Kanbak M, Karagoz A H, Erdem N, Oc B, Saricaoglu F, Ertas N, Berkkan A, Abbasoglu O, Aypar U
Department of Anesthesiology and Reanimation, Hacettepe University Faculty of Medicine, Sihhiye, Ankara 06100, Turkey.
Transplant Proc. 2007 Jun;39(5):1544-8. doi: 10.1016/j.transproceed.2007.01.081.
The main metabolic pathway for defluorination of sevoflurane in the liver produces inorganic fluoride (Fl). The metabolism and effect of sevoflurane on the kidney is not clear during anhepatic phase in liver transplantation. The goal of the present study was to investigate the metabolism and renal effect of sevoflurane by measuring plasma and urine inorganic fluoride, urinary N-acetyl-glucosaminidase (NAG), and plasma creatinine levels in patients undergoing liver transplantations.
After institutional approval and informed consent, we studied nine cases of orthotopic liver transplantation after anesthesia was induced with 5 mg . kg(-1) thiopental, 1 mug . kg(-1) fentanyl intravenously, the trachea was intubated after vecuronium bromide 0.1 mg . kg(-1). Anesthesia was maintained with sevoflurane (2%), O(2), and N(2)O at a total gas flow of 6 L . min(-1) using a semiclosed circle system with a sodalime canister. Blood and urine samples were obtained to measure plasma and urine fluoride concentrations and urinary NAG excretions before induction (P0), hourly during resection (P1, P2, P3), every 15 minutes during anhepatic phase (A1, A2, A3), hourly after reperfusion (neohepatic phase) (N1, N2, N3), and postoperative first hour (Po1). Preoperative (T0) and postoperative day 1 (T1), 3 (T3), 7 (T7) plasma blood urea nitrogen (BUN) and creatinine (Cr) levels were also recorded.
Mean duration of surgery was 9:06 +/- 0:09 hours. Mean inorganic fluoride concentrations in plasma were in the range of 0.71 +/- 0.30 to 28.73 +/- 3.31 mumole . L(-1). In P3, N1, N2, N3, increases in plasma inorganic fluoride concentrations were significant (P < .05) and reached a peak value at Po1. The mean urine inorganic fluoride concentrations were 12.49 +/- 2.04 to 256.7 +/- 49.62 mumole . L(-1). In A2, A3, N1, N2, and N3, mean urine inorganic fluoride concentrations were significantly increased (P < .05) and the peak value was observed at Po1. Mean NAG concentrations in urine varied (5.6 +/- 1.6 IU . L(-1) to 12.5 +/- 1.14 IU . L(-1)) and peak level was observed at 30 minutes of the anhepatic phase (A2), which did not exceed the normal values for urine NAG levels (1.5 to 6.1 U . L(-1)). No impairment was observed in serum BUN and creatinine levels at any time. While there was only a slight increase in NAG during anhepatic phase, there was no change in plasma F1.
Sevoflurane seemed to have minimal effect on kidney functions of BUN and Cr levels during liver transplantation. Although urine F1 and NAG levels increased during the anhepatic phase plasma F1, BUN, and Cr levels did not, suggesting that renal F1 production may occur in the absence of hepatic function. The renal effect of sevoflurane in chronic liver disease is controversial and must be investigated in further studies.
七氟醚在肝脏中脱氟的主要代谢途径会产生无机氟（Fl）。在肝移植的无肝期，七氟醚对肾脏的代谢及影响尚不清楚。本研究的目的是通过测量肝移植患者的血浆和尿液无机氟、尿N - 乙酰 - 氨基葡萄糖苷酶（NAG）以及血浆肌酐水平，来研究七氟醚的代谢及其对肾脏的影响。
经机构批准并获得知情同意后，我们对9例原位肝移植患者进行了研究。患者静脉注射5mg·kg⁻¹硫喷妥钠、1μg·kg⁻¹芬太尼诱导麻醉，静脉注射0.1mg·kg⁻¹维库溴铵后行气管插管。使用带有钠石灰罐的半封闭循环系统，以2%的七氟醚、氧气和氧化亚氮维持麻醉，总气体流量为6L·min⁻¹。在诱导前（P0）、切除期间每小时（P1、P2、P3）、无肝期每15分钟（A1、A2、A3）、再灌注后（新肝期）每小时（N1、N2、N3）以及术后第1小时（Po1）采集血样和尿样，测量血浆和尿液中的氟浓度以及尿NAG排泄量。还记录了术前（T0）和术后第1天（T1）、3天（T3）、7天（T7）的血浆血尿素氮（BUN）和肌酐（Cr）水平。
手术平均时长为9:06±0:09小时。血浆中无机氟的平均浓度范围为0.71±0.30至28.73±3.31μmol·L⁻¹。在P3、N1、N2、N3阶段，血浆无机氟浓度显著升高（P<.05），并在Po1时达到峰值。尿中无机氟的平均浓度为12.49±2.04至256.7±49.62μmol·L⁻¹。在A2、A3、N1、N2和N3阶段，尿中无机氟的平均浓度显著升高（P<.05），且在Po1时达到峰值。尿中NAG的平均浓度有所变化（5.6±1.6IU·L⁻¹至12.5±1.14IU·L⁻¹），并在无肝期30分钟（A2）时达到峰值，但未超过尿NAG水平的正常值（1.5至6.1U·L⁻¹）。在任何时间点，血清BUN和肌酐水平均未观察到损害。虽然在无肝期NAG仅有轻微升高，但血浆F1没有变化。
在肝移植过程中，七氟醚似乎对BUN和Cr水平的肾功能影响极小。尽管在无肝期尿F1和NAG水平升高，但血浆F1、BUN和Cr水平并未升高，这表明在没有肝功能的情况下可能会发生肾脏F1生成。七氟醚在慢性肝病中的肾脏影响存在争议，必须在进一步研究中进行探讨。
