Background : The pharmacokinetics and clinical efficacy of ropivacaine (2.5 mg/ml) during a 24-h continuous epidural infusion for postoperative pain relief in 20 patients scheduled for abdominal hysterectomy were characterized using an open-label, increasing-dose design. Methods : Through an epidural catheter inserted at T10-T12, a test dose of 7.5 mg ropivacaine was given 3 min before a bolus dose of 42.5 mg and immediately followed by a 24-h continuous epidural infusion with either 10 or 20 mg/h. Peripheral venous plasma samples were collected up to 48 h after infusion, and urinary excretion was followed up to the end of infusion. Postoperative pain at rest, on coughing, and at mobilization was assessed by means of a visual analog scale 2, 4, 6, 8, 12, and 24 h after the end of surgery. Sensory (pinprick) and motor block (modified Bromage scale) were assessed at the same intervals. Results : The total plasma concentrations of ropivacaine increased markedly and consistently during the 24-h epidural infusion, in contrast to stable unbound concentrations. Both total and unbound plasma concentrations at the end of infusion were proportional to the total dose, although only the latter was proportional to the infusion rate. The total and unbound plasma clearance was independent of dose. Total mean clearance decreased on average by 21% (P<0.001) during the last 12 h of epidural infusion, i.e., from 539 ± 191 ml/min to 418 ± 138 ml/min, indicating time-dependent kinetics. The unbound clearance also varied between estimates after 8 h of infusion and the end of treatment, i.e., a 5.3% decrease from 10.4 ± 5.3 l/min to 9.5 ± 3.9 l/min (P < 0.05). The unbound fraction of ropivacaine in plasma decreased during treatment, and this was related to the increase in α 1 -acid glycoprotein concentration. Pain was generally well controlled, and median visual analog scale scores during mobilization were less than 30 mm in patients receiving ropivacaine at 20 mg/h. Conclusions : The pharmacokinetics of ropivacaine were independent of dose, but total clearance decreased with time over 24 h. The consistent increase in total plasma concentration during the postoperative epidural infusion contrasted to much less variation in the unbound plasma concentrations of ropivacaine.

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

UNLABELLED: In this randomized double-blinded study, we sought to determine an optimal dose-combination of sufentanil with ropivacaine 0.2% wt/vol as postoperative epidural analgesics. One hundred twenty patients undergoing major abdominal surgery under general and thoracic epidural anesthesia (T9-11) were assigned to groups receiving patient-controlled epidural analgesia with ropivacaine 0.2% wt/vol (R), ropivacaine 0.2% wt/vol + sufentanil 0.5 microg/mL (R+S0.5), 0. 75 microg/mL (R+S0.75), 1.0 microg/mL (R+S1). A visual analog score of less than 40 was considered effective, and all side effects were recorded. In randomized subgroups (10 patients per group), plasma pharmacokinetic data were obtained for both epidural drugs. Four patients in Group R and two in Group R+S0.5 were excluded because of inadequate analgesia. The drug infusion rates (range of means: 5.4-5. 9 mL/h) were similar in all patients. Analgesia was superior for sufentanil 0.75 microg/mL with no further enhancement by the larger sufentanil concentration of 1 microg/mL. Sufentanil plasma levels were within the range of the minimal effective concentrations (highest in R+S1), and there was no covariation between plasma levels and pain relief. Free ropivacaine plasma concentrations remained stable for 96 h. No severe side effects were detected, although pruritus correlated with an increasing dose of sufentanil. We conclude that the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil provided the best analgesia with the fewest side effects of the three combinations tested. IMPLICATIONS: Sufentanil is added to epidural infusions of ropivacaine 0.2% wt/vol to improve the effectiveness of postoperative pain management. Regarding the risk of side effects, however, it is still unclear what concentration of sufentanil should be added to the local anesthetic. For postoperative thoracic epidural analgesia after major abdominal surgery, the combination of ropivacaine 0.2% wt/vol and 0.75 microg/mL sufentanil resulted in an appropriate cost:benefit ratio between good analgesia and side effects.

What concentration of sufentanil should be combined with ropivacaine 0.2% wt/vol for postoperative patient-controlled epidural analgesia?

BackgroundChanging 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.MethodsTwenty-eigh

Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery: pharmacokinetic evaluation.

BackgroundIn this open, randomized study, the pharmacokinetics, clinical efficacy, and safety of a 48-h continuous interscalene infusion of 2 mg/ml ropivacaine for postoperative pain relief were investigated in patients undergoing open major shoulder surgery.MethodsAn initial interscalene block with

Continuous interscalene analgesia with ropivacaine 2 mg/ml after major shoulder surgery.

BACKGROUND Continuous epidural infusion of bupivacaine is widely practiced for postoperative pain relief in pediatric patients. However, bupivacaine may induce adverse effects in infants (convulsions or cardiac arrhythmias), likely because of decreased hepatic clearance and serum protein binding capacity. The authors wanted to examine the complex relations between age, alpha-1 acid glycoprotein (AAG) concentration, and unbound and total bupivacaine serum concentrations in infants receiving bupivacaine epidurally for 2 days. METHODS Twenty-two infants aged 1-7 months (12 with biliary atresia and 10 with another disease) received a continuous epidural infusion of 0.375 mg x kg(-1) x h(-1) bupivacaine during 2 days (during and after surgery). Unbound and total bupivacaine concentration in serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG concentration was measured in serum before and 2 days after surgery. In eight additional infants, the blood/plasma concentration ratio was measured in vitro at whole blood concentrations of 2 and 20 microg/ml. Bupivacaine concentration was fitted to a one-compartment model to calculate basic pharmacokinetic parameters. RESULTS No adverse effects were observed. AAG increased markedly after surgery, and the increase was correlated to both age and preoperative AAG concentration. Two infants aged 1.8 months had unbound concentrations greater than 0.2 microg/ml. Clearance of unbound drug significantly increased with age. Because of increased drug binding, clearance of bound drug decreased both with time (from 0.5 to 48 h) and with age. Blood/plasma ratio was 0.77+/-0.08 and 0.85+/-0.24 at 2 and 20 microg/ml, respectively. CONCLUSIONS Because of a low AAG concentration and a low intrinsic clearance, unbound bupivacaine increased to concentrations greater than 0.2 microg/ml in two infants younger than 2 months, after 2 days of infusion at a rate of 0.375 mg x kg(-1) x h(-1). The increase in AAG observed after surgery did not fully buffer this unbound fraction. Similarly, the buffer capacity of erythrocytes did not sufficiently increase at high concentration to compensate the saturation of the AAG system. Thus, we propose the use of a maximum dose of 0.25 mg x kg(-1) x h(-1) in infants younger than 4 months and a maximum of 0.3 mg x kg(-1) x h(-1) in infants older than 4 months.

Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia.

We describe a method, which is both specific and rapid, for the measurement of bupivacaine concentrations in plasma using high-performance liquid chromatography. Bupivacaine plasma concentrations, pharmacokinetics and protein binding in the postoperative period were investigated in seven patients (58–77 years old) following hip surgery. Postoperative analgesia was achieved by epidural bolus injections of 25 mg bupivacaine 0.25% every 6 h. Sufficient pain relief without side-effects was obtained. Total (maximum 1.13 μg/ml) as well as free (maximum 0.1 μg/ml) bupivacaine plasma concentrations remained below toxic threshold levels and no cumulation occurred. Increased protein binding in the postoperative period is reported, emphasizing the importance of measuring the free fraction in addition to the total plasma concentration. The free fraction decreased from 5.4% preoperatively to 2.7% in the postoperative period (P<0.05). Changes in plasma protein binding of bupivacaine and changes in plasma levels of the acute phase reactant α-1-acid glycoprotein were correlated (r = 0.8, P<0.05). Difficulties in interpreting the elimination parameters following epidural administration are discussed, leading to the conclusion that the derivation of dosage regimens from kinetic parameters following epidural administration is not warranted.

Pharmacokinetics and protein binding of bupivacaine in postoperative epidural analgesia

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Pharmacokinetics and protein binding of bupivacaine in postoperative epidural analgesia