Ropivacaine is a long-acting enantiomerically pure (S-enantiomer) amide local anaesthetic that is uniquely suited for peripheral nerve blockade. Clinically it offers the advantage of a dense sensory/motor block that is fast in onset and extended in duration. More importantly, numerous in vitro studies indicate that it is significantly less cardiotoxic and offers a higher threshold for CNS toxicity than bupivacaine (1,2). This broader therapeutic safety window is essential when evaluating which long acting local anesthetic to select for bolus injection.

An ideal local anesthetic provides quick onset, prolonged analgesia, and reduced motor block. Ropivacaine fulfills these requirements. Extensive clinical trials have demonstrated that ropivacaine provides excellent anesthesia for peripheral nerve block use. When administered for upper and lower extremity block, the onset time of ropivacaine 0.5% is the same or faster when compared to bupivacaine 0.5% (3,4). Duration of analgesia is also profound. For brachial plexus anesthesia utilizing the axillary or interscalene approach there is an equivalent duration of pain relief when comparing equal concentrations of ropivacaine and bupivacaine (4,5). Studies examining lower extremity analgesia demonstrate identical or only slightly shorter (<4 h) duration when compared with bupivacaine (3). And for local infiltration using large milligram doses, ropivacaine has been shown to provide superior extended analgesia compared with bupivacaine (6). But perhaps the most unique property of ropivacaine is its sensory/motor differential. This is most evident when dilute concentrations are used or when administered for epidural use.

When ropivacaine 0.5% is administered in the epidural space for major orthopedic surgery it provides the equivalent duration of analgesia as bupivacaine 0.5% but does so with less motor blockade (7). When used for continuous postoperative infusion ropivacaine 0.2% has also been shown effective for analgesia after major abdominal and orthopedic surgery (8). And when dilute concentrations of ropivacaine 0.625% and 0.125% with fentanyl 2 µg/ml are compared to equal concentrations of bupivacaine they produce equivalent sensory analgesia associated with less motor block (9). This has tremendous advantages for ambulation, earlier physiotherapy and quicker discharge times.

Efficacy, Potency and Safety -Why bupivacaine shouldn't be our agent of choice.

Critics argue that ropivacaine is less potent than bupivacaine. Although randomized data conclude that ropivacaine has similar sensory and motor blockade to an equal concentration of bupivacaine, one recent study has led to confusion by suggesting that ropivacaine may be less potent than bupivacaine when administered for obstetric epidural use (10). In this study, Polley et al. examined the effective analgesic dose that provided 50% of patients pain relief (ED50). Using this theoretical value they concluded that bupivacaine was ~20% more potent than ropivacaine. Unfortunately, analysis of this type does not translate directly to clinical practice. Primarily because the ED50 is only one theoretical point on the dose response curve, where 50% of patients are comfortable and 50% still have pain, a clinically unacceptable scenario. In the clinical setting (ED95-where 95% of patients are comfortable) all current studies suggest equal efficacy when clinically relevant concentrations are delivered. When slight differences are detected this usually relates to the sensory/motor advantages of ropivacaine.

However, even if subsequent studies invalidate the extensive current literature base, the safety data remains the most compelling factor to select ropivacaine as a long-acting amide anesthetic. When administered intravenously to volunteers, ropivacaine was simply less cardiotoxic and had a significantly higher threshold for CNS toxicity than bupivacaine (1,2). This resulted in a higher tolerated unbound plasma concentration in the ropivacaine recipients. Even more convincing was the fact that when subjects reported the initial subtle signs of local anesthetic toxicity, serial EKG analysis already demonstrated cardiac conduction changes in the bupivacaine group. This is further supported by data examining resuscitation in dogs after local anesthetic cardiac arrest (11). In this study after two times the convulsant dose was administered, 83% of the bupivacaine dogs died, in contrast with only 17% in the ropivacaine group. In addition, 83% of the bupivacaine treated dogs demonstrated ventricular arrhythmias, compared with 33% in the ropivacaine group. Levobupivacaine, the S -enantiomer preparation of bupivacaine, has also shown greater toxicity in similar comparisons to ropivacaine (12). To date in over a million administrations of ropivacaine there have been no documented cardiac deaths.

How much cost, for how much benefit? -Ropivacaine costs approximately three times more than bupivacaine-Why ropivacaine is still a better selection.

As physicians we are obligated to analyze risk versus benefit for every intervention we perform. And a paramount tenet is to “first do no harm.” Yet despite these concepts people die every year from cardiac toxicity secondary to bupivacaine intravascular injection. Despite the low incidence of this occurrence, toxicity from inadvertent intravascular injection remains the single greatest danger from long acting peripheral nerve blocks. The incidence of seizure associated with inadvertent intravascular injection of local anesthetic is still 1-in-1,500 blocks, both in the pediatric and adult population (13). Current guidelines of incremental injection and monitoring have not eradicated this problem (14). Even worse, this potential danger is risked solely to provide an analgesic intervention for our patients. Unfortunately, in the United States last year patients still died after accidental bupivacaine injection (15). Due, to concerns of pending litigation many of these adverse outcomes go unreported and as a result the exact incidence of the problem is difficult to ascertain. Anecdotal communication with practice groups throughout the country indicates that in fact cardiac toxicity from bupivacaine remains a real problem and a constant threat to patients. Ropivacaine offers a long-acting alternative with an improved safety profile for a potentially catastrophic event.

Cost analysis can be confusing. In a competitive environment anesthesiologists are pressed to choose the least expensive agent. Yet, over simplifying drug selection can be misleading. Relative to the costs of inhalational anesthetics, muscle relaxants and side effects of general anesthesia, the greater cost of ropivacaine pales in comparison because the entire class of drugs is relatively inexpensive. Simply put, at a small price, ropivacaine is safer. Choosing a potentially lethal drug instead becomes an actuarial calculation in the likelihood that your practice will encounter a disaster. The human toll and physical and emotional costs of patients deaths are difficult to quantify, however they seem unjustified when a safer, equally efficacious drug is available for a nominally greater price.

References:

1. Scott D, Lee A, Fagan D, Bowler G, Bloomfield P, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 563-9.

2. Knudsen K, Beckman Suurkula M, Blomberg S, Sjovall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. British Journal of Anaesthesia 1997; 78: 507-14.

3. Greengrass R, Klein S, D'Ercole F, Gleason D, Shimer C, Steele S. Lumbar plexus and sciatic nerve block for total knee arthroplasty: A comparison of 0.5% bupivacaine. Can J. Anesth 1998; 45: 1094-6.

4. Klein S, Greengrass R, Steele S, D'Ercole F, Speer K, Gleason D, DeLong E, Warner D. A Comparison of 0.5% Bupivacaine, 0.5% Ropivacaine, and 0.75% Ropivacaine for Interscalene Brachial Plexus Block. Anesth Analg 1998; 87: 1316-9.

5. Bertini L, Tagariello V, Mancini S, Ciaschi A, Posteraro C, Benedetto P, Martini O. 0.75% and 0.5% ropivacaine for axillary brachial plexus block: a clinical comparison with 0.5% bupivacaine. Reg Anes and Pain Med 1999; 24: 514-18.

6. Pettersson N, Emanuelsson B, Reventlid H, al. e. Pain relief by wound infiltration with bupivacaine or high-dose ropivacaine after inguinal hernia repair. Reg Anesth Pain Med 1999; 24: 569-75.

7. Brown D, Carpenter R, Thompson G. Comparison of 0.5% Ropivacaine and 0.5% Bupivacaine for Epidural Anesthesia in Patients Undergoing Lower-Extremity Surgery. Anesthesiology 1990; 72: 633-636.

8. Badner N, Sullivan P, Ganapathy S, Crosby E, McKenna J, Lui A. Continuous epidural infusion of ropivacaine for the prevention of postoperative pain after major orthopaedic surgery: a dose-finding study. Can J Anaesth 1996; 43: 17-22.

9. Meister G, D'Angela R, Owen M, Nelson K, Gaver R. A Comparison of epidural analgesia with 0.125% ropivacaine with fentanyl vs. 0.125% bupvacaine with fentanyl during labor. Anesth Analg 2000; 90: 632-7.

10. Polley L, Columb M, Naughton N. Relative analgesic potencies of ropvacaine and bupvacaine for epidural analgesia in labor; implications for therapeutic indexes. Anesthesiology 1999; 90: 944-50.

11. Feldman H, Arthur G, Covino B. Comparative systemic toxicity of convulsant and supraconvulsant doses of intravenous ropivacaine, bupivacaine and lidocaine in the conscious dogD. Anesth Analg 1989; 69: 794-801.

12. Morrison S, Dominquez J, Frascarolo P, Reiz S. A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine. Anesth Analg 2000; 90: 1308-14.

13. Yves A, Patrick N, Messiah A, Litt L, Rouvier B, Kamran S. Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthesiology 1997; 87: 479-86.

14. Yan AC, Newman RD. Bupivacaine-induced seizures and ventricular fibrillation in a 13-year-old girl undergoing wound debridement. Pediatric Emergency Care 1998; 14: 354-5.

15. Ballou B: Mother of 4 dies in minor surgery: painkiller gets in blood of Ortonville woman, Detroit Free Press. http://www.freep.com/news/locoak/nrose10_19991210.htm

Susan M. Steele, MD *
Stephen M. Klein, MD **
Karen C. Nielsen, MD***
Roy A. Greengrass, MD, F.R.C.P. #

*Associate Professor, Director of Ambulatory Anesthesiology
**Assistant Professor, Department of Anesthesiology
***Associate, Department of Anesthesiology
#Associate Professor, Co-Directory of Ambulatory Anesthesiology