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.

Conditions

• Acute Kidney Injury
• Crush Injury
• Rhabdomyolysis

Interventions

DRUG

Dexmedetomidine

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

Remifentanil

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.

PROCEDURE

Laparotomy

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.

PROCEDURE

Compression

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

Sponsors & Collaborators

• Ankara City Hospital Bilkent

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-10

Primary Completion

2025-03-07

Completion

2025-03-10

Countries

• Turkey (Türkiye)

Study Locations