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2.
Acta Cir Bras ; 34(9): e201900905, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800679

RESUMO

PURPOSE: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. METHODS: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. RESULTS: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. CONCLUSION: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Colecistectomia Laparoscópica/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Dexmedetomidina/administração & dosagem , Isoxazóis/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , /tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Pressão Arterial/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
4.
Expert Opin Ther Pat ; 29(10): 805-815, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486689

RESUMO

Introduction: Glaucoma is a neurodegenerative disease of the eye characterized by selective retinal ganglion cell loss that provokes progressive defects in the visual field. Elevated intraocular pressure (IOP) is an important contributor for the progression of glaucoma. The current therapeutic arsenal for reducing IOP includes prostaglandin analogs, ß-blockers, carbonic anhydrase inhibitors, α-adrenergic agonist, miotics, rho-kinase inhibitors and combinations thereof, generally administered as eye drops. Areas covered: This manuscript reviews the state of art on adrenergic modulators for treating glaucoma. Both monotherapy and fixed-drugs combinations including α2-adrenergic agonists and ß-blockers are discussed as well as drug delivery systems where these classes of drugs are used. The review then covers the patent literature involving adrenoceptors modulators over the period 2013-2019. Expert opinion: While the scientific community is moving forward novel targets and related modulators for treating glaucoma and ocular hypertension, adrenergic modulators held a prominent position in the therapy of glaucoma and related disorders. Indeed, though not embodying anymore the first-choice monotherapy, they are widely marketed worldwide ordinarily in combination with other drugs, are subjects of many studies for identifying new drug compositions and have been assessed as active ingredients in several innovative ocular drug delivery systems.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Glaucoma/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Animais , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Desenho de Drogas , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Patentes como Assunto
5.
Medicine (Baltimore) ; 98(33): e16772, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415378

RESUMO

BACKGROUND: Pneumoperitoneum and steep Trendelenburg position during robot-assisted laparoscopic prostatectomy (RALP) can increase intracranial pressure (ICP). Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, can cause cerebral vasoconstriction and decrease cerebral blood flow by stimulating the postsynaptic alpha-2 adrenergic receptors on cerebral blood vessels. However, the effects of dexmedetomidine on ICP are controversial and have not been evaluated during RALP under the establishment of pneumoperitoneum in the steep Trendelenburg position. Therefore, we evaluated the effect of dexmedetomidine on optic nerve sheath diameter (ONSD) as a surrogate for assessing ICP during RALP. METHODS: Patients were randomly allocated to receive dexmedetomidine (n = 63) (loading dose, 1 µg/kg for 10 minutes and continuous infusion, 0.4 µg/kg/hr) or normal saline (n = 63). The ONSD was measured at 10 minutes after induction of anesthesia in the supine position (T1), 30 minutes (T2) and 60 minutes (T3) after establishment of pneumoperitoneum in the steep Trendelenburg position, and at closing the skin in the supine position (T4). Hemodynamic and respiratory variables were measured at every time point. RESULTS: ONSDs at T2, T3, and T4 were significantly smaller in the dexmedetomidine group than in the control group (5.26 ±â€Š0.25 mm vs 5.71 ±â€Š0.26 mm, 5.29 ±â€Š0.24 mm vs 5.81 ±â€Š0.23 mm, and 4.97 ±â€Š0.24 mm vs 5.15 ±â€Š0.28 mm, all P <.001). ONSDs at T2, T3, and T4 were significantly increased compared to T1 in both groups. Hemodynamic and respiratory variables, except heart rate, did not significantly differ between the 2 groups. The bradycardia and atropine administration were not significantly different between the 2 groups. CONCLUSION: Dexmedetomidine attenuates the increase of ONSD during RALP, suggesting that intraoperative dexmedetomidine administration may effectively attenuate the ICP increase during pneumoperitoneum in the Trendelenburg position.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Hipertensão Intracraniana/prevenção & controle , Pressão Intracraniana/efeitos dos fármacos , Nervo Óptico/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Idoso , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Período Intraoperatório , Laparoscopia , Masculino , Nervo Óptico/diagnóstico por imagem , Prostatectomia , Procedimentos Cirúrgicos Robóticos , Resultado do Tratamento
6.
Am J Vet Res ; 80(9): 868-877, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31449445

RESUMO

OBJECTIVE: To determine the effects of 3 α2-adrenergic receptor agonists (α2-ARAs), alone or in combination with butorphanol tartrate, on objective measurements of lameness in horses. ANIMALS: 17 adult polo horses with naturally occurring forelimb or hind limb lameness (or both). PROCEDURES: In a crossover design, each horse received each protocol (saline [0.09% NaCl] solution [2 mL, IV] or xylazine hydrochloride [0.33 mg/kg, IV], detomidine hydrochloride [0.007 mg/kg, IV], or romifidine hydrochloride [0.033 mg/kg, IV] alone or in combination with butorphanol [0.007 mg/kg, IV]) in random order, with a washout period (≥ 7 days) between protocols. Horses were assessed immediately prior to (baseline) and 10, 15, 20, 30, and 40 minutes after administration of each protocol for degree of sedation, mechanical nociceptive threshold (MNT), and objective lameness measurements. RESULTS: Compared with baseline values, sedation scores and MNTs were significantly higher at all evaluated time points following administration of all sedation protocols except xylazine alone; following administration of xylazine alone, sedation scores and MNTs were significantly higher at ≤ 30 minutes and ≤ 20 minutes, respectively. Significant differences in objective forelimb lameness measurements were noted after administration of the 3 α2-ARA-butorphanol combinations. Most significant differences in objective measurements of hind limb lameness were detected after administration of detomidine or romifidine, alone or in combination with butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE: In the study horses, xylazine alone had the least impact on objective lameness measurements. The administration of α2-ARAs, particularly detomidine or romifidine, alone or in combination with butorphanol, resulted in small but significant effects on objective lameness measurements.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Butorfanol/uso terapêutico , Imidazóis/uso terapêutico , Coxeadura Animal/tratamento farmacológico , Xilazina/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Estudos Cross-Over , Quimioterapia Combinada , Feminino , Membro Anterior/efeitos dos fármacos , Marcha/efeitos dos fármacos , Cavalos , Imidazóis/administração & dosagem , Masculino , Distribuição Aleatória
7.
Eur Arch Otorhinolaryngol ; 276(11): 3095-3104, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31363901

RESUMO

PURPOSE: Intense bleeding of the surgical field is a potential factor influencing success of functional endoscopic sinus surgery (FESS). Hypotensive anesthesia with α2 intravenous agonists reduces intraoperative bleeding, but which is the best agent is unknown. The main objective of this trial was to compare the current standard adjuvant drug for hypotensive anesthesia, clonidine, with the recently available alternative dexmedetomidine. METHODS: A randomized clinical trial compared the efficacy of clonidine and dexmedetomidine during FESS. Treatment was open label for the anesthesiologist and operating surgeon, but blind for an external evaluator who evaluated video-recorded surgeries. A Boezaart scale was assessed every 30 min during FESS until surgery completion. Main end-point was the proportion of patients with mean Boezaart scores > 2 (heavy bleeding) by external blinded evaluator. Secondary end-points included other bleeding parameters, surgery duration, hemodynamic measures and surgical complications. RESULTS: 94 patients were randomized. There were no significant differences in the proportion of patients with mean Boezaart scores > 2 in clonidine (42.6%) and dexmedetomidine (42.6%). Consistently, no differences were observed in secondary variables of bleeding, duration or complications. Small differences in mean heart rate were observed that might reflect different pharmacological profiles of the products, but are of uncertain clinical relevance. CONCLUSIONS: No significant differences were observed between clonidine and dexmedetomidine when used as anesthetic adjuvants in the reduction of surgical bleeding in FESS. A longer experience with clonidine and its lower costs suggest it may be a preferable option as an adjuvant for hypotensive anesthesia.


Assuntos
Anestesia/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Clonidina , Dexmedetomidina , Endoscopia , Seios Paranasais/cirurgia , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Doença Crônica , Clonidina/administração & dosagem , Clonidina/efeitos adversos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Endoscopia/efeitos adversos , Endoscopia/métodos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/cirurgia , Duração da Cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Resultado do Tratamento
8.
BMC Vet Res ; 15(1): 258, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340857

RESUMO

BACKGROUND: Heart rate variability (HRV) provides information about autonomic nervous system (ANS) activity and is therefore a possible tool with which to assess anaesthetic depth. The aim of the present study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on HRV before and after nociceptive stimulation at different anaesthetic depths. Seven healthy domestic short-hair cats were used, and each cat was anaesthetized three times - group I with isoflurane alone, group IR with isoflurane and a constant rate infusion (CRI) of remifentanil (18 µg/kg/h), and group ID with isoflurane and a CRI of dexmedetomidine (3 µg/kg/h). Minimum alveolar concentration (MAC) values were determined via electrical supramaximal nociceptive stimulation for each treatment group. Nociceptive stimulation was repeated at 3 different MAC multiples (0.75, 1.0 and 1.5 MAC), and electrocardiographic recordings were performed for 3 min before and after stimulation. Only the 1 min epochs were used for further statistical analysis. Electrocardiographic data were exported for offline HRV analysis. RESULTS: The mean isoflurane MAC ± standard deviation (SD) was 1.83 ± 0.22 vol% in group I, 1.65 ± 0.13 vol% in group IR and 0.82 ± 0.20 vol% in group ID. Nociception was indicated by several HRV parameters, however, with high variability between treatments. The best correlation with MAC was found for the SD of heart rate (STD HR) in group I (rs = - 0.76, p = 0.0001, r2 = 0.46). STD HR was also able to distinguish 0.75 MAC from 1.5 MAC and 1.0 MAC from 1.5 MAC in group I, as well as 0.75 MAC from 1.5 MAC in group ID. CONCLUSIONS: The choice of anaesthetic protocol influences the HRV parameters in cats. Frequency domain parameters respond to nociception at lower MAC levels. The STD HR has the potential to provide additional information for the assessment of anaesthetic depth in isoflurane-anaesthetized cats. The utility of HRV analysis for the assessment of anaesthetic depth in cats is still questionable.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestésicos Inalatórios/administração & dosagem , Dexmedetomidina/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Isoflurano/administração & dosagem , Remifentanil/administração & dosagem , Anestesia por Inalação/veterinária , Animais , Gatos , Estimulação Elétrica , Eletrocardiografia/veterinária , Feminino , Masculino , Nociceptividade/efeitos dos fármacos
9.
AAPS PharmSciTech ; 20(7): 260, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332579

RESUMO

Orthodontic retainers are wearable customizable medical devices for dental protection or alignment. Here, clonidine hydrochloride (CH)-loaded wearable personalized 3D printed orthodontic retainers were studied for local sustained-release of drugs. CH powders were mixed with PEG 4000, Tween 80, poly(lactic acid), and polycaprolactone. The mixture was hot-melt extruded to form a filament that was 3D printed to a customizable original orthodontic retainer with the fused deposition modeling (FDM) method. The original retainer showed a burst release of CH in the early stage of the dissolution process though a sustained release appeared in the late stage. The in vivo burst release of CH would lead to unexpected side effect. The original retainer was modified by coating with hydrophilic polymers or washing with buffered solutions to obtain the coated or washed retainer. The coated retainer still showed a burst release while the washed retainer showed an optimal sustained release. Many CH microparticles existed on the surface of original retainers according to the scanning electron microscopic image so that the burst release was unavoidable. The hydrophilic polymer coating method did not change the release profile because the polymer was also rapidly dissolved. However, most of the surface CH can be eliminated by washing so that the burst release dissappeared in the washed retainer. Furthermore, the simulated CH concentration-time profiles in the circulation of humans of the washed retainer showed the stable and appropriate drug levels for more than 3 days. Wearable personalized 3D printed drug-loaded orthodontic retainers are a promising drug-device for sustained release of drugs.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Clonidina/administração & dosagem , Preparações de Ação Retardada , Contenções Ortodônticas , Impressão Tridimensional , Dispositivos Eletrônicos Vestíveis , Adulto , Feminino , Humanos , Polímeros
11.
Curr Opin Anaesthesiol ; 32(3): 327-333, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31045639

RESUMO

PURPOSE OF REVIEW: Clonidine, an α2-receptor agonist is a widely used drug in pediatrics with a large scope of indications ranging from prevention of postoperative emergence agitation, analgesia, anxiolysis, sedation, weaning to shivering. In the era of 'opioid-free' medicine with much attention be directed toward increasing problems with opioid use, clonidine due to its global availability, low cost and safety profile has become an even more interesting option. RECENT FINDINGS: Increasing evidence from randomised clinical trials support the use of clonidine in healthy children in the perioperative setting. Clonidine appears to significantly reduce postoperative emergence agitation, opioid consumption, shivering, nausea and vomiting. In addition, emerging evidence support the use of clonidine for sedation of critically ill children in ICUs. In this review, the current evidence for clonidine in pediatrics is described and analyzed including a meta-analysis for prevention of emergence agitation. SUMMARY: Clonidine appears a safe and beneficial drug with moderate to high-quality evidence supporting its use in pediatric anesthesia. However, for some indications and populations such as children younger than 12 months old and those with hemodynamic instability, there is an urgent need for high-quality trials.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Anestesia/métodos , Clonidina/administração & dosagem , Delírio do Despertar/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Fatores Etários , Anestesia/efeitos adversos , Criança , Clonidina/efeitos adversos , Delírio do Despertar/etiologia , Humanos , Seleção de Pacientes , Náusea e Vômito Pós-Operatórios/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tremor por Sensação de Frio/efeitos dos fármacos
12.
Medicine (Baltimore) ; 98(18): e15383, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045788

RESUMO

BACKGROUND: Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is still unclear. This study performed a meta-analysis on outcomes of studies which examined neurocognitive performance and inflammatory factors to investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) and inflammation in patients after general anaesthesia. METHODS: Literatures were searched in several electronic databases and studies were selected by following precise inclusion criteria. We searched PubMed, EMBASE, the Cochrane Library, China Academic Journals full-text database (CNKI), and Google Scholar to find randomized controlled trials (RCTs) of the influence of dexmedetomidine on POCD and inflammation in patients who had undergone general anaesthesia. Two researchers independently screened the literature, extracted data, and evaluated quality of methodology against inclusion and exclusion criteria. Meta-analyses of pooled ORs of POCD incidences and mean differences in neurocognitive assessment scores and inflammation levels were carried out and subgroup analyses were performed. Stata 12.0 was used to conduct our meta-analysis. RESULTS: Twenty-six RCTs were included. Compared with controls, perioperative dexmedetomidine treatment significantly reduced the incidence of POCD (pooled ORs = 0.59, 95% confidence interval (CI) 0.45-2.95) and improved Mini-Mental State Examination (MMSE) score (standardized mean difference (SMD) = 1.74, 95% CI 0.43-3.05) on the first postoperative day. Furthermore, perioperative dexmedetomidine treatment significantly decreased IL-6 (SMD = -1.31, 95% CI -1.87-0.75, P < .001) and TNF-α (SMD = -2.14, 95% CI -3.14-1.14, P < .001) compared to saline/comparators treatment. In the stratified analysis by surgical type, age, type of control, and study region, the differences were also significant between dexmedetomidine- and saline-treated patients. CONCLUSION: Perioperative dexmedetomidine treatment is associated with significantly reduced incidence of POCD and inflammation and better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Anestesia Geral/efeitos adversos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle , Dexmedetomidina/administração & dosagem , China , Humanos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Interleucina-6/biossíntese , Testes de Estado Mental e Demência , Razão de Chances , Período Perioperatório , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/biossíntese
13.
Indian J Ophthalmol ; 67(5): 636-640, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31007226

RESUMO

Purpose: We conducted a prospective, randomized study to evaluate the efficacy of dexmedetomidine as an additive to peribulbar block for vitreoretinal surgery in terms of onset time of block, hemodynamic stability profile, patient comfort, and surgeon satisfaction. Methods: One hundred patients of American Society of Anesthesiologists grade 1 and 2 scheduled for vitreoretinal surgery were randomly assigned into two groups: control group (n = 50) received lignocaine bupivacaine block, and Dex group (n = 50) received lignocaine bupivacaine plus 20 µg dexmedetomidine peribulbar block. Information regarding time for onset of block, hemodynamic data, visual analog scale for pain, sedation levels, total duration of surgery, and surgeon satisfaction levels were collected. Results: All the demographic characteristics including age, gender, American Society of Anesthesiologists grade, onset of anesthesia, and duration of surgery were comparable in both groups. At the baseline, there was no statistically significant difference in heart rate, mean arterial pressure, diastolic blood pressure, and respiratory rate between the two groups, with a difference noted in systolic blood pressure at the baseline. There was significant difference noted in the systolic blood pressure and mean arterial pressure at different time intervals with a decreasing trend as time progressed. The mean sedation score was significantly higher in the Dex group than that in the control group. The surgeon satisfaction was higher in the Dex group than that in the control group. Conclusion: Dexmedetomidine is a useful and safe drug in combination with lignocaine bupivacaine in peribulbar for vitreoretinal surgery as it maintains hemodynamic stability and provides sedation, which enables full cooperation and potentially better operating conditions.


Assuntos
Anestesia Local/métodos , Dexmedetomidina/administração & dosagem , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Cirurgia Vitreorretiniana/métodos , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Estudos Prospectivos , Doenças Retinianas/cirurgia , Fatores de Tempo , Adulto Jovem
14.
Am J Vet Res ; 80(5): 455-460, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31034277

RESUMO

OBJECTIVE: To evaluate the cardiovascular effects of atipamezole administered at half the volume or the same volume as dexmedetomidine to isoflurane-anesthetized cats. ANIMALS: 6 adult (1 to 2 years old) domestic shorthair cats (body weight, 3 to 6 kg). PROCEDURES: Each cat was anesthetized with isoflurane and rocuronium 3 times; there was a 1-week washout period between successive anesthetic procedures. For each anesthetic procedure, dexmedetomidine (5 µg/kg) was administered IV. Five minutes after dexmedetomidine was administered, atipamezole (25 or 50 µg/kg) or saline (0.9% NaCl) solution was administered IM. Pulse rate, mean arterial blood pressure (MAP), cardiac output (CO), and systemic vascular resistance (SVR) were measured during anesthesia before dexmedetomidine administration (baseline), after dexmedetomidine administration, and 15, 30, 60, and 120 minutes after administration of atipamezole or saline solution. Pulse rate and MAP were also recorded when MAP was at its lowest value. Hemodynamic variables were compared among treatments at baseline, after dexmedetomidine administration, and after administration of atipamezole or saline solution. Effects of treatment and time on all variables were assessed with mixed-effects models. RESULTS: Both doses of atipamezole resulted in a significantly lower MAP than did saline solution. Pulse rate, CO, and SVR were not significantly different among treatments after atipamezole or saline solution were administered. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole administered IM at half the volume or the same volume as dexmedetomidine was ineffective at increasing pulse rate or CO in anesthetized cats that received dexmedetomidine. However, atipamezole caused short-lasting but severe arterial hypotension.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Anestesia/veterinária , Gatos , Dexmedetomidina/antagonistas & inibidores , Imidazóis/uso terapêutico , Animais , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Isoflurano/administração & dosagem , Masculino , Distribuição Aleatória , Resistência Vascular/efeitos dos fármacos
15.
Vet Anaesth Analg ; 46(3): 325-334, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30935776

RESUMO

OBJECTIVE: To determine the required rate of a detomidine infusion (loading dose 5 µg kg-1; initial rate 12.5 µg kg-1 hour-1) added to a constant infusion of methadone (0.2 mg kg-1; 0.05 mg kg-1 hour-1) for sedation in standing horses and ponies undergoing elective surgeries with appropriate local anaesthetic techniques. STUDY DESIGN: Prospective, clinical study. ANIMALS: Adult, healthy, client-owned, non-food-producing horses or ponies sedated for elective standing surgeries longer than 45 minutes. METHODS: At baseline (in the stables before administration of sedative agents), at 10 minutes after sedation and every 5 minutes thereafter, ataxia, sedation and surgical condition were evaluated; each scored 0-3. These scores were used to adjust the detomidine administration rate using the Ghent Sedation Algorithm. A 10 cm visual analogue scale (VAS) was used by the main surgeon at the end of the procedure to evaluate the surgical conditions. Heart rate, systolic arterial pressure and respiratory frequency were also recorded at each time point. For statistical analysis, anova for normal, Kruskal-Wallis H-test for non-normal variables, and Mann-Whitney U test for VAS were used. RESULTS: From the 42 horses/ponies included in this study, 28 underwent dental procedures and 14 other types of procedures. Overall, dental procedures required higher mean detomidine rates compared with other types of surgeries (16.9 ± 4.5 versus 9.0 ± 1.9 µg kg-1 hour-1) (p < 0.001). Dental procedures were assigned similar VAS scores, median (range), of 7.8 (5.8-10) with other procedures, 8.7 (2.8-10). Cardiovascular changes were not clinically significant. No signs or behavioural changes of abdominal pain were observed postoperatively. CONCLUSIONS AND CLINICAL RELEVANCE: Satisfactory surgical conditions were achieved using a combination of detomidine and methadone infusions with locoregional anaesthesia, with no adverse effects. Dental procedures required higher detomidine dose rates compared with other surgeries.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Anestesia/veterinária , Anestésicos Combinados/administração & dosagem , Cavalos/cirurgia , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , Metadona/administração & dosagem , Anestesia Dentária/veterinária , Animais , Infusões Intravenosas/veterinária , Estudos Prospectivos
17.
Curr Opin Anaesthesiol ; 32(3): 334-342, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30893120

RESUMO

PURPOSE OF REVIEW: In recent years, ultrafast-track anesthesia with on-table extubation and concepts of accelerated postoperative care have gained increasing support in pediatric congenital cardiac surgery. It is believed that such approaches might ideally combine economic benefits with a striving for continuous improvement of patient outcomes. The present review summarizes the role of dexmedetomidine (DEX) in this setting. RECENT FINDINGS: DEX is a clinical multipurpose drug that mediates its diverse responses through the activation of α2-adrenoreceptors. In pediatric cardiac surgery it has various applications. Used as a premedication, DEX provides arousable sedation and anxiolysis. As an intraoperative adjunctive agent of balanced general anesthesia the primary objectives for its administration are attenuation of the neuro-humoral stress response and facilitation of early extubation. During ICU treatment DEX spares opioids, prevents the risk of postoperative delirium or emergence agitation and impacts on important patient-centered outcomes, such as duration of mechanical ventilation, restart of enteral nutrition or length of ICU stay. SUMMARY: Due to a favorable mix of beneficial physiologic actions and a limited adverse effect profile, DEX is established in the perioperative pediatric cardiac surgery setting. However, evidence from high-quality randomized controlled trials on the effects of supplemental DEX on meaningful patient outcomes is scarce, and research on the role of DEX in providing cardioprotection, neuroprotection, or renoprotection is still at its beginning. DEX has developed to one of the main agents in the armamentarium of cardiac anesthesiologists and pediatric intensivists, but it should not be regarded as the new 'magic bullet'.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Anestesia em Procedimentos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Dexmedetomidina/administração & dosagem , Dor/prevenção & controle , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Criança , Dexmedetomidina/efeitos adversos , Coração/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Dor/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
J Vet Med Sci ; 81(4): 538-540, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30745521

RESUMO

Medetomidine, an α2-adrenoceptor agonist, was reported to decrease tear flow in some species. However, there are no reports about the effect of medetomidine on tear flow in pigs. The purpose of this study was to elucidate it. The study was performed in 10 clinically normal female Landrace pigs aged 3 months. Tear flow was measured by the Schirmer tear test (STT) I before (baseline) and 15 and 30 min after intramuscular administration of 80 µg/kg medetomidine. Compared to the STT I value at baseline, the value decreased significantly at 30 min after administration in both the left and right eyes. In pigs treated with medetomidine, an artificial tear solution or ophthalmic gel should be applied to protect the ocular surface.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Medetomidina/administração & dosagem , Sus scrofa/fisiologia , Lágrimas/efeitos dos fármacos , Animais , Técnicas de Diagnóstico Oftalmológico/veterinária , Feminino
19.
J Clin Psychopharmacol ; 39(2): 124-128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30707118

RESUMO

BACKGROUND: Guanfacine is Food and Drug Administration approved for hypertension and attention-deficit hyperactivity disorder and has been used off-label for migraine prophylaxis, heroin withdrawal, and more recently smoking cessation. Previous studies have shown positive effects of 3 mg/d of immediate-release (IR) guanfacine on smoking outcomes, but the dose equivalency of the IR and extended-release (ER) formulations is unknown. PROCEDURES: A within-subject design was used to compare the pharmacokinetics and pharmacodynamics of 3 mg/d of IR, 4 mg/d of ER, and 6 mg/d of ER guanfacine in adult daily smokers (n = 5). Plasma medication levels, vital signs, cigarettes per day, tobacco craving, and adverse events were assessed. Medication was titrated to stable dosing after each laboratory day (3 mg/d IR, then 4 mg/d ER, then 6 mg/d ER). RESULTS: Plasma medication levels did not differ between the 3 mg/d of IR and 4 mg/d of ER doses after 24 hours from last dose and were highest at the 6 mg/d of ER dose (3 mg/d IR: M = 3.40 ng/mL, SE = 0.34 vs 4 mg/d ER: M = 3.46 ng/mL, SE = 0.67 vs 6 mg/d ER: M = 5.92 ng/mL, SE = 1.02). All doses of guanfacine decreased heart rate and blood pressure from baseline. Absolute values of cigarettes per day (6 mg/d ER) and tobacco craving (4 and 6 mg/d ER) were lowest with the ER formulations. Treatment-emergent adverse events were subject rated as minimal to mild, except dry mouth. CONCLUSIONS: We demonstrated similar pharmacokinetic profiles between 3 mg/d of IR guanfacine and 4 mg/d of ER guanfacine, as hypothesized. All doses of guanfacine were well tolerated.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Guanfacina/administração & dosagem , Abandono do Hábito de Fumar/métodos , Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Feminino , Guanfacina/farmacocinética , Guanfacina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Neuropsychopharmacology ; 44(6): 1062-1067, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30797222

RESUMO

Schizophrenia is a complex brain disease involving several neurotransmitter systems, including aberrant noradrenergic activity, which might underlie cognitive deficits. Clonidine is an α2A-agonist and previous research has demonstrated that single dosages of clonidine normalize sensori(motor) gating in schizophrenia. Currently, we investigated whether clonidine is able to normalize mismatch negativity (MMN) and P3a amplitude deficits in this same group of patients. This is important, since reports have shown that MMN amplitude is associated with cognitive functioning and daily life functions in schizophrenia. Twenty chronically ill, male schizophrenia patients were tested with the MMN paradigm from the Copenhagen Psychophysiological Test Battery (CPTB) on 5 occasions, separated by a week. Patients received randomized, yet balanced, either a placebo or a single dose (25, 50, 75 or 150 µg) of clonidine (each dose only once) on top of their usual medication on each occasion. Patients were matched on age and gender with 20 healthy controls (HC) who did not receive any treatment. We found decreased MMN and P3a amplitudes in our patients compared to HC. Although clonidine did neither significantly increase MMN nor P3a amplitude in our patients, it did increase certain levels of MMN and P3a amplitude such that these were not significantly different anymore from the healthy controls. Together with our previous reports indicating normalized sensori(motor) gating in the same patients following administration of clonidine, our results could be of potential high clinical relevance in treating schizophrenia. Future studies should focus on longer trial periods to investigate if clonidine also improves cognitive functioning in schizophrenia.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Percepção Auditiva/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Clonidina/farmacologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Esquizofrenia/fisiopatologia , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Adulto , Antipsicóticos/uso terapêutico , Clonidina/administração & dosagem , Eletroencefalografia , Potencial Evocado P300/efeitos dos fármacos , Potencial Evocado P300/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico
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