Effects of Continuous Dexmedetomidine Infusion on Canine Hematology and Serum Biochemistry

Effects of Continuous Dexmedetomidine Infusion on Canine Hematology and Serum Biochemistry | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Effects of Continuous Dexmedetomidine Infusion on Canine Hematology and Serum Biochemistry Bruno Henrique Silva Nogueira, Pedro Henrique Duarte Sandmann, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7528986/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The hematological, biochemical and glycemic changes related to dexmedetomidine in dogs still require in-depth studies, and their mechanisms have not been fully elucidated. Furthermore, different individuals may present different responses to the pharmacodynamics of the compound in question. The aim of this study was to determine the profile in dogs and compare the results before, during and after continuous infusion. Six healthy dogs, with a mean weight of 10.40 ± 4.81 kg, were used in a randomized study. The animals received 3 µg/kg of dexmedetomidine at a concentration of 100 µg/mL intramuscularly and 10 minutes later, an infusion of 3 µg/kg/hr was started for 30 minutes by diluting 0.2 mL of dexmedetomidine in 20 mL of water for injection, reaching a concentration of 1 µg/mL. Venous blood samples of 4 mL were collected using a 5 mL syringe and a 25 x 0.70 mm hypodermic needle through the jugular vein at times T0’ (baseline), T15’, T30’ minutes of infusion and T120’ (90 minutes after the end of the infusion). The results were analyzed in a specialized laboratory taking into account the reference values ​​for the species. The parameters verified were total erythrocytes, hematocrit, hemoglobin, total leukocytes, total proteins, alanine transferase, alkaline phosphatase, plasma urea and blood glucose. There was no difference between the doses and forms of administration among the patients. Concluding that the drug induces transient hyperglycemia, as well as significant increases in ALT. Alpha 2-adrenergic agonists Canis lupus familiaris hyperglycemia hematocrit Figures Figure 1 Introduction In veterinary medicine, α2-adrenergic agonists are frequently used as preanesthetic agents for their sedative, muscle relaxant, hypnotic, and analgesic effects, in addition to being used as adjuvants in pain management and in general anesthesia (Bao and Tang 2020 ). The main mechanism of action of these drugs is to reduce the concentration of catecholamines (such as norepinephrine) in the blood by up to 90%, in addition to reducing the activity of the central nervous system. They act on a type of receptor with pre and postsynaptic location, divided into 4 subtypes that are responsible for some specific effects (Bacchiega et al. 2008 ). This group includes xylazine, romifidine, detomidine, medetomidine and dexmedetomidine, however, in recent years, there has been a growing search for more specific effects on α-2 receptors than α-1. Of the α-adrenergic agonists, dexmedetomidine stands out, an agent that causes dose-dependent sedation by stimulating α2 adrenoreceptors in the central nervous system (Fantoni and Cortopassi 2010 ). The biotransformation of these substances also occurs in the liver through cytochrome P450 enzymes (Panzer et al. 2009 ). During the use of infusions in anesthetic procedures, complications often occur, which can cause significant changes in different organs and systems of the patient. Therefore, these changes can be potentiated by the use of medications that cause segregation of different volumes of organs or systems (Picioli et al. 2013 ). Most medications used in anesthesiology undergo biotransformation in the liver, and drug interactions may occur when there is an urgent need to combine substances. These, in turn, lead to hepatic overload, reducing the elimination of substances, directly affecting hemodynamic variables and the recovery period from anesthesia (Muir 2007 ). Important hematological and biochemical changes have already been described in animal patients after the use of α2-adrenergic agonists (Ambrisko and Hikasa 2002 ; Boff et al. 2022 ), but data on this information at an acute level are scarce. Therefore, the present study aimed to verify the hematological, biochemical and glycemic effects of dexmedetomidine for up to 2 hours after its continuous infusion during general anesthesia in healthy dogs, based on the hypothesis that this drug can induce acute changes. Materials and methods Ethical approval The study was approved by the Animal Ethics Committee, registered under number CEUA UNIC 002/2024 and all stages of the study were conducted following the ethical principles and good practices of animal experimentation determined by the Brazilian College of Animal Experimentation. Animals and local Six adult dogs (all male), of no defined breed, not neutered, with an average weight of 10.84 kg ± 3 kg, age of 3.5 ± 1.5 years, clinically healthy, were evaluated through physical and hematological evaluation, renal and hepatic biochemistry. A prior fasting of 12 hours for solids and 6 hours for liquids was established, to perform the elective orchiectomy procedure. The guardians were duly notified and signed a term of knowledge of the project. Experimental design The dogs were randomly selected to undergo the procedure in a crossover study, respecting the average minimum interval of 7 days between procedures. Thus, a combination of dexmedetomidine 3 μg/kg and ketamine 3 mg/kg was used intramuscularly in the quadriceps femoris muscle, application performed with a 20 x 0.55 mm hypodermic needle. The parameters were assessed and recorded every 15 minutes, as well as blood samples collected at times T0’ to T120’, with T0’ being prior to intramuscular administration of the drug and the other times respecting the intervals of 15, 30 and 120 minutes after the start of the infusion of dexmedetomidine at a dose of 3 μg/kg/hr. The animal was induced with propofol (2 mg/kg) to allow intubation, and was maintained with isoflurane during the procedure. Concomitantly, local intratesticular blockade was performed with 2% lidocaine without vasoconstrictor, at a volume of 0.1 mL/kg, with a 20 x 0.55 mm hypodermic needle, and then the elective orchiectomy procedure was performed without notable changes induced by the painful stimulus of the procedure. Hematological Profile Prior to the blood collection, the ventral portion of the cervical region was properly cleaned, respecting the anatomical reference of the right and left external jugular veins, and antisepsis was performed on the site with 70% alcohol. 4 mL of blood were collected using a 5 mL plastic syringe via percutaneous puncture of the right and left jugular veins with a 25 x 0.70 mm hypodermic needle, distributed on both sides. 0.5 mL was then added to a tube containing ethylenediaminetetraacetic acid (EDTA) in sufficient quantities for the examination. The tubes were homogenized manually and sent to a specialized laboratory, with the examination being performed within 30 minutes after each collection. The erythrogram and leukogram values were obtained using a Mindray BC 2800 Vet hematology analyzer. A portable veterinary refractometer RTP-20ATC was used to determine total plasma proteins. Biochemical Profile Blood samples were collected using the same technique as for the hematological profile, adding 2 mL to a tube without anticoagulant with clot activator gel and 1 mL to a tube containing sodium fluoride. The values of ALT, ALP, plasma urea and glucose were obtained using the semi-automatic biochemical analyzer GTA 30, Global Analyzer®, with reagent kits from Labtest®. Each biochemical test was performed according to the instructions of the test manufacturer. Others Parameters Throughout the study, heart rate (bpm) was monitored and recorded using an electrocardiogram; respiratory rate (rpm) using a capnograph; temperature (ºC) using an esophageal temperature sensor; non-invasive blood pressure using a multi-parametric monitor; and evaluation of the surgical plane using Guedel's plans were monitored and recorded, evaluating the eyelid reflex, capillary refill time, eyeball, mucosal coloration, and pupillary reflex, keeping the animal in the surgical plane. Statistical Analysis All data will be presented using the simple arithmetic mean of their values, as well as their respective standard deviations. Results In the hematological profile, it is possible to observe, through the time averages, as described in the respective tables, a significant effect of the dexmedetomidine infusion on red blood cells, hemoglobin, hematocrit and total proteins. Table 1. Mean, standard deviation (SD) and standard error (SE) of the results of red blood cells, hemoglobin, hematocrit, platelets and total proteins respectively of dogs submitted to dexmedetomidine infusion at different evaluation times. In these parameters, it is possible to note that during the infusion (times T15' and T30') there was a reduction in their values, with a subsequent increase at T120' (90 minutes after the end of the dexmedetomidine infusion). This effect has a special impact on hemoglobin, which presents in its T15' and T30' averages, numbers lower than the lower limit of the reference values for a healthy animal, which implies a worse prognosis for a sick animal. In other parameters such as leukocytes, MCV and MCHC, no changes were observed, or they were inconsistent with the administration of the pharmacological infusion of the α2-agonist. Similar effects were observed by Bisht et al. (2018), in research using dexmedetomidine in dogs, as well as by Margeti et al. (2024) using dexmedetomidine in cats and by Ragab et al. (2022) in goats. This same change was also reported in the administration of other α2-adrenergic drugs in different species, as described by Picioli et al. (2013) with the use of xylazine in sedation protocols in dogs, by Wilson et al. (2004) administering xylazine in sheep, Kiliç (2008) using detomidine in cattle and Tiburcio et al. (2014) working with the effects of detomidine and xylazine in horses. Some possibilities can be pointed out as causes of such changes, among them is blood sequestration in organs and tissues, with one of the main sites being the spleen, due to adrenergic suppression of α2-adrenergics, decreased systemic vascular resistance (SVR), vasodilation and hemodynamic imbalance (Ragab et al. 2022; Margeti et al. (2024). Hemodilution is also possible due to the transport of extravascular fluid to the intravascular space (Tiburcio et al. 2014; Picioli et al. 2013). Although this effect is seen as temporary, with a return to baseline levels after a certain time (Tiburcio et al. 2014), in the present study, the reduction in values was maintained while the drug was administered by continuous infusion, improving again only minutes after the end of the procedure, which may indicate possible risks in patients who present hemodynamic decompensation and needed to undergo surgical or clinical procedures that require sedation (Picioli et al. 2013). In terms of red blood cells, hemoglobin, hematocrit and total proteins, we can observe a notable reduction in their values during the continuous infusion of dexmedetomidine, followed by a gradual increase after the end of the continuous administration of the drug. Regarding the biochemical profile, it is possible to observe primarily a large change in plasma glucose levels during maintenance of pharmacological administration. Their numbers increase gradually, exceeding the upper limit of the reference values described in the literature, causing a picture of transient hyperglycemia, which regresses after the end of continuous infusion, as observed in the average at T120'. This transient increase in serum glucose was also observed in other studies using dexmedetomidine, such as Ragab et al. (2022) with goats and Margeti et al. (2024) with cats. Table 2. Mean, standard deviation (SD) and standard error (SE) of ALT, AP, urea and blood glucose respectively levels in dogs undergoing dexmedetomidine infusion at different evaluation times. This effect is caused mainly by the action of the drug on α2 receptors in the β cells of the pancreas, causing insulin suppression and decreasing the degree of circulating insulin (Julião et al. 2019; Margeti et al. 2024). Although momentary, this hyperglycemic condition can trigger problems in diabetic patients, in whom protocols containing α2-agonist drugs must be used with caution as there are no compensatory mechanisms to return to baseline values after completing the procedure with the use of dexmedetomidine. Discussion In this study, only healthy, non-neutered male dogs with an average weight were used, focusing on the hematological changes of dexmedetomidine infusion for a period of 30 minutes, and its effect 90 minutes after the infusion ceased. The induction of transient hyperglycemia (not exceeding 180 mg/dL in this study), as a result of activation of α-2A-adrenergic receptors in pancreatic β cells suppressing insulin release, may be harmful to dogs with diabetes or endocrine diseases, because they cannot compensate for the increase in blood glucose levels like a healthy dog can. Hematological changes related to hemoglobin, red blood cells and hematocrit may lead to increased respiratory distress, taking into account the synergism that the reduction of these parameters has with the hemodynamic effects of dexmedetomidine on the respiratory tract, requiring careful use in critical cases and in hemodynamically decompensated patients. The reduction of ALT, as an enzyme that participates in the processes of protein synthesis, neoglycogenesis and the hepatic biotransformation of ammonia into urea, can lead to greater problems in patients who already have liver failure, making it difficult to metabolize drugs. The reduction in platelets, in cases where thrombocytopenia has already been observed, depending on the procedure to be performed, will impair the patient's coagulation, and in cases of considerable bleeding may compromise the quality of the post-operative period and recovery time, worsening the prognosis. During dexmedetomidine infusions, reductions in total proteins were observed, making prognosis difficult for patients without prior blood tests or prior stabilization, who may present with hypoproteinemia, which leads to an increased risk of hypotension during anesthesia, promotes tissue edema and increases sensitivity to drugs with high protein binding, such as phenothiazines and benzodiazepines. Conclusion The variety of effects of alpha 2 adrenergic receptors is evident, and when we focus on the hematological and biochemical profile it is no different, requiring extreme caution in its administration, individualizing the protocol to the patient, placing the risks and benefits that the drug can generate, because when used inadvertently, it triggers adverse effects that will impact the prognosis. Declarations Data Availability No datasets were generated or analysed during the current study. Funding Declaration The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. References Ambrisko TD, Hikasa Y (2002) Neurohormonal and metabolic effects of medetomidine compared with xylazine in beagle dogs. CJVR. PMC226981 PMID, PMCID, p 11858648 Bacchiega TS, Simas RDC, Pinto EADT (2008) Dexmedetomidina: um novo medicamento na anestesiologia veterinária. Rev Cient Elet Med Vet 6:1679–7353 Bao N, Tang B (2020) Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine. Mediators Inflamm. https://doi.org/10.1155/2020/6136105 Bisht DS, Jadon NS, Bodh D, Kandpal M (2018) Clinicophysiological and haematobiochemical evaluation of dexmedetomidine, propofol, sevoflurane anaesthesia in dogs. Indian J Anim Sci. https://doi.org/10.56093/ijans.v88i8.82910 Boff GA, Lima CM, Nobre MO, Gehrcke MI (2022) Hemodynamic and respiratory changes from a continuous infusion of dexmedetomidine in general anesthesia in dogs: a systematic review and meta-analysis. Res Soc Dev. https://doi.org/10.33448/rsd-v11i7.29980 Braga SM, Moreno JCD (2012) Uso de fármacos agonistas dos receptores α-2 adrenérgicos em Medicina Veterinária. Dissertation, Federal University of Goiás Fantoni DT, Cortopassi SRG (2010) Anestesia em cães e gatos. 2. ed. São Paulo: Roca, 2010 Julião GH, Abimussi CJX (2019) Uso de dexmedetomidina em Medicina Veterinária: revisão de literatura. Rev Educ Contin Em Med. https://doi.org/10.36440/recmvz.v17i1.37840 . Veterinária E Zootec CRMV-SP Kiliç N (2008) Cardiopulmonary, biochemical and haematological changes after detomidine-midazolam-ketamine anaesthesia in calves. Bull Vet Inst Pulawy 52(3):423–426 Margeti C, Kazakos G, Galatos AD (2024) The Effect of a Subsequent Dose of Dexmedetomidine or Other Sedatives following an Initial Dose of Dexmedetomidine on Electrolytes, Acid-Base Balance, Creatinine, Glucose, and Cardiac Troponin I in Cats: Part II. Vet Sci. https://doi.org/10.3390/vetsci11040143 Muir WW (2007) Considerations for general anesthesia. In: Tranquili WJ, Thurmon JC, Grimm KA (ed) Lumb & Jones veterinary anesthesia and analgesia. 4. th. ed. 2007. pp. 7–30 Panzer O, Moitra V, Sladen RN (2009) Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol Clin., v.29, n.4, pp. 587–605, 2011. PMID: 19576524 10.1016/j.ccc.2009.04.004 Picioli A, Martini MV, Minervino AHH et al (2013) O uso da acepromazina, dexmedetomidina e xilazina na sedação em cães: alterações hematológicas e bioquímicas. https://doi.org/10.22409/rbcv.v20i1.163 . Rev bras ciênc vet Ragab G, Hassan SE, Fathi MZ, Hagag U (2022) Clinicophysiological and hematobiochemical effect of dexmedetomidine or diazepam with ketamine and propofol in total intravenous anesthesia in goats. Beni-Suef Univ J Basic Appl Sci. https://doi.org/10.1186/s43088-022-00232–0 Thurmon JC, Tranquili WJ, Benson GJ (1996) Preanesthetics and anesthetic adjuncts. In: Lumb and Jones veterinary anaesthesia. 3rd ed. Baltimore: William and Wilkins, 1996, pp.183–209 Tiburcio M, Oliveira MS, Martini MV et al (2014) Acepromazina, detomidina ou xilazina na sedação em equinos: efeitos hematológicos e bioquímicos. Rev Acad Ciênc Anim. https://doi.org/10.7213/academica.12.01.AO04 Wilson DV, Evans AT, Carpenter RA, Mullineaux DR (2004) The effect of four anesthetic protocols on splenic size in dogs. Vet Anaesth Analg. https://doi.org/10.1111/j.1467-2987.2004.00152.x Additional Declarations No competing interests reported. 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The main mechanism of action of these drugs is to reduce the concentration of catecholamines (such as norepinephrine) in the blood by up to 90%, in addition to reducing the activity of the central nervous system. They act on a type of receptor with pre and postsynaptic location, divided into 4 subtypes that are responsible for some specific effects (Bacchiega et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). This group includes xylazine, romifidine, detomidine, medetomidine and dexmedetomidine, however, in recent years, there has been a growing search for more specific effects on α-2 receptors than α-1.\u003c/p\u003e\u003cp\u003eOf the α-adrenergic agonists, dexmedetomidine stands out, an agent that causes dose-dependent sedation by stimulating α2 adrenoreceptors in the central nervous system (Fantoni and Cortopassi \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). The biotransformation of these substances also occurs in the liver through cytochrome P450 enzymes (Panzer et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2009\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDuring the use of infusions in anesthetic procedures, complications often occur, which can cause significant changes in different organs and systems of the patient. Therefore, these changes can be potentiated by the use of medications that cause segregation of different volumes of organs or systems (Picioli et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Most medications used in anesthesiology undergo biotransformation in the liver, and drug interactions may occur when there is an urgent need to combine substances. These, in turn, lead to hepatic overload, reducing the elimination of substances, directly affecting hemodynamic variables and the recovery period from anesthesia (Muir \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). Important hematological and biochemical changes have already been described in animal patients after the use of α2-adrenergic agonists (Ambrisko and Hikasa \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2002\u003c/span\u003e; Boff et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), but data on this information at an acute level are scarce.\u003c/p\u003e\u003cp\u003eTherefore, the present study aimed to verify the hematological, biochemical and glycemic effects of dexmedetomidine for up to 2 hours after its continuous infusion during general anesthesia in healthy dogs, based on the hypothesis that this drug can induce acute changes.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003ch2\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe study was approved by the Animal Ethics Committee, registered under number CEUA UNIC 002/2024 and all stages of the study were conducted following the ethical principles and good practices of animal experimentation determined by the Brazilian College of Animal Experimentation.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eAnimals and local\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eSix adult dogs (all male), of no defined breed, not neutered, with an average weight of 10.84 kg ± 3 kg, age of 3.5 ± 1.5 years, clinically healthy, were evaluated through physical and hematological evaluation, renal and hepatic biochemistry. A prior fasting of 12 hours for solids and 6 hours for liquids was established, to perform the elective orchiectomy procedure. The guardians were duly notified and signed a term of knowledge of the project.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eExperimental design\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe dogs were randomly selected to undergo the procedure in a crossover study, respecting the average minimum interval of 7 days between procedures. Thus, a combination of dexmedetomidine 3 μg/kg and ketamine 3 mg/kg was used intramuscularly in the quadriceps femoris muscle, application performed with a 20 x 0.55 mm hypodermic needle.\u003c/p\u003e\n\u003cp\u003eThe parameters were assessed and recorded every 15 minutes, as well as blood samples collected at times T0’ to T120’, with T0’ being prior to intramuscular administration of the drug and the other times respecting the intervals of 15, 30 and 120 minutes after the start of the infusion of dexmedetomidine at a dose of 3 μg/kg/hr.\u003c/p\u003e\n\u003cp\u003eThe animal was induced with propofol (2 mg/kg) to allow intubation, and was maintained with isoflurane during the procedure. Concomitantly, local intratesticular blockade was performed with 2% lidocaine without vasoconstrictor, at a volume of 0.1 mL/kg, with a 20 x 0.55 mm hypodermic needle, and then the elective orchiectomy procedure was performed without notable changes induced by the painful stimulus of the procedure.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eHematological Profile\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003ePrior to the blood collection, the ventral portion of the cervical region was properly cleaned, respecting the anatomical reference of the right and left external jugular veins, and antisepsis was performed on the site with 70% alcohol.\u003c/p\u003e\n\u003cp\u003e4 mL of blood were collected using a 5 mL plastic syringe via percutaneous puncture of the right and left jugular veins with a 25 x 0.70 mm hypodermic needle, distributed on both sides. 0.5 mL was then added to a tube containing ethylenediaminetetraacetic acid (EDTA) in sufficient quantities for the examination. The tubes were homogenized manually and sent to a specialized laboratory, with the examination being performed within 30 minutes after each collection. The erythrogram and leukogram values were obtained using a Mindray BC 2800 Vet hematology analyzer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA portable veterinary refractometer RTP-20ATC was used to determine total plasma proteins.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eBiochemical Profile\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eBlood samples were collected using the same technique as for the hematological profile, adding 2 mL to a tube without anticoagulant with clot activator gel and 1 mL to a tube containing sodium fluoride.\u003c/p\u003e\n\u003cp\u003eThe values of ALT, ALP, plasma urea and glucose were obtained using the semi-automatic biochemical analyzer GTA 30, Global Analyzer®, with reagent kits from Labtest®. Each biochemical test was performed according to the instructions of the test manufacturer.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eOthers Parameters\u0026nbsp;\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThroughout the study, heart rate (bpm) was monitored and recorded using an electrocardiogram; respiratory rate (rpm) using a capnograph; temperature (ºC) using an esophageal temperature sensor; non-invasive blood pressure using a multi-parametric monitor; and evaluation of the surgical plane using Guedel's plans were monitored and recorded, evaluating the eyelid reflex, capillary refill time, eyeball, mucosal coloration, and pupillary reflex, keeping the animal in the surgical plane.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eAll data will be presented using the simple arithmetic mean of their values, as well as their respective standard deviations.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u0026nbsp;In the hematological profile, it is possible to observe, through the time averages, as described in the respective tables, a significant effect of the dexmedetomidine infusion on red blood cells, hemoglobin, hematocrit and total proteins.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 1.\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u0026nbsp;Mean, standard deviation (SD) and standard error (SE) of the results of red blood cells, hemoglobin, hematocrit, platelets and total proteins respectively of dogs submitted to dexmedetomidine infusion at different evaluation times.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cimg width=\"278\" height=\"309\" 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\" alt=\"image\"\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn these parameters, it is possible to note that during the infusion (times T15\u0026apos; and T30\u0026apos;) there was a reduction in their values, with a subsequent increase at T120\u0026apos; (90 minutes after the end of the dexmedetomidine infusion). This effect has a special impact on hemoglobin, which presents in its T15\u0026apos; and T30\u0026apos; averages, numbers lower than the lower limit of the reference values for a healthy animal, which implies a worse prognosis for a sick animal. In other parameters such as leukocytes, MCV and MCHC, no changes were observed, or they were inconsistent with the administration of the pharmacological infusion of the \u0026alpha;2-agonist.\u003c/p\u003e\n\u003cp\u003eSimilar effects were observed by Bisht et al. (2018), in research using dexmedetomidine in dogs, as well as by Margeti et al. (2024) using dexmedetomidine in cats and by Ragab et al. (2022) in goats. This same change was also reported in the administration of other \u0026alpha;2-adrenergic drugs in different species, as described by Picioli et al. (2013) with the use of xylazine in sedation protocols in dogs, by Wilson et al. (2004) administering xylazine in sheep, Kili\u0026ccedil; (2008) using detomidine in cattle and Tiburcio et al. (2014) working with the effects of detomidine and xylazine in horses.\u003c/p\u003e\n\u003cp\u003eSome possibilities can be pointed out as causes of such changes, among them is blood sequestration in organs and tissues, with one of the main sites being the spleen, due to adrenergic suppression of \u0026alpha;2-adrenergics, decreased systemic vascular resistance (SVR), vasodilation and hemodynamic imbalance (Ragab et al. 2022; Margeti et al. (2024).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHemodilution is also possible due to the transport of extravascular fluid to the intravascular space (Tiburcio et al. 2014; Picioli et al. 2013). Although this effect is seen as temporary, with a return to baseline levels after a certain time (Tiburcio et al. 2014), in the present study, the reduction in values was maintained while the drug was administered by continuous infusion, improving again only minutes after the end of the procedure, which may indicate possible risks in patients who present hemodynamic decompensation and needed to undergo surgical or clinical procedures that require sedation (Picioli et al. 2013).\u003c/p\u003e\n\u003cp\u003eIn terms of red blood cells, hemoglobin, hematocrit and total proteins, we can observe a notable reduction in their values during the continuous infusion of dexmedetomidine, followed by a gradual increase after the end of the continuous administration of the drug.\u003c/p\u003e\n\u003cp\u003eRegarding the biochemical profile, it is possible to observe primarily a large change in plasma glucose levels during maintenance of pharmacological administration. Their numbers increase gradually, exceeding the upper limit of the reference values described in the literature, causing a picture of transient hyperglycemia, which regresses after the end of continuous infusion, as observed in the average at T120\u0026apos;. This transient increase in serum glucose was also observed in other studies using dexmedetomidine, such as Ragab et al. (2022) with goats and Margeti et al. (2024) with cats.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eTable 2.\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e\u0026nbsp;Mean, standard deviation (SD) and standard error (SE) of ALT, AP, urea and blood glucose respectively levels in dogs undergoing dexmedetomidine infusion at different evaluation times.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"278\" height=\"267\" 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\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003eThis effect is caused mainly by the action of the drug on \u0026alpha;2 receptors in the \u0026beta; cells of the pancreas, causing insulin suppression and decreasing the degree of circulating insulin (Juli\u0026atilde;o et al. 2019; Margeti et al. 2024). Although momentary, this hyperglycemic condition can trigger problems in diabetic patients, in whom protocols containing \u0026alpha;2-agonist drugs must be used with caution as there are no compensatory mechanisms to return to baseline values after completing the procedure with the use of dexmedetomidine.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, only healthy, non-neutered male dogs with an average weight were used, focusing on the hematological changes of dexmedetomidine infusion for a period of 30 minutes, and its effect 90 minutes after the infusion ceased.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe induction of transient hyperglycemia (not exceeding 180 mg/dL in this study), as a result of activation of \u0026alpha;-2A-adrenergic receptors in pancreatic \u0026beta; cells suppressing insulin release, may be harmful to dogs with diabetes or endocrine diseases, because they cannot compensate for the increase in blood glucose levels like a healthy dog can.\u003c/p\u003e\n\u003cp\u003eHematological changes related to hemoglobin, red blood cells and hematocrit may lead to increased respiratory distress, taking into account the synergism that the reduction of these parameters has with the hemodynamic effects of dexmedetomidine on the respiratory tract, requiring careful use in critical cases and in hemodynamically decompensated patients.\u003c/p\u003e\n\u003cp\u003eThe reduction of ALT, as an enzyme that participates in the processes of protein synthesis, neoglycogenesis and the hepatic biotransformation of ammonia into urea, can lead to greater problems in patients who already have liver failure, making it difficult to metabolize drugs.\u003c/p\u003e\n\u003cp\u003eThe reduction in platelets, in cases where thrombocytopenia has already been observed, depending on the procedure to be performed, will impair the patient\u0026apos;s coagulation, and in cases of considerable bleeding may compromise the quality of the post-operative period and recovery time, worsening the prognosis.\u003c/p\u003e\n\u003cp\u003eDuring dexmedetomidine infusions, reductions in total proteins were observed, making prognosis difficult for patients without prior blood tests or prior stabilization, who may present with hypoproteinemia, which leads to an increased risk of hypotension during anesthesia, promotes tissue edema and increases sensitivity to drugs with high protein binding, such as phenothiazines and benzodiazepines.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe variety of effects of alpha 2 adrenergic receptors is evident, and when we focus on the hematological and biochemical profile it is no different, requiring extreme caution in its administration, individualizing the protocol to the patient, placing the risks and benefits that the drug can generate, because when used inadvertently, it triggers adverse effects that will impact the prognosis.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmbrisko TD, Hikasa Y (2002) Neurohormonal and metabolic effects of medetomidine compared with xylazine in beagle dogs. CJVR. PMC226981 PMID, PMCID, p 11858648\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBacchiega TS, Simas RDC, Pinto EADT (2008) Dexmedetomidina: um novo medicamento na anestesiologia veterin\u0026aacute;ria. Rev Cient Elet Med Vet 6:1679\u0026ndash;7353\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBao N, Tang B (2020) Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine. Mediators Inflamm. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2020/6136105\u003c/span\u003e\u003cspan address=\"10.1155/2020/6136105\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBisht DS, Jadon NS, Bodh D, Kandpal M (2018) Clinicophysiological and haematobiochemical evaluation of dexmedetomidine, propofol, sevoflurane anaesthesia in dogs. Indian J Anim Sci. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.56093/ijans.v88i8.82910\u003c/span\u003e\u003cspan address=\"10.56093/ijans.v88i8.82910\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoff GA, Lima CM, Nobre MO, Gehrcke MI (2022) Hemodynamic and respiratory changes from a continuous infusion of dexmedetomidine in general anesthesia in dogs: a systematic review and meta-analysis. Res Soc Dev. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.33448/rsd-v11i7.29980\u003c/span\u003e\u003cspan address=\"10.33448/rsd-v11i7.29980\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBraga SM, Moreno JCD (2012) Uso de f\u0026aacute;rmacos agonistas dos receptores α-2 adren\u0026eacute;rgicos em Medicina Veterin\u0026aacute;ria. Dissertation, Federal University of Goi\u0026aacute;s\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFantoni DT, Cortopassi SRG (2010) Anestesia em c\u0026atilde;es e gatos. 2. ed. S\u0026atilde;o Paulo: Roca, 2010\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJuli\u0026atilde;o GH, Abimussi CJX (2019) Uso de dexmedetomidina em Medicina Veterin\u0026aacute;ria: revis\u0026atilde;o de literatura. Rev Educ Contin Em Med. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.36440/recmvz.v17i1.37840\u003c/span\u003e\u003cspan address=\"10.36440/recmvz.v17i1.37840\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Veterin\u0026aacute;ria E Zootec CRMV-SP\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKili\u0026ccedil; N (2008) Cardiopulmonary, biochemical and haematological changes after detomidine-midazolam-ketamine anaesthesia in calves. Bull Vet Inst Pulawy 52(3):423\u0026ndash;426\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMargeti C, Kazakos G, Galatos AD (2024) The Effect of a Subsequent Dose of Dexmedetomidine or Other Sedatives following an Initial Dose of Dexmedetomidine on Electrolytes, Acid-Base Balance, Creatinine, Glucose, and Cardiac Troponin I in Cats: Part II. Vet Sci. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/vetsci11040143\u003c/span\u003e\u003cspan address=\"10.3390/vetsci11040143\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMuir WW (2007) Considerations for general anesthesia. In: Tranquili WJ, Thurmon JC, Grimm KA (ed) Lumb \u0026amp; Jones veterinary anesthesia and analgesia. 4. th. ed. 2007. pp. 7\u0026ndash;30\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePanzer O, Moitra V, Sladen RN (2009) Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Anesthesiol Clin., v.29, n.4, pp. 587\u0026ndash;605, 2011. PMID: 19576524 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ccc.2009.04.004\u003c/span\u003e\u003cspan address=\"10.1016/j.ccc.2009.04.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePicioli A, Martini MV, Minervino AHH et al (2013) O uso da acepromazina, dexmedetomidina e xilazina na seda\u0026ccedil;\u0026atilde;o em c\u0026atilde;es: altera\u0026ccedil;\u0026otilde;es hematol\u0026oacute;gicas e bioqu\u0026iacute;micas. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.22409/rbcv.v20i1.163\u003c/span\u003e\u003cspan address=\"10.22409/rbcv.v20i1.163\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Rev bras ci\u0026ecirc;nc vet\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRagab G, Hassan SE, Fathi MZ, Hagag U (2022) Clinicophysiological and hematobiochemical effect of dexmedetomidine or diazepam with ketamine and propofol in total intravenous anesthesia in goats. Beni-Suef Univ J Basic Appl Sci. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s43088-022-00232\u0026ndash;0\u003c/span\u003e\u003cspan address=\"10.1186/s43088-022-00232\u0026ndash;0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThurmon JC, Tranquili WJ, Benson GJ (1996) Preanesthetics and anesthetic adjuncts. In: Lumb and Jones veterinary anaesthesia. 3rd ed. Baltimore: William and Wilkins, 1996, pp.183\u0026ndash;209\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTiburcio M, Oliveira MS, Martini MV et al (2014) Acepromazina, detomidina ou xilazina na seda\u0026ccedil;\u0026atilde;o em equinos: efeitos hematol\u0026oacute;gicos e bioqu\u0026iacute;micos. Rev Acad Ci\u0026ecirc;nc Anim. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7213/academica.12.01.AO04\u003c/span\u003e\u003cspan address=\"10.7213/academica.12.01.AO04\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWilson DV, Evans AT, Carpenter RA, Mullineaux DR (2004) The effect of four anesthetic protocols on splenic size in dogs. Vet Anaesth Analg. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1467-2987.2004.00152.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1467-2987.2004.00152.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Alpha 2-adrenergic agonists, Canis lupus familiaris, hyperglycemia, hematocrit","lastPublishedDoi":"10.21203/rs.3.rs-7528986/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7528986/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe hematological, biochemical and glycemic changes related to dexmedetomidine in dogs still require in-depth studies, and their mechanisms have not been fully elucidated. Furthermore, different individuals may present different responses to the pharmacodynamics of the compound in question. The aim of this study was to determine the profile in dogs and compare the results before, during and after continuous infusion. Six healthy dogs, with a mean weight of 10.40\u0026thinsp;\u0026plusmn;\u0026thinsp;4.81 kg, were used in a randomized study. The animals received 3 \u0026micro;g/kg of dexmedetomidine at a concentration of 100 \u0026micro;g/mL intramuscularly and 10 minutes later, an infusion of 3 \u0026micro;g/kg/hr was started for 30 minutes by diluting 0.2 mL of dexmedetomidine in 20 mL of water for injection, reaching a concentration of 1 \u0026micro;g/mL. Venous blood samples of 4 mL were collected using a 5 mL syringe and a 25 x 0.70 mm hypodermic needle through the jugular vein at times T0\u0026rsquo; (baseline), T15\u0026rsquo;, T30\u0026rsquo; minutes of infusion and T120\u0026rsquo; (90 minutes after the end of the infusion). The results were analyzed in a specialized laboratory taking into account the reference values ​​for the species. The parameters verified were total erythrocytes, hematocrit, hemoglobin, total leukocytes, total proteins, alanine transferase, alkaline phosphatase, plasma urea and blood glucose. There was no difference between the doses and forms of administration among the patients. Concluding that the drug induces transient hyperglycemia, as well as significant increases in ALT.\u003c/p\u003e","manuscriptTitle":"Effects of Continuous Dexmedetomidine Infusion on Canine Hematology and Serum Biochemistry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-17 04:58:18","doi":"10.21203/rs.3.rs-7528986/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e72ff38c-0a10-4008-bba3-84b6683f89df","owner":[],"postedDate":"September 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-27T08:38:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-17 04:58:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7528986","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7528986","identity":"rs-7528986","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}