Comparison of the renal effects of six sedating agents in rats

This study was designed to compare the renal effects of sedation with alphaxalone-alphadolone, etomidate, propofol, midazolam, fentanyl-fluanisone, and thiopental in rats. The sedative dose was defined as the highest dose that abolished the escape response without affecting the righting reflex. Female Wistar rats were chronically catheterized with a jugular vein catheter, and urine flow rate and renal clearances of inulin (glomerular filtration rate = GFR), sodium, and lithium (used as an index of proximal tubular function) were measured in the conscious, unrestrained state (n = 107 experiments). In a separate series (n = 70 experiments), the effect of sedative doses of each drug on the nociceptive threshold was tested with the tail-flick test. Responses in sedated animals were compared to responses in animals infused with the vehicle. Fentanyl-fluanisone and thiopental had hypoalgesic actions in sedating doses. Propofol, fentanyl-fluanisone, and thiopental reduced GFR by 20-30%. Urine flow rate was significantly decreased by propofol (-24%) and thiopental (-48%). Propofol and fentanyl-fluanisone reduced fractional lithium excretion by 9-13%. Only alphaxalone-alphadolone, etomidate, and midazolam produced sedation without affecting renal function in rats. Because midazolam produced the most consistent degree of sedation, we conclude that midazolam is the least confounding sedative agent for renal function studies in conscious rats.