Department of Anesthesiology, Vita-Salute San Raffaele University School of Medicine-IRCCS San Raffaele, Milan, Italy.
Clin Pharmacokinet. 2010;49(2):131-9. doi: 10.2165/11317690-000000000-00000.
In a previous article, we showed that the pharmacokinetic set of remifentanil used for target-controlled infusion (TCI) might be biased in obese patients because it incorporates flawed equations for the calculation of lean body mass (LBM), which is a covariate of several pharmacokinetic parameters in this set. The objectives of this study were to determine the predictive performance of the original pharmacokinetic set, which incorporates the James equation for LBM calculation, and to determine the predictive performance of the pharmacokinetic set when a new method to calculate LBM was used (the Janmahasatian equations).
This was an observational study with intraoperative observations and no follow-up. Fifteen morbidly obese inpatients scheduled for bariatric surgery were included in the study. The intervention included manually controlled continuous infusion of remifentanil during the surgery and analysis of arterial blood samples to determine the arterial remifentanil concentration, to be compared with concentrations predicted by either the unadjusted or the adjusted pharmacokinetic set. The statistical analysis included parametric and non-parametric tests on continuous variables and determination of the median performance error (MDPE), median absolute performance error (MDAPE), divergence and wobble.
The median values (interquartile ranges) of the MDPE, MDAPE, divergence and wobble for the James equations during maintenance were -53.4% (-58.7% to -49.2%), 53.4% (49.0-58.7%), 3.3% (2.9-4.7%) and 1.4% h(-1) (1.1-2.5% h(-1)), respectively. The respective values for the Janmahasatian equations were -18.9% (-24.2% to -10.4%), 20.5% (13.3-24.8%), 2.6% (-0.7% to 4.5%) and 1.9% h(-1) (1.4-3.0% h(-1)). The performance (in terms of the MDPE and MDAPE) of the corrected pharmacokinetic set was better than that of the uncorrected one. The predictive performance of the original pharmacokinetic set is not clinically acceptable. Use of a corrected LBM value in morbidly obese patients corrects this pharmacokinetic set and allows its use in obese patients. The 'fictitious height' can be a valid alternative for use of TCI infusion of remifentanil in morbidly obese patients until commercially available infusion pumps and research software are updated and new LBM equations are implemented in their algorithms.
在之前的一篇文章中，我们发现用于靶控输注（TCI）的瑞芬太尼药代动力学集可能存在偏倚，因为它包含用于计算瘦体重（LBM）的有缺陷的方程，而 LBM 是该药代动力学集中几个药代动力学参数的协变量。本研究的目的是确定包含 LBM 计算的 James 方程的原始药代动力学集的预测性能，并确定使用新的 LBM 计算方法（Janmahasatian 方程）时药代动力学集的预测性能。
这是一项具有术中观察且无随访的观察性研究。纳入 15 名拟行减重手术的病态肥胖住院患者。干预措施包括手术期间手动控制瑞芬太尼持续输注，并分析动脉血样以确定动脉瑞芬太尼浓度，与未经调整或调整后的药代动力学集预测的浓度进行比较。统计分析包括对连续变量进行参数和非参数检验，并确定中位性能误差（MDPE）、中位绝对性能误差（MDAPE）、发散和摆动。
维持期 James 方程的 MDPE、MDAPE、发散和摆动的中位数（四分位距）分别为-53.4%（-58.7%至-49.2%）、53.4%（49.0%至 58.7%）、3.3%（2.9%至 4.7%）和 1.4% h（1.1%至 2.5% h）。Janmahasatian 方程的相应值分别为-18.9%（-24.2%至-10.4%）、20.5%（13.3%至 24.8%）、2.6%（-0.7%至 4.5%）和 1.9% h（1.4%至 3.0% h）。校正药代动力学集的性能（以 MDPE 和 MDAPE 表示）优于未校正药代动力学集。原始药代动力学集的预测性能不能临床接受。在病态肥胖患者中使用校正后的 LBM 值可纠正该药代动力学集，并允许在肥胖患者中使用。“虚构身高”可以是在商业上可用的输注泵和研究软件更新之前，以及在其算法中实施新的 LBM 方程之前，在病态肥胖患者中使用瑞芬太尼 TCI 输注的有效替代方法。
