d

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Introduction Ropivacaine is a local anaesthetic that has similar chemical properties as Bupivacaine that was noted to be associated with incidence of cardiac arrest. Knudsen et al. (1997) states that ropivacaine was tolerated at a higher dose and unbound plasma concentration before CNS symptoms such as depression of conduction and diastolic function developed as compared to bupivacaine. Groban et al. (2001) suggested that concentration associated with cardiovascular collapse were significantly higher than those required for bupivacaine toxicity and this conclusion is made based on a study in anaesthetized dog. Zaric et al. (1996) A similar spread of sensory block but a reduced intensity of motor block and quicker recovery after ropivacaine as compared to bupivacaine in adult volunteers. Points mentioned could offer benefit of ropivacaine in paediatric anaesthesia. Aim of this study was to characterize ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) pharmacokinetics and factors affecting them in paediatric anaesthesia. Six ropivacaine studies were sponsored by AstraZeneca to further establish the effective and safe dose recommendation. Information that is known beforehand of the study is the unbound plasma concentration is related to systemic toxicity of local anaesthetic. In addition, Ropivacaine is metabolised to 3-hydroxyprovacaine (37%) and PPX (3%) and 1% excreted unchanged in the urine. Halldin (2010) When compared to unbound ropivacaine, unbound PPX needs 12 fold higher concentration to produce CNS toxicity in rats. Ropivacaine is 94% bound to an acute phase protein named AAG that increase after operation. Methods 193 eligible patients were pooled from three studies on a single caudal block , two studies on ... ... middle of paper ... ...l PPX and PPX in urine. However weakness of this paper would be problems with sampling could occur in paediatric studies, the residual variability (composite of model misspecification) estimate is probably a rather inflated prediction of intra patient variability. Moreover these studies might involve in ethical issues since study is done on neonates, infants and children. Conclusion MHRA (2011) states that even though liver function is still immature in paediatric population, the plasma concentration after administration of recommended dose is well below the threshold for systemic toxicity in all age group. The results from the population pharmacokinetic analysis support the approved dose recommendations of ropivacaine for single caudal block and continuos72 h epidural infusion in neonates, infants and up to 12 yr. children and it is systemically safe for them.

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