C. Riff (1), A. Marsot(1), A. Bourgoin(2) J. Dupouey(1), C. Martin(2), L. Alanioux(1), O. Blin(1), R. Guilhaumou(1)
(1)Service de Pharmacologie Clinique et Pharmacovigilance, AP-HM, Pharmacologie intégrée et interface clinique et industriel, Institut des Neurosciences Timone – AMU-CNRS 7289, Aix Marseille Université - Marseille (France), (2)Service d'Anesthésie Réanimation, Hôpital Nord - Marseille (France).
Objectives: In breast cancer, tumescent lidocaine anaesthesia could increase accessibility to mastectomy in elderly women with comorbidities and relieve post-operative pain. In this procedure, high-dose diluted lidocaine was administrated together with epinephrine [1]. However, few pharmacokinetics data are actually available and potential concentration dependant toxicity was never investigated. We present in this study the first pharmacokinetic model of lidocaine in tumescent anaesthesia for mastectomy with safety and post-operative pain data.
Methods: Elderly women undergoing total mastectomy were included in this prospective study. A tumescent solution containing 10 mg/kg of lidocaine 0.1% with epinephrine was infiltrated. Lidocaine serum concentrations were determined using gas chromatography in the course of 48h and were analysis by a population pharmacokinetic approach using NONMEM 7.3. Age, body weight and body mass index (BMI) were investigated as covariates. Side effects, opioid requirement and post-operative pain evaluated by EVA scale were registered.
Results: Ten women were included and patients’ characteristics were as follow (mean±sd):79 ±5 years, 67.7 ±12.5 kg and a BMI of 27.5 ±5. No symptoms of local anaesthetic systemic toxicity were observed. EVA scales registered were above 2 during the 48h and no opioid treatment was required. Lidocaine maximal observed concentration (1.65 ±0.56µg/ml) occurred 6.3 ±2.9 hour after the beginning of infusion. A one-compartment model with zero-order and first-order input for infiltration and infusion respectively, best described the data. Clearance, volume of distribution and first-order absorption rate were (intersubject variability) 30.2 L/h (65.1%), 390 L (57.6%) and 0.19 h-1 (44.3%), respectively. No covariate significantly improves predictions although diagnostic plots shown a trend between body weight and volume of distribution.
Conclusions: We developed the first pharmacokinetic model of lidocaine administered in tumescent anaesthesia. Lidocaine pharmacokinetics was characterized by a quick absorption after subcutaneous infiltration with a wide-interindividual variability, followed by an extensive and absorption-limited distribution. Moreover, our results demonstrate that tumescent lidocaine anaesthesia is a safe and effective anaesthetic procedure in mastectomy, with an additional effect on post-operative pain. Additional studies with larger cohorts are necessary to confirm these results.
References:
[1] Klein JA., Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. J Dermatol Surg Oncol. 1990 Mar;16(3):248-63.
Reference: PAGE 25 () Abstr 5817 [www.page-meeting.org/?abstract=5817]
Poster: Drug/Disease modeling - Other topics