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Ropivacaine for peripheral nerve blocks: Are there advantages?
Ropivacaine for Peripheral Nerve Blocks: Are There Advantages? Ewa Lew, MD, Jerry D. Vloka, MD, PhD, and Admir Hadzˇic´, MD, PhD
Many peripheral nerve block techniques require relatively large doses and volumes of a local anesthetic for their success. The traditional amide-type, long-acting local anesthetics have been associated with a risk of serious or lethal cardiotoxicity. A more recently introduced long-acting local anesthetic, ropivacaine, has a significantly greater safety margin over bupivacaine. The neuronal blocking characteristics of ropivacaine, when used in peripheral nerve blockade, seem to be equal or superior to bupivacaine. This report summarizes recently published data on the use of ropivacaine in peripheral nerve blockade. Copyright © 2001 by W.B. Saunders Company
practicing peripheral nerve blocks, significantly doses and volumes of local anesthetics than Ithosenhigher used in neuraxial anesthesia are administered. Consequently, systemic toxicity of local anesthetics is of special concern. Since the report by Albright in 1979 of lethal cardiotoxicity associated with the long-acting local anesthetics bupivacaine and etidocaine,1 the industry has focused on developing a long-acting local anesthetic with a wider margin of safety. The goal was to synthesize a longacting local anesthetic that is not only less toxic but also equally effective in its neuroblocking characteristic as the already available long-acting local anesthetics. Ropivacaine, a new aminoamide local anesthetic, is a direct result of these efforts. By now, much is known about the neuronal blocking characteristics of ropivacaine when used in epidural and spinal anesthesia. However, the neuronal blocking characteristics, when used in peripheral neuronal blockade, have not been recently reviewed. Thus, in this review, we summarize and discuss recently published information related to the use of ropivacaine in peripheral nerve blocks.
Neuronal Blocking Characteristics Speed of onset, duration of neuronal blockade, propensity for neurotoxicity, local irritation or pain on injection, From the Department of Anesthesiology, St Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY. Address correspondence to Admir Hadz˘ic´, MD, PhD, Department of Anesthesiology, St Luke’s-Roosevelt Hospital Center, 1111 Amsterdam Ave, New York, NY 10025. Copyright © 2001 by W.B. Saunders Company 1084-208X/01/0502-0003$35.00/0 doi:10.1053/trap.2001.23680
potency, and sensory-motor differentiation are crucially important characteristics when choosing a local anesthetic. Several of these characteristics are highlighted in the following sections. Speed of Onset Latency to block onset in early laboratory studies was reported to be similar between ropivacaine and bupivacaine in similar concentrations, with a tendency toward a more rapid onset with ropivacaine.2 A weaker binding to extraneural fat and tissues with ropivacaine than bupivacaine may also contribute to a greater availability of ropivacaine for transfer to the site of action in the nerves in peripheral nerve blockade.3 In a study with infant rats, ropivacaine produced sciatic nerve blockade that seemed quite similar in duration and modality-selectivity to that seen with bupivacaine.4 Of note, these investigators did not find significant differences in sensory versus motor blockade over a range of volumes and concentrations.4 In studies involving epidural anesthesia in animals, it has been suggested that ropivacaine is less potent than bupivacaine.5 However, in humans, the results are conflicting, with some studies showing no difference compared with bupivacaine6-11 and others suggesting that ropivacaine has a longer duration and frequency of sensory block relative to motor block when compared with bupivacaine.12-20 Duration of Neuronal Blockade In early laboratory studies, both ropivacaine and bupivacaine (0.25% to 1%) produced similar motor and sensory block when used for a variety of nerve blocks.2 They both resulted in comparable duration of peripheral blockade such as sciatic nerve, brachial plexus, and infraorbital blocks.21 Although the addition of a vasoconstrictor in some studies prolonged the duration of sciatic block compared with plain solutions for both ropivacaine and bupivacaine, this is not a consistent finding. For instance, Nolte et al22 reported that the addition of epinephrine in volunteers undergoing ulnar nerve block did not improve the latency or duration of ropivacaine. Of note, after epidural injection, kinetic profiles of both ropivacaine and bupivacaine are similar, and the addition of epinephrine (1:200,000) to the epidurally injected solutions of either
ropivacaine or bupivacaine has a minimal effect in reducing blood concentrations. Neurotoxicity In the studied concentrations, ropivacaine seems to be devoid of neural toxicity. Detailed histologic studies in guinea pigs and dogs also indicate that ropivacaine does not induce localized irritation in peripheral nerves or the spinal cord. In a study by Akerman et al,2 recovery from block was complete in all animals, with no apparent sequeale. In this study, there were no behavioral signs of local irritation with either ropivacaine or bupivacaine. In contrast, the combination of 1% bupivacaine with 5 g/mL of epinephrine in a sciatic nerve block caused neuroirritation, as documented by gnawing at the foot of the blocked leg in 33% of the blocked animals. Furthermore, in a study evaluating tissue irritation after injection of ropivacaine into dermal layers of the ear, the 1.0% solution of ropivacaine gave a significantly lower score than 1.0% bupivacaine.2 Although there was no tissue necrosis seen with any of the studied agents, the maximum intensity of hyperemia and edema and their extent occurred within 6 hours for ropivacaine and lidocaine versus after 24 hours for bupivacaine.2 These results do seem to correlate with the clinical evidence suggesting that ropivacaine is significantly less painful on injection than bupivacaine.23-25 Potency Ropivacaine may be less potent than bupivacaine when used for epidural and spinal anesthesia.22,26,27 Although some studies report a difference in potency of 20% to 40%,20,28,29 this difference may be eliminated or decreased at higher concentrations. For instance, in a study comparing 0.75% ropivacaine and 0.75% bupivacaine in patients undergoing abdominal surgery with epidural anesthesia, both drugs provided adequate anesthesia.30 Of note, patients receiving ropivacaine had weaker and shorter lasting lower extremity motor blocks with ropivacaine, suggesting that ropivacaine seems to have the propensity to produce a greater sensory block.31 In contrast, experimental and clinical evidence suggest that ropivacaine is equipotent to bupivacaine when used in peripheral nerve blockade, and this is discussed further.32-34
The Use in Specific Nerve Blocks Studies in adult animals and humans suggest that ropivacaine may have several important advantages over bupivacaine. These advantages are noted in the following sections. Ropivacaine for Peribulbar Blocks in Ophtalmic Surgery The efficacy of peribulbar anesthesia has made it an excellent alternative to a more traditional retrobulbar anes-
thesia because it is technically simpler to perform and causes fewer complications.35 In a comparative study, peribulbar anesthesia with 0.75% ropivacaine provided better occular akinesia 8 to 10 minutes after block placement than a bupivacaine/mepivacaine (0.5%/2%) mixture.33 Importantly, patients who received ropivacaine had less burning sensation on injection and required less supplementary injections. In another study, Gioia et al36 found that 0.75% ropivacaine had an equal speed of onset for peribulbar anesthesia and better quality of postoperative pain than a mixture of 0.5% bupivacaine and 2% lidocaine. Similarly, Nociti et al24 found that 1% ropivacaine resulted in faster onset of anesthesia and less pain on injection than 1% bupivacaine. Upper Extremity Nerve Blocks In patients undergoing lower arm surgery under axillary brachial plexus block, McGlade et al37 compared 0.5% ropivacaine with 0.5% bupivacaine. Using a 30-mL solution and a nerve-stimulator technique, they achieved an onset time of 10 to 20 minutes for ropivacaine and 10 to 30 minutes with bupivacaine. The investigators concluded that 0.5% ropivacaine and 0.5% bupivacaine are equally efficacious for axillary brachial plexus block in terms of the onset time, motor blockade, and overall success rate. However, the duration of residual blockade was significantly longer with bupivacaine (6.8 hours v 16 hours). Using the same volume of local anesthetic for interscalene block, Klein et al38 compared 0.5% and 0.75% ropivacaine and 0.5% bupivacaine in patients undergoing shoulder surgery. All solutions contained epinephrine in 1:400,000 concentration. In this study, there were also no differences in success rate or onset of sensory (⬍6 minutes) or motor (7 to 9 minutes) blocks, but the duration of analgesia was comparable among the 3 groups. Similarly, Bertini et al34 compared 0.5% and 0.75% ropivacaine with 0.5% bupivacaine for axillary brachial plexus block. Using a nerve-stimulator technique and 32 mL of local anesthetic, they found that both concentrations of ropivacaine produced a faster onset time than the bupivacaine. They and other investigators also noted that the 2 concentrations of ropivacaine (0.5% and 0.75%) were equipotent in this application.38-40 Some other reports, however, suggest that there may be an advantage to increasing the concentration of ropivacaine above 0.5%. For instance, Reder et al41 found that 0.75% ropivacaine for axillary block resulted in superior analgesia and muscle relaxation than 0.5% bupivacaine. On the other hand, decreasing the concentration of ropivacaine to 0.25% results in a virtually identical quality of anesthesia as 0.25% bupivacaine. However, this low concentration was associated with inadequate sensory or motor block when used in subclavian perivascular brachial plexus block.8
Somatic Nerve Blocks Ilioinguinal-iliohypogastric blocks can be very useful adjuncts to general anesthesia in patients undergoing inguinal hernia repair. Wulf et al42 suggested that 0.5% could be an optimal concentration because 0.75% solution resulted in an occasional femoral nerve block, which can delay the discharge. Plasma concentrations in all groups (0.2%, 0.5%, and 0.75%) resulted in safe plasma concentrations that reached their peaks at 30 to 45 minutes after injection.42 In search of an appropriate long-acting local anesthetic replacement for bupivacaine in patients undergoing total knee arthroplasty with lumbar plexus (30 mL)/sciatic (15 mL) nerve blocks, Greengrass et al43 compared 0.5% ropivacaine with 0.5% bupivacaine. Each local anesthetic mixture contained epinephrine in 1:400,000 concentration. Although the onset times and success rates were identical, the blocks with bupivacaine lasted 4 hours longer than the blocks with ropivacaine.
lower potential for serious cardiotoxicity after an inadvertent intravascular injection is a major advantage of ropivacaine in a peripheral nerve blockade in which the doses and volumes of local anesthetics are significantly larger than those used in neuraxial anesthesia.47-49 The onset of CNS toxicity symptoms before those of cardiac toxicity and a likely higher survival rate after a massive overdose also are important advantages over bupivacaine.50 In addition, a more rapid clearance of ropivacaine, more predictable duration of blockade, faster block onset, and less pain on injection are all advantages that make ropivacaine a long-acting local anesthetic with significant advantages over bupivacaine.45,51 Future studies are needed to discern the effects of epinephrine and increasing concentration of ropivacaine on the block onset, quality, and duration. Additional research also should focus on elucidating the clinically perceived sensory-motor differential blockade of ropivacaine and its blocking characteristics when compared with levobupivacaine.
Lower Extremity Nerve Blocks Casati et al44 have suggested that 225 mg of ropivacaine at a concentration greater than 0.5% is the optimal dose/ volume combination for lower extremity blocks. In this multicenter study, patients undergoing foot and ankle surgery were randomized to receive sciatic-femoral blocks with 0.5%, 0.75%, or 1% ropivacaine, respectively. The fourth group of patients received 2% mepivacaine and served as a control. Although the increasing concentration of ropivacaine from 0.5% to 1.0% had no effect on the success rate, it did shorten the latency to block onset and prolong the duration of analgesia. Of note, in this study, 1% ropivacaine was as fast to onset as 2% mepivacaine. The investigators chose mepivacaine as the control because bupivacaine has a wide and unpredictable latency as well as duration of blockade.45 They concluded that based on their results, 0.75% concentration is the best compromise between the onset, duration, and required volume of the drug. Using the 0.75% solution of ropivacaine, the same investigators also shortened the onset time and improved the quality of femoral nerve blockade with small volumes and a multiple injection technique.44 With this technique, the individual branches to the quadriceps muscle are identified by using nerve stimulation and separately blocked with smaller volumes of local anesthetic. When used for 3-in-1 blocks, 20 mL of 0.5% ropivacaine or 0.5% bupivacaine results in similar sensory onset times and quality of the block.46
Conclusions Although ropivacaine administered for epidural and spinal anesthesia seems to be less potent than bupivacaine, the published evidence indicates that ropivacaine and bupivacaine are equipotent over a wide range of concentrations when used in peripheral nerve blockade. The
References 1. Albright G: Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285-287, 1979 2. Akerman B, Hellberg IB, Trossvik C: Primary evaluation of the local anesthetic properties of the amino-amide agent ropivacaine (LEA 103). Acta Anaesthesiol Scand 32:571-578, 1998 3. Rosenberg PH, Kytta J, Alila A: Absorption of bupivacaine, etidocaine, lignocaine and ropivacaine into n-heptane, rat sciatic nerve, and human extradural and subcutaneous fat. Br J Anaesth 58:310314, 1986 4. Kohane DS, Sankar WN, Shubina M, et al: Sciatic nerve blockade in infant, adolescent and adult rats. Anesthesiology 89:1199-1208, 1998 5. Covino GB, Feldman HS: Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg 67:1047-1052, 1988 6. McGlade DP, Kalpokas MV, Mooney PH, et al: Comparison of 0.5% ropivacaine and 0.5% bupivacaine in lumbar epidural anesthesia for lower limb orthopedic surgery. Anaesth Intensive Care 25:262-266, 1997 7. Eddleston JM, Holland JJ, Griffin RP, et al: A double-blind comparison of 0.25% ropivacaine and 0.25% bupivacaine for extradural analgesia in labor. Br J Anesth 76:66-71, 1996 8. Hickey R, Rowley CL, Candidio KD, et al: A comparative study of 0.25% ropivacaine and 0.25% bupivacaine for brachial plexus block. Anesth Analg 75:602-606, 1992 9. Kopacz DJ, Emanuelsson BM, Thompson GE, et al: Pharmacokinetics of ropivacaine and bupivacaine for bilateral intercostal blockade in healthy male volunteers. Anesthesiology 81:1139-1148, 1994 10. McCrae AF, Jozwiak H, McClure JH: Comparison of ropivacaine and bupivacaine in extradural analgesia for the relief of pain in labor. Br J Anesth 74:261-265, 1995 11. Brown DL, Carpenter RL, Thompson GE: Comparison of 0.5% ropivacaine and 0.5% bupivacaine for epidural anesthesia in patients undergoing lower extremity surgery. Anesthesiology 72:633-639, 1990 12. Cederholm I: Preliminary risk-benefit analysis of ropivacaine in labour and following surgery. Drug Saf 16:391-402, 1997 13. Feldman HS, Dvoskin S, Arthur GR, et al: Antinociceptive and motorblocking efficacy of ropivacaine and bupivacaine after epidural administration in the dog. Reg Anesth 21:318-326, 1996 14. Griffin RP, Reynolds F: Extradural anesthesia for caeserian section: A double-blind comparison of 0.5% bupivacaine. Br J Anesth 74:512516, 1995 15. Morrison LM, Emanuelsson BM, McClure JH, et al: Efficacy and
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kinetics of extradural ropivacaine: Comparison with bupivacaine. Br J Anesth 72:164-169, 1994 Kerkkamp HE, Gielen MJ, Eldstrom HH: Comparison of 0.75% ropivacaine with epinephrine and 0.75% bupivacaine with epinephrine in lumbar epidural anesthesia. Reg Anesth 15:204-207, 1990 Markham A, Faulds D: Ropivacaine. A review of its pharmacokinetic and therapeutic use in regional anesthesia. Drugs 52:429-449, 1996 de Jong RH: Ropivacaine. White knight or dark horse? Reg Anesth 20:474-481, 1995 Brockway MS, Bannister J, McClure JH, et al: Comparison of extradural ropivacaine and bupivacaine. Br J Anesth 66:31-37, 1991 Zaric D, Nydahl PA, Philipson PA, et al: The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and motor block in volunteers: A double blind study. Reg Anesth 21:14-25, 1996 Dyhre H, Lang M, Wallin R, et al: The duration of action of bupivacaine, levobupivacaine, ropivacaine and pethidine in peripheral nerve block in the rat. Acta Anaesthesiol Scand 41:1346-1352, 1997 Nolte H, Fruhstorfer H, Edstrom HH: Local anesthetic efficacy of ropivacaine (LEA 103) in ulnar nerve block. Reg Anesth 15:118-124, 1990 Krishnan SK, Benzon HT, Siddiqui T, et al: Pain of intramuscular injection of bupivacaine, ropivacaine, with and without dexamethasone. Reg Anesth Pain Med 25:615-619, 2000 Nociti JR, Serzedo PS, Zuccolotto EB, et al: Ropivacaine in peribulbar block: A comparative study with bupivacaine. Acta Anaesthesiol Scand 43:799-802, 1999 Luchetti M, Magni G, Marraro G: A prospective randomized doubleblinded controlled study of ropivacaine 0.75% versus bupivacaine 0.5%–mepivacaine 2% for peribulbar anesthesia. Reg Anesth Pain Med 25:195-200, 2000 McDonald SB, Liu SS, Kopacz DJ, et al: Hyperbaric spinal ropivacaine: A comparison to bupivacaine in volunteers. Anesthesiology 90:971-977, 1999 Polley LS, Columb MO, Naughton NN, et al: Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: Implications for therapeutic indexes. Anesthesiology 90:94449450, 1999 Scott DB, Chamley D, Mooney P, et al: Epidural ropivacaine infusion for postoperative analgesia after major abdominal surgery: A dosefinding study. Anesth Analg 81:82-86, 1995 Gautier PE, De Kock M, Van Steenberge A, et al: Intrathecal ropivacaine for ambulatory surgery. Anesthesiology 91:1239-1245, 1999 Tuttle AA, Katz JA, Bridenbaugh PO, et al: A double-blind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery. Reg Anesth 20:515-520, 1995 Emanuleson BM, Person J, Alm C, et al: Systemic absorption and block after epidural injection of ropivacaine in healthy volunteers. Anesthesiology 87:1309-1317, 1997 Whiteside J: Regional anesthesia with ropivacaine. Reg Anesth Pain Med 25:659, 2000 (letter) Bertini L, Benedetto PD: Equipotency of ropivacaine and bupivacaine in peripheral nerve block. Reg Anesth Pain Med 25:659-660, 2000 (letter)
34. Bertini L, Tagariello V, Mancini S, et al: 0.75% and 0.5% ropivacaine for axillary brachial plexus block: A clinical comparison with 0.5% bupivacaine. Reg Anesth Pain Med 24:514-518, 1999 35. Weiss JL, Deichman CB: A comparison of retrobulbar and periocular anesthesia for cataract surgery. Arch Ophtalmol 107:96-98, 1989 36. Gioia L, Prandi E, Codenotti M, et al: Peribulbar anesthesia with either 0.75% ropivacaine or a 2% lidocaine and 0.5% bupivacaine mixture for vitreoretinal surgery: A double-blinded study. Anesth Analg 89:739-742, 1999 37. McGlade DP, Kalpokas MV, Mooney PH, et al: A comparison of 0.5% ropivacaine and 0.5% bupivacaine for axillary brachial plexus aneaesthesia. Anaesth Intensive Care 26:515-520, 1998 38. Klein S, Greengrass RA, Steele S, et al: A comparison of 0.5% bupivacaine and 0.75% ropivacaine for interscalene brachial plexus block. Anesth Analg 87:1316-1319, 1998 39. Vilho V, Ermo H, Teija H, et al: A clinical and pharmacokinetic comparison of ropivacaine and bupivacaine in axillary plexus block. Anesth Analg 81:534-538, 1995 40. Vaghadia H, Chan V, Ganapathy S, et al: A multicentre trail of ropivacaine 7.5 md/ml vs bupivacaine 5 mg for supraclavicular brachial plexus anesthesia. Can J Anesth 46:946-951, 1999 41. Reder JC, Drosdahl S, Klaastad O, et al: Axillary brachial plexus block with ropivacaine 7.5 mg/ml. A comparative study with bupivacaine 5 mg/ml. Acta Anaesthesiol Scand 43:794-798, 1999 42. Wulf H, Worthman F, Behnke H, et al: Pharmacokinetics and pharmacodynamics of ropivacaine 2 mg/ml, 5 mg/ml, or 7.5 mg/ml after ilioinguinal blockade for inguinal hernia repair in adults. Anesth Analg 89:1471-1474, 1999 43. Greengrass RA, Klein SM, D’Ercole FJ, et al: Lumbar plexus block for knee arthroplasty: Comparison of ropivacaine and bupivacaine. Can J Anaesth 45:1094-1096, 1998 44. Casati A, Fanelli G, Beccaria P, et al: The effects of the single or multiple injection technique on the onset time of femoral nerve blocks with 0.75% ropivacaine. Anesth Analg 91:181-184, 2000 45. Fanelli G, Casati A, Beccaria P, et al: A double blind comparison of ropivacaine, bupivacaine and mepivacaine during sciatic and femoral nerve blockade. Anesth Analg 87:597-600, 1998 46. Marhofer P, Oismuller C, Faryniak B, et al: Three-in-one blocks with ropivacaine: Evaluation of sensory onset time and quality of sensory block. Anesth Analg 90:125-128, 2000 47. Vloka JD, Hadzˇic´ A, Lesser JB, et al: A common epineural sheath for the nerves in the popliteal fossa and its possible implications for sciatic nerve block. Anesth Analg 84:387-390, 1997 48. Hadzˇic´ A, Vloka JD, Saff GN, et al: The “three-in-one block” for treatment of pain in a patient with acute herpes zoster infection. Reg Anesth 22:575-578, 1997 49. Hadzˇic´ A, Vloka JD: A comparison of the posterior versus lateral approaches to the block of the sciatic nerve in the popliteal fossa. Anesthesiology 88:1480-1486, 1988 50. Dony P, Dewinde V, Vanderick Cuignet O, et al: The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats. Anesth Analg 91:1489-1492, 2000 51. Arthur GR, Feldman HS, Covino BG: Comparative pharmacokinetics of bupivacaine and ropivacaine, a new amide local anesthetic. Anesth Analg 67:1053-1058, 1988
Many peripheral nerve block techniques require relatively large doses and volumes of a local anesthetic for their success. The traditional amide-type, long-acting local anesthetics have been associated with a risk of serious or lethal cardiotoxicity. A more recently introduced long-acting local anesthetic, ropivacaine, has a significantly greater safety margin over bupivacaine. The neuronal blocking characteristics of ropivacaine, when used in peripheral nerve blockade, seem to be equal or superior to bupivacaine. This report summarizes recently published data on the use of ropivacaine in peripheral nerve blockade. Copyright © 2001 by W.B. Saunders Company
practicing peripheral nerve blocks, significantly doses and volumes of local anesthetics than Ithosenhigher used in neuraxial anesthesia are administered. Consequently, systemic toxicity of local anesthetics is of special concern. Since the report by Albright in 1979 of lethal cardiotoxicity associated with the long-acting local anesthetics bupivacaine and etidocaine,1 the industry has focused on developing a long-acting local anesthetic with a wider margin of safety. The goal was to synthesize a longacting local anesthetic that is not only less toxic but also equally effective in its neuroblocking characteristic as the already available long-acting local anesthetics. Ropivacaine, a new aminoamide local anesthetic, is a direct result of these efforts. By now, much is known about the neuronal blocking characteristics of ropivacaine when used in epidural and spinal anesthesia. However, the neuronal blocking characteristics, when used in peripheral neuronal blockade, have not been recently reviewed. Thus, in this review, we summarize and discuss recently published information related to the use of ropivacaine in peripheral nerve blocks.
Neuronal Blocking Characteristics Speed of onset, duration of neuronal blockade, propensity for neurotoxicity, local irritation or pain on injection, From the Department of Anesthesiology, St Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY. Address correspondence to Admir Hadz˘ic´, MD, PhD, Department of Anesthesiology, St Luke’s-Roosevelt Hospital Center, 1111 Amsterdam Ave, New York, NY 10025. Copyright © 2001 by W.B. Saunders Company 1084-208X/01/0502-0003$35.00/0 doi:10.1053/trap.2001.23680
potency, and sensory-motor differentiation are crucially important characteristics when choosing a local anesthetic. Several of these characteristics are highlighted in the following sections. Speed of Onset Latency to block onset in early laboratory studies was reported to be similar between ropivacaine and bupivacaine in similar concentrations, with a tendency toward a more rapid onset with ropivacaine.2 A weaker binding to extraneural fat and tissues with ropivacaine than bupivacaine may also contribute to a greater availability of ropivacaine for transfer to the site of action in the nerves in peripheral nerve blockade.3 In a study with infant rats, ropivacaine produced sciatic nerve blockade that seemed quite similar in duration and modality-selectivity to that seen with bupivacaine.4 Of note, these investigators did not find significant differences in sensory versus motor blockade over a range of volumes and concentrations.4 In studies involving epidural anesthesia in animals, it has been suggested that ropivacaine is less potent than bupivacaine.5 However, in humans, the results are conflicting, with some studies showing no difference compared with bupivacaine6-11 and others suggesting that ropivacaine has a longer duration and frequency of sensory block relative to motor block when compared with bupivacaine.12-20 Duration of Neuronal Blockade In early laboratory studies, both ropivacaine and bupivacaine (0.25% to 1%) produced similar motor and sensory block when used for a variety of nerve blocks.2 They both resulted in comparable duration of peripheral blockade such as sciatic nerve, brachial plexus, and infraorbital blocks.21 Although the addition of a vasoconstrictor in some studies prolonged the duration of sciatic block compared with plain solutions for both ropivacaine and bupivacaine, this is not a consistent finding. For instance, Nolte et al22 reported that the addition of epinephrine in volunteers undergoing ulnar nerve block did not improve the latency or duration of ropivacaine. Of note, after epidural injection, kinetic profiles of both ropivacaine and bupivacaine are similar, and the addition of epinephrine (1:200,000) to the epidurally injected solutions of either
ropivacaine or bupivacaine has a minimal effect in reducing blood concentrations. Neurotoxicity In the studied concentrations, ropivacaine seems to be devoid of neural toxicity. Detailed histologic studies in guinea pigs and dogs also indicate that ropivacaine does not induce localized irritation in peripheral nerves or the spinal cord. In a study by Akerman et al,2 recovery from block was complete in all animals, with no apparent sequeale. In this study, there were no behavioral signs of local irritation with either ropivacaine or bupivacaine. In contrast, the combination of 1% bupivacaine with 5 g/mL of epinephrine in a sciatic nerve block caused neuroirritation, as documented by gnawing at the foot of the blocked leg in 33% of the blocked animals. Furthermore, in a study evaluating tissue irritation after injection of ropivacaine into dermal layers of the ear, the 1.0% solution of ropivacaine gave a significantly lower score than 1.0% bupivacaine.2 Although there was no tissue necrosis seen with any of the studied agents, the maximum intensity of hyperemia and edema and their extent occurred within 6 hours for ropivacaine and lidocaine versus after 24 hours for bupivacaine.2 These results do seem to correlate with the clinical evidence suggesting that ropivacaine is significantly less painful on injection than bupivacaine.23-25 Potency Ropivacaine may be less potent than bupivacaine when used for epidural and spinal anesthesia.22,26,27 Although some studies report a difference in potency of 20% to 40%,20,28,29 this difference may be eliminated or decreased at higher concentrations. For instance, in a study comparing 0.75% ropivacaine and 0.75% bupivacaine in patients undergoing abdominal surgery with epidural anesthesia, both drugs provided adequate anesthesia.30 Of note, patients receiving ropivacaine had weaker and shorter lasting lower extremity motor blocks with ropivacaine, suggesting that ropivacaine seems to have the propensity to produce a greater sensory block.31 In contrast, experimental and clinical evidence suggest that ropivacaine is equipotent to bupivacaine when used in peripheral nerve blockade, and this is discussed further.32-34
The Use in Specific Nerve Blocks Studies in adult animals and humans suggest that ropivacaine may have several important advantages over bupivacaine. These advantages are noted in the following sections. Ropivacaine for Peribulbar Blocks in Ophtalmic Surgery The efficacy of peribulbar anesthesia has made it an excellent alternative to a more traditional retrobulbar anes-
thesia because it is technically simpler to perform and causes fewer complications.35 In a comparative study, peribulbar anesthesia with 0.75% ropivacaine provided better occular akinesia 8 to 10 minutes after block placement than a bupivacaine/mepivacaine (0.5%/2%) mixture.33 Importantly, patients who received ropivacaine had less burning sensation on injection and required less supplementary injections. In another study, Gioia et al36 found that 0.75% ropivacaine had an equal speed of onset for peribulbar anesthesia and better quality of postoperative pain than a mixture of 0.5% bupivacaine and 2% lidocaine. Similarly, Nociti et al24 found that 1% ropivacaine resulted in faster onset of anesthesia and less pain on injection than 1% bupivacaine. Upper Extremity Nerve Blocks In patients undergoing lower arm surgery under axillary brachial plexus block, McGlade et al37 compared 0.5% ropivacaine with 0.5% bupivacaine. Using a 30-mL solution and a nerve-stimulator technique, they achieved an onset time of 10 to 20 minutes for ropivacaine and 10 to 30 minutes with bupivacaine. The investigators concluded that 0.5% ropivacaine and 0.5% bupivacaine are equally efficacious for axillary brachial plexus block in terms of the onset time, motor blockade, and overall success rate. However, the duration of residual blockade was significantly longer with bupivacaine (6.8 hours v 16 hours). Using the same volume of local anesthetic for interscalene block, Klein et al38 compared 0.5% and 0.75% ropivacaine and 0.5% bupivacaine in patients undergoing shoulder surgery. All solutions contained epinephrine in 1:400,000 concentration. In this study, there were also no differences in success rate or onset of sensory (⬍6 minutes) or motor (7 to 9 minutes) blocks, but the duration of analgesia was comparable among the 3 groups. Similarly, Bertini et al34 compared 0.5% and 0.75% ropivacaine with 0.5% bupivacaine for axillary brachial plexus block. Using a nerve-stimulator technique and 32 mL of local anesthetic, they found that both concentrations of ropivacaine produced a faster onset time than the bupivacaine. They and other investigators also noted that the 2 concentrations of ropivacaine (0.5% and 0.75%) were equipotent in this application.38-40 Some other reports, however, suggest that there may be an advantage to increasing the concentration of ropivacaine above 0.5%. For instance, Reder et al41 found that 0.75% ropivacaine for axillary block resulted in superior analgesia and muscle relaxation than 0.5% bupivacaine. On the other hand, decreasing the concentration of ropivacaine to 0.25% results in a virtually identical quality of anesthesia as 0.25% bupivacaine. However, this low concentration was associated with inadequate sensory or motor block when used in subclavian perivascular brachial plexus block.8
Somatic Nerve Blocks Ilioinguinal-iliohypogastric blocks can be very useful adjuncts to general anesthesia in patients undergoing inguinal hernia repair. Wulf et al42 suggested that 0.5% could be an optimal concentration because 0.75% solution resulted in an occasional femoral nerve block, which can delay the discharge. Plasma concentrations in all groups (0.2%, 0.5%, and 0.75%) resulted in safe plasma concentrations that reached their peaks at 30 to 45 minutes after injection.42 In search of an appropriate long-acting local anesthetic replacement for bupivacaine in patients undergoing total knee arthroplasty with lumbar plexus (30 mL)/sciatic (15 mL) nerve blocks, Greengrass et al43 compared 0.5% ropivacaine with 0.5% bupivacaine. Each local anesthetic mixture contained epinephrine in 1:400,000 concentration. Although the onset times and success rates were identical, the blocks with bupivacaine lasted 4 hours longer than the blocks with ropivacaine.
lower potential for serious cardiotoxicity after an inadvertent intravascular injection is a major advantage of ropivacaine in a peripheral nerve blockade in which the doses and volumes of local anesthetics are significantly larger than those used in neuraxial anesthesia.47-49 The onset of CNS toxicity symptoms before those of cardiac toxicity and a likely higher survival rate after a massive overdose also are important advantages over bupivacaine.50 In addition, a more rapid clearance of ropivacaine, more predictable duration of blockade, faster block onset, and less pain on injection are all advantages that make ropivacaine a long-acting local anesthetic with significant advantages over bupivacaine.45,51 Future studies are needed to discern the effects of epinephrine and increasing concentration of ropivacaine on the block onset, quality, and duration. Additional research also should focus on elucidating the clinically perceived sensory-motor differential blockade of ropivacaine and its blocking characteristics when compared with levobupivacaine.
Lower Extremity Nerve Blocks Casati et al44 have suggested that 225 mg of ropivacaine at a concentration greater than 0.5% is the optimal dose/ volume combination for lower extremity blocks. In this multicenter study, patients undergoing foot and ankle surgery were randomized to receive sciatic-femoral blocks with 0.5%, 0.75%, or 1% ropivacaine, respectively. The fourth group of patients received 2% mepivacaine and served as a control. Although the increasing concentration of ropivacaine from 0.5% to 1.0% had no effect on the success rate, it did shorten the latency to block onset and prolong the duration of analgesia. Of note, in this study, 1% ropivacaine was as fast to onset as 2% mepivacaine. The investigators chose mepivacaine as the control because bupivacaine has a wide and unpredictable latency as well as duration of blockade.45 They concluded that based on their results, 0.75% concentration is the best compromise between the onset, duration, and required volume of the drug. Using the 0.75% solution of ropivacaine, the same investigators also shortened the onset time and improved the quality of femoral nerve blockade with small volumes and a multiple injection technique.44 With this technique, the individual branches to the quadriceps muscle are identified by using nerve stimulation and separately blocked with smaller volumes of local anesthetic. When used for 3-in-1 blocks, 20 mL of 0.5% ropivacaine or 0.5% bupivacaine results in similar sensory onset times and quality of the block.46
Conclusions Although ropivacaine administered for epidural and spinal anesthesia seems to be less potent than bupivacaine, the published evidence indicates that ropivacaine and bupivacaine are equipotent over a wide range of concentrations when used in peripheral nerve blockade. The
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