Pharmacokinetics and Analgesic Effect of Ropivacaine during Continuous Epidural Infusion for Postoperative Pain Relief

Erichsen, C.J.; Sjövall, Jan; Kehlet, Henrik; Hedlund, Cecilia; Arvidsson, Torbjörn

doi:10.1097/00000542-199604000-00010

Cited by 77 publications

(33 citation statements)

References 14 publications

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“…Threshold levels for central hours and the end of the infusion suggests that a steady state was not reached after 48 hours. Although only an estimate of the actual value, these observations strongly contrast with previous studies that reported stable unbound concentrations during continuous infusion (11,14,20). A possible explanation is variability in the intrinsic metabolic clearance of ropivacaine (CL int ), assuming that the hepatic extraction ratio of ropivacaine is low and the intrinsic clearance corresponds to the unbound clearance (CL u ).…”

Section: Discussioncontrasting

confidence: 62%

Continuous Extrapleural Infusion of Ropivacaine 0.2% After Cardiovascular Surgery Via the Lateral Thoracotomy Approach

Maurer

Blumenthal

Rentsch

et al. 2008

Journal of Cardiothoracic and Vascular Anesthesia

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Continuous extrapleural infusion of ropivacaine 0.2% after cardiovascular surgery via the lateral thoracotomy approach Abstract OBJECTIVE: The pharmacokinetics of ropivacaine 0.2% were evaluated during a 48-hour continuous extrapleural infusion with 2 different infusion rates in patients undergoing cardiovascular surgery. The hypotheses that no toxic plasma concentrations of ropivacaine would be reached and that proportionality exists among plasma concentrations and dosage used were tested. DESIGN: A prospective, randomized, nonblinded study. SETTING: The investigation was performed as a single-center study in the Division of Cardiovascular Anesthesia, University Hospital of Zurich, in Switzerland. PARTICIPANTS: Seventeen consenting adults scheduled for elective cardiovascular surgery, with or without extracorporeal bypass, via the lateral thoracotomy approach were enrolled. INTERVENTIONS: For postoperative pain relief, patients were randomly assigned to receive continuous extrapleural infusion of ropivacaine 0.2% at a rate of either 6 or 9 mL/h over 48 hours. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of ropivacaine reached toxic levels (>2.2 mg/L) in 25% of cases. No proportionality of plasma concentrations of ropivacaine existed when the 2 dosing regimens were compared. CONCLUSIONS: Plasma concentrations of ropivacaine, administered at the given dose and rates during continuous extrapleural infusion, are unpredictable and may reach toxic levels in patients undergoing major cardiothoracic surgery. Continuous Extrapleural

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Section: Discussioncontrasting

confidence: 62%

Continuous Extrapleural Infusion of Ropivacaine 0.2% After Cardiovascular Surgery Via the Lateral Thoracotomy Approach

Maurer

Blumenthal

Rentsch

et al. 2008

Journal of Cardiothoracic and Vascular Anesthesia

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“…For highly proteinbound drugs such as ropivacaine, small changes in protein binding will have significant effects on the unbound concentration [14].…”

mentioning

confidence: 99%

“…This may be due to the fact that factors other than plasma AAG concentration may alter the relationship between plasma AAG concentration and unbound drug. Erichsen et al [14] noted that alterations in plasma AAG concentration in a surgical population accounted for only 50% of the observed variation in unbound ropivacaine concentrations. In our study, umbilical venous AAG concentration was 5.25 (1.8) mmol.l 21 , similar to concentrations noted by Irestedt et al [15] in parturients undergoing elective operative delivery under ropivacaine epidural anaesthesia at term.…”

mentioning

confidence: 99%

Epidural ropivacaine hydrochloride during labour: protein binding, placental transfer and neonatal outcome

Porter¹,

Kelleher

Flynn

et al. 2001

Anaesthesia

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SummaryThis study was undertaken: (i) to quantify the effects of labour and epidural analgesia on plasma a 1 -acid glycoprotein concentration, (ii) to examine the effects of changes in plasma a 1 -acid glycoprotein concentration on plasma protein binding and placental transfer of ropivacaine, and (iii) to examine the association between umbilical venous ropivacaine concentration and neurobehavioural function in the neonate. Multiparous patients undergoing induction of labour received a continuous epidural infusion of 0.1% ropivacaine following an epidural bolus. A significant association was demonstrated between maternal plasma a 1 -acid glycoprotein concentration and 1/free fraction of ropivacaine 60 min after starting ropivacaine administration (r 2 0.77) but not at delivery. No significant correlation was demonstrable between maternal unbound ropivacaine concentration and either neonatal (cord) ropivacaine concentration or UV/MV (a measure of placental transfer). Thirty minutes after delivery, 9/10 neonates had neurological and adaptive capacity scores , 35, whereas only three infants had scores , 35 at 2 h. All scores exceeded 35 16 h after delivery. No association between mean (SD) umbilical venous ropivacaine concentration [0.09 (0.08) mg.l 21 ] and neurological and adaptive capacity scores was demonstrated.

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“…2 Epidural opioids combined with local anesthetic solution improve the quality of postoperative analgesia reducing the dose related adverse effects of either class of drug alone. [3][4][5] Ropivacaine is a new, long-acting local anesthetic with a more favourable toxic profile than previous long acting local anesthetics, like bupivacaine, 6,7 and is available as a 0.2% solution for epidural analgesia. However, little information is available on the association of low concentrations of ropivacaine and fentanyl for epidural postoperative analgesia after major abdominal surgery.…”

mentioning

confidence: 99%

Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl

Berti

Fanelli

Casati

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: To compare analgesic efficacy and occurrence of motor block and other side effects during patient supplemented epidural analgesia (PSEA) with either ropivacaine/fentanyl or bupivacaine/fentanyl mixtures. Methods:In a prospective, randomized, double-blind study, 32 ASA I-III patients undergoing major abdominal surgery received an epidural catheter at the T 8 -T 10 , followed by integrated general epidural anesthesia. Postoperative epidural analgesia was provided using a patient controlled pump with either ropivacaine 0.2%/2 µg·ml -1 fentanyl (group Ropivacaine, n = 16) or bupivacaine 0.125%/2 µg·ml -1 fentanyl (group Bupivacaine, n = 16) [background infusion 4 -6 ml·hr -1 , 1.5 ml Incremental Doses and 20 min lock out]. Verbal pain rating score, number of incremental doses, consumption of epidural analgesic solution and rescue analgesics, sedation (four-point scale), and pulse oximetry were recorded by a blind observer for 48 hr after surgery. Conclusion: Using a ropivacaine 0.2% / 2 µg·ml -1 fentanyl mixture for patient supplemented epidural analgesia after major abdominal surgery provided similar successful pain relief as bupivacaine 0.125%/2 µg·ml -1 fentanyl, but patients receiving bupivacaine/fentanyl requested more supplemental.Objectif : Comparer l'efficacité analgésique, l'occurrence de blocage moteur et autres effets secondaires pendant une analgésie épidurale complétée (AEC) avec un mélange de ropivacaïne/fentanyl ou de bupivacaïne/fentanyl.Méthode : L'étude prospective, randomisée et à double insu a porté sur 32 patients d'état physique ASA I-III qui devaient subir une intervention chirurgicale abdominale majeure. Un cathéter épidural a été mis en place à T 8 -T 10 et une anesthésie générale/péridurale intégrée a suivi. L'analgésie épidurale postopératoire, administrée par une pompe contrôlée par le patient, comprenait soit un mélange de ropivacaïne à 0,2 %/2 µg·ml -1 de fentanyl (groupe Ropivacaïne, n = 16) soit un mélange de bupivacaïne à 0,125 %/2 µg·ml -1 de fentanyl (groupe Bupivacaïne, n = 16) [perfusion de base de 4-6 ml·h -1 , doses en incréments de 1,5 ml et période réfractaire de 20 min]. Le score verbal d'estimation de la douleur, le nombre de doses incrémentielles, la consommation d'analgésique épidural et de doses d'appoint, la sédation (selon une échelle en quatre points) et l'oxymétrie de pouls ont été enregistrés par un observateur impartial pendant 48 h après l'opération.Résultats : Aucune différence intergroupe n'a été observée quant au soulagement de la douleur, au blocage moteur, au degré de sédation, à l'oxymétrie de pouls et aux autres effets secondaires. Conclusion : Un mélange de ropivacaïne à 0,2 %/2 µg·ml -1 de fentanyl, comme analgésie épidurale d'appoint à la suite d'une intervention chirurgicale abdominale majeure, a fourni un soulagement de la douleur d'efficacité similaire à un mélange de bupivacaïne à 0,125 %/2 µg·ml -1 de fentanyl, mais ce dernier a nécessité plus de doses d'appoint.Patient supplemented epidural analgesia after major abdominal surgery with bupi...

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Pharmacokinetics and Analgesic Effect of Ropivacaine during Continuous Epidural Infusion for Postoperative Pain Relief

Cited by 77 publications

References 14 publications

Continuous Extrapleural Infusion of Ropivacaine 0.2% After Cardiovascular Surgery Via the Lateral Thoracotomy Approach

Continuous Extrapleural Infusion of Ropivacaine 0.2% After Cardiovascular Surgery Via the Lateral Thoracotomy Approach

Epidural ropivacaine hydrochloride during labour: protein binding, placental transfer and neonatal outcome

Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl

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