Comparative study between fast and slow induction of propofol given by target-controlled infusion: expected propofol concentration at the effect site. Randomized controlled trial

Abstract

Background and objective: Studies have shown that the rate of propofol infusion may influence the predicted propofol concentration at the effect site (Es). The aim of this study was to evaluate the Es predicted by the Marsh pharmacokinetic model (ke0 0.26 min −1 ) in loss of consciousness during fast or slow induction. Method: The study included 28 patients randomly divided into two equal groups. In slow induction group (S), target-controlled infusion (TCI) of propofol with plasma, Marsh pharmacokinetic model (ke0 0.26 min −1 ) with target concentration (Tc) at 2.0-g mL −1 were administered. When the predicted propofol concentration at the effect site (Es) reached half of Es value, Es was increased to previous Es + 1 g mL −1 , successively, until loss of consciousness. In rapid induction group (R), patients were induced with TCI of propofol with plasma (6.0 g mL −1 ) at effect site, and waited until loss of consciousness.Results: In rapid induction group, Tc for loss of consciousness was significantly lower compared to slow induction group (1.67 ± 0.76 and 2.50 ± 0.56 g mL −1 , respectively, p = 0.004). Conclusion: The predicted propofol concentration at the effect site for loss of consciousness is different for rapid induction and slow induction, even with the same pharmacokinetic model of propofol and the same balance constant between plasma and effect site.Estudo comparativo entre indução rápida e lenta de propofol em infusão alvo-controlada: concentração de propofol prevista no local de ação. Ensaio clínico aleatório Resumo Justificativa e objetivo: Estudos mostraram que a taxa de infusão de propofol pode influenciar na concentração prevista de propofol no local de ação (Ce). O objetivo deste estudo foi avaliar a Ce prevista pelo modelo farmacocinético de Marsh (ke0 0,26 min −1 ) na perda da consciência durante indução rápida ou lenta. Método: Participaram deste estudo 28 pacientes, divididos aleatoriamente em dois grupos iguais. No grupo indução lenta (L), foram induzidos com propofol em infusão alvo-controlada (IAC) plasmática, modelo farmacocinético de Marsh (ke0 0,26 min −1 ), com concentração alvo (Ca) em 2,0 g.ml −1 . Quando a concentração de propofol prevista no local de ação (Ce) atingia metade do valor da Ca, aumentava-se a Ca para Ca anterior + 1 g.ml −1 . Assim sucessivamente até o momento da perda da consciência do paciente. No grupo indução rápida (R), os pacientes foram induzidos com propofol em IAC plasmática com Ca em 6,0 g.ml −1 e aguardava-se a perda da consciência do paciente. Resultados: No grupo indução rápida, a Ce na perda da consciência foi significativamente mais baixa em relação ao grupo de indução lenta (1,67 ± 0,76 e 2,50 ± 0,56 g.ml −1 , respectivamente, p = 0,004). Conclusão: A concentração prevista de propofol no local de ação durante a perda da consciência é diferente numa indução rápida e numa indução lenta, até com o mesmo modelo farmacocinético de propofol e a mesma constante de equilíbrio entre o plasma e o local de ação.

The influence of target concentration, equilibration rate constant (ke0) and pharmacokinetic model on the initial propofol dose delivered in effect-site target-controlled infusion

“…They found that, with fast k e0 s of 0.45 min À1 with the Schnider model and 1.21 min À1 with the Marsh model, Ce CALC values after a rapid infusion were greater than those observed after a slow infusion, whereas the opposite was seen with the slower k e0 of 0.26 min À1 using the original Marsh model. Similar results were obtained in another study with the Marsh model and a k e0 of 0.26 min À1 [19] and a marked difference in predicted effect site concentrations at loss of consciousness was seen with the Marsh model and k e0 s of 0.26 min À1 or 1.2 min À1 [20]. The results of our simulations of the two infusion rates used (Table 4) replicate the results with the model/k e0 combinations studied in the original study of Sepulveda.…”

A robust model predictive control framework for the regulation of anesthesia process with Propofol

“…Target controlled infusion systems, usually make use of syringe pumps with maximum infusion rates between 10 and 160 mg/kg/h. 60 In our simulations, we considered 85 mg/kg/h as the upper bound on the infusion rate, which is converted to u max =200 mg/min (= 3.3 mg/sec), considering a heavy patient weighted 140 kg. It should be noted, however, that the actual infusion rates computed by the controllers are much lower than this bound, which agrees with other observations reported in the literature.…”

AnesthesiaGUIDE: a MATLAB tool to control the anesthesia

“…Because of the negligible volume of the effect-site abstract compartment, the constants k 1e and k e0 are equal [9,14]. The PK parameters depend on the patient's characteristics only such as age, gender, height, and weight [9,10,14,15].…”

“…9 and considering the adjustment mechanism from Eq. 6, the variation of the controller's parameters k p and k i is [15]: where p = d∕dt.…”