Anesth Analg 2003;97:605-606
© 2003 International Anesthesia Research Society
LETTERS TO THE EDITOR
Interscalene Brachial Plexus Anesthesia and Analgesia for Open Shoulder Surgery: What About Pharmacokinetics?
Marco Nadig, MD,
Stephan Blumenthal, MD,
Georgios Ekatodramis, MD, and
Alain Borgeat, MD
Department of Anesthesia, Balgrist University Hospital, Zurich, Switzerland
To the Editor:
We disagree with Casati et al. (1) since they assess that the reduced toxic potential of ropivacaine is particularly important when continuous peripheral nerve blocks are planned because of the increased risk for drug accumulation.
In the context of systemic local anesthetic toxicity the unbound rather than total plasma local anesthetic concentration has to be considered. The authors cited Tuominen et al. (2) to strengthen their argumentation. But in their study, Tuominen et al. (2) conclude that the unbound plasma concentration of bupivacaine was below detectable levels, which contradicts Casati et al.’s assessment. Moreover the study of Ekatodramis et al. (3) showed that a continuous infusion of ropivacaine of 2 mg/mL over 48 h leads to an increased total ropivacaine concentration indeed, but the unbound ropivacaine concentration remains well below the threshold levels for toxicity. In this study, the highest individual plasma concentration of unbound ropivacaine was 0.05 mg/L. Knudsen et al. (4) found that an unbound ropivacaine concentration of 0.34–0.85 mg/L was necessary to observe early signs of central nervous toxicity, which is 10 times higher than what we measured. The absence of increase of the free ropivacaine concentration is explained by a rise in  1-glycoprotein (3). The most important point is that the risk of systemic toxicity is particularly high after the initial bolus (e.g., 250 mg ropivacaine through an interscalene catheter, unbound ropivacaine concentration 30 min later 0.252 mg/l, unpublished data) and not during a continuous infusion. In the context of Casati et al.’s study, the administration of ropivacaine 0.2% or levobupivacaine 0.125% for postoperative analgesia is in terms of toxicity clinically irrelevant.
References
- Casati A, Borghi B, Fanelli G, et al. Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: a randomized, double-blinded comparison between levobupivacaine and ropivacaine. Anesth Analg 2003; 96: 253–9.[Abstract/Free Full Text]
- Tuominen M, Haasio J, Rosenberg Ph. Continuous interscalene brachial plexus block: clinical efficacy, technical problems and bupivacaine plasma concentrations. Acta Anesthesiol Scand 1989; 33: 84–8.[Web of Science][Medline]
- Ekatodramis G, Borgeat A, Huledal G, et al. Continuous interscalene analgesia with ropivacaine 2mg/mL after major shoulder surgery. Anesthesiology 2003; 98: 143–50.[Web of Science][Medline]
- Knudsen K, Beckmann Suurküla M, et al. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78: 507–14.[Abstract/Free Full Text]
Response
Andrea Casati, MD,
Guido Fanelli, MD, and
Jacques E. Chelly, MD
Department of Anesthesiology, Vita-Salute University of Milan, Milan, Italy
Department of Anesthesiology, University of Parma, Parma, Italy
Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA
In Response:
Once again we feel privileged that Dr Borgeat’s group has read our article (1), providing us with interesting comments on ropivacaine pharmacokinetics during continuous interscalene analgesia [maybe they wanted to remind us of their article recently published on this topic (2)]. However, the authors must recognize that our study was only designed to provide a clinical comparison between levobupivacaine and ropivacaine for continuous interscalene blockade, and we only made comments on the possible toxicity of the two local anesthetics in the Discussion. Dr. Borgeat and colleagues also must keep in mind that the potential for systemic toxicity is always present with peripheral nerve blocks. Although, we agree that the increase in plasma concentration of local anesthetics is mainly related to the initial bolus (3), it also depends on the volume of the initial bolus, the time at which the infusion is started [Borgeat’s group started the infusion 6 h after the initial bolus, while most physicians start immediately after the initial bolus or at the end of surgery (4)], the concentration of local anesthetic, and the rate of infusion (5). In fact, their study clearly confirmed a significant between-subject variability between subject variability (in one patient, ropivacaine plasma concentration was well above 2.5 mg/L) and demonstrated that even with a 9 mL/h rate only 63% of patients reported excellent results, suggesting that indeed a higher infusion rate would be necessary to provide appropriate pain control for these indications (2). Pharmacokinetic studies have also demonstrated that after 48 h we are still not at steady state (2,4,5), and in some instances the plasma level may reach the "toxic level" and be associated with clinical symptoms similar to those related to local anesthetic toxicity (4,5). Although, we agree with Borgeat et al. that the use of ropivacaine or levobupivacaine is "safe," especially for postoperative analgesia, the potential for systemic toxicity cannot be ignored. In these conditions, it is very difficult to conclude on the "absolute safety" of ropivacaine or levobupivacaine on the basis of one study with a particular mode of infusion. We hope that they would also acknowledge that additional studies are required to conclude that indeed we must not be concerned when infusing ropivacaine or levobupivacaine to our patients.
References
- Casati A, Borghi B, Fanelli G, et al. Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: a randomized, double-blinded comparison between levobupivacaine and ropivacaine. Anesth Analg 2003; 96; 253–9.
- Ekatodramis G, Borgeat A, Huledal G, et al. Continuous interscalene analgesia with ropivacaine 2 mg/ml after major shoulder surgery. Anesthesiology 2003; 98: 143–50.
- Ilfeld BM, Morey TE, Enneking FK. Continuous infraclavicular brachial plexus block for postoperative pain control at home: a randomized, double-blinded, placebo-controlled study. Anesthesiology 2002; 96: 1297–304.[Web of Science][Medline]
- Tuominen MK, Pere P, Rosenberg PH. Unintentional arterial catheterization and bupivacaine toxicity associated with continuous interscalene brachial plexus block. Anesthesiology 1991; 75: 356–8.[Web of Science][Medline]
- Pere P, Tuominen M, Rosenberg PH. Cumulation of bupivacaine, desbutylbupivacaine and 4-hydroxybupivacaine during and after continuous interscalene brachial plexus block. Acta Anaesthesiol Scand 1991; 35: 647–50.[Medline]
|
