Cousins M J, Fulton A, David W, Haynes G, Whitehead R
Anaesth Intensive Care. 1978 Nov;6(4):277-89. doi: 10.1177/0310057X7800600401.
This study provides the first morphological evidence of significant structural damage following high doses of enflurane alone and confirms previous findings of transient renal functional abnormalities following high dosage enflurane. The study also indicates that enflurane may have a greater potential for renal toxicity in the presence of renal impairment. Treatment of Fischer 344 rats with a nephrotoxic dose of gentamicin prior to six hours of enflurane (GE) anaesthesia at 1 MAC resulted in increased serum concentration of the enflurance metabolite inorganic fluoride (GE, 43.9 +/- 1.5; E, 34.5 +/- 1.8 mu mol/L), increased urine flow rate and a greater degree of structural damage in renal proximal convoluted tubule cells than was observed with either gentamicin (G) or enflurane (E) alone. Treatment with gentamicin prior to enflurane also resulted in reduced urinary osmolality compared to enflurane or gentamicin alone (GE, 742 +/- 57; E, 1709 +/- 66; G, 985 +/- 32 m0sm/kg).
本研究首次提供了单独使用高剂量安氟醚后出现显著结构损伤的形态学证据，并证实了先前关于高剂量安氟醚后出现短暂肾功能异常的研究结果。该研究还表明，在存在肾功能损害的情况下，安氟醚可能具有更大的肾毒性潜力。在对Fischer 344大鼠进行1 MAC浓度的安氟醚（GE）麻醉6小时之前，先用肾毒性剂量的庆大霉素进行处理，结果发现安氟醚代谢产物无机氟的血清浓度升高（GE组为43.9±1.5；E组为34.5±1.8 μmol/L），尿流率增加，并且与单独使用庆大霉素（G）或安氟醚（E）相比，肾近端小管细胞的结构损伤程度更大。在安氟醚之前使用庆大霉素进行处理，与单独使用安氟醚或庆大霉素相比，尿渗透压也降低了（GE组为742±57；E组为1709±66；G组为985±32 mOsm/kg）。
