RESUMO
Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 µm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 µg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/sangue , Dexmedetomidina/sangue , Teste em Amostras de Sangue Seco/métodos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/normas , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/sangue , Analgésicos não Narcóticos/normas , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/normas , Teste em Amostras de Sangue Seco/normas , Teste em Amostras de Sangue Seco/estatística & dados numéricos , Hematócrito , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/normas , Lactente , Recém-Nascido , Padrões de Referência , Espectrometria de Massas em Tandem/métodosRESUMO
PURPOSE: To evaluate the effects of single intravenous administration of Dexmedetomidine (DEX) on hemodynamics in rabbits. METHODS: A total of 32 New Zealand white rabbits were randomly divided into the control group (Group C), Group D1 (2.75 µg/kg), Group D2 (5.5 µg/kg), and Group D3 (8.25 µg/kg) to compare systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), central venous pressure (CVP), left ventricular systolic pressure (LVSP), left ventricular end-stage diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax at different time points. RESULTS: The levels of SBP, DBP, HR, LVSP, and LVEDP in Group D1, D2, and D3 were lower than that of Group C from T1 to T5 (P<0.05), but there was no significant difference at T6 and T7 (P>0.05). Compared with T0, the levels of SBP, DBP, HR, LVSP, LVEDP, and left arterial pressure (LAP) from T1 to T7 were decreased (P<0.05), but there was no significant difference in the other indexes (P>0.05). CONCLUSION: Dexmedetomidine can decrease blood pressure and heart rate in rabbits in a dose-dependent manner, but there is no effect on the myocardial systolic and diastolic function.
Assuntos
Dexmedetomidina/farmacologia , Hemodinâmica/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Animais , Dexmedetomidina/sangue , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Hemodinâmica/fisiologia , Hipnóticos e Sedativos/sangue , Masculino , Coelhos , Distribuição Aleatória , Valores de Referência , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Abstract Purpose: To evaluate the effects of single intravenous administration of Dexmedetomidine (DEX) on hemodynamics in rabbits. Methods: A total of 32 New Zealand white rabbits were randomly divided into the control group (Group C), Group D1 (2.75 μg/kg), Group D2 (5.5 μg/kg), and Group D3 (8.25 μg/kg) to compare systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), central venous pressure (CVP), left ventricular systolic pressure (LVSP), left ventricular end-stage diastolic pressure (LVEDP), left ventricular developmental pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax at different time points. Results: The levels of SBP, DBP, HR, LVSP, and LVEDP in Group D1, D2, and D3 were lower than that of Group C from T1 to T5 (P<0.05), but there was no significant difference at T6 and T7 (P>0.05). Compared with T0, the levels of SBP, DBP, HR, LVSP, LVEDP, and left arterial pressure (LAP) from T1 to T7 were decreased (P<0.05), but there was no significant difference in the other indexes (P>0.05). Conclusion: Dexmedetomidine can decrease blood pressure and heart rate in rabbits in a dose-dependent manner, but there is no effect on the myocardial systolic and diastolic function.
Assuntos
Animais , Masculino , Ratos , Dexmedetomidina/farmacologia , Hemodinâmica/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Valores de Referência , Fatores de Tempo , Distribuição Aleatória , Reprodutibilidade dos Testes , Dexmedetomidina/sangue , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Hemodinâmica/fisiologia , Hipnóticos e Sedativos/sangueRESUMO
Purpose: To evaluate hemodynamics and bispectral index (BIS) in bitches anesthetized with ketamine and midazolam in combination with dexmedetomidine or medetomidine and submitted to ovariohysterectomy. Methods: Twenty bitches pretreated with levomedetomidine and buprenorphine were anesthetized with 5 mg.kg-1 ketamine and 0.2 mg.kg-1 midazolam i.v. Continuous infusion of 0.4 mg.kg-1.h-1 midazolam and 20 mg.kg-1.h-1 ketamine was initiated in combination with DEX (n=10): 20 µg.kg-1.h-1 dexmedetomidine or MED (n=10): 30 µg.kg-1.h-1 medetomidine over 30 minutes. A pharmacokinetic study provided dexmedetomidine plasma concentration, set to be 3.0 ng.mL-1. Results: BIS decreased in both groups (P<0.05), but it was lower in DEX (P<0.05) as compared to MED. No differences were found in hemodynamic parameters (heart rate, systolic, diastolic and mean arterial pressure) between groups (P>0.05), but heart rate decreased in both groups, as compared to control values (P<0.05). Respiratory rate decreased (P<0.05) and expired end tidal CO2 increased progressively (P<0.05) and similarly in both groups. Anesthetic recovery period was similar between groups (P<0.05) with no adverse effects. Conclusion: Continuous administration of dexmedetomidine with calculated plasma concentration equal to 3 ng.mL-1 in combination with midazolam and ketamine provides suitable anesthesia for spay surgery in bitches, hemodynamic stability and calm awakening with no adverse effects.
Objetivo: Verificar o comportamento hemodinâmico e o índice bispectral de cadelas anestesiadas com cetamina e midazolam associados à dexmedetomidina ou medetomidina. Métodos: Vinte cadelas receberam pré-tratamento com levomepromazina e buprenorfina e foram anestesiadas com cetamina, 5 mg.kg-1 i.v., e midazolam, 0,2 mg.kg-1 i.v., seguidos da administração contínua de midazolam, 0,4 mg.kg-1.h-1, e cetamina, 20 mg.kg-1.h-1, associados, conforme o grupo, à: DEX (n=10): dexmedetomidina 20 µg.kg-1.h-1 ou MED (n=10): medetomidina 30 µg.kg-1.h-1, mantidos por 30 minutos. A dose de dexmedetomidina foi obtida por meio de estudo farmacocinético planejando-se concentração plasmática de 3,0 ng.mL-1. Resultados: Os valores do BIS diminuíram em ambos os grupos (P<0,05), mas foram menores no grupo DEX (P<0,05), em comparação com o grupo MED. Não houve diferença significativa nos atributos hemodinâmicos (frequência cardíaca, pressão arterial sistólica, diastólica e média) entre os grupos, mas a frequência cardíaca diminuiu em ambos os grupos em relação ao momento controle (P<0,05). A frequência respiratória diminuiu (P<0,05) e o CO2 expirado aumentou progressivamente em ambos os grupos (P<0,05). O tempo de recuperação anestésica foi semelhante entre os grupos (P>0,05), sem a presença de efeitos adversos. Conclusão: A administração contínua de dexmedetomidina em concentração plasmática calculada de 3 ng.mL-1, em combinação com midazolam e cetamina, resulta em plano anestésico adequado para castração de cadelas, estabilidade hemodinâmica e despertar tranquilo, sem efeitos adversos.
Assuntos
Animais , Cães , Feminino , Anestésicos Combinados/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Histerectomia/veterinária , Ovariectomia/veterinária , Anestésicos Combinados/efeitos adversos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/sangue , Eletromiografia/veterinária , Hipnóticos e Sedativos/efeitos adversos , Histerectomia/métodos , Ketamina/administração & dosagem , Medetomidina/administração & dosagem , Midazolam/administração & dosagem , Monitorização Intraoperatória/veterinária , Ovariectomia/métodosRESUMO
PURPOSE: To evaluate hemodynamics and bispectral index (BIS) in bitches anesthetized with ketamine and midazolam in combination with dexmedetomidine or medetomidine and submitted to ovariohysterectomy. METHODS: Twenty bitches pretreated with levomedetomidine and buprenorphine were anesthetized with 5 mg*kg(-1) ketamine and 0.2 mg*kg(-1) midazolam i.v. Continuous infusion of 0.4 mg*kg(-1)*h(-1) midazolam and 20 mg*kg(-1)*h(-1) ketamine was initiated in combination with DEX (n=10): 20 microg*kg(-1)*h(-1) dexmedetomidine or MED (n=10): 30 microg*kg(-1)*h(-1) medetomidine over 30 minutes. A pharmacokinetic study provided dexmedetomidine plasma concentration, set to be 3.0 ng*mL(-1). RESULTS: BIS decreased in both groups (P<0.05), but it was lower in DEX (P<0.05) as compared to MED. No differences were found in hemodynamic parameters (heart rate, systolic, diastolic and mean arterial pressure) between groups (P>0.05), but heart rate decreased in both groups, as compared to control values (P<0.05). Respiratory rate decreased (P<0.05) and expired end tidal CO(2) increased progressively (P<0.05) and similarly in both groups. Anesthetic recovery period was similar between groups (P<0.05) with no adverse effects. CONCLUSION: Continuous administration of dexmedetomidine with calculated plasma concentration equal to 3 ng.mL-1 in combination with midazolam and ketamine provides suitable anesthesia for spay surgery in bitches, hemodynamic stability and calm awakening with no adverse effects.