title: A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study.
abstract: BACKGROUND
  Mixtures of lidocaine with a long-acting local anesthetic are commonly used for peripheral nerve block. Few data are available regarding the safety, efficacy, or pharmacokinetics of mixtures of local anesthetics. In the current study, we compared the effects of bupivacaine 0.5% or ropivacaine 0.75% alone or in a mixed solution of equal volumes of bupivacaine 0.5% and lidocaine 2% or ropivacaine 0.75% and lidocaine 2% for surgery after femoral-sciatic peripheral nerve block. The primary end point was onset time.
  
  
  METHODS
  In a double-blind, randomized study, 82 adults scheduled for lower limb surgery received a sciatic (20 mL) and femoral (20 mL) peripheral nerve block with 0.5% bupivacaine (200 mg), a mixture of 0.5% bupivacaine 20 mL (100 mg) with 2% lidocaine (400 mg), 0.75% ropivacaine (300 mg) or a mixture of 0.75% ropivacaine 20 mL (150 mg) with 2% lidocaine (400 mg). Each solution contained epinephrine 1:200,000. Times to perform blocks, onset times (end of injection to complete sensory and motor block), duration of sensory and motor block, and morphine consumption via IV patient-controlled analgesia were compared. Venous blood samples of 5 mL were collected for determination of drug concentration at 0, 5, 15, 30, 45, 60, and 90 min after placement of the block.
  
  
  RESULTS
  Patient demographics and surgical times were similar for all four groups. Sciatic onset times (sensory and motor block) were reduced by combining lidocaine with the long-acting local anesthetic. The onset of bupivacaine-lidocaine was 16 +/- 9 min versus 28 +/- 12 min for bupivacaine alone. The onset of ropivacaine-lidocaine was 16 +/- 12 min versus 23 +/- 12 for ropivacaine alone. Sensory blocks were complete for all patients within 40 min for those receiving bupivacaine-lidocaine versus 60 min for those receiving bupivacaine alone and 30 min for those receiving ropivacaine-lidocaine versus 40 min for those receiving ropivacaine alone (P < 0.05). Duration of sensory and motor block was significantly shorter in mixture groups. There was no difference among groups for visual analog scale pain scores and morphine consumption during the 48 h postoperative period, except for bupivacaine alone (median: 9 mg) versus bupivacaine-lidocaine mixture (15 mg), P < 0.01. There was no difference in the incidence of adverse events among groups. Plasma concentrations of bupivacaine and ropivacaine were higher, and remained elevated longer, in patients who received only the long-acting local anesthetic compared to patients who received the mixture of long-acting local anesthetic with lidocaine (P < 0.01).
  
  
  CONCLUSIONS
  Mixtures of long-acting local anesthetics with lidocaine induced faster onset blocks of decreased duration. Whether there is a safety benefit is unclear, as the benefit of a decreased concentration of long-acting local anesthetic may be offset by the presence of a significant plasma concentration of lidocaine.
authors.affiliation: Division of the Department of Anesthesiology and Pain Management, University Groupe Caremeau Hospital, France. philippe.cuvillon@wanadoo.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Cuvillon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nouvellon
authors.forename: Jacques
authors.initials: J
authors.lastname: Ripart
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Boyer
authors.forename: Laurence
authors.initials: L
authors.lastname: Dehour
authors.forename: Aba
authors.initials: A
authors.lastname: Mahamat
authors.forename: Joel
authors.initials: J
authors.lastname: L'hermite
authors.forename: Christophe
authors.initials: C
authors.lastname: Boisson
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vialles
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Lefrant
authors.forename: Jean Emmanuel
authors.initials: JE
authors.lastname: de La Coussaye
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000493:pharmacokinetics; D000779:Anesthetics, Local / Q000493:pharmacokinetics; D002045:Bupivacaine / Q000493:pharmacokinetics; D004311:Double-Blind Method; D023381:Endpoint Determination; D004837:Epinephrine; D005260:Female; D005267:Femoral Nerve; D006801:Humans; D007866:Leg / Q000601:surgery; D008012:Lidocaine; D008297:Male; D008875:Middle Aged; D009407:Nerve Block; D010147:Pain Measurement; D011446:Prospective Studies; D000077212:Ropivacaine; D012584:Sciatic Nerve; D014662:Vasoconstrictor Agents
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine; D004837:Epinephrine