The Effects of Dexmedetomidine and Remifentanil on Kidney Injury After Muscle Compression Injury in Rats

Summary

The goal of this interventional preclinical study is to evaluate the potential protective effects of two intravenous anesthetic agents-dexmedetomidine and remifentanil-on kidney function in the context of muscle crush injury, which is known to be a major contributor to acute kidney injury (AKI) following trauma, entrapment, or disasters such as earthquakes. AKI following crush syndrome results from rhabdomyolysis, hypovolemia, oxidative stress, and systemic inflammation, and it significantly increases morbidity and mortality. This study explores whether anesthetic choice during the acute phase of injury influences renal outcomes. This study used a rat model of crush injury. A total of 28 healthy adult male Wistar rats were randomly divided into four groups (n=7 per group): 1. Control group - no surgical procedure, no injury, no drug. 2. Sham group - anesthesia and cannulation were performed but no crush injury or drug administered. 3. Dexmedetomidine group - crush injury + intravenous dexmedetomidine infusion (3 µg/kg/h) for 1 hour. 4. Remifentanil group - crush injury + intravenous remifentanil infusion (1 µg/kg/h) for 1 hour. Crush injury was induced by applying a metal clamp with a constant pressure of 3 kg to both gastrocnemius muscles for 2 hours, under anesthesia. After the clamp was removed, animals in the two treatment groups received a one-hour intravenous infusion of their assigned drug. Blood samples were taken at baseline and at 6 hours post-injury. After euthanasia, bilateral kidney tissues were harvested for biochemical and histopathological evaluation. The main questions this study aimed to answer were: * Does dexmedetomidine reduce serum and tissue levels of AKI biomarkers (such as NGAL, KIM-1, TIMP-2, IGFBP7) more effectively than remifentanil in a rat model of crush injury? * Are there histological differences in kidney damage between the treatment groups? * What is the impact of both drugs on oxidative stress markers (TAC - total antioxidant capacity, TOS - total oxidant status) and renal function parameters such as creatinine and urea? Biochemical analyses included ELISA-based quantification of NGAL, KIM-1, TIMP-2, IGFBP7, TAC, TOS, serum creatinine, and BUN. Histopathological scoring was performed by a blinded pathologist, assessing tubular necrosis, interstitial edema, and inflammatory cell infiltration. The study found that rats in the dexmedetomidine group exhibited lower levels of renal injury markers and histopathological damage scores compared to those in the remifentanil group. These findings suggest that dexmedetomidine may offer superior renal protection during acute crush injury compared to remifentanil, potentially via anti-inflammatory and antioxidant mechanisms. The results of this study may help guide anesthetic drug selection in trauma patients at high risk of kidney injury, and lay the foundation for future translational research.

Timeline

Start

2024-07-10

Primary completion

2025-03-07

Completion

2025-03-10

Publications

• Results Bao N, Dai D. Dexmedetomidine Protects against Ischemia and Reperfusion-Induced Kidney Injury in Rats. Mediators Inflamm. 2020 Apr 3;2020:2120971. doi: 10.1155/2020/2120971. eCollection 2020.
• Results Bywaters EG, Beall D. Crush Injuries with Impairment of Renal Function. Br Med J. 1941 Mar 22;1(4185):427-32. doi: 10.1136/bmj.1.4185.427. No abstract available.
• Results Bostankolu E, Ayoglu H, Yurtlu S, Okyay RD, Erdogan G, Deniz Y, Hanci V, Can M, Turan IO. Dexmedetomidine did not reduce the effects of tourniquet-induced ischemia-reperfusion injury during general anesthesia. Kaohsiung J Med Sci. 2013 Feb;29(2):75-81. doi: 10.1016/j.kjms.2012.08.013. Epub 2012 Oct 13.
• Results Celikmen MF, Sarikaya S, Ozucelik DN, Sever MS, Aciksari K, Celikmen DM, Yazicioglu M, Kandemir A, Dogan H, Ayvaci BM, Ozasir Abuska D, Sadillioglu S. Effects of acetaminophen and mannitol on crush injuries in rats: An experimental study. Ulus Travma Acil Cerrahi Derg. 2016 Jul;22(4):305-14. doi: 10.5505/tjtes.2015.76824.
• Results de Carvalho AL, Vital RB, Kakuda CM, Braz JR, Castiglia YM, Braz LG, Modolo MP, Ribeiro OR, Domingues MA, Modolo NS. Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology. Ren Fail. 2015 Apr;37(3):526-30. doi: 10.3109/0886022X.2015.1006118. Epub 2015 Jan 23.
• Results Erkilic E, Kesimci E, Alaybeyoglu F, Kilinc I, Tural R, Yazgan A, Gumus T, Sepici Dincel A, Dumlu EG, Kanbak O. Does remifentanil attenuate renal ischemia-reperfusion injury better than dexmedetomidine in rat kidney? Drug Des Devel Ther. 2017 Mar 8;11:677-683. doi: 10.2147/DDDT.S126701. eCollection 2017.
• Results Gonullu E, Ozkardesler S, Kume T, Duru LS, Akan M, Guneli ME, Ergur BU, Meseri R, Dora O. Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats. Braz J Anesthesiol. 2014 May-Jun;64(3):152-8. doi: 10.1016/j.bjane.2013.06.002. Epub 2013 Oct 16.
• Results Kanbak O, Aydogan B, Gumus T. Effects of remifentanil and propofol on distant organ lung injury in an ischemia-reperfusion model. Open Med (Wars). 2021 Nov 8;16(1):1673-1680. doi: 10.1515/med-2021-0381. eCollection 2021.
• Results Kocoglu H, Ozturk H, Ozturk H, Yilmaz F, Gulcu N. Effect of dexmedetomidine on ischemia-reperfusion injury in rat kidney: a histopathologic study. Ren Fail. 2009;31(1):70-4. doi: 10.1080/08860220802546487.
• Results Sugita S, Okabe T, Sakamoto A. Continuous infusion of dexmedetomidine improves renal ischemia-reperfusion injury in rat kidney. J Nippon Med Sch. 2013;80(2):131-9. doi: 10.1272/jnms.80.131.
• Results Si YN, Bao HG, Xu L, Wang XL, Shen Y, Wang JS, Yang XB. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney. Eur Rev Med Pharmacol Sci. 2014 Jul;18(13):1843-51.

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