scholarly journals Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations

2002 ◽  
Vol 49 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Pilar Prieto-Alvarez ◽  
Isabel Tello-Galindo ◽  
Jesus Cuenca-Peña ◽  
Maria Rull-Bartomeu ◽  
Carmen Gomar-Sancho
Keyword(s):  
Postoperative Analgesia ◽  
Plasma Concentrations ◽  
Epidural Infusion ◽  
Continuous Epidural Infusion

Pharmacokinetics of Bupivacaine during Postoperative Epidural Infusion

2002 ◽  
Vol 96 (5) ◽  
pp. 1062-1069 ◽  
Author(s):  
Bernadette Th. Veering ◽  
Anton G. L. Burm ◽  
Hilde-Marieken Feyen ◽  
Wim Olieman ◽  
John H. M. Souverijn ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Pain Relief ◽  
Protein Binding ◽  
Bolus Dose ◽  
Plasma Concentrations ◽  
Epidural Infusion ◽  
Total Plasma ◽  
Continuous Epidural Infusion ◽  
Acid Glycoprotein ◽  
Constant Rate

Background Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative period. This study examined the effect of postoperative increases (in response to surgery) in plasma alpha1-acid-glycoprotein (AAG) concentrations on the plasma concentrations of the enantiomers of bupivacaine during continuous epidural infusion of racemic bupivacaine for postoperative pain relief. Methods Six patients scheduled for total hip surgery with combined epidural and general anesthesia received a bolus dose of bupivacaine (65 mg) followed by constant-rate (8 ml/h) epidural infusion of 2.5 mg/ml bupivacaine for 48 h. Total and unbound plasma concentrations of the enantiomers of bupivacaine and plasma AAG concentrations during the 48-h epidural infusion were determined. Results Total plasma concentrations of the enantiomers of bupivacaine increased steadily during the infusion (P < 0.0001), whereas unbound concentrations did not change after 12 h (P > 0.1). Total plasma concentrations of S(-)-bupivacaine were higher than those of R(+)-bupivacaine (P < 0.02), whereas unbound concentrations of S(-)-bupivacaine were lower than those of R(+)-bupivacaine (P < 0.002). AAG concentrations initially decreased, but thereafter increased steadily (P < 0.0001). Consequently, free fractions of the enantiomers initially increased and then decreased with time (P = 0.0002). Free fractions of S(-)-bupivacaine were smaller than those of R(+)-bupivacaine (P = 0.0003). Conclusions The study confirmed that the pharmacokinetics of bupivacaine are enantioselective. During postoperative epidural infusion, changing plasma AAG concentrations affect the protein binding of both enantiomers of bupivacaine. Consequently, total plasma concentrations of the enantiomers increase with time, whereas unbound concentrations reach a plateau.

Epidural Infusion of Ropivacaine for Postoperative Analgesia after Major Orthopedic Surgery

2000 ◽  
Vol 93 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Anton G. L. Burm ◽  
Rudolf Stienstra ◽  
Rolf P. Brouwer ◽  
Britt-Marie Emanuelsson ◽  
Jack W. van Kleef
Keyword(s):  
Protein Binding ◽  
Postoperative Analgesia ◽  
Orthopedic Surgery ◽  
Plasma Concentrations ◽  
Epidural Infusion ◽  
Acid Glycoprotein ◽  
Constant Rate ◽  
Major Orthopedic Surgery ◽  
Group 2 ◽  
Group 1

Background Changing plasma protein concentrations may affect the protein binding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia. Methods Twenty-eight patients, scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3 mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were determined. In addition, the urinary excretion of ropivacaine and major metabolites was measured. Results Total plasma concentrations of ropivacaine increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations reached average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2) after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values. Conclusions Postoperative increases in plasma alpha1-acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, causing divergence of total and unbound plasma concentrations.

Patient-Controlled Epidural Analgesia Versus Continuous Epidural Infusion with Ropivacaine for Postoperative Analgesia in Children

2003 ◽  
Vol 97 (6) ◽  
pp. 1608-1611 ◽  
Author(s):  
Emmanuel Antok ◽  
Fabienne Bordet ◽  
Frédéric Duflo ◽  
Sabine Lansiaux ◽  
Sylvie Combet ◽  
...  
Keyword(s):  
Epidural Analgesia ◽  
Postoperative Analgesia ◽  
Epidural Infusion ◽  
Continuous Epidural Infusion

Efficacy, Safety, and Pharmacokinetics of Levobupivacaine with and without Fentanyl after Continuous Epidural Infusion in Children

2003 ◽  
Vol 99 (5) ◽  
pp. 1166-1174 ◽  
Author(s):  
Jerrold Lerman ◽  
Judith Nolan ◽  
Rob Eyres ◽  
Mark Schily ◽  
Peter Stoddart ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Venous Blood ◽  
Plasma Concentrations ◽  
Epidural Infusion ◽  
Healthy Children ◽  
Rescue Analgesia ◽  
Continuous Epidural Infusion ◽  
Number Of Children ◽  
Intention To Treat ◽  
Double Blinded

Background Levobupivacaine, the levo-enantiomer of bupivacaine, is as potent as bupivacaine but less toxic. Therefore, the authors investigated the efficacy, safety, and pharmacokinetics of perioperative epidural levobupivacaine with and without fentanyl in children. Methods After Research Ethics Board approval and informed written consent, 120 healthy children aged 6 months to 12 yr who were scheduled to undergo urologic or abdominal surgery were randomized in a double-blinded and concealed manner to receive one of four epidural solutions as a continuous infusion for 24 h: 0.125% levobupivacaine; 0.0625% levobupivacaine; 1 mug/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 mug/ml fentanyl. After induction of anesthesia and tracheal intubation, a lumbar epidural catheter was sited, a loading dose was administered (0.75 ml/kg levobupivacaine, 0.175%), and the epidural infusion was commenced. The primary endpoint was the need for rescue analgesia (morphine) in the first 10 h after surgery. Pain, motor strength, and side effects were recorded for 24 h. Venous blood was collected from 18 children to determine the plasma concentrations of levobupivacaine and/or fentanyl before and 2, 4, 8, 16, 24, and 26 or 30 h after the start of the epidural infusion. Results Of the 114 children who were analyzed for intention to treat, a similar number of children in each group reached the 10-h mark. The time to the first dose of morphine in the first 10 h was less in the plain fentanyl group (P < 0.044). All other effects were similar among the four groups. The plasma concentration of levobupivacaine increased during the infusion period, reaching a maximum of 0.76 +/- 0.11 mug/ml in the 0.125% group and 0.48 +/- 0.12 mug/ml in the 0.0625% group by 24 h. The plasma concentration of fentanyl also increased steadily, reaching a maximum concentration of 0.37 +/- 0.11 ng/ml by 24 h. Conclusion We conclude that 0.0625% levobupivacaine without fentanyl is an effective perioperative epidural solution in children when infused at a rate of 0.3 ml. kg-1. h-1. The plasma concentrations of 0.125% and 0.0625% levobupivacaine and fentanyl (1 mug/ml) at the end of a 24-h infusion are low.

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