion of the International Human Genome Project. We should not forget, however, that a personal or family history of one of several uncommon pharmacogenetic conditions has influenced the use of the implicated drug(s) during anaesthesia for the past 50 yr. ⋯ The situation is different for most currently available drugs, including those used by anaesthetists, where genetic variability to drug response is presumed to be the result of a complex interaction of multiple factors. We review the nature and investigation of pharmacogenomic variability and contrast the progress made with research into opioid variability with the more limited literature concerning i.v. and inhalation anaesthetics.
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The recently introduced open-target-controlled infusion (TCI) systems can be programmed with any pharmacokinetic model, and allow either plasma- or effect-site targeting. With effect-site targeting the goal is to achieve a user-defined target effect-site concentration as rapidly as possible, by manipulating the plasma concentration around the target. Currently systems are pre-programmed with the Marsh and Schnider pharmacokinetic models for propofol. ⋯ The Schnider model should thus always be used in effect-site targeting mode, in which larger initial doses are administered, albeit still smaller than for the Marsh model. Users of the Schnider model should be aware that in the morbidly obese the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Finally, the two currently available open TCI systems implement different methods of effect-site targeting for the Schnider model, and in a small subset of patients the induction doses generated by the two methods can differ significantly.
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Immunotherapy in the critically ill is an appealing notion because of the apparent abnormal immune and inflammatory responses seen in so many patients. The administration of a medication that could alter immune responses and decrease mortality in patients with sepsis could represent a 'magic bullet'. ⋯ However, in some respects, research along these lines has been unsuccessful or disappointing at best. The current state of knowledge is summarized with particular reference to sepsis and the acute respiratory distress syndrome.
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The use of anticholinesterases to reverse residual neuromuscular block is efficacious only if recovery is already established. It was originally advised that at least the second twitch (T2) of the train-of-four response should be detectable before neostigmine is administered. Even in these circumstances, the full effect of anticholinesterases takes up to 10 min to achieve. ⋯ Sugammadex is ineffective in antagonizing the benzylisoquinolinium NMBAs. The dose should be adjusted according to the degree of residual block: sugammadex 16 mg kg(-1) for immediate reversal; 4-8 mg kg(-1) for antagonizing profound block (post-tetanic count 1-2); and 2 mg kg(-1) to antagonize moderate block (when T2 is detectable). As yet, the extent of any side-effects that may occur with this new antagonist is not fully known, although rarely adverse cardiovascular effects (hypotension, hypertension, prolonged QT interval) have already been reported.