Henry R, Patterson L, Avery N, Tanzola R, Tod D, Hunter D, Nickel J C, Morales A
Department of Anesthesiology, Queen's University, Kingston, Ontario, Canada.
J Urol. 2001 Jun;165(6 Pt 1):1900-3. doi: 10.1097/00005392-200106000-00014.
Pharmacokinetic studies have shown that intravesical lidocaine is not sufficiently absorbed by human bladders to achieve significant serum levels and it only provides a superficial local anesthetic effect. We investigated the pharmacokinetics of alkalized intravesical lidocaine in healthy volunteers and patients with interstitial cystitis to determine a safe dose of buffered lidocaine, the effect of interstitial cystitis on lidocaine uptake and the acute local anesthetic effect on bladder pain in interstitial cystitis.
An initial dose finding study was done in 12 healthy volunteers using 4, 5 and 6 mg./kg. 5% lidocaine buffered with 8.4% sodium bicarbonate. Serial lidocaine levels were measured for 3 hours. Serum measurement was repeated in 12 patients with interstitial cystitis using 5 mg/kg. 5% lidocaine with sodium bicarbonate daily for 2 days. Patients rated pain before and during treatment.
Healthy volunteers and patients with interstitial cystitis had similar lidocaine absorption profiles with a peak of 1.06 microg/ml. (range 0.66 to 1.71) and 1.3 (range 0.2 to 2.0) at about 30 minutes. Mean pain score in the interstitial cystitis group decreased from a baseline of 6.0 to 1.8 on day 1 and 0.6 on day 2. There were complaints of urethral discomfort after voiding the buffered lidocaine in each group.
Alkalization provides safe and predictable lidocaine absorption into the bladder, as indicated by therapeutic systemic levels in healthy and inflamed bladders. Furthermore, the decrease in acute pain scores in the interstitial cystitis group indicated a concentration of local anesthetic within the bladder wall that was sufficient to block the sensory neurons within the submucosal plexus.
药代动力学研究表明,膀胱内注入利多卡因后人体膀胱对其吸收不足,无法达到显著的血清浓度,仅能产生浅表局部麻醉效果。我们研究了碱化膀胱内利多卡因在健康志愿者和间质性膀胱炎患者中的药代动力学,以确定缓冲利多卡因的安全剂量、间质性膀胱炎对利多卡因摄取的影响以及对间质性膀胱炎患者膀胱疼痛的急性局部麻醉效果。
对12名健康志愿者进行初始剂量探索研究,使用4、5和6mg/kg用8.4%碳酸氢钠缓冲的5%利多卡因。连续3小时测量利多卡因水平。对12名间质性膀胱炎患者重复进行血清测量,每天使用5mg/kg用碳酸氢钠缓冲的5%利多卡因,共2天。患者在治疗前和治疗期间对疼痛进行评分。
健康志愿者和间质性膀胱炎患者的利多卡因吸收情况相似,约30分钟时峰值分别为1.06μg/ml(范围0.66至1.71)和1.3(范围0.2至2.0)。间质性膀胱炎组的平均疼痛评分从基线的6.0降至第1天的1.8和第2天的0.6。每组在排出缓冲利多卡因后均有尿道不适的主诉。
碱化可使利多卡因安全且可预测地被膀胱吸收,健康和发炎膀胱中的治疗性全身水平表明了这一点。此外,间质性膀胱炎组急性疼痛评分的降低表明膀胱壁内局部麻醉药的浓度足以阻断黏膜下丛内的感觉神经元。