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

NCT07094165 | Completed

• 1 other identifier: AnkaraCHBilkent0741
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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):

• 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.

Conditions

Acute Kidney Injury; Crush Injury; Rhabdomyolysis

Keywords

remifentanil; dexmedetomidine; crush injury; renal injury; KIM-1; NGAL

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level

  0, 2, and 6 hours after intervention

• Histopathological Tubular Injury Score

  At 6 hours after intervention (after sacrifice)

• Kidney Injury Molecule-1 (KIM-1) Level

  0, 2, and 6 hours after intervention

• TIMP-2) × (IGFBP7) Product Level

  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.

Study Arms (4)

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.

Drug: Dexmedetomidine; Procedure: Laparotomy; Procedure: Compression

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.

Drug: Remifentanil; Procedure: Laparotomy; Procedure: Compression

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.

Procedure: Laparotomy; Procedure: Compression

Interventions

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.

Dexmedetomidine

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.

Remifentanil

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.

Dexmedetomidine; Remifentanil; Sham

Compression PROCEDURE

Bilateral compression was applied to the gastrocnemius muscles for a duration of 2 hours.

Dexmedetomidine; Remifentanil; Sham

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Rat Experiment

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Ankara City Hospital Bilkent: lead

Study Sites (1)

Ankara Bilkent City Hospital

Ankara, Turkey (Türkiye)

Location

Related Publications (11)

• 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.

  PMID: 32317860 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.

  PMID: 20783577 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.

  PMID: 23347808 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.

  PMID: 27598600 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.

  PMID: 25613736 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.

  PMID: 28331287 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.

  PMID: 24907872 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.

  PMID: 34761118 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.

  PMID: 19142813 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.

  PMID: 23657066 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.

  PMID: 25010612 RESULT

MeSH Terms

Conditions

Acute Kidney Injury; Crush Injuries; Rhabdomyolysis

Interventions

Dexmedetomidine; Remifentanil; Laparotomy

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Muscular Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 30, 2025
• Study Start: July 10, 2024
• Primary Completion: March 7, 2025
• Study Completion: March 10, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)