Abstract: Dexmedetomidine infusions are beneficial in anaesthetised endotoxaemic horses when administered concurrent to endotoxin, but post-conditioning effects are unknown. Objective: To evaluate whether a dexmedetomidine infusion is beneficial in horses administered Escherichia coli O55:B5 lipopolysaccharides (LPS) endotoxin prior to anaesthesia. Methods: Randomised controlled in vivo experiment. Methods: Ten systemically healthy horses were instrumented for acquisition of cardiac index (CI) using thermodilution. Horses received IV LPS (0.1 μg/kg bwt) immediately prior to anesthesia. Horses received IV xylazine (control, LPS; n = 5) or dexmedetomidine (treatment, LPS-Dex; n = 5), followed by IV ketamine and midazolam and sevoflurane in oxygen. In LPS-Dex, dexmedetomidine (1.75 μg/kg bwt/h IV) was administered and target end-tidal sevoflurane concentration was reduced (1.8% vs. 3% LPS). Cardiopulmonary function, acid-base, cytokine, and creatinine values were assessed every 30 min for 180 min. Data were compared between groups using mixed model analysis (p < 0.05). Results: Mean ± standard deviation CI was significantly higher in LPS-Dex at 30 and 60 min (57.9 ± 15.6 mL/min/kg bwt versus 43.1 ± 9.4, 30 min, p = 0.03; 60.2 ± 11.8 mL/min/kg bwt versus 38.9 ± 11.2, 60 min, p = 0.003). Creatinine was elevated and significantly higher in LPS from 90 min onward but remained normal in LPS-Dex throughout (201 ± 38 μmol/L versus 124 ± 26, 180 min, p = 0.003). Significantly improved base excess values were seen in LPS-Dex at 150 and 180 min (2.9 ± 2 mmol/L versus 0.6 ± 1, 150 min, p = 0.03; 3.4 ± 1.96 mmol/L versus 0.6 ± 1.41, 180 min, p = 0.01). Cytokine concentrations were similar between groups. Conclusions: The experimental protocol is not representative of all surgical colics. Conclusions: Dexmedetomidine infusion and concurrent reduction in inhalant anaesthetic could benefit anaesthetic management of horses even when endotoxaemia is already present.
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Overview
This study investigated whether dexmedetomidine, a sedative drug, provides cardiovascular and renal benefits when given to horses that have been exposed to endotoxin before anesthesia.
The results showed that dexmedetomidine infusion improved heart function and kidney health during anesthesia in endotoxaemic horses compared to a control group.
Background and Aim
Endotoxaemia, caused by bacterial toxins like lipopolysaccharides (LPS), can severely affect horses undergoing anesthesia, compromising cardiovascular and renal functions.
Previous studies showed benefits of dexmedetomidine given concurrently with endotoxin, but it was unclear if the drug is beneficial when endotoxin exposure occurs prior to anesthesia (post-conditioning effects).
The main goal was to evaluate cardiovascular and renal effects of dexmedetomidine infusion started after endotoxin administration but before anesthesia in healthy horses.
Methods
Study design: Randomized controlled in vivo experiment with 10 healthy horses.
Endotoxaemia induction: All horses received intravenous Escherichia coli O55:B5 LPS at 0.1 µg/kg immediately before anesthesia to mimic endotoxaemia.
Group allocation:
Control group (LPS; n=5): Received IV xylazine, ketamine, midazolam, and sevoflurane anesthesia.
Treatment group (LPS-Dex; n=5): Received IV dexmedetomidine infusion (1.75 µg/kg/h) after LPS, plus ketamine, midazolam, and a reduced sevoflurane dose.
Instrumentation: Thermodilution catheter was used to measure cardiac index (CI) to assess heart function.
Monitoring: Cardiopulmonary parameters, blood acid-base status, cytokine concentrations, and creatinine (kidney function marker) were measured every 30 minutes for 180 minutes under anesthesia.
Statistical analysis: Mixed model analysis was performed to compare groups, with significance set at p < 0.05.
Key Findings
Cardiac function:
The dexmedetomidine group had significantly higher cardiac index values at 30 and 60 minutes compared to control, indicating better heart output during anesthesia.
Example: At 30 minutes, CI was 57.9 ± 15.6 mL/min/kg in LPS-Dex vs. 43.1 ± 9.4 in LPS (p=0.03).
Renal function:
Control horses showed elevated creatinine from 90 minutes onward, indicating kidney impairment.
In contrast, creatinine remained within normal range in the dexmedetomidine group throughout the 180 minutes.
Example: At 180 minutes, creatinine was 201 ± 38 μmol/L in LPS vs. 124 ± 26 in LPS-Dex (p=0.003).
Acid-base balance:
Base excess values, reflecting metabolic status, were significantly better (more positive) in the dexmedetomidine group at 150 and 180 minutes, suggesting better acid-base homeostasis.
Example: At 180 minutes, base excess was 3.4 ± 1.96 mmol/L in LPS-Dex vs. 0.6 ± 1.41 in LPS (p=0.01).
Cytokine levels:
Inflammatory cytokine concentrations did not differ significantly between groups during the anesthesia period.
Conclusions and Implications
The study suggests that dexmedetomidine infusion started after endotoxin exposure and continued through anesthesia can improve heart function and protect kidney function in endotoxaemic horses.
Reduction of sevoflurane dose alongside dexmedetomidine may contribute to better cardiovascular stability.
The findings support using dexmedetomidine as part of anesthetic management in horses already affected by endotoxaemia, such as in cases of colic complicated by endotoxin release.
However, the experimental model may not fully represent the complexity of all clinical surgical colic cases, so clinical trials are needed to confirm applicability.
No significant effect on inflammatory cytokines was observed, indicating dexmedetomidine’s benefits are likely mediated through cardiovascular and renal mechanisms rather than immune modulation.
Cite This Article
APA
Lee S, Hector RC, Pezzanite L, Gilleland E, Rezende ML.
(2026).
Dexmedetomidine infusions improve cardiovascular and renal function in anaesthetised, experimentally endotoxaemic horses.
Equine Vet J.
https://doi.org/10.1002/evj.70173
Steverink PJ, Sturk A, Rutten VP, Wagenaar‐Hilbers JP, Klein WR, Van der Velden MA. Endotoxin, interleukin‐6 and tumor necrosis factor concentrations in equine acute abdominal disease: relation to clinical outcome.. J Endotoxin Res 1995;2(4):289–299.
Flanders CA, Rocke AS, Edwardson SA, Baillie JK, Walsh TS. The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies.. Crit Care 2019;23(1):402.
She H, Hu Y, Zhao G, Du Y, Wu Y, Chen W. Dexmedetomidine ameliorates myocardial ischemia‐reperfusion injury by inhibiting MDH2 Lactylation via regulating metabolic reprogramming.. Adv Sci (Weinh) 2024;11(48):e2409499.
Chow SL, Maisel AS, Anand I, Bozkurt B, de Boer RA, Felker GM. Role of biomarkers for the prevention, assessment, and Management of Heart Failure: a scientific Statement from the American Heart Association.. Circulation 2017;135(22):e1054‐91.
Kesumarini D, Widyastuti Y, Boom CE, Dinarti LK. Effectiveness of dexmedetomidine as myocardial protector in children with classic tetralogy of Fallot having corrective surgery: a randomized controlled trial.. J Cardiothorac Vasc Anesth 2024;38(6):1369–1377.
Kesumarini D, Widyastuti Y, Boom CE, Dinarti LK. Dexmedetomidine as a myocardial protector in pediatric heart surgery using cardiopulmonary bypass: a systematic review.. Ann Med Surg (Lond) 2023;85(10):5075–5084.
Moore SS, Lapointe A, Rampakakis E, Simoneau J, Elias P, Poccia A. Cardiac biomarkers predict low right ventricle performance in neonatal encephalopathy.. J Perinatol 2025;45(7):927–934.
Cavefors O, Einarsson F, Holmqvist J, Bech‐Hanssen O, Ricksten SE, Redfors B. Cardiac biomarkers for screening and prognostication of cardiac dysfunction in critically ill patients.. ESC Heart Fail 2024;11(6):4009–4018.
Gopal DM, Sam F. New and emerging biomarkers in left ventricular systolic dysfunction‐‐insight into dilated cardiomyopathy.. J Cardiovasc Transl Res 2013;6(4):516–527.
Gu J, Sun P, Zhao H, Watts HR, Sanders RD, Terrando N. Dexmedetomidine provides renoprotection against ischemia‐reperfusion injury in mice.. Crit Care 2011;15(3):R153.
Yang SJ, Fan CN, Wang MJ, Fan SZ, Tsai JC, Sun WZ. Effects of dexmedetomidine on renal microcirculation in ischemia/reperfusion‐induced acute kidney injury in rats.. Sci Rep 2021;11(1):2026.
Kiyonaga N, Moriyama T, Kanmura Y. Effects of dexmedetomidine on lipopolysaccharide‐induced acute kidney injury in rats and mitochondrial function in cell culture.. Biomed Pharmacother 2020;125:109912.
Jiang L, Zhang T, Zhang Y, Yu D, Zhang Y. Dexmedetomidine postconditioning provides renal protection in patients undergoing laparoscopic partial nephrectomy: a randomized controlled trial.. Front Pharmacol 2022;13:988254.
Nakashima T, Miyamoto K, Shima N, Kato S, Kawazoe Y, Ohta Y. Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial.. J Intensive Care 2020;8:1.
Abuelazm MT, Ghanem A, Johanis A, Mahmoud A, Hassan AR, Katamesh BE. Reno‐protective effects of perioperative dexmedetomidine in kidney transplantation: a systematic review and meta‐analysis of randomized controlled trials.. Int Urol Nephrol 2023;55(10):2545–2556.
Ammar AS, Mahmoud KM, Kasemy ZA, Helwa MA. Cardiac and renal protective effects of dexmedetomidine in cardiac surgeries: a randomized controlled trial. Saudi J Anaesth 2016;10(4):395–401.
Calzavacca P, Evans RG, Bailey M, Bellomo R, May CN. Cortical and medullary tissue perfusion and oxygenation in experimental septic acute kidney injury. Crit Care Med 2015;43(10):e431–e439.
Bellomo R, Kellum JA, Ronco C, Wald R, Martensson J, Maiden M. Acute kidney injury in sepsis. Intensive Care Med 2017;43(6):816–828.
Lankadeva YR, Ma S, Iguchi N, Evans RG, Hood SG, Farmer DGS. Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury. Kidney Int 2019;96(5):1150–1161.
Villela NR, do Nascimento Júnior P, de Carvalho LR, Teixeira A. Effects of dexmedetomidine on renal system and on vasopressin plasma levels. Experimental study in dogs. Rev Bras Anestesiol 2005;55(4):429–440.
Bickel M. The role of interleukin‐8 in inflammation and mechanisms of regulation. J Periodontol 1993;64(5 Suppl):456–460.
Ihim SA, Abubakar SD, Zian Z, Sasaki T, Saffarioun M, Maleknia S. Interleukin‐18 cytokine in immunity, inflammation, and autoimmunity: biological role in induction, regulation, and treatment. Front Immunol 2022;13:919973.
Chen R, Kang Z, Wang Y, Zhao J, Li S. The anti‐inflammatory effect of dexmedetomidine administration on patients undergoing intestinal surgery: a randomized study.. Drugs R D 2021;21(4):445–453.
Mokhlesian M, Heydari F, Boskabadi SJ, Baradari AG, Ajami A, Alizadeh‐Navaei R. The effect of dexmedetomidine on inflammatory factors and clinical outcomes in patients with septic shock: a randomized clinical trial.. Clin Ther 2025;47(1):e9–e17.
Li B, Li Y, Tian S, Wang H, Wu H, Zhang A. Anti‐inflammatory effects of perioperative dexmedetomidine administered as an adjunct to general anesthesia: a meta‐analysis.. Sci Rep 2015;5:12342.
Zhang J, Wang Z, Wang Y, Zhou G, Li H. The effect of dexmedetomidine on inflammatory response of septic rats.. BMC Anesthesiol 2015;15:68.
Liu Z, Wang Y, Wang Y, Ning Q, Zhang Y, Gong C. Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti‐inflammatory pathway.. Int Immunopharmacol 2016;35:210–216.