1 Department of Anaesthesiology and Intensive Care Medicine, Hospital of the Philipps-University, Baldingerstrasse, D-35033 Marburg, Germany. 2 Department of Anaesthesiology and Intensive Care Medicine, Hospital of the Christian-Albrechts University, Schwanenweg 21, D-24105 Kiel, Germany*Corresponding author
Accepted for publication: February 22, 2002
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Methods. After informed consent and ethics committee approval, 64 patients were randomly allocated to four groups for intercostal nerve block (ropivacaine 2, 5, 7.5 or 10 mg ml1 at the end of surgery). Central (mixed) venous and arterial plasma samples were collected before the start of intercostal application, and 2, 5, 10, 15, 20, 30, 45, 60 and 90 min afterwards. Plasma concentrations of ropivacaine were measured by high performance liquid chromatography.
Results. Maximum venous plasma concentrations occurred after the mean times of 10.7 (range, 515), 10.8 (520), 11.3 (520) and 12.2 (545) min, respectively for each group. The groups had mean concentrations of 1.3 (SD, 0.6; range, 0.32.3), 2.1 (1.0; 0.54.5), 2.4 (1.0; 1.25.1) and 2.5 (0.9; 1.75.6) µg ml1, respectively. Maximum arterial plasma concentration following 1.0% ropivacaine occurred after 16 (545) min with a mean of 2.3 (0.6; 1.53.6) µg ml1. No signs of central nervous system or cardiac toxicity were observed.
Conclusions. After intercostal blocks the absorption of ropivacaine is rapid compared with other techniques for regional anaesthesia and results in relatively high venous and arterial plasma concentrations, especially if a dose of 100 mg or more is used.
Br J Anaesth 2002; 89: 2513
Keywords: anaesthetic techniques, regional, intercostal; anaesthetics local, ropivacaine; pharmacokinetics, ropivacaine; toxicity
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Several studies have demonstrated that S-ropivacaine is less toxic compared with bupivacaine in preclinical studies25 and is suitable for epidural anaesthesia.69 However, information about the absorption kinetics of ropivacaine following ICB is lacking. In the present study, we measured plasma concentrations of ropivacaine following intraoperative ICB for pain prophylaxis after thoracic surgery using increasing concentrations of ropivacaine (0.21.0%).
![]() |
Methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
A high performance liquid chromatographic (HPLC) method previously described10 was modified in order to determine plasma concentrations of ropivacaine. All concentrations were determined in duplicate. The absorption was measured at a wavelength of 203 nm and integrated using HPLC-Manager, D-6000 A Interface. The coefficient of variation showed acceptable precision of the assay in the range of 0.0110 µg ml1 (<5%).
Data are presented as median, mean, SD and range. For the comparison of maximum plasma concentrations, ANOVA with Dunnetts post-hoc test was performed using GraphPad Prism, version 3.02 for Windows (GraphPad Software, San Diego, CA, USA). For comparison between arterial and venous plasma concentrations a paired t-test was used. Alpha was set at 0.05. Thus, the study had an 80% chance of detecting an absolute difference of 1 SD within the unpaired comparisons.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
On average, maximum central venous plasma concentrations occurred after 11 min, without significant difference between the groups. Mean maximum plasma concentrations were 1.3 (0.6; 0.32.3), 2.1 (1.0; 0.54.5), 2.4 (1.0; 1.25.1) and 2.5 (0.9; 1.75.6) µg ml1 in groups 0.2, 0.5, 0.75 and 1.0, respectively (Fig. 1). The highest individual plasma concentration was 5.6 µg ml1 5 min after intercostal injection of 1.0% ropivacaine 200 mg. Maximum plasma concentrations were not significantly different between groups 0.5, 0.75 and 1.0 but were significantly higher compared with group 0.2 (P<0.05, P<0.01 and P<0.001, respectively) (Table 2).
|
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We found one previous study on the pharmacokinetics of ropivacaine after intercostal blocks in the literature.15 Maximum plasma concentration was 1.1 (0.4) µg ml1 with 56 ml of 0.25% ropivacaine (140 mg) after 21 min. In our study, peaks occurred somewhat earlier and were considerably higher. This discrepancy could be due to the fact that in the previous study, bilateral blocks (14 blocks each) were performed in awake healthy male volunteers without premedication (n=7; mean age, 34 yr) using 0.25% ropivacaine (a concentration not commercially available). In contrast, we performed four unilateral blocks each in patients of both genders (age range, 4472 yr) under general anaesthesia.
Toxic plasma ropivacaine concentrations for humans are still not well characterized. Scott and colleagues16 reported mild central nervous symptoms at venous plasma concentrations ranging from 1 to 2 µg ml1 after i.v. administration of ropivacaine in unpremedicated volunteers. Despite rather high individual plasma concentrations (>5 µg ml1) no signs of central nervous system or cardiovascular toxicity were observed in our patients, confirming a higher threshold for toxic reactions compared with racemic bupivacaine. A limitation of the present study with regard to toxicity is that our patients were premedicated with a benzodiazepine and general anaesthesia was just finished (blocks were performed before extubating the trachea) at the time of maximum plasma concentrations. Therefore, any signs of central nervous system toxicity could have been suppressed.
![]() |
Acknowledgement |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
2 Akerman B, Hellberg IB, Trossvig G. Local anaesthetic properties of the optically active isomers of prilocaine (Citanest). Acta Pharmacol Toxicol 1967; 25: 23341[Medline]
3 Aberg G. Toxicological and local anaesthetic effects of optically active isomers of two local anaesthetic compounds. Acta Pharmacol Toxicol 1972; 31: 27386[Medline]
4 Moller R, Covino BG. Cardiac electrophysiologic properties of bupivacaine and lidocaine compared with those of ropivacaine, a new amide local anesthetic. Anesthesiology 1990; 72: 3229[ISI][Medline]
5 Reiz S, Nath S. Cardiotoxicity of LEA 103a new local amide anesthetic agent. Anesthesiology 1986; 65: 3A
6 Kerkamp HE, Gielen MJ, Edstrom HH. An open study comparison of 0.5%, 0.75% and 1% ropivacaine with epinephrine in epidural anesthesia in patients undergoing urological surgery. Reg Anesth 1990; 15: 538[ISI][Medline]
7 Niesel HC, Eilingsfeld T, Kaiser H, Klimpel L. Ropivacaine for peridural anesthesia. Studies on the dose-response relationship in orthopedic surgery. Reg Anesth 1990; 13: 737
8 Wahedi W, Nolte H, Witte P. Ropivacaine in epidural anesthesia. Dose response relationship and a comparison with bupivacaine. Reg Anesth 1990; 13: 5765
9 Brockway MS, Bannister J, McClure JH, McKeown D, Wildsmith JA. Comparison of extradural ropivacaine and bupivacaine. Br J Anaesth 1991; 66: 317[Abstract]
10 Wulf H, Winckler K, Maier C, Heinzow B. Pharmacokinetics and protein binding of bupivacaine in postoperative epidural analgesia. Acta Anaesthesiol Scand 1988; 32: 5304[ISI][Medline]
11 Concepcion M, Arthur GA, Steele SM, Bader AM, Covino BG. A new local anesthetic, ropivacaine. Its epidural effects in humans. Anesth Analg 1990; 70; 805[Abstract]
12 Datta S, Camann W, Bader A, Vanderburgh L. Clinical effects and maternal and fetal plasma concentrations of epidural ropivacaine versus bupivacaine for cesarian section. Anesthesiology 1995; 82: 134652[ISI][Medline]
13 Katz JA, Knarr D, Bridenbaugh PO. A double blind comparison of 0.5% bupivacaine and 0.75% ropivacaine given epidurally in humans. Reg Anesth 1990; 15: 2502[ISI][Medline]
14 Quitmann J, Kern A, Wulf H. Pharmacokinetics of ropivacaine during extradural anesthesia for total hip replacement. J Clin Anesth 2000; 12: 369[ISI][Medline]
15 Kopacz DJ, Emmanuelsson BM, Thompson GE, Carpenter RL, Stephenson CA. Pharmacokinetics of ropivacaine and bupivacaine for bilateral intercostal blockade in healthy male volunteers. Anesthesiology 1994; 81: 113948[ISI][Medline]
16 Scott DB, Lee A, Fagan D, Bowler GMR, Bloomfield P, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 5629