Efficacy of a single dose of esmolol to prevent extubation-related complications during emergence from anesthesia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Few trials have examined the efficacy of esmolol to attenuate hemodynamic and respiratory responses during extubation. However, the most appropriate dose of esmolol and an optimal protocol for administering this beta-blocker are uncertain. METHODS: Ninety patients ASA physical status I, II, and III (aged 18...60 years) scheduled to procedures with general anesthesia and tracheal extubation were selected. Patients were randomized into esmolol and placebo group to evaluate the efficacy and safety of a single bolus dose of esmolol (2...mg.kg-1) on cardiorespiratory responses during the peri-extubation period. The primary outcome was the rate of tachycardia during extubation. RESULTS: The rate of tachycardia was significantly lower in esmolol-treated patients compared to placebo-treated patients (2.2% vs. 48.9%, relative risk (RR): 0.04, 95% confidence interval (95% CI)...=...0.01 to 0.32, p...=...0.002). The rate of hypertension was also significantly lower in the esmolol group (4.4% vs. 31.1%, RR: 0.14, 95% CI 0.03 to 0.6, p...=...0.004). Esmolol-treated patients were associated with higher extubation quality compared to patients who received placebo (p...<...0.001), with an approximately two-fold increase in the rate of patients without cough (91.1%) in the esmolol group compared to the placebo group (46.7%). The rate of bucking was approximately 5-fold lower in the esmolol group (8.9% vs. 44.5%, respectively, RR: 0.20 (95% CI, 0.1 to 0.5, p...=...0.002, with an NNT of 2.8). CONCLUSION: A single bolus dose of esmolol is an effective and safe therapeutic strategy to attenuate cardiorespiratory responses during the peri-extubation period.

Efficacy of a single dose of esmolol to prevent extubation-related complications during emergence from anesthesia: a randomized, double-blind, placebo-controlled trial

Abstract Background Few trials have examined the efficacy of esmolol to attenuate hemodynamic and respiratory responses during extubation. However, the most appropriate dose of esmolol and an optimal protocol for administering this beta-blocker are uncertain. Methods Ninety patients ASA physical status I, II, and III (aged 18-60 years) scheduled to procedures with general anesthesia and tracheal extubation were selected. Patients were randomized into esmolol and placebo group to evaluate the efficacy and safety of a single bolus dose of esmolol (2 mg.kg-1) on cardiorespiratory responses during the peri-extubation period. The primary outcome was the rate of tachycardia during extubation. Results The rate of tachycardia was significantly lower in esmolol-treated patients compared to placebo-treated patients (2.2% vs. 48.9%, relative risk (RR): 0.04, 95% confidence interval (95% CI) = 0.01 to 0.32, p= 0.002). The rate of hypertension was also significantly lower in the esmolol group (4.4% vs. 31.1%, RR: 0.14, 95% CI 0.03 to 0.6, p= 0.004). Esmolol-treated patients were associated with higher extubation quality compared to patients who received placebo (p< 0.001), with an approximately two-fold increase in the rate of patients without cough (91.1%) in the esmolol group compared to the placebo group (46.7%). The rate of bucking was approximately 5-fold lower in the esmolol group (8.9% vs. 44.5%, respectively, RR: 0.20 (95% CI, 0.1 to 0.5, p= 0.002, with an NNT of 2.8). Conclusion A single bolus dose of esmolol is an effective and safe therapeutic strategy to attenuate cardiorespiratory responses during the peri-extubation period.

Amiodarona: fortalezas y debilidades / Amiodarone strengths and weaknesses

Prescritos en la práctica clínica por su eficacia. En su inicio se utilizó para tratar la angina de pecho. hoy día es usado para el tratamiento de cualquier forma de taquicardia. Objetivo: Reconocer la prescripción de la Amiodarona y sus efectos adversos. Métodos: Se realizó una revisión descriptiva en las bases de datos de Lilacs donde se encontraron 18 artículos y en PubMed/Medline (Mesh) 206 artículos, de los cuales se le aplicaron los criterios de inclusión a 51 artículos. Conclusiones: La amiodarona es uno de los antiarrítmicos más utilizados para el tratamiento de las arritmias, su variedad de efectos adversos y toxicidad es conocida, por tanto, los pacientes en tratamiento ameritan un minucioso monitoreo(AU)

Introduction: Amiodarone is one of the most prescribed antiarrhythmic drugs in clinical practice due to its efficacy. Initially it was used to treat angina pectoris, however, today it is used to treat any form of tachycardia. Objective: To identify the prescription of amiodarone and its adverse effects. Methods: A descriptive review was carried out in Lilacs databases where 18 articles were found and in PubMed/Medline (Mesh) 206 articles were retrieved. The inclusion criteria were applied to 51 articles. Conclusions: Amiodarone is one of the most widely used antiarrhythmic drugs for the treatment of arrhythmias, its variety of adverse effects and toxicity is known, therefore, patients undergoing treatment justify careful monitoring(AU)

Role of CRF1 and CRF2 receptors in the lateral hypothalamus in cardiovascular and anxiogenic responses evoked by restraint stress in rats: Evaluation of acute and chronic exposure.

We investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the lateral hypothalamus (LH) in cardiovascular and anxiogenic-like responses evoked by acute and repeated restraint stress in rats. For this, animals were subjected to intra-LH microinjection of a selective CRF1 (CP376395) or CRF2 (antisauvagine-30) receptor antagonist before either an acute or the 10th session of restraint stress. Restraint-evoked arterial pressure and heart rate increases, tail skin temperature decrease and anxiogenic-like effect in the elevated plus maze (EPM) were evaluated. We also assessed the effect of 10 daily sessions of restraint on expression of CRF1 and CRF2 receptors within the LH. We identified that antagonism of either CRF1 or CRF2 receptor within the LH decreased the tachycardia during both the acute and 10th session of restraint, but the effect of the CRF1 receptor antagonist was more pronounced during the 10th session. Acute restraint stress also caused anxiogenic-like effect, and this response was inhibited in animals treated with either CP376395 or antisauvagine-30. Anxiety-like behaviors were not changed following the 10th session of restraint, and pharmacological treatments did not affect the behavior in the EPM in chronically stressed animals. Repeated restraint also did not change the level of the CRF receptors within the LH. Taken together, the findings indicate that CRF1 and CRF2 receptors within the LH are involved in tachycardic and anxiogenic-like responses to aversive stimuli. Control of tachycardia by the CRF1 receptor is sensitized by previous stressful experience, and this effect seems to be independent of changes in expression of the receptor.

Effects of lidocaine and esmolol on hemodynamic response to tracheal intubation: a randomized clinical trial.

INTRODUCTION AND OBJECTIVES: Although lidocaine is widely used to prevent cardiovascular changes resulting from laryngoscopy and orotracheal intubation, it is still unclear whether there are more efficacious drugs. This study aimed to compare the beta-blocker esmolol with lidocaine regarding the effects on hemodynamic response after orotracheal intubation. METHODS: The study has a prospective, randomized, double-blind, superiority design, and assessed 69 participants between 18 and 70 years of age, ASA I-II, scheduled for elective or emergency surgery under general anesthesia with orotracheal intubation. Participants were randomly allocated to receive 1.5 mg.kg-1 esmolol bolus followed by 0.1 mg.kg-1.min-1 esmolol infusion (n = 34) or 1.5 mg.kg-1 lidocaine bolus followed by 1.5 mg.kg-1.h-1 lidocaine infusion (n = 35). We recorded changes in heart rate, arterial blood pressure and incidence of adverse events. RESULTS: Post-intubation tachycardia episodes were significantly less frequent in the esmolol group (5.9% vs. 34.3%; Relative Risk (RR) 0.17; 95% Confidence Interval (95% CI) 0.04-0.71; Number Needed to Treat (NNT) 3.5; p = 0.015. After orotracheal intubation, mean heart rate was significantly lower in the esmolol group (74.5 vs. 84.5, p = 0.006). Similar results were observed in the subsequent 3 and 6 minutes (75.9 vs. 83.9, p = 0.023 and 74.6 vs. 83.0, p = 0.013, respectively). CONCLUSION: Esmolol was a safe and more effective intervention to reduce incidence of tachycardia and control heart rate immediately after tracheal intubation when compared to lidocaine.

Reconhecimento da paralisia periódica hipocalêmica tireotóxica na emergência: relato de caso e revisão da literatura / Recognizing thyrotoxic hypokalemic periodic paralysis on emergency settings: a case report and literature revie

A paralisia periódica hipocalêmica tireotóxica é uma complicação inusitada do hipertireoidismo, porém é considerada urgência endocrinológica e ainda frequentemente subdiagnosticada. Sua apresentação clínica consiste na tríade de défice de potássio, tireotoxicose e fraqueza muscular ­ sendo esse último sintoma comum em diversas patologias. Realizamos uma revisão bibliográfica e destacamos, por meio do relato de caso, a importância do diagnóstico precoce dessa doença, possibilitando uma evolução favorável ao paciente, independente de sua etnia, sexo ou região geográfica. Atentamos ainda ao tratamento da doença, que, apesar de sua simplicidade, acarreta muitos equívocos.

The thyrotoxic hypokalemic periodic paralysis is a rare complication of hyperthyroidism, but is considered an endocrinological urgency, and yet frequently underdiagnosed. Its clinical presentation consists of potassium deficit, thyrotoxicosis, and muscular weakness, with the latter symptom being very common in several pathologies. We performed a bibliographic review and highlight, through a case report, the importance of the early diagnosis of this disease to allow favorable progression to the patient, regardless of ethnicity, sex, or geographical region. We also reinforce the importance of the disease treatment which, despite its simplicity, leads to many mistakes.

Chronic 5-HT2 receptor blockade unmasks the role of 5-HT1F receptors in the inhibition of rat cardioaccelerator sympathetic outflow.

Serotonin (5-hydroxytryptamine; 5-HT) inhibits the rat cardioaccelerator sympathetic outflow by 5-HT1B/1D/5 receptors. Because chronic blockade of sympatho-excitatory 5-HT2 receptors is beneficial in several cardiovascular pathologies, this study investigated whether sarpogrelate (a 5-HT2 receptor antagonist) alters the pharmacological profile of the above sympatho-inhibition. Rats were pretreated for 2 weeks with sarpogrelate in drinking water (30 mg/kg per day; sarpogrelate-treated group) or equivalent volumes of drinking water (control group). Animals were pithed and prepared for spinal stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or for intravenous (i.v.) bolus injections of noradrenaline. Both procedures produced tachycardic responses remaining unaltered after saline. Continuous i.v. infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT receptor agonists 5-carboxamidotryptamine (5-CT; 5-HT1/5A), CP 93,129 (5-HT1B), or PNU 142633 (5-HT1D), but not by indorenate (5-HT1A) in both groups; whereas LY344864 (5-HT1F) mimicked 5-HT only in sarpogrelate-treated rats. In sarpogrelate-treated animals, i.v. GR 127935 (310 µg/kg; 5-HT1B/1D/1F receptor antagonist) attenuated 5-CT-induced sympatho-inhibition and abolished LY344864-induced sympatho-inhibition; while GR 127935 plus SB 699551 (1 mg/kg; 5-HT5A receptor antagonist) abolished 5-CT-induced inhibition. These results confirm the cardiac sympatho-inhibitory role of 5-HT1B, 5-HT1D, and 5-HT5A receptors in both groups; nevertheless, sarpogrelate treatment specifically unmasked a cardiac sympatho-inhibition mediated by 5-HT1F receptors.

Pharmacological evidence that metformin blocks the vasopressor responses mediated by stimulation of α1- and α2-adrenoceptors in pithed rats.

It has been reported that metformin reduces blood pressure although the mechanisms have not been described. Indeed, several mechanisms could be implicated including the interaction with α-adrenoceptors or inhibition of sympathetic outflow. Therefore, this study was designed to determine the capability of metformin to block the vasopressor responses induced by α1/2-adrenoceptor agonists or selective electrical stimulation of sympathetic outflow. For this purpose, Wistar male rats were anesthetized, pithed and cannulated for selective preganglionic stimulation of the vasopressor sympathetic outflow or drugs administration. The effect of i.v. bolus injection of metformin (180 and 310mg/kg) or its vehicle (bidistilled water) was studied on the vasopressor responses induced by: (1) selective sympathetic stimulation (0.03-3Hz); (2) exogenous noradrenaline (0.03-3µg/kg); (3) methoxamine (1-100µg/kg); and (4) UK 14,304 (0.1-30µg/kg). The tachycardic responses to noradrenaline were also investigated in presence of metformin. The vasopressor responses induced by selective electrical stimulation of sympathetic outflow were diminished by metformin (180 and 310mg/kg) and remained unchanged in presence of vehicle. Moreover, the vasopressor responses induced by exogenous noradrenaline, methoxamine and UK 14,304 were dose-dependently inhibited by i.v. bolus injections of metformin (180 and 310mg/kg) and were not affected by vehicle. Metformin practically did not block the tachycardic responses to noradrenaline except at the dose of 3µg/kg. Taken together, these results demonstrate that metformin is capable to block vascular α1/2-adrenoceptors but not cardiac ß-adrenoceptors. Thus, this mechanism could contribute, at least in part, on the hypotensive responses induced by metformin.

Impact of citrate pretreatment on ventricular arrhythmia and myocardial capase-3 expression in ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury often triggers ventricular arrhythmia. Citrate binds calcium ions, forming a soluble calcium citrate complex that may reduce I/R injury by affecting calcium ion concentration. We tested the effects of citrate pretreatment on ventricular heart rate and related factors in a rat I/R model. Fifty male Sprague Dawley rats weighing 350-400 g were randomly divided into equally sized control (A), model (B), and 0.1 M (C), 0.05 M (D), and 0.025 M (E) citrate groups. An I/R model was established by ligating the left anterior descending coronary artery. Serum calcium ion concentration was measured before and after citrate treatment. Triphenyltetrazolium chloride staining and spectrophotometry were used to determine infarction area and caspase-3 protein levels in myocardial tissue, respectively. Polymerase chain reaction was performed to test myocardial calmodulin (CAM) expression. The frequency of ventricular arrhythmia in group B was significantly higher than in the sham surgery group (P < 0.05). Citrate pretreatment resulted in lower and higher frequencies than those observed in the model and control groups, respectively, in a dose-independent manner. The most obvious reduction in ventricular arrhythmia was seen in Group D. Serum calcium ion concentration decreased markedly after citrate treatment (P < 0.05), with a specific pattern emerging over time. Infarction area and caspase-3 and CAM levels were significantly lower in the citrate groups compared with the model group (P < 0.05). Citrate can reduce myocardial cell apoptosis, alleviating ventricular arrhythmia and protecting the myocardium by reducing serum calcium ion concentration and downregulating caspase-3 and CAM expression.

Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised / Vinte anos de tratamento da síndrome vasoplégica em cirurgia cardíaca. Azul de metileno revisado

Objective: This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. Methods: A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. Results: The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. Conclusion: MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies. .

Objetivo: O presente estudo foi realizado com a finalidade de reavaliar conceitos estabelecidos em 20 anos, com ênfase nos últimos 5 anos, sobre a utilização do azul de metileno no tratamento da síndrome vasoplégica em cirurgia cardíaca. Métodos: Foram considerados dados da literatura utilizando-se três bases de dados (MEDLINE, SCOPUS e ISI Web of Science). Resultados: Os conceitos reavaliados e reafirmados foram: 1) Nas doses recomendadas o AM é seguro (a dose letal é de 40 mg/kg); 2) O AM não causa disfunção endotelial; 3) O efeito do AM só aparece em caso de supra nivelamento do NO; 4) O AM não é um vasoconstritor, pelo bloqueio da via GMPc ele libera a via do AMPc, facilitando o efeito vasoconstritor da norepinefrina; 5) A dosagem mais utilizada é de 2 mg/kg, como bolus EV, seguida de infusão contínua porque as concentrações plasmáticas decaem fortemente nos primeiros 40 minutos, e; 6) Existe uma "janela de oportunidade" precoce para efetividade do AM. Nos últimos cinco anos, os principais desafios foram: 1) Observações de efeitos colaterais; 2) A necessidade de diretrizes, e; 3) A necessidade da determinação de uma janela terapêutica para o uso do AM em humanos. Conclusão: O efeito do AM no tratamento da SV é dependente do tempo, portanto, o grande desafio atual é a necessidade do estabelecimento da janela terapêutica do AM em humanos. Esse seria o primeiro passo para a sistematização de uma diretriz a ser seguida por possíveis estudos multicêntricos. .

Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 µL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P < 0.05), blunted tachycardia in the stress trial (ΔHR: GS 115 ± 14, EL 117 ± 10, GL 74 ± 9 bpm; P<0.05) and spent more time in the open arms of elevated plus maze (EL 6 ± 2 vs. GL 18 ± 5%; P = 0.028) compared with GS and EL groups. These results indicate that liposome-entrapped GABA can be a potential tool for exploring the chronic effects of GABA in specific regions and pathways of the central nervous system.

Opioid receptors in the prelimbic cortex modulate restraint stress-induced cardiovascular responses in the rat.

The prelimbic cortex (PL) is involved in the control of behavioral and autonomic responses to stress. The present study aimed to investigate whether opioid neurotransmission in the PL modulates autonomic responses evoked by restraint stress (RS). Bilateral microinjection of 0.03, 0.3 and 3 nmol/100 nL of the nonselective opioid antagonist naloxone into the PL reduced pressure and tachycardiac responses evoked by RS. However, no effects were observed after its injection at doses of 0.003 and 30 nmol/100 nL, thus resulting in an inverted U-shaped dose-inhibition curve. Similar to naloxone, the selective µ-opioid antagonist CTAP, and the selective κ-opioid antagonist nor-BNI, also reduced MAP and HR increases induced by RS when injected into the PL, whereas treatment with the selective δ-opioid antagonist naltrindole did not affect the pressor and tachycardiac response caused by RS. Blockade of opioid neurotransmission in the PL did not affect the fall in tail temperature and increase in body temperature induced by RS. The present results confirm the involvement of PL opioid neurotransmission in the modulation of cardiovascular responses evoked during the exposure to an aversive situation, and suggest that responses observed after the blockade of local opioid receptors is due to alterations in PL neuronal activity. Furthermore, these results suggest that a distinct circuitry is involved in modulation of the sympathetic output to different vascular territories.

Bidirectional ventricular tachycardia?

A 65-year-old woman was admitted to the hospital because of a syncopal episode with documented transient complete atrioventricular block. A DDD pacemaker was implanted. Post implantation, the patient was diagnosed with bidirectional ventricular tachycardia. Analysis of the arrhythmia and differential diagnosis is performed.

Chronic activation of endogenous angiotensin-converting enzyme 2 protects diabetic rats from cardiovascular autonomic dysfunction.

In this study, we evaluated whether the activation of endogenous angiotensin-converting enzyme 2 (ACE2) would improve the cardiovascular autonomic dysfunction of diabetic rats. Ten days after induction of type 1 diabetes (streptozotocin, 50 mg kg(-1) i.v.), the rats were treated orally with 1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one (XNT), a newly discovered ACE2 activator (1 mg kg(-1) day(-1)), or saline (equivalent volume) for 30 days. Autonomic cardiovascular parameters were evaluated in conscious animals, and an isolated heart preparation was used to analyse cardiac function. Diabetes induced a significant decrease in the baroreflex bradycardia sensitivity, as well as in the chemoreflex chronotropic response and parasympathetic tone. The XNT treatment improved these parameters by ≈ 76% [0.82 ± 0.09 versus 1.44 ± 0.17 Ratio between changes in pulse interval and changes in mean arterial pressure (ΔPI/ΔmmHg)], ∼85% (-57 ± 9 versus -105 ± 10 beats min(-1)) and ≈ 205% (22 ± 2 versus 66 ± 12 beats min(-1)), respectively. Also, XNT administration enhanced the bradycardia induced by the chemoreflex activation by v 74% in non-diabetic animals (-98 ± 16 versus -170 ± 9 Δbeats min(-1)). No significant changes were observed in the mean arterial pressure, baroreflex tachycardia sensitivity, chemoreflex pressor response and sympathetic tone among any of the groups. Furthermore, chronic XNT treatment ameliorated the cardiac function of diabetic animals. However, the coronary vasoconstriction observed in diabetic rats was unchanged by ACE2 activation. These findings indicate that XNT protects against the autonomic and cardiac dysfunction induced by diabetes. Thus, our results provide evidence for the viability and effectiveness of oral administration of an ACE2 activator for the treatment of the cardiovascular autonomic dysfunction caused by diabetes.

Repeated amygdala-kindled seizures induce ictal rebound tachycardia in rats.

It is thought that cardiovascular changes may contribute to sudden death in patients with epilepsy. To examine cardiovascular alterations that occur during epileptogenesis, we measured the heart rate of rats submitted to the electrical amygdala kindling model. Heart rate was recorded before, during, and after the induced seizures. Resting heart rate was increased in stages 1, 3, and 5 as compared with the unstimulated control condition. In the initial one third of the seizures, we observed bradycardia, which increased in intensity with increasing stage and was blocked by injecting methyl atropine. During stage 5 seizures, a rebound tachycardia was observed that also increased in intensity with increasing number of seizures. This study demonstrated the influence of seizure frequency on cardiac autonomic modulation, providing a basis for discussion of potential mechanisms that cause patients with epilepsy to die suddenly.