Aim. A double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy of continuous intraoperative infusion of S(+)-ketamine under intravenous anesthesia with target-controlled infusion of remifentanil and propofol for postoperative pain control. Methods. Forty-eight patients undergoing laparoscopic cholecystectomy were assigned to receive continuous S(+)-ketamine infusion at a rate of 0.3 mg·kg−1·h−1 (n = 24, intervention group) or an equivalent volume of saline at the same rate (n = 24, placebo group). The same target-controlled intravenous anesthesia was induced in both groups. Pain was assessed using a 0 to 10 verbal numeric rating scale during the first 12 postoperative hours. Pain scores and morphine consumption were recorded in the postanesthesia care unit (PACU) and at 4 and 12 hours after surgery. Results. Pain scores were lower in the intervention group at all time points. Morphine consumption did not differ significantly between groups during PACU stay, but it was significantly lower in the intervention group at each time point after PACU discharge (P = 0.0061). At 12 hours after surgery, cumulative morphine consumption was also lower in the intervention group (5.200 ± 2.707) than in the placebo group (7.525 ± 1.872). Conclusions. Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control than placebo, reducing morphine requirement. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02421913.

Methadone was more effective than clonidine in the control of postoperative pain in videolaparoscopic surgeries under total intravenous anesthesia with remifentanil; and using clonidine was not better than not using it.

Background and objective: The constant equilibrium between the plasma and effect site (ke0) is used by pharmacokinetic models to calculate a drug concentration in its site of action (Ce). It would be interesting if Ce of propofol was similar at loss and recovery of consciousness. The objective of this study was to evaluate the clinical performance of two different ke0 (fast = 1.21 min-1 , and slow = 0.26 min-1) in relation to Ce during loss and recovery of consciousness using Marsh pharmacokinetic model. Methods: Twenty healthy adult male volunteers participated in this study. In all volunteers propofol was administered as target-controlled infusion, Marsh pharmacokinetic model for fast ke0 and, at a different time, the same pharmacokinetic model with slow ke0 was used. Initially, propofol was infused with a serum target-controlled infusion of 3.0 µg.mL-1. Loss of consciousness and recovery of consciousness were based on response to verbal stimulus. Ce was recorded at the moment of loss and recovery of consciousness. Results: On loss and recovery of consciousness, the Ce for fast ke0 was different (3.64 ± 0.78 and 1.47 ± 0.29 µg.mL-1 , respectively, p < 0.0001), while with slow ke0 the Ce was similar (2.20 ± 0.70 and 2.14 ± 0.43 µg.mL-1 , respectively, p = 0.5425). Conclusions: Clinically, the slow ke0 (0.26 min-1) incorporated in the Marsh pharmacokinetic model showed better performance than the fast ke0 (1.21 min-1), since the calculated concentration of propofol at the effect site on loss and recovery of consciousness was similar.

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.