Reversal of Rocuronium-Induced Neuromuscular Block with Sugammadex and Resulting Histopathological Effects in Rat Kidneys

Abstract

Background: This study investigated the effect of injection of rocuronium or sugammadex alone and rocuronium + sugammadex on urea, creatinine, electrolyte levels, and histopathological findings in rats. Methods: Thirty-six SpragueDawley male rats were divided to receive intravenously 16 or 96 mg/kg sugammadex, 1 mg/kg rocuronium, 1 mg/kg rocuronium + 16 mg/kg sugammadex, or 1 mg/kg rocuronium + 96 mg/kg sugammadex. The control group received an equal volume of physiological serum. Rats receiving rocuronium were ventilated until resumption of spontaneous ventilation and followed for 72 h. Blood samples were withdrawn from the tail vein to measure urea, creatinine, and electrolyte values; then both kidneys were excised, and the tissues were used for histopathological examination. Results: Rats receiving rocuronium and high doses of sugammadex (96 mg/kg) showed increased glomerular vacuolation, tubular dilatation, vascular vacuolation and hypertrophy, lymphocyte infiltration, and tubular cell sloughing compared to the control group (p = 0.002). Biochemical markers of renal function were not significantly altered after treatment with high doses of sugammadex. Conclusion: The elimination half-life of the rocuronium-sugammadex complex was found to be greater than that of free rocuronium or sugammadex, which led to marginal histopathological changes in the kidney without affecting any renal functions.

The effects of low and high doses of sugammadex on kidney tissue in streptozotocin-induced diabetic rats

“…So we can conclude that it was not the dose of 16 mg/kg of sugammadex, rather it was that of 96 mg/kg that resulted in signifi cant renal tissue damage in diabetic rats. Bostan et al (18) showed similar fi ndings in non-diabetic rats treated with 96 mg/kg sugammadex and concluded that elongated exposure of renal tissue to sugammadex-rocuronium complex might result in such pathologic changes. In contrast to histopathological fi ndings they could fi nd no abnormalities in blood urea and creatinine levels.…”

“…The rats were classifi ed as diabetic if their fasting blood glucose (FBG) levels exceeded 250 mg/dl, and only the animals with FBG levels > 250 mg/dl were included in the diabetic groups. The rats were kept alive for four weeks after streptozotocin injection to allow the development of chronic diabetes (18).…”

“…In contrast to previous studies we showed a suffi cient safety profi le with 16 mg/ kg sugammadex, however renal injury and increased infl ammatory response were observed in the 96 mg/kg sugammadex group. There is only one study (18) that investigates renal histopathological changes in rats after different doses (16 versus 96 mg/ml) of sugammadex. Bostan et al (18) showed histopathological damage in high-dose group (96 mg/kg) while blood urea, creatinine and electrolyte levels were similar to those in both control and low-dose group.…”

“…There is only one study (18) that investigates renal histopathological changes in rats after different doses (16 versus 96 mg/ml) of sugammadex. Bostan et al (18) showed histopathological damage in high-dose group (96 mg/kg) while blood urea, creatinine and electrolyte levels were similar to those in both control and low-dose group. Most of previous studies have investigated renal adverse events via RFT results or urine levels of several metabolites (such as albumin, N acetylglucosaminidase, etc.)…”

Effectiveness of sugammadex for cerebral ischemia/reperfusion injury

“…After 24 hours, the neurological condition of the rats was assessed with a scoring system [9,10]. The sugammadex doses were determined according to doses used in previous experimental studies [11–14].…”