title: Local anaesthetic use for the iliac crest-donor site: pharmacokinetic and pharmacodynamic evaluations.
abstract: During orthopaedic surgery of the limb, we performed a prospective, double blind controlled study on three parallel groups in 30 patients to evaluate the pharmacokinetic and pharmacodynamic effect of infiltration of the iliac crest bone graft harvest site with 20 ml of bupivacaine (100 mg), ropivacaine (150 mg) or saline as control group (n = 10 in each group). Then, in a sheep model of iliac crest infiltration, we compared the pharmacokinetics of single administration of plain bupivacaine (100 mg) and bupivacaine (500 mg)-loaded microspheres. In the clinical control group, pain from the iliac crest was worse than pain from the primary surgical site. Pain from the iliac crest was significantly reduced during the first 12 postoperative hours in local anaesthetic groups compared to the control group. However, during this period, pain from the primary surgical site was increased compared to the control group. Finally, there was no difference between the three groups in the average intake of PCA morphine. There was no significant pharmacokinetic and pharmacodynamic difference between plain bupivacaine and ropivacaine. The maximal plasma concentration (Cmax) of ropivacaine and bupivacaine were 964 (282) ng ml(-1) and 638 (366) ng ml(-1), respectively. In the sheep model, it was clearly shown that the release of bupivacaine from microspheres was controlled and prolonged despite the largest dose of bupivacaine used (500 mg; n = 4). Wound infiltration of iliac crest harvest site with local anaesthetic is an easy technique for postoperative analgesia. However, this effect lasts only 12 hours without reducing the morphine consumption due to an increase of pain from the primary surgical site. The local anaesthetic infiltration produced a significant peak of plasma level, which could be dangerous if another infiltration or regional anaesthetic technique was associated with it. Experimentally, as a drug delivery system, the use of local anaesthetic-loaded microspheres could be an interesting alternative.
authors.affiliation: Service d'Anesthésie Réanimation 2, CHRU de Rennes, Hôpital Hôtel Dieu, Rennes, France. jean-pierre.estebe@chu-rennes.fr
authors.forename: J P
authors.initials: JP
authors.lastname: Estebe
authors.forename: P
authors.initials: P
authors.lastname: Le Corre
authors.forename: A
authors.initials: A
authors.lastname: Le Naoures
authors.forename: C
authors.initials: C
authors.lastname: Eliat
authors.forename: F
authors.initials: F
authors.lastname: Chevanne
authors.forename: J L
authors.initials: JL
authors.lastname: Husson
authors.forename: C
authors.initials: C
authors.lastname: Ecoffey
mesh_terms: D000577:Amides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016058:Analgesia, Patient-Controlled / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000772:Anesthesia, Local / Q000379:methods*; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D002045:Bupivacaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005121:Extremities / Q000601:surgery; D005260:Female; D006801:Humans; D007085:Ilium / Q000637:transplantation*; D008297:Male; D008863:Microspheres; D009020:Morphine / Q000008:administration & dosage; D010147:Pain Measurement / Q000706:statistics & numerical data; D010149:Postoperative Pain / Q000188:drug therapy; D011446:Prospective Studies; D000077212:Ropivacaine; D012756:Sheep; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D000577:Amides; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D012965:Sodium Chloride; D009020:Morphine; D000077212:Ropivacaine; D002045:Bupivacaine