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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):
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | No Intervention | The control group did not receive any intervention or pharmacological treatment. | |
| Dexmedetomidine | Experimental | Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion. |
|
| Remifentanil | Experimental | Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion. |
|
| Sham | Sham Comparator | In the sham group, bilateral gastrocnemius muscle compression was applied for 2 hours and laparotomy was performed, but no pharmacological intervention was given. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine | Drug | Following 2 hours of bilateral muscle compression, rats in the dexmedetomidine group underwent a 1-hour period including both laparotomy and continuous intravenous dexmedetomidine infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Creatinine Level | Change in serum creatinine levels measured at 0, 2, and 6 hours after experimental crush injury in Wistar Albino rats receiving either dexmedetomidine or remifentanil. This outcome is used to assess renal function and the nephroprotective effect of the interventions. | Baseline (0 hour), 2 hours, and 6 hours after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level | NGAL levels measured in serum at three time points to assess early renal tubular injury following experimental crush injury and treatment with dexmedetomidine or remifentanil. NGAL is an early biomarker for acute kidney injury (AKI) and reflects renal stress. | 0, 2, and 6 hours after intervention |
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Rat Experiment
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ankara Bilkent City Hospital | Ankara | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32317860 | Result | 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. | |
| 20783577 | Result | 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. |
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This is a preclinical animal study conducted on Wistar Albino rats. Since no human subjects were enrolled, there is no individual participant data (IPD) to share.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 23, 2025 | Jul 23, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| D000071576 | Crush Injuries |
| D012206 | Rhabdomyolysis |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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Not provided
| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| D000077208 | Remifentanil |
| D007813 | Laparotomy |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Remifentanil | Drug | Following 2 hours of bilateral muscle compression, rats in the remifentanil group underwent a 1-hour period including both laparotomy and continuous intravenous remifentanil infusion. |
|
| Laparotomy | Procedure | A standardized laparotomy was carried out for 1 hour, during which the abdominal cavity was opened and subsequently closed. This procedure aimed to mimic the physiological impact of a one-hour surgical operation. |
|
| Compression | Procedure | Bilateral compression was applied to the gastrocnemius muscles for a duration of 2 hours. |
|
| Histopathological Tubular Injury Score | Histopathological evaluation of renal tissue samples using scoring for tubular necrosis, brush border loss, dilatation, congestion, and apoptotic cell count. Quantitative damage scoring was performed blindly by two pathologists to compare the nephroprotective effects of dexmedetomidine and remifentanil. | At 6 hours after intervention (after sacrifice) |
| Kidney Injury Molecule-1 (KIM-1) Level | Serum levels of KIM-1 measured by ELISA to evaluate renal tubular epithelial injury and compare the protective effects of the two anesthetic agents. | 0, 2, and 6 hours after intervention |
| TIMP-2) × (IGFBP7) Product Level | 0, 2, and 6 hours after intervention | The combined serum levels of TIMP-2 and IGFBP7, representing G1 cell cycle arrest, were measured to detect early renal stress and predict AKI development in the experimental model. |
| 23347808 | Result | 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. |
| 27598600 | Result | 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. |
| 25613736 | Result | 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. |
| 28331287 | Result | 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. |
| 24907872 | Result | 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. |
| 34761118 | Result | 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. |
| 19142813 | Result | 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. |
| 23657066 | Result | 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. |
| 25010612 | Result | 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. |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D014947 | Wounds and Injuries |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D011422 |
| Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D013514 | Surgical Procedures, Operative |