Echocardiographic evaluation of healthy cats under the effect of Dexmedetomidine and ButorphanolABSTRACT
The study aimed to evaluate the applicability of the association of two classes of drugs. Ten healthy cats were used, who underwent echocardiographic evaluation and measurement of systemic blood pressure at baseline and after administration of dexmedetomidine at a dose of (10 mcg/kg) and butorphanol at a dose of (0.4mg/kg) intramuscularly. In the results obtained, there was a 12% decrease in free wall thickness in diastole in M mode (p=0.017), in addition to a 47% decrease in heart rate (p< 0.0001) and a 30% increase in systemic blood pressure (p<0.0001) after sedation. The TEI index increased (p<0.0001) and there was a significant impact on the systolic function of sedated cats, with a decrease in shortening fraction (p<0.0001), cardiac output (p = 20.003), S' wave (p = 0.007) and increased left ventricular diameter in M-mode systole (p = 0.0003). And the maximum velocities of the aorta (p = 0.015) and pulmonary artery (p < 0.0001) flows decreased, in addition to promoting alterations compatible with pulmonary artery hypertension. The association promotes sedation, but decreases systolic function, cardiac output and heart rate and increases afterload, therefore it is not suitable for echocardiographic evaluation.
Keywords:
feline; cardiology; α2-agonist
RESUMO
O estudo teve como objetivo avaliar a aplicabilidade da associação de duas classes de fármacos. Foram utilizados 10 gatos hígidos, que foram submetidos à avaliação ecocardiográfica e aferição da pressão arterial sistêmica no momento basal e após a administração da dexmedetomidina, na dose de (10mcg/kg), e o butorfanol, na dose de (0,4mg/kg), por via intramuscular. Nos resultados obtidos, houve diminuição de 12% na espessura da parede livre na diástole no modo M (P = 0,017), além da diminuição em 47% da frequência cardíaca (P < 0,0001) e do aumento em 30% na pressão arterial sistêmica (P < 0,0001) após a sedação. O índice TEI aumentou (P < 0,0001) e houve impacto significativo na função sistólica dos gatos sedados, com a diminuição da fração de encurtamento (P < 0,0001), do débito cardíaco (P = 0,003), da onda S’ (P = 0,007) e o aumento do diâmetro do ventrículo esquerdo na sístole em modo M (P = 0,0003). Além desses resultados, diminuíram as velocidades máximas dos fluxos da artéria aorta (P = 0,015) e da artéria pulmonar (P < 0,0001), bem como houve promoção das alterações compatíveis com hipertensão da artéria pulmonar. A associação promove sedação, porém diminui a função sistólica, o débito cardíaco e a frequência cardíaca e aumenta a pós-carga, portanto não é adequada para avaliação ecocardiográfica.
Palavras-chave:
felinos; cardiologia; α2-agonista
INTRODUCTION
Heart diseases of myocardial origin are the most common species in felines, whether of primary or secondary origin to other diseases (Fuentes et al., 2020). Cats tend to be discreet in their clinical manifestations, and in retrospective studies it was demonstrated that in a population of 106 cats with heart disease, only 55% presented changes in cardiac auscultation (Ferasin et al., 2003). Thus, the echocardiographic examination is essential for the diagnosis of cardiomyopathies in cats, in addition to helping in the staging of the disease (Fuentes et al., 2020).
Dexmedetomidine is a selective alpha-2 adrenergic agonist drug that binds to the alpha-2 receptor, located in the cerebral cortex, brainstem and spinal cord, promoting sedation, muscle relaxation and analgesia. Its desirable action has dose-dependen characteristics, as well as its adverse effects such as bradycardia and vasoconstriction of peripheral vessels (Vickery et al., 1988; Bagatine et al., 2002) and a way to decrease the dose of this medication, without compromising sedation, is the association with other classes of drugs, such as opioids (Nagore et al., 2012).
Butorphanol is an antagonist opioid widely used in feline medicine, capable of promoting mild sedation and analgesia (Mathews et al., 2014). The associated use of dexmedetomidine and butorphanol has the benefit of decreasing both doses, promoting sedation and interaction with side effects.
This research aimed to evaluate the applicability of dexmedetomidine associated with butorphanol in the sedation of healthy cats to perform the echocardiographic exam, as well as to evaluate the effects on the echocardiographic variables.
MATERIAL AND METHODS
Ten healthy cats, male and female, mixed breed, aged over 12 months were used. Those responsible for the animals used in the experiment were previously informed about the procedures that would be performed and signed a free and clear term for authorization. The cats were fasted for eight hours and without water restriction. A complete physical examination was performed, with trichotomy of the cervical and thoracic regions and the palmar region of the metacarpal near the pad. Three milliliters of blood were collected by puncture of the jugular vein for laboratory tests such as: complete blood count, renal and hepatic profile. The animals were kept in individual cages, where there was no presence of other animals and water ad libitum, the cages were covered to minimize stress, until all the tests in the experiment were carried out.
After carrying out the measurement of systemic blood pressure and the echocardiogram to obtain baseline values, the animals received the drugs dexmedetomidine at a dose of (10mcg/Kg) and butorphanol at a dose (0.4mg/kg), the medications were drawn in separate syringes and then placed in the same syringe to be applied together, intramuscularly in the quadriceps muscle on the right side. The sedation of the cats was evaluated, and the adverse effects observed during this period were noted. After 10 minutes of application, the animals underwent a new physical examination, measurement of systemic blood pressure and echocardiographic examination. And throughout the text, post-sedation time refers to a time of 10 minutes.
The cats were sedated by a single evaluator, at 5 and 10 minutes using the sedation scale suggested by Biermann et al. (2012) with a score from 0 to 5 (Table 1). To carry out this evaluation, the cats received auditory stimulus with the snapping of the fingers and were called by their respective names, in addition to being stimulated with the changes of decubitus.
Systemic systolic blood pressure was measured using the non-invasive method of vascular Doppler, with the Medmega® device1. The cuff used for the measurement was selected according to the measurement of the circumference of the left forelimb in the radioulnar region, and the width of the cuff should correspond to 30% to 40% of that measurement. The Doppler probe was positioned in the palmar region of the metacarpa proximal to the pad, to identify the arterial pulse and subsequently the measurement was performed.
The cats were positioned in sternal decubitus and the measurement was performed on the left forelimb, with at least five consecutive measurements being taken, for late calculation of the mean arterial pressures.
The echocardiographic examination, which was conducted by an experienced cardiologist veterinarian, with the MySono U6® 2 equipment, using the pediatric sector transducer.
The cats were positioned in lateral decubitus and the echocardiographic evaluation was performed using the transthoracic pattern using the M-mode, two-dimensional mode and spectral Doppler techniques. The echocardiographic examination began in the right parasternal region, in the cross-section of the left ventricle (LV) at the level of the chorda tendineae, focusing the ultrasound beam between the papillary muscles for the M-mod analysis of the thickness of the interventricular septum in diastole (IVSd), diameter of the left ventricle in systole (DVEs), diameter of the left ventricle in diastole (DVEd) and free wall thickness in diastole (PLd) through the formula DVEd - DVEs / DVEd x 100 (Madron, 2016a).
In two-dimensional mode in the right parasternal region in the cross-section at the level of the aortic valve, the left atrium diameter at the end of systole (AE), aortic diameter at the end of systole (Ao), left atrium and aorta ratio (AE/ Ao) (Selmi et al., 2003), and aortic valve area (AVA). The transpulmonary flow was analyzed using the pulsed spectral Doppler method, focusing the ultrasound beam between the pulmonary valve leaflets in a cross-section, thus obtaining the maximum velocity of this flow (Madron, 2016a), in addition to the acceleration time (TA), the time ejection (ET) and pulmonary TA/ET ratio (Chetboul, 2016a). And in the longitudinal section, the SIVd thickness, PLd thickness and LA diameter at the end of systole were measured (Freeman et al., 2015).
In the left parasternal region, the transmitral flow was evaluated in the apical four- chamber view, using pulsed Doppler to obtain the E, A waves and the E/A ratio (Afonso and Reis, 2012). In the same image, the measurement of the time between closing and opening of the mitral valve (MCO) was performed, which was used to calculate the myocardial performance index (TEI) (Madron, 2016c). Subsequently, the Doppler beam was positioned so that it reached the aorta and mitral valve flows simultaneously, in the apical five-chamber position for measuring the isovolumetric relaxation time (IVRT) (Madron, 2016a).
The transaortic flow was performed with the pulsed Doppler beam incident parallel to the aorta flow in the apical five-chamber view, to identify the maximum velocity of this flow (Madron, 2016c), and the TE of the aorta artery, thus being able to calculate the TEI index, for half of the TEI index formula = MCO - aortic TE / aortic TE (Madron, 2016b). With regard to pulsed tissue Doppler, the analysis was performed at the insertion of the mitral valve with the LV free wall in the apical four- chamber image, obtaining the E', A', S' waves and the A'/E' ratio (Chetboul, 2016b).
The systolic volume (SV) value could be measured using the following formula: aortic velocity integral time (VTI) multiplied by the aortic valve area (AVA). And cardiac output (CO) was calculated using the formula CO volume = SV x HR.
Statistical analysis of the echocardiographic parameters were performed using the GraphPad Prism® software, with the Student's t test, and for all analyzes a significance level of 5% of probability was considered.
RESULTS AND DISCUSSION
The study was carried out with 10 adult cats, healthy, 7 males and 3 females, castrated, mixed breed. The mean body weight was 4.28 kg ± 0.70 and the mean age was 34.7 months ± 25.16 and all cats were considered clinically healthy after performing the physical examination and laboratory tests.
Sedation at 5 minutes reached a mean score of 2.2 on the sedation table and at 10 minutes, a score of 3.6. Sedation was considered satisfactory, as it was possible to position the cats in lateral decubitus without resistance, only one cat had a score of 0 at 5 minutes and at 10 minutes presented a score of 1 sedation. Good muscle relaxation was observed, but all cats maintained a slightly decreased muscle tone in the limbs. Side effects observed in all cats were mydriasis and pale mucous membranes, and one cat had nausea.
The mean HR before sedation was 169.5 ± 44.73 beats per minute (bpm), and after sedation the mean was 90 ± 15.19 bpm, demonstrating that there was a sharp drop in HR after sedation, with statistically significant difference (p<0.0001). The systolic blood pressure of the animals before sedation averaged 122.4±12.13 mmHg and increased in all cats, reaching a mean of 159.5±18.27mmHg, with a statistically significant difference (p<0.0001). The average of all echocardiographic parameters analyzed, baseline and after sedation with dexmedetomidine and butorphanol are described below (Table 2).
Of the parameters analyzed in the M mode, the SIVd and DVEd did not change, but there was a significant increase in the DVEs (p < 0.0003) and a significant decrease in the PLd measurement (p<0.017). In mode B, in the cross-sectional measurements, the measurements of Ao, AE and AE/Ao and in the longitudinal section AE, SIVd, PLd had no statistically significant change.
In the flow evaluations, the E, A, E/A and IVRT waves did not show significant changes, but there was a decrease in the average of the A wave and an increase in the E/A ratio. Regarding MCO, a significant increase was observed (p < 0.0001). In tissue Doppler, there was no significant difference in the E', A' waves, but the S' wave decreased significantly (p < 0.007). The E/E' ratio did not change, but the E'/A' ratio increased significantly (p < 0.021).
The maximum velocities of the aorta and pulmonary artery flows decreased significantly, being (p < 0.015) and (p < 0.0001) respectively. Other parameters analyzed in relation to aortic and pulmonary flows also changed significantly, such as: aortic TE (p = 0.0009), pulmonary TE (p = 0.003), increasing after sedation; pulmonary AT (p = 0.015) and pulmonary AT/ET (p = 0.002) decreased in relation to the baseline value. SV did not change after sedation, but there was a significant decrease in the shortening fraction (p < 0.0001) of CO (p < 0.003). And in relation to the TEI index there was a significant increase (p = 0.014).
The present study found that the sedation protocol with the association of dexmedetomidine (10mcg/kg) and butorphanol (0.4mg/kg) for cats promoted excellent sedation, but caused significant changes in heart rate, systemic blood pressure, systolic function and in the velocities of the flows of the pulmonary artery and aortic artery, which limit its use for the performance of the echocardiographic examination.
Sedation was considered satisfactory in 9 of the 10 cats that participated in the experiment, in addition to promoting excellent muscle relaxation. The animals were easily positioned in lateral decubitus, with no need for additional physical restraint. This effect was possibly obtained due to the association of dexmedetomidine with butorphanol, as in a study carried out by Selmi et al. (2003), in which they compared sedation and muscle relaxation in cats under the effect of dexmedetomidine alone, at the same dose as used in the present study and associated with butorphanol (0.2 mg/kg) or ketamine (5mg/kg), the authors could conclude that dexmedetomidine associated with butorphanol or ketamine promoted muscle relaxation and significantly greater sedation when compared to isolated dexmedetomidine.
Despite reaching a deep sedation, the cats did not completely lose consciousness because, when changing positions, the animals showed a slight muscle tone, mainly in the forelimbs. The deep sedation observed in cats is possibly related to the mechanism of action produced by dexmedetomidine in the locus coeruleus, which is a noradrenergic nucleus in the brain with a high concentration of alpha-2 adrenoreceptor. Regarding side effects, emesis is a side effect commonly reported in the literature (Paspatefanou et al., 2015), however, no cat in this experiment showed this adverse effect, which may be related to the dose used, since the desirable and undesirable effects of dexmedetomidine are doses- dependents (Pascoe, 2015). Another possible explanation is due to the association of dexmedetomidine with butorphanol, as in a study conducted by Papastefanou et al. (2015), demonstrated that butorphanol at doses (0.1mg/kg) and (0.2mg/kg) helped to prevent vomiting caused by dexmedetomidine when used at doses (20mcg/kg) and (25mcg/kg) in cats.
Regarding cardiovascular parameters, after sedation, HR showed a significant drop and SBP a significant increase. Stimulation of alpha-2b receptors on vascular smooth muscle is thought to be the cause of the increase in blood pressure, and the dose-dependent bradycardic effect of dexmedetomidine is primarily mediated by a decrease in sympathetic signal and in part by baroreceptor reflex and vagal activity high (Afonso and Reis, 2012).
The sedation protocol used caused changes in measures related to systolic function. The S' wave velocity decreased significantly after drug application. According to Madron (2016b), the maximum velocity of the systolic S' wave obtained in the mitral annulus through tissue Doppler is correlated with the ejection fraction in humans, in the absence of regional dyskinesia. Thus, since it is formed during the systolic ejection phase, it can be considered an indirect measure of the ejection fraction, in addition to being an important parameter to be analyzed in cats, since it tends to decrease in cases of HCM (Madron, 2016d).
Other factors that corroborate the interpretation that the systolic function was greatly influenced by the medications were: the decrease in the shortening fraction and the increase in the left ventricular systolic diameter (LVDs). Fractional shortening reduced by 23% compared to baseline and M-mode EVDs increased by 29%. The shortening fraction is easy to obtain and was one of the first indices developed to assess systolic function by echocardiography, but it has some limitations since it measures only radial function, in addition to suffering interference from pre- and post-load (Madron, 2016c). Therefore, the increase in afterload observed in this study possibly contributed to the decrease in the shortening fraction. However, a possible effect of drugs on contractility cannot be excluded.
Regarding the TEI index, which is an index of the global performance of the LV myocardium (systolic and diastolic), in this study there was a significant increase compared to the baseline value, thus indicating a loss of myocardial performance (Madron, 2016c), which may be correlated with the afterload increase, as demonstrated by Hori et al. (2013) in cats, in which the TEI was altered due to the increase in afterload, on the other hand, this parameter does not seem to be influenced by HR and preload.
The flows of the aorta and pulmonary artery suffered a significant decrease in their maximum velocity with the use of the combination of drugs, which can be explained by the abrupt increase in LV afterload and a possible transient increase in RV afterload, which can cause the flow to encounter greater resistance during systole, reducing its peak velocity.
In addition to the decrease in the maximum velocity of the pulmonary artery flow, there was an increase in TE, a decrease in the pulmonary flow TA, and consequently, a decrease in the pulmonary TA/ET ratio. Currently, the AT and the pulmonary AT/ET ratio are some of the ways of evaluating the probability of pulmonary hypertension in dogs using Doppler echocardiography (Reinero et al., 2020).
In this study, the E'/A' ratio increased significantly after sedation, which may characterize a diastolic dysfunction, however, the evaluation of this function should be done together with other echocardiographic parameters, such as: IVRT, E, A waves and the E/A ratio (Madron, 2016b), and such parameters were not altered after the use of associated dexmedetomidine to butorphanol in this study.
Regarding the evaluation of the thickness of the myocardial wall, it is of great value to emphasize the importance of these parameters in felines, since most heart diseases in the species is of myocardial origin. In addition, the LA size and the LA/Ao ratio must be carefully analyzed, as they are criteria for classifying the stages of these diseases in cats (Fuentes et al., 2020).
In our study, the measurements performed in two-dimensional mode of PLd and SIVd did not change statistically. In the M mode, the SIVd also did not undergo significant modification, however, an alteration in the PLd measurement was observed, with a value 12% lower after sedation. Kellihan et al. (2003) also obtained similar findings in dogs using the same protocol for sedation, which may suggest that due to the decrease in heart rate, the myocardial relaxation time is longer, thus being able to characterize more reliable measures of PLd.
The measurements made of the LA and the aorta in B-mode in the cross-sectional view were not altered by the protocol used in this study, in agreement with Kellihan et al. (2003) who used the same protocol in dogs. And in another study that used (40 mcg/kg) dexmedetomidine associated with buprenorphine in cats, it also did not find alterations in the LA and aorta (Johard et al., 2018), seeming to have no important influence of dexmedetomidine in these sites.
This work showed significant changes with the use of the association of dexmedetomidine with butorphanol in felines, but it also presented some limitations. The study evaluated the association of drugs, but it would be interesting to evaluate how each drug behaves individually in the face of this analysis. Furthermore, the reduced sample size may have interfered with other variables that did not show significant values.
However, this work used drugs duly authorized and commonly used in association with felines. Thus, the results obtained in this study may impact the choice of the veterinary anesthesiologist regarding the use of this protocol for feline sedation.
CONCLUSION
There were changes in indirect echocardiographic signs that indicate an increased probability of pulmonary hypertension.
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Publication Dates
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Publication in this collection
27 Jan 2025 -
Date of issue
Jan-Feb 2025
History
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Received
11 July 2023 -
Accepted
02 Apr 2024
