Ropivacaine plasma concentrations during 120-hour epidural infusion

Abstract

The pharmacokinetics of ropivacaine were evaluated during long-term continuous epidural analgesia (CEDA) for about 120 h. The total and free plasma concentrations of ropivacaine and the alpha1-acid glycoprotein (AAG) concentration were measured in 12 patients after total knee arthroplasty. The infusion rate was adjusted according to patients' analgesic needs or side effects. The mean (SD) rate of infusion of ropivacaine (Naropin 2 mg ml(-1)) was 14.6 (3.2) mg h(-1) on the day of surgery and was increased after surgery to 15.4 (4.4) mg h(-1) on days 1-5. This was equivalent to an absolute dose of 1786 (553) mg of ropivacaine over the entire infusion period. After an initial increase, the mean free ropivacaine plasma concentration nearly plateaued and than decreased slightly after approximately 70 h. The individual peak free plasma concentration was 0.096 (0.034) microg ml(-1). The highest individual free plasma concentration was 0.16 microg ml(-1). The individual peak total plasma concentration, 4.1 (1.2) microg ml(-1), was achieved after 67.7 (16.5) h, although the AAG concentration increased throughout the observation period. Our data support the safety and efficacy of long-term ropivacaine CEDA.

Ropivacaine, Interleukin-6 and Tumor Necrosis Factor Alpha Plasma Levels during Intermittent Epidural and Continuous Wound Infusion of Ropivacaine for Analgesia after Hysterectomy or Myomectomy: An Observational Study

“…However, with continuous EP infusion of the drug total mean plasma concentrations were found to increase continuously [7,9,10] or to plateau for a certain time within the dosage interval and then to increase again [6] , in contrast to the relatively stable mean concentrations found in the present study. Also, when total ropivacaine doses administered were compared, higher mean total ropivacaine plasma concentrations at the end of infusion were achieved after continuous EP infusion according to previous studies [6,7,8,10] than after intermittent infusion in our patients, and these higher concentrations were reported to be mainly within or below the range reported to be safe in adults (1.0-3.0 μg/ml) [10] .…”

“…The concentration-time profile after EP administration of ropivacaine at fixed time inter-vals or continuous subcutaneous (SC) infusion have not been fully evaluated. Knowledge of ropivacaine systemic levels is very important in order to ensure a high therapeutic ratio [8][9][10] . Furthermore, the role of ropivacaine on the inflammatory response following surgical trauma is still unclear.…”

Flip-flop kinetics of ropivacaine during continuous epidural infusion influences its accumulation rate

“…Ropivacaine total clearance depends on liver enzyme activity and on the [25,26] Therefore, changes in the fraction bound to proteins (alpha 1 -acid glycoprotein) may affect the drug's total clearance but might also alter the relationship between total drug concentration and possible toxic effects. [26,27,28] We did not measure alpha 1 acid glycoprotein concentrations and to some extent this is a limitation of our study. However, the postoperative course of the patients included in our trial did not exhibit any pathophysiological changes other than those expected in patients undergoing this type of surgical procedure.…”

Infiltration continue prépéritonéale d'anesthésiques locaux pour l'analgésie après laparotomie. Données préliminaires

“…Les doses que nous avons utilisées sont plutôt plus élevées que ce qui est fait en général, mais nous avons considéré qu'un volume minimal horaire de 10 ml devait être perfusé pour obtenir une efficacité. Dans cette série limitée, nous n'avons observé aucun accident de toxicité et les dosages sanguins pratiqués à j1 et j2 chez des patients qui avaient reçu 600 mg/24 heures pendant 48 heures, ont montré un taux de ropivacaïne totale aux alentour de 2 µg/ml, c'est-à-dire correspondant à la limite supé-rieure du seuil de toxicité observé chez le volontaire sain après injection intraveineuse directe [29], mais en dessous du seuil de toxicité chez le patient opéré, généralement considéré aux alentours de 4 µg/ml [30,31]. Contrairement à ce qui est observé chez le volontaire sain, la réaction inflammatoire à la chirurgie augmente les protéines porteuses sériques et augmente le seuil toxique de la molécule en réduisant sa fraction libre [31].…”