Pharmacokinetics and safety of lidocaine and monoethylglycinexylidide in liposuction: a microdialysis study.
High doses of lidocaine are administered to patients undergoing liposuction. Monoethylglycinexylidide, the active metabolite of lidocaine, is 80 to 90 percent as potent as lidocaine, and its relative toxicity is approximately that of lidocaine. Monoethylglycinexylidide has not previously been measured in studies on lidocaine in liposuction. The aims of this study were to characterize systemic exposure to lidocaine and monoethylglycinexylidide and to measure lidocaine and monoethylglycinexylidide levels within the tissues. Five female volunteers between the ages of 29 and 40 years underwent liposuction. Lidocaine (1577 to 2143 mg, corresponding to 19.9 to 27.6 mg/kg) was infiltrated during the procedure. Levels of lidocaine and monoethylglycinexylidide in blood and lipoaspirate were assessed perioperatively. Tissue lidocaine and monoethylglycinexylidide levels were measured postoperatively using a microdialysis technique in vivo. The peak (maximal) concentration of lidocaine plus monoethylglycinexylidide was 2.2 to 2.7 microg/ml. Time to peak lidocaine plus monoethylglycinexylidide was 8 to 28 hours after infiltration began. Absorbed lidocaine was estimated to be 911 to 1596 mg; therefore, 45 to 93 percent (mean, 64 percent) of the infiltrated dose was ultimately absorbed. Lipoaspirate analysis showed that 9.1 to 10.8 percent (mean, 9.7 percent) of the infiltrated dose was removed during the procedure. Tissue lidocaine levels below 5 microg/ml were demonstrated from 4 to 8 hours postoperatively. The peak lidocaine plus monoethylglycinexylidide concentration was within safe limits in this group of subjects. Time to peak lidocaine plus monoethylglycinexylidide signifies a delayed peak and therefore a longer period of potential lidocaine toxicity than was originally thought. Microdialysis results demonstrated that tissue lidocaine levels may be subtherapeutic within 4 to 8 hours of the procedure. Investigation into factors controlling the resorption of lidocaine during liposuction is warranted in an effort to improve the duration of effect. Furthermore, considering the active metabolite monoethylglycinexylidide, longitudinal studies are necessary to determine whether improving the side effect profile of lidocaine by reducing the dose administered during liposuction may be possible without decreasing the perioperative analgesic effect.
Kenkel
Jeffrey M
JM
Department of Plastic Surgery, Nancy Lee and Perry R. Bass Advanced Plastic Surgery and Wound Healing Laboratory, University of Texas Southwestern Medical Center, Dallas, 75390-9132, USA. jeffrey.kenkel@utsouthwestern.edu
Lipschitz
Avron H
AH
Shepherd
Greene
G
Armstrong
Victor W
VW
Streit
Frank
F
Oellerich
Michael
M
Luby
Maureen
M
Rohrich
Rod J
RJ
Brown
Spencer A
SA
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000633:toxicity; D015187:Lipectomy; D008657:Metabolic Clearance Rate / Q000502:physiology; D017551:Microdialysis; D011184:Postoperative Period; D018570:Risk Assessment
D000779:Anesthetics, Local; D008012:Lidocaine; C001173:monoethylglycinexylidide