Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies.
Abstract: Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. Objective: To study pharmacokinetics and cardiopulmonary effects of i.v. DEX. Methods: Pharmacokinetics of 3.5 microg/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 45 and 60 mins after administration of DEX 3.5 microg/kg bwt i.v. Data were analysed using ANOVA for repeated measures, and where appropriate Dunnett's t test was used to detect differences from resting values (P < 0.05). Results: Within 2 h after DEX administration, plasma levels were beyond limits of quantification (0.05 ng/ml). Mean values for kinetic parameters for mature and old ponies were: Cmax (ng/ml) 4.6 and 3.8, t 1/2 (min) 19.8 and 28.9 and AUC (ng.min/ml) 34.5 and 44.3, respectively. Heart rate, central venous pressure, pulmonary artery pressure and pulmonary capillary wedge pressure did not change significantly compared to presedation values throughout the 60 min observation period. Compared to presedation values, stroke volume and mixed venous PO2 were reduced for the first 5 mins, paralleled by an increase in systemic and pulmonary vascular resistance. Cardiac index was reduced for the first 10 mins, arterial blood pressures at 20, 30 and 45 mins and respiratory rate throughout the 60 min observation period, but no change in arterial PO2 or PCO2 occurred. Conclusions: DEX administration i.v. causes similar cardiopulmonary changes to those caused by other alpha-2 adrenoceptor agonists, but of very short duration. DEX is redistributed particularly rapidly. Conclusions: DEX might be safer for sedation of horses because of its very short-lasting cardiopulmonary side effects. For long duration sedation, its kinetics favour its use as a continuous infusion.
Publication Date: 2005-01-18 PubMed ID: 15651736DOI: 10.2746/0425164054406801Google Scholar: Lookup
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- Journal Article
Summary
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The researchers conducted a study to assess the cardiovascular and respiratory side effects of a new sedative drug, dexmedetomidine (DEX), on horses. The study found out that DEX is fast-acting, has short duration effects on vital signs, and might be a safer option for horse sedation.
Research Methodology
- The study examined the pharmacokinetics (how a drug is absorbed, distributed, metabolized, and excreted) and cardiopulmonary (heart and lung) effects of the sedative drug DEX when administered intravenously (IV).
- The test subjects were two groups of ponies, 8 mature ones with a mean age of 4.4 years and 6 older ones averaging 20 years.
- Each subject was given DEX at a dosage of 3.5 micrograms/kg body weight (bwt).
- The ponies’ cardiopulmonary data were recorded prior and at several intervals (5,10,20,30,45, and 60 minutes) after drug administration.
- The data were statistically analyzed using Analysis of Variance (ANOVA) for repeated measures and Dunnett’s t-test where appropriate to discover any significant differences from the pre-sedation values.
Research Results
- Within two hours of administration, DEX was almost completely eliminated from the bloodstream. This suggests the drug’s rapid absorption and metabolism.
- DEX brought about certain changes in the ponies’ vital parameters, including reduction in stroke volume (amount of blood pumped by the heart per beat) and mixed venous PO2 (a measure of oxygen in the blood after it has circulated in the body), increased systemic and pulmonary vascular resistance (resistance faced by blood flow), reduction in cardiac index (a measure of heart function) and respiratory rate, and fluctuations in arterial blood pressure.
- However, these changes were very short-lived and the levels returned to normal reasonably quickly. This indicates DEX’s quick-acting and short-duration influence on these vital signs.
- Notably, the drug didn’t significantly alter heart rate, central venous pressure (pressure in the central veins when the heart is at rest), pulmonary artery pressure (pressure in the pulmonary artery), and pulmonary capillary wedge pressure (pressure applied to a small balloon within the pulmonary artery) compared to the pre-sedation values.
Research Conclusions
- The side effects of DEX on the heart and lungs were found to be similar to those caused by other alpha-2 adrenoceptor agonists (drugs that work by activating receptors for norepinephrine and adrenaline).
- However, these side effects were brief, implying that DEX might be a safer option for horse sedation owing to these short-lived cardiopulmonary impacts.
- The rapid absorption, metabolism, and clearance of DEX make it potentially suitable for continuous infusion, particularly in the case of extended sedation requirements.
Cite This Article
APA
Bettschart-Wolfensberger R, Freeman SL, Bowen IM, Aliabadi FS, Weller R, Huhtinen M, Clarke KW.
(2005).
Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies.
Equine Vet J, 37(1), 60-64.
https://doi.org/10.2746/0425164054406801 Publication
Researcher Affiliations
- Department of Farm Animal and Equine Medical Surgery, The Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK.
MeSH Terms
- Aging / metabolism
- Aging / physiology
- Analysis of Variance
- Animals
- Area Under Curve
- Blood Pressure / drug effects
- Cardiovascular System / drug effects
- Dexmedetomidine / administration & dosage
- Dexmedetomidine / pharmacokinetics
- Dexmedetomidine / pharmacology
- Heart Rate / drug effects
- Horses / physiology
- Hypnotics and Sedatives / administration & dosage
- Hypnotics and Sedatives / pharmacokinetics
- Hypnotics and Sedatives / pharmacology
- Infusions, Intravenous / veterinary
- Partial Pressure
- Respiration / drug effects
Citations
This article has been cited 9 times.- Verhaar N, Kopp V, Pfarrer C, Neudeck S, König K, Rohn K, Kästner S. Alpha(2) Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine.. Animals (Basel) 2023 Aug 30;13(17).
- Verhaar N, Hoppe S, Grages AM, Hansen K, Neudeck S, Kästner S, Mazzuoli-Weber G. Dexmedetomidine Has Differential Effects on the Contractility of Equine Jejunal Smooth Muscle Layers In Vitro.. Animals (Basel) 2023 Mar 10;13(6).
- Abass M, Ibrahim H, Salci H, Hamed MA. Evaluation of the effect of different sedative doses of dexmedetomidine on the intestinal motility in clinically healthy donkeys (Equus asinus).. BMC Vet Res 2022 Jul 14;18(1):274.
- Kerr CL, Keating SCJ, Arroyo LG, Viel L. Cardiopulmonary effects and recovery characteristics associated with 2 sedative protocols for assisted ventilation in healthy neonatal foals.. Can J Vet Res 2021 Oct;85(4):251-260.
- Wiederkehr A, Barbarossa A, Ringer SK, Jörger FB, Bryner M, Bettschart-Wolfensberger R. Clinical Randomized Comparison of Medetomidine and Xylazine for Isoflurane Balanced Anesthesia in Horses.. Front Vet Sci 2021;8:603695.
- Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC, Vainio O. Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.. Equine Vet J 2019 Sep;51(5):646-652.
- Hopster K, Wittenberg-Voges L, Kästner SBR. Xylazine infusion in isoflurane-anesthetized and ventilated healthy horses: Effects on cardiovascular parameters and intestinal perfusion.. Can J Vet Res 2017 Oct;81(4):249-254.
- Marly-Voquer C, Schwarzwald CC, Bettschart-Wolfensberger R. The use of dexmedetomidine continuous rate infusion for horses undergoing transvenous electrical cardioversion--A case series.. Can Vet J 2016 Jan;57(1):70-5.
- Grimsrud KN, Ait-Oudhia S, Durbin-Johnson BP, Rocke DM, Mama KR, Rezende ML, Stanley SD, Jusko WJ. Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine, medetomidine, and dexmedetomidine in the horse: a population analysis.. J Vet Pharmacol Ther 2015 Feb;38(1):24-34.
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