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Based on findings that the cardiotoxicity infrequently observed with racemic bupivacaine shows enantioselectivity, i.e. it is more pronounced with the R(+)-enantiomer, the S(−)-enantiomer (levobupivacaine) has been developed for clinical use as a long acting local anaesthetic.
The majority of in vitro, in vivo and human pharmacodynamic studies of nerve block indicate that levobupivacaine has similar potency to bupivacaine. However, levobupivacaine had a lower risk of cardiovascular and CNS toxicity than bupivacaine in animal studies. In human volunteers, levobupivacaine had less of a negative inotropic effect and, at intravenous doses >75mg, produced less prolongation of the QTc interval than bupivacaine. Fewer changes indicative of CNS depression on EEG were evident with levobupivacaine.
Levobupivacaine is long acting with a dose-dependent duration of anaesthesia. The onset of action is ≤15 minutes with various anaesthetic techniques. In studies of surgical anaesthesia in adults, levobupivacaine provided sensory block for up to 9 hours after epidural administration of ≤202.5mg, 6.5 hours after intrathecal 15mg, and 17 hours after brachial plexus block with 2 mg/kg. Randomised, double-blind clinical studies established that the anaesthetic and/or analgesic effects of levobupivacaine were largely similar to those of bupivacaine at the same dose. Sensory block tended to be longer with levobupivacaine than bupivacaine, amounting to a difference of 23 to 45 minutes with epidural administration and approximately 2 hours with peripheral nerve block. With epidural administration, levobupivacaine produced less prolonged motor block than sensory block. This differential was not seen with peripheral nerve block. Conditions satisfactory for surgery and good pain management were achieved by use of local infiltration or peribulbar administration of levobupivacaine. Levobupivacaine was generally as effective as bupivacaine for pain management during labour, and was effective for the management of postoperative pain, especially when combined with clonidine, morphine or fentanyl.
The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials. No clinically significant ECG abnormalities or serious CNS events occurred with the doses used. The most common adverse event associated with levobupivacaine treatment was hypotension (31%).
Conclusions: Levobupivacaine is a long acting local anaesthetic with a clinical profile closely resembling that of bupivacaine. However, current preclinical safety and toxicity data show an advantage for levobupivacaine over bupivacaine. Clinical data comparing levobupivacaine with ropivacaine are needed before the role of the drug can be fully established. Excluding pharmacoeconomic considerations, levobupivacaine is an appropriate choice for use in place of bupivacaine.
Levobupivacaine is a long acting, amide-type local anaesthetic that is the S(−) \3- isomer of the racemate bupivacaine. In general, in vitro, in vivo and human volunteer studies of nerve block indicate that levobupivacaine is as potent as bupivacaine and produces similar sensory and motor block. A trend towards a longer sensory block with levobupivacaine was seen in some studies, and may be related to the greater vasoconstrictive activity of levobupivacaine than that of the R(+)-enantiomer (dexbupivacaine) at lower doses. The minimum local analgesic concentration was 0.083% for epidural levobupivacaine 20ml and 0.081% for bupivacaine 20ml in women in the first stage of labour.
Levobupivacaine has been consistently less toxic than bupivacaine in animal models. The lethal dose of levobupivacaine was 1.3- to 1.6-fold higher than that of bupivacaine in most animal studies, providing supportive evidence for a safety advantage over bupivacaine. In vitro findings indicating a lower risk of cardiotoxicity with levobupivacaine compared with dexbupivacaine and/or bupivacaine have included lesser effects or lower potency in: blocking cardiac sodium channels in the inactivated state; blocking cardiac potassium channels; reducing the maximal rate of depolarisation; prolonging atrioventricular conduction; and prolonging QRS interval duration. Differences between the agents with regards to effects on contractility seem to be less consistent, but levobupivacaine also appears to be less detrimental in this regard. In animal studies, levobupivacaine was associated with fewer and less severe cardiac disturbances, especially ventricular arrhythmias. In human volunteers, intravenous levobupivacaine (mean dose 56mg) produced less of a negative inotropic effect than bupivacaine (48mg). In another study of intravenous administration, the mean maximum increase in QTc interval was significantly less with levobupivacaine than with bupivacaine (3 vs 24 msec) in volunteers receiving >75mg.
A lower risk of CNS toxicity with levobupivacaine compared with dexbupivacaine and/or bupivacaine has also been reported, including less propensity to cause apnoea and higher convulsive doses (levobupivacaine 103mg vs bupivacaine 85mg) in animal studies. In human volunteers, 64% of intravenous bupivacaine recipients (mean dose 65.5mg) compared with 36% of levobupivacaine (67.7mg) recipients experienced central or peripheral nervous system disorders. Intravenous levobupivacaine 40mg produced fewer changes indicative of CNS depression on EEG than bupivacaine 40mg in volunteers.
When compared with ropivacaine in animals, levobupivacaine had similar or more pronounced nerve blocking effects, depending on the concentration and model. Levobupivacaine and ropivacaine had generally similar cardiovascular effects in in vitro and animal studies, although some studies reported greater QRS interval prolongation and/or arrhythmogenic risk with levobupivacaine at some concentrations, but no difference in mortality rates. However, cardiotoxicity has not been compared at established equipotent anaesthetic doses.
Only limited pharmacokinetic data are available for levobupivacaine. The plasma concentrations of levobupivacaine are dependent on dose and route of administration. Maximum plasma concentrations were 0.58 to 1.02 mg/L after epidural administration of 75 to 150mg, and 0.47 and 0.96 mg/L after brachial plexus block with 1 and 2 mg/kg, respectively, in patients. The elimination half-life after intravenous administration of 40mg in volunteers was 1.3 hours and the volume of distribution was 67L. Levobupivacaine is highly protein bound (>97%). The drug is extensively metabolised by the cytochrome P450 (CYP) system, primarily CYP1A2 and CYP3A4 isoforms, and then excreted in the urine (71% within 48 hours) and faeces (24%).
Levobupivacaine crosses the placenta, with an umbilical vein/maternal vein drug concentration ratio of 0.3 after epidural levobupivacaine 0.5% (150mg) in women undergoing Caesarean section.
After administration of racemic bupivacaine, it appears that systemic disposition is enantioselective, particularly with regards to plasma protein binding, which is higher with levobupivacaine than dexbupivacaine. Levobupivacaine does not undergo racaemisation in vivo.
Most trials of levobupivacaine have been randomised and double-blind and have involved 20 to 137 patients. All but 1 trial were in adults.
Surgical Anaesthesia: Levobupivacaine is long acting with an onset of action ≤15 minutes. The duration of action is dose-dependent and varies according to the anaesthetic technique. Adequate sensory and motor block for surgery was achieved in ≥90% of adult patients receiving adequate doses of levobupivacaine with satisfactory anaesthetic technique in most of the 10 available clinical trials. The anaesthetic and/or analgesic effects of levobupivacaine were largely similar to those with bupivacaine at the same dose in all comparative studies, including those of epidural, peripheral nerve block (supraclavicular or axillary brachial plexus nerve block), local infiltration and peribulbar administration. The duration of sensory block tended to be longer with levobupivacaine, although the difference was not statistically significant compared with bupivacaine in most cases. After epidural administration, the duration of sensory block with levobupivacaine was 8 to 9 hours with 0.75% (112.5 to 202.5mg), 7.5 hours with 0.5% (150mg) and 6 hours with 0.5% (75mg), and was 23 to 45 minutes longer than with bupivacaine at the same dose. The duration of sensory block after intrathecal levobupivacaine 15mg was 6.5 hours. With peripheral nerve block, the duration of sensory block was 17 hours with levobupivacaine 0.5% (2 mg/kg) versus 15 hours with bupivacaine 0.5% (2 mg/kg) or levobupivacaine 0.25% (1 mg/kg). With epidural administration, levobupivacaine produced less prolonged motor block than sensory block. This differential was not seen with peripheral nerve block.
Pain Management: Analgesia attained with epidural levobupivacaine was generally similar to that with bupivacaine in women in labour in the 2 available studies. The median time to onset of pain relief was 12 minutes and the duration of pain relief was approximately 50 minutes with levobupivacaine or bupivacaine 0.25% (25mg). With another regimen (mean dose of levobupivacaine 28 mg/h, bupivacaine 27 mg/h), 43% of the first stage of labour was pain free in both groups.
Effective postoperative pain relief was attained by combining epidural levobupivacaine 0.125% (7.5 mg/h) with clonidine, levobupivacaine 0.25% (10 mg/h) with morphine or levobupivacaine 0.125% (5 mg/h) with fentanyl or using higher doses of levobupivacaine 0.25% (15 mg/h). The time to first request for rescue analgesia was 10 to 17 hours. The combined regimens were more effective than any of the comparator agents alone, and the higher dose was more effective than lower doses of levobupivacaine. Ilioinguinal/iliohypogastric nerve block with levobupivacaine 0.5% (1.25 mg/kg per operated side) at the conclusion of surgery provided better pain relief than placebo in children.
When used at the lower doses needed for pain management, most patients did not have significant motor block.
The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials. The most common adverse events associated with levobupivacaine anaesthesia in 1141 patients in phase II/III trails (regardless of causality to the drug; route not stated) were: hypotension (31%), nausea (21%), postoperative pain (18%), fever (17%), vomiting (14%), anaemia (12%), pruritus (9%), pain (8%), headache (7%), constipation (7%), dizziness (6%) and fetal distress (5%).
Levobupivacaine and bupivacaine generally exerted similar effects on blood pressure and heart rate. No clinically significant ECG abnormalities occurred in clinical trials. No serious adverse CNS events were caused by levobupivacaine at the doses used; a small number of patients reported transient hypoaesthesia or paraesthesia, but these effects may have been operation-related. When levobupivacaine was used in obstetric indications, fetal outcome was not significantly different with levobupivacaine and bupivacaine. No significant CNS toxicity or cardiotoxicity was seen in a patient who received prompt treatment following an unintentional intravascular injection of levobupivacaine 142.5mg.
Dosage and Administration
Indications and recommended dosages for levobupivacaine differ markedly between Europe and the US.
The indications for levobupivacaine in Europe include epidural, intrathecal, peripheral nerve block, peribulbar administration and local infiltration for surgical anaesthesia in adults. Levobupivacaine is also indicated for epidural use for the management of pain, including labour and postoperative pain in adults. In children, levobupivacaine is indicated for ilioinguinal/iliohypogastric nerve block. The recommended maximum single dose for surgical anaesthesia in adults (other than for intrathecal administration) is generally 150mg. Additional doses may be required for a prolonged procedure. The recommended maximum single dose for intrathecal administration is 15mg. The recommended maximum epidural dose for labour analgesia is a 0.125% infusion of 12.5 mg/h or epidural injections of 0.25% up to 25mg at ≥15-minute intervals. For postoperative pain management in adults, the dose should not exceed 18.75 mg/h. The maximum dose for children undergoing ilioinguinal/iliohypogastric block is 1.25 mg/kg/ side.
In the US, levobupivacaine is indicated for epidural, peripheral nerve block, peribulbar administration and local infiltration for surgical anaesthesia in adults. Levobupivacaine is also indicated for epidural use for the management of pain, including labour and postoperative pain in adults. The drug is not currently indicated in the US for intrathecal administration or use in children. Surgical anaesthesia doses are similar to those in Europe, but doses of up to 50mg can be given for labour analgesia and up to 25 mg/h for postoperative pain management.
According to European prescribing information, the use of 0.75% (7.5 mg/ml) of levobupivacaine is contraindicated in obstetric patients; this is based on experience with bupivacaine and the 0.75% concentration of levobupivacaine has not been studied in obstetric patients. Concentrations up to 0.5% (150mg) can be used for Caesarean section. The drug is contraindicated for paracervical block in obstetrics and intravenous regional anaesthesia (Bier’s block) as well as in patients with severe hypotension or known hypersensitivity to local anaesthetics of the amide type.
US product labelling carries warnings against the use of levobupivacaine in obstetric patients at the 0.75% concentration, obstetrical paracervical block, and intravenous regional anaesthesia. Use of levobupivacaine in patients with known hypersensitivity to amide-type local anaesthetics is contraindicated.
Levobupivacaine should be used with caution in patients with impaired cardiovascular function or liver disease or reduced liver blood flow.
As with all local anaesthetics, epidural levobupivacaine can cause hypotension, bradycardia and possibly cardiac arrest. Appropriate treatments, equipment and personnel should be readily available in the event that a serious adverse event occurs. The toxic effects of other local anaesthetics, antiarrhythmic agents with local anaesthetic activity or class III antiarrhythmic agents may be additive to those of levobupivacaine.
- McCaughey W, Mirakhur RK. Drugs in anaesthetic practice and analgesia. In: Speight TM, Holford NHG, editors. Avery’s drug treatment. 4th ed. Auckland: Adis International, 1997: 451–514
- British National Formulary. No. 38. London: British Medical Association and Royal Pharmaceutical Society of Great Britain, 1999
- Albaladejo P, Bouaziz H, Benhamou D. Epidural analgesics: how can safety and efficacy be improved? CNS Drugs 1998 Aug; 10: 91–104 CrossRef
- Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51(4): 285–6 CrossRef
- Heath ML. Deaths after intravenous regional anaesthesia. BMJ 1982 Oct 2; 285: 913–4 CrossRef
- Åberg G. Toxicological and local anaesthetic effects of optically active isomers of two local anaesthetic compounds. Acta Pharmacol et Toxicol 1972; 31: 273–86 CrossRef
- Luduena FP, Bogado EF, Tullar BE Optical isomers of mepivacaine and bupivacaine. Arch Int Pharmacodyn 1972; 200: 359–69
- McClellan KJ, Spencer CM. Levobupivacaine. Drugs 1998 Sep; 56: 355–62 CrossRef
- Gristwood RW, Greaves JL. Levobupivacaine: a new safer long acting local anaesthetic agent. Expert Opin Invest Drug 1999 Jun; 8: 861–76 CrossRef
- 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 1997 Nov; 41: 1346–52 CrossRef
- Kanai Y, Tateyama S, Nakamura T, et al. Effects of levobupivacaine, bupivacaine, and ropivacaine on tail-flick response and motor function in rats following epidural or intrathecal administration. Region Anesth Pain Med 1999 Sep–Oct; 24: 444–52
- Bardsley H, Gristwood R, Watson N, et al. The local anaesthetic activity of levobupivacaine does not differ from racemic bupivacaine (Marcain): first clinical evidence. Expert Opin Invest Drug 1997 Dec; 6: 1883–5 CrossRef
- Lyons G, Columb M, Wilson RC. Epidural pain relief in labour: potencies of levobupivacaine and racemic bupivacaine. Br J Anaesth 1998 Dec; 81: 899–901 CrossRef
- Robinson APC, Lyons GR, Wilson RC, et al. Levobupivacaine for extradural analgesia in labour; the sparing effect of extradural fentanyl [abstract]. Br J Anaesth 1999 Jun; 82 Suppl. 1:208
- Aps C, Reynolds F. An intradermal study of the local anaesthetic and vascular effects of the isomers of bupivacaine. Br J Clin Pharmacol 1978; 6: 63–8 CrossRef
- Morrison SG, Dominguez JJ, Frascarolo P, et al. Cardiotoxic effects of levobupivacaine, bupivacaine and ropivacaine — an experimental study in pentobarbital anesthetized swine [abstract]. Region Anesth Pain Med 1998 May–June; 23 (3 Suppl.): 50 CrossRef
- Burke D, MacKenzie M, Newton D, et al. A comparison of vasoactivity between levobupivacaine and bupivacaine [abstract]. Br J Anaesth 1998; 81(4): 631P-2P
- Santos AC, Karpel B, Noble G. The placental transfer and fetal effects of levobupivacaine, racemic bupivacaine, and ropivacaine. Anesthesiology 1999 Jun; 90: 1698–703 CrossRef
- Fernandes L, Simonetti MPB. Vascular effects of S(−) bupivacaine, RS(±) bupivacaine and ropivacaine on isolated strips of human umbilical vein: preliminary results [abstract]. Reg Anesth 1997 Mar–Apr; 22 Suppl.: 65
- Valenzuela C, Snyders DJ, Bennett PB, et al. Stereoselective block of cardiac sodium channels by bupivacaine in guinea pig ventricular myocytes. Circulation 1995; 92: 3014–24 CrossRef
- Huang YF, Pryor ME, Mather LE, et al. Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg 1998; 86: 797–804
- Vanhoutte F, Vereecke J, Verbeke N, et al. Stereoselective effects of the enantiomers of bupivacaine on the electrophysiological properties of the guinea-pig papillary muscle. Br J Pharmacol 1991; 103: 1275–81 CrossRef
- Valenzuela C, Delpón E, Tamkun MM, et al. Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine enantiomers. Biophys J 1995; 69: 418–27 CrossRef
- Harding DP, Collier PA, Huckle RM, et al. Cardiotoxic effects of levobupivacaine, bupivacaine and ropivacaine: an in vitro study in guinea-pig and human cardiac muscle [abstract]. Br J Pharmacol 1998 Dec; 125 Suppl.: 127P CrossRef
- Graf BM, Martin E, Bosnjak ZJ, et al. Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused guinea pig heart. Anesthesiology 1997 Feb; 86(2): 410–9 CrossRef
- Mazoit JX, Boïco O, Samii K. Myocardial uptake of bupivacaine: II. Pharmacokinetics and pharmacodynamics of bupivacaine enantiomers in the isolated perfused rabbit heart. Anesth Analg 1993; 77: 477–82
- Mazoit JX, Decaux J, Bouaziz H, et al. Comparative effect of racemic bupivacaine, levobupivacaine and ropivacaine on isolated rabbit heart [abstract]. Anesthesiology 1999 Sep; 91(3A): A885
- Simonetti MPB, Fernandes L. S(−) bupivacaine and RS(±) bupivacaine: a comparison of effects on the right and left atria of the rat [abstract]. Reg Anesth 1997 Mar–Apr; 22 Suppl.: 58
- Graf BM, Eberl S, Abraham I, et al. Comparison of the direct cardiotoxicity of the isomers of ropivacaine and bupivacaine [abstract]. Anesthesiology 1998 Sep; 89 (3A Suppl.): A876 CrossRef
- Denson DD, Behbehani MM, Gregg RV. Enantiomer-specific effects of an intravenously administered arrhythmogenic dose of bupivacaine on neurons of the nucleus tractus solitarius and the cardiovascular system in the anesthetized rat. Reg Anesth 1992 Nov–Dec; 17: 311–6
- Chang DHT, Mather LE, Ladd LA, et al. Effects of high doses of levobupivacaine on the cardiovascular and central nervous systems of the sheep [abstract]. Proceedings of the Annual Scientific Meeting of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 1997 Dec; 4: 76
- Santos AC. Comparative systemic toxicity of levobupivacaine, bupivacaine and ropivacaine during ovine pregnancy [abstract]. Anesth Analg 1999 Feb; 88 Suppl.: S265 CrossRef
- Ericson A-C, Avesson M. Effects of ropivacaine, bupivacaine and S(−)-bupivacaine on the ECG after rapid IV injections to conscious rats [poster]. International Monitor on Regional Anaesthesia 1996; 8(2): 51
- Bardsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998 Sep; 46: 245–9 CrossRef
- Nimmo W. Evidence of improved safety over bupivacaine in human volunteers [abstract]. European Society of Anaesthesiologists. 1998 Apr 25–28; Barcelona, Spain
- Burke D, Henderson DJ, Simpson AM, et al. Comparison of 0.25% S(−)-bupivacaine with 0.25% RS-bupivacaine for epidural analgesia in labour. Br J Anaesth 1999; 83(5): 750–5 CrossRef
- Bader AM, Tsen LC, Camann WR, et al. Clinical effects and maternal and fetal plasma concentrations of 0.5% epidural levobupivacaine versus bupivacaine for cesarean delivery. Anesthesiology 1999 Jun; 90: 1596–601 CrossRef
- Cox CR, Faccenda KA, Gilhooly C, et al. Extradural S(−)-bupivacaine: comparison with racemic RS-bupivacaine. Br J Anaesth 1998 Mar; 80: 289–93 CrossRef
- Cox CR, Checketts MR, MacKenzie N, et al. Comparison of S(−)-bupivacaine with racemic (RS)-bupivacaine in supraclavicular brachial plexus block. Br J Anaesth 1998; 80: 594–8 CrossRef
- Gunter JB, Gregg T, Varughese AM, et al. Levobupivacaine for ilioinguinal/iliohypogastric nerve block in children. Anesth Analg 1999 Sep; 89: 647–9
- McLure HA, Rubin AP Comparison of 0.75% levobupivacaine with 0.75% racemic bupivacaine for peribulbar anaesthesia. Anaesthesia 1998 Dec; 53: 1160–4 CrossRef
- Kopacz DJ, Allen HW, Thompson GE. A comparison of epidural levobupivacaine 0.75% with racemic bupivacaine for lower abdominal surgery. Anesth Analg 2000; 90: 642–8 CrossRef
- Van F, Rolan PE, Brennan N, et al. Differential effects of levo-and racemic bupivacaine on the EEG in volunteers [abstract]. Region Anesth Pain Med 1998 May–Jun; 23 Suppl.: 48 CrossRef
- Purdue Pharma L.P Chirocaine (levobupivacaine injection) prescribing information. Norwalk (CT), USA, 1 Dec 1999
- Faccenda KA, Morrison LMM. The pharmacokinetics of levobupivacaine and racemic bupivacaine following extradural administration [abstract]. Region Anesth Pain Med 1998 May–Jun; 23 Suppl.: 52 CrossRef
- Abbott Laboratories. Chirocaine 2.5 mg/ml: summary of product characteristics. Cambridge, UK, 1999
- Thomas JM, Schug SA. Recent advances in the pharmacokinetics of local anaesthetics: long-acting amide enantiomers and continuous infusions. Clin Pharmacokinet 1999 Jan; 36: 67–83 CrossRef
- Mather M, McCall P, McNicol PL. Bupivacaine enantiomer pharmacokinetics after intercostal neural blockade in liver transplantation patients. Anesth Analg 1995; 80: 328–35
- Palkama VJ, Neuvonen PJ, Olkkola KT. Effect of itraconazole on the pharmacokinetics of bupivacaine enantiomers in healthy volunteers. Br J Anaesth 1999; 83(4): 659–61 CrossRef
- Groen K, Mantel M, Zeijlmans PWM, et al. Pharmacokinetics of the enantiomers of bupivacaine and mepivacaine after epidural administration of the racemates. Anesth Analg 1998; 86: 361–6
- Burm AGL, van der Meer AD, van Kleef JW, et al. Pharmacokinetics of the enantiomers of bupivacaine following intravenous administration of the racemate. Br J Clin Pharmacol 1994 Aug; 38: 125–9 CrossRef
- Crews JC, Foreman AS, Weller RS, et al. Onset, duration, and dose tolerability of levobupivacaine 0.5% for axillary brachial plexus neural blockade [abstract]. Anesthesiology 1998 Sep; 89(3A) Suppl.: A894 CrossRef
- Convery PN, Weir P, Quinn P, et al. Epidural levobupivacaine for hip arthroplasty anesthesia and analgesia. Region Anesth Pain Med 1998 May–Jun; 23 Suppl.: 86 CrossRef
- Carr D. Levobupivacaine for postoperative pain management: new strategies [symposia presentation]. In: From anesthesia to analgesia: a single agent. Abingdon, Oxfordshire: TMG Healthcare Communications, 1999: 9–11
- Burke D, Kennedy S, Bannister J. Spinal Anesthesia with 0.5% s(≡)-bupivacaine for elective lower limb surgery. Region Anesth Pain Med 1999; 24(6): 519–23
- Convery P, Burke D, Donaldson L, et al. Comparison of 0.125% levobupivacaine and 0.125% bupivacaine epidural infusions for labour analgesia [abstract]. Br J Anaesth 1999 Jun; 82 Suppl. 1: 163
- Convery PN, Milligan KR, Weir P, et al. The efficacy and safety of epidural infusions of levobupivacaine with and without clonidine for post-operative pain relief in patients undergoing total hip replacement. Anesthesiology 1998 Sep; 89 (3A Suppl.): A850 CrossRef
- Kopacz DJ, Sharrock NE, Allen HW. A comparison of levobupivacaine 0.125%, fentanyl 4 μg/mL, or their combination for patient-controlled epidural analgesia after major orthopedic surgery. Anesth Analg 1999; 89: 1497–503
- Dickson U, Murdoch J, Wilson P, et al. The efficacy and safety of levobupivacaine administered as a continuous epidural infusion for post-operative analgesia in patients undergoing elective orthopaedic surgery [abstract]. Region Anesth Pain Med 1999 May–Jun; 24 Suppl.: 18
- Crews JC, Hord AH, Denson DD, et al. A comparison of the analgesic efficacy of 0.25% levobupivacaine combined with 0.005% morphine, 0.25% levobupivacaine alone, or 0.005% morphine alone for the management of postoperative pain in patients undergoing major abdominal surgery. Anesth Analg 1999; 89: 1504–9
- Bay-Nielsen M, Klarskov B, Bech K, et al. Levobupivacaine vs bupivacaine as infiltration anaesthesia in inguinal herniorrhaphy. Br J Anaesth 1999 Feb; 82(2): 280–2 CrossRef
- Kingsnorth A, Bennett D, Cummings C, et al. A randomised, double-blind study to compare the efficacy of 0.25% levobupivacaine with 0.25% bupivacaine (racemic) infiltration anaesthesia in elective inguinal hernia repair. Region Anesth Pain Med 1998 May–Jun; 23 Suppl.: 106 CrossRef
- Carr DB, Sternlicht A, Carabuena J, et al. Preemptive interscalene block for elective, short-stay shoulder surgery: loss of early benefits by one week after discharge [abstract]. Anesthesiology 1999 Sep; 91 Suppl.: A943
- Stead SW. Innovations in ophthalmic anesthesia. Anesth Analg 1998 Mar; 86 Suppl.: 128–38
- O’Sullivan ER Comparison of 0.75% levobupivacaine with 0.75% racemic bupivacaine for peribulbar anaesthesia [letter]. Anaesthesia 1999 Jun; 54: 610 CrossRef
- Curatolo M, Scaramozzino P, Venuti FS, et al. Factors associated with hypotension and bradycardia after epidural blockade. Anesth Analg 1996; 83: 1033–40
- Kopacz DJ, Allen HW. Accidental intravenous levobupivacaine. Anesth Analg 1999 Oct; 89: 1027–9
- Yun EM, Meadows W, Santos AC. New amide local anaesthetics for obstetric use. Baillieres Clin Obstet Gynaecol 1998 Sep; 12:461–71 CrossRef
- Markham A, Faulds D. Ropivacaine: a review of its pharmacology and therapeutic use in regional anesthesia. Drugs 1996 Sep; 52(3): 429–49 CrossRef
- Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labour. Anesthesiology 1999; 90: 944–50 CrossRef
- Capogna G, Celleno D, Fusco P, et al. Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 1999; 82(3): 371–3 CrossRef
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