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1.
Curr Opin Anaesthesiol ; 33(3): 417-422, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32324663

RESUMO

PURPOSE OF REVIEW: Although the indications for ß-blockers in the management of patients with congestive heart failure and myocardial infarction are well established, the use of ß-blockers in the perioperative setting remains controversial. RECENT FINDINGS: Since 2008 PeriOperative ISchemic Evaluation Trial, there have been numerous studies suggesting that perioperative ß-blockers are associated with adverse events such as hypotension, bradycardia, increased mortality, and stroke. SUMMARY: In this article, we review the most recent evidence to suggest an approach to perioperative ß-blocker use tailored to patient and surgical risk factors. We also review recent studies on off-label uses for perioperative ß-blockers.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Anestesiologia/métodos , Doenças Cardiovasculares/induzido quimicamente , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/induzido quimicamente , Antagonistas Adrenérgicos beta/uso terapêutico , Bradicardia/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Infarto do Miocárdio/induzido quimicamente , Assistência Perioperatória , Período Perioperatório , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente
2.
J Spec Oper Med ; 20(1): 31-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203601

RESUMO

Ketamine's favorable hemodynamic and safety profile is motivating increasing use in the prehospital environment. Despite these advantages, certain side effects require advanced planning and training. We present a case of rapid intravenous administration of ketamine causing bradycardia and hypotension. A 46-year-old man presented to the emergency department for an exacerbation of chronic shoulder pain. Given the chronicity of the pain and multiple failed treatment attempts, ketamine at an analgesic dose was used. Despite the local protocol directing administration over several minutes, it was pushed rapidly, resulting in malaise, nausea, pallor, bradycardia, and hypotension. The patient returned to his baseline without intervention. This and other known side effects of ketamine, such as behavioral disturbances, altered sense of reality, and elevated heart rate and blood pressure, are well documented in the literature. With this report, the authors aim to raise awareness of transient bradycardia and hypotension associated with the rapid administration of ketamine at an analgesic dose.


Assuntos
Analgésicos/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Ketamina/efeitos adversos , Analgésicos/administração & dosagem , Serviço Hospitalar de Emergência , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade
3.
Anesth Analg ; 130(3): 685-695, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30896593

RESUMO

BACKGROUND: The anticholinesterase neostigmine and the muscarinic inhibitor glycopyrrolate are frequently coadministered for the reversal of neuromuscular blockade. This practice can precipitate severe bradycardia or tachycardia, but whether it affects the incidence of cardiovascular complications remains unclear. We hypothesized that anticholinesterase reversal with neostigmine and glycopyrrolate versus no anticholinesterase reversal increases the risk of postoperative cardiovascular complications among adult patients undergoing noncardiac surgery with general anesthesia. METHODS: We conducted a prespecified retrospective analysis of hospital registry data from a major health care network for patients undergoing surgery with general anesthesia from January 2007 to December 2015. The primary outcome was a composite of cardiac dysrhythmia, acute heart failure, transient ischemic attack, ischemic stroke, and acute myocardial infarction within 30 days after surgery. We performed sensitivity analyses in subgroups and propensity score adjustment and explored the association between exposure and outcome in subgroups of patients with high risk of cardiovascular complications. RESULTS: Of the 98,147 cases receiving neuromuscular blockade, 73,181 (74.6%) received neostigmine and glycopyrrolate, while 24,966 (25.4%) did not. A total of 5612 patients (7.7%) in the anticholinesterase reversal group and 1651 (6.6%) in the control group (P < .001) experienced the primary outcome. After adjustment for clinical covariates, neostigmine and glycopyrrolate exposure was significantly associated in a dose-dependent fashion (P for trend <.001, respectively) with tachycardia (adjusted odds ratio = 2.1 [95% CI, 1.97-2.23]; P < .001) and bradycardia (adjusted odds ratio = 2.84 [95% CI, 2.49-3.24]; P < .001) but not with postoperative cardiovascular complications (adjusted odds ratio = 1.03 [95% CI, 0.97-1.1]; P = .33). We identified a significant effect modification of anticholinesterase reversal by high age, high-risk surgery, and history of atrial fibrillation (P for interaction = .002, .001, and .02, respectively). By using linear combinations of main effect and exposure-risk interaction terms, we detected significant associations between anticholinesterase reversal and cardiovascular complications toward a higher vulnerability in these patient subgroups. CONCLUSIONS: Neuromuscular blockade reversal with neostigmine and glycopyrrolate was associated with an increased incidence of intraoperative tachycardia and bradycardia but not with 30-day postoperative cardiovascular complications. Exploratory analyses suggest that a high postoperative cardiovascular complication risk profile may modify the effects of anticholinesterase reversal toward clinical relevance.


Assuntos
Anestesia Geral/efeitos adversos , Bradicardia/induzido quimicamente , Inibidores da Colinesterase/efeitos adversos , Glicopirrolato/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Antagonistas Muscarínicos/efeitos adversos , Neostigmina/efeitos adversos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Taquicardia/induzido quimicamente , Adulto , Idoso , Boston/epidemiologia , Bradicardia/diagnóstico , Bradicardia/epidemiologia , Bradicardia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taquicardia/diagnóstico , Taquicardia/epidemiologia , Taquicardia/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
4.
BMJ Case Rep ; 12(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31831516

RESUMO

A 34-year-old patient underwent a laparoscopic myomectomy, complicated by a profound episode of bradycardia and hypotension following intramyometrial infiltration of vasopressin (20 IU), promptly corrected with intravenous ephedrine (6 mg) and glycopyrrolate (200 µg). At extubation, pink frothy fluid was noted in the endotracheal tube; she was visibly distressed, desaturated to 89% in air and was coughing up pink stained fluid. Acute pulmonary oedema secondary to vasopressin was suspected. A tight-fitting oxygen mask (100%) with positive end expiratory pressure was applied and intravenous furosemide (20 mg) and diamorphine (4 mg, 1 mg increments) were administered to facilitate diuresis and oxygenation. Chest X-ray confirmed acute pulmonary oedema. Arterial blood gas demonstrated type 2 respiratory failure. Over 12 hours, the oxygen was weaned to 1 L/min. She demonstrated excellent diuresis. Troponin and brain-natriuretic peptide were elevated, but echocardiogram was normal. The cardiology diagnosis was vasopressin-induced coronary vasospasm, precipitating acute pulmonary oedema. She was discharged home on day 5.


Assuntos
Edema Pulmonar/induzido quimicamente , Miomectomia Uterina/métodos , Vasoconstritores/efeitos adversos , Vasopressinas/efeitos adversos , Adulto , Extubação/efeitos adversos , Bradicardia/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Humanos , Respiração com Pressão Positiva , Edema Pulmonar/terapia , Miomectomia Uterina/efeitos adversos , Vasoconstritores/administração & dosagem , Vasoconstritores/farmacocinética , Vasopressinas/administração & dosagem , Vasopressinas/farmacocinética
5.
Isr Med Assoc J ; 21(11): 724-727, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713359

RESUMO

BACKGROUND: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined. OBJECTIVES: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring. METHODS: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%), cardiomyopathy 11 (7.2%) and migraine 4 (2.6%). The controls were infants of mothers with hypertension not exposed to BBs who were born at the same gestational age and born closest (before or after) to the matched infant in the study group. RESULTS: Compared to the control group, the infants in the study group had a higher prevalence of early asymptomatic hypoglycemia (study 30.7% vs. control 18.3%, P = 0.016), short symptomatic bradycardia events, other cardiac manifestations (P = 0.016), and longer hospitalization (P < 0.001). No life-threatening medical conditions were documented. The birth weight was significantly lower for the high-dose subgroup compared to the low-dose subgroup (P = 0.03), and the high-dose subgroup had a higher incidence of small-for-gestational-age (P = 0.02). CONCLUSIONS: No alarming or life-threatening medical conditions were observed among term infants born to BB treated mothers. These infants can be safely observed for 48 hours after birth close to their mothers in the maternity ward. Glucose follow-up is needed, especially in the first hours of life.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Bradicardia/induzido quimicamente , Hipoglicemia/induzido quimicamente , Doenças do Recém-Nascido/induzido quimicamente , Troca Materno-Fetal , Resultado da Gravidez , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Risco
6.
Anesth Analg ; 129(4): 1124-1129, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31584918

RESUMO

BACKGROUND: Sugammadex, with its novel mechanism of action of encapsulation and noncompetitive binding of aminosteroid neuromuscular-blocking agents (rocuronium and vecuronium), may offer distinct advantage to pediatric patients where residual neuromuscular blockade may be poorly tolerated. Data describing its use in the pediatric population are limited, and no large-scale studies are available evaluating the occurrence of adverse event across the full spectrum of ages. We sought to measure the occurrence of adverse events, assess the severity and clinical significance of the events, and quantify a surrogate measure of efficacy of sugammadex compared to neostigmine in a large population and in the full age range of children. METHODS: Beginning in September 2016 through initiation of data collection, we identified from our data warehouse that all patients were treated with sugammadex for reversal of neuromuscular blockade, from birth through adolescence, and retrospectively matched, by case type and age group, to historical neostigmine-treated controls. From subsequent chart review, we quantified occurrence of adverse events and administration of medications to treat adverse events. All cases in the originally identified cohort treated with epinephrine after administration of sugammadex underwent chart review to elicit the cause, in the event that an infrequently occurring event was not captured after the case-matching process. "End-Interval Time," the time from administration of reversal agent to time out of the procedure room, was measured as an indirect assessment of efficacy. RESULTS: Fewer cases of bradycardia were observed in the sugammadex group compared to the neostigmine group in the overall cohort (P < .001) and in the subgroups of older children (P < .001) and adolescents (P < .001). End-interval time, the time measured from administration of neuromuscular blockade (NMB) reversal agent to time out of the operating room, was significantly shorter in sugammadex-treated groups in the overall cohort (mean difference, 2.8; 95% CI, 1.85-3.77; P < .001) and all age groups except for first year (31 days through 12 months). This observation was most pronounced in the neonatal subgroup (mean difference, 11.94 minutes; 95% CI, 4.79-19.1; P < .001). No other adverse events measured were found to be different between treatment groups. CONCLUSIONS: This study provides data supporting the safe and effective use of sugammadex for reversal of neuromuscular blockade throughout the entire range of ages in the pediatric population. Within age groups, sugammadex demonstrates faster completion of operation compared with neostigmine, with the greatest difference observed in the neonatal population.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Neostigmina/uso terapêutico , Bloqueio Neuromuscular , Sugammadex/uso terapêutico , Adolescente , Fatores Etários , Período de Recuperação da Anestesia , Bradicardia/induzido quimicamente , Bradicardia/fisiopatologia , Criança , Pré-Escolar , Inibidores da Colinesterase/efeitos adversos , Data Warehousing , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neostigmina/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Sugammadex/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
7.
Br J Anaesth ; 123(6): 795-807, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31623842

RESUMO

BACKGROUND: Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented. METHODS: We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 µg kg-1 or with continuous administration alone. CONCLUSIONS: Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia. PROTOCOL REGISTRATION: CRD42017071583.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Clonidina/efeitos adversos , Dexmedetomidina/efeitos adversos , Complicações Intraoperatórias/induzido quimicamente , Complicações Pós-Operatórias/induzido quimicamente , Bradicardia/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Período Pré-Operatório , Taquicardia/induzido quimicamente
9.
Cochrane Database Syst Rev ; 9: CD013435, 2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31544227

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) have yielded conflicting results regarding the ability of beta-blockers to influence perioperative cardiovascular morbidity and mortality. Thus routine prescription of these drugs in unselected patients remains a controversial issue. A previous version of this review assessing the effectiveness of perioperative beta-blockers in cardiac and non-cardiac surgery was last published in 2018. The previous review has now been split into two reviews according to type of surgery. This is an update and assesses the evidence in cardiac surgery only. OBJECTIVES: To assess the effectiveness of perioperatively administered beta-blockers for the prevention of surgery-related mortality and morbidity in adults undergoing cardiac surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Biosis Previews and Conference Proceedings Citation Index-Science on 28 June 2019. We searched clinical trials registers and grey literature, and conducted backward- and forward-citation searching of relevant articles. SELECTION CRITERIA: We included RCTs and quasi-randomized studies comparing beta-blockers with a control (placebo or standard care) administered during the perioperative period to adults undergoing cardiac surgery. We excluded studies in which all participants in the standard care control group were given a pharmacological agent that was not given to participants in the intervention group, studies in which all participants in the control group were given a beta-blocker, and studies in which beta-blockers were given with an additional agent (e.g. magnesium). We excluded studies that did not measure or report review outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 63 studies with 7768 participants; six studies were quasi-randomized and the remaining were RCTs. All participants were undergoing cardiac surgery, and in most studies, at least some of the participants were previously taking beta-blockers. Types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. In twelve studies, beta-blockers were titrated according to heart rate or blood pressure. Duration of administration varied between studies, as did the time at which drugs were administered; in nine studies this was before surgery, in 20 studies during surgery, and in the remaining studies beta-blockers were started postoperatively. Overall, we found that most studies did not report sufficient details for us to adequately assess risk of bias. In particular, few studies reported methods used to randomize participants to groups. In some studies, participants in the control group were given beta-blockers as rescue therapy during the study period, and all studies in which the control was standard care were at high risk of performance bias because of the open-label study design. No studies were prospectively registered with clinical trials registers, which limited the assessment of reporting bias. We judged 68% studies to be at high risk of bias in at least one domain.Study authors reported few deaths (7 per 1000 in both the intervention and control groups), and we found low-certainty evidence that beta-blockers may make little or no difference to all-cause mortality at 30 days (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.47 to 1.90; 29 studies, 4099 participants). For myocardial infarctions, we found no evidence of a difference in events (RR 1.05, 95% CI 0.72 to 1.52; 25 studies, 3946 participants; low-certainty evidence). Few study authors reported cerebrovascular events, and the evidence was uncertain (RR 1.37, 95% CI 0.51 to 3.67; 5 studies, 1471 participants; very low-certainty evidence). Based on a control risk of 54 per 1000, we found low-certainty evidence that beta-blockers may reduce episodes of ventricular arrhythmias by 32 episodes per 1000 (RR 0.40, 95% CI 0.25 to 0.63; 12 studies, 2296 participants). For atrial fibrillation or flutter, there may be 163 fewer incidences with beta-blockers, based on a control risk of 327 incidences per 1000 (RR 0.50, 95% CI 0.42 to 0.59; 40 studies, 5650 participants; low-certainty evidence). However, the evidence for bradycardia and hypotension was less certain. We found that beta-blockers may make little or no difference to bradycardia (RR 1.63, 95% CI 0.92 to 2.91; 12 studies, 1640 participants; low-certainty evidence), or hypotension (RR 1.84, 95% CI 0.89 to 3.80; 10 studies, 1538 participants; low-certainty evidence).We used GRADE to downgrade the certainty of evidence. Owing to studies at high risk of bias in at least one domain, we downgraded each outcome for study limitations. Based on effect size calculations in the previous review, we found an insufficient number of participants in all outcomes (except atrial fibrillation) and, for some outcomes, we noted a wide confidence interval; therefore, we also downgraded outcomes owing to imprecision. The evidence for atrial fibrillation and length of hospital stay had a moderate level of statistical heterogeneity which we could not explain, and we, therefore, downgraded these outcomes for inconsistency. AUTHORS' CONCLUSIONS: We found no evidence of a difference in early all-cause mortality, myocardial infarction, cerebrovascular events, hypotension and bradycardia. However, there may be a reduction in atrial fibrillation and ventricular arrhythmias when beta-blockers are used. A larger sample size is likely to increase the certainty of this evidence. Four studies awaiting classification may alter the conclusions of this review.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Procedimentos Cirúrgicos Cardíacos , Assistência Perioperatória/métodos , Antagonistas Adrenérgicos beta/efeitos adversos , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Bradicardia/induzido quimicamente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/prevenção & controle , Humanos , Hipotensão/induzido quimicamente , Hipotensão/mortalidade , Hipotensão/prevenção & controle , Morbidade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/prevenção & controle , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Transplant Proc ; 51(6): 2081-2098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399186

RESUMO

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that acts through the members of a family of 5 G protein-coupled receptors (S1P1 to S1P5). Among these, S1P1 is a major regulator of lymphocyte trafficking. Fingolimod, whose active metabolite, fingolimod phosphate, acts as a nonselective S1P-receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating lymphocyte trafficking via downregulation of S1P1 expression on lymphocytes. Here, we describe the pharmacologic profile of a novel S1P1 agonist, ASP1126. ASP1126 preferentially activated S1P1 compared to S1P3 in rat and human guanosine-5'-(γ-thio)-triphosphate (GTPγS) assays. Oral single administration of ASP1126 decreased the number of peripheral lymphocytes and repeated dosing showed a cumulative effect on lymphopenia in both rats and monkeys. ASP1126 prolonged allograft survival in a rat heterotopic heart transplantation model in combination with a subtherapeutic dose of tacrolimus that was independent of drug-drug interactions. In addition, in nonhuman primate (NHP) renal transplantation, pretreatment with ASP1126 reduced not only the number of naive T cells and central memory T cells but also effector memory T cells in the peripheral blood, all of which could contribute to acute graft rejection and prolonged allograft survival in combination with tacrolimus. Further, we confirmed that ASP1126 has a broad ranging safety margin with respect to its effect on lung weight in rats and bradycardia in NHPs, which were the adverse events found in clinical studies of fingolimod. ASP1126 with improved safety profile has the potential to be an adjunct therapy in combination with tacrolimus in clinical transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/farmacologia , Lisofosfolipídeos/agonistas , Esfingosina/análogos & derivados , Aloenxertos/efeitos dos fármacos , Aloenxertos/metabolismo , Animais , Bradicardia/induzido quimicamente , Sinergismo Farmacológico , Humanos , Linfócitos/efeitos dos fármacos , Macaca fascicularis , Masculino , Ratos , Esfingosina/agonistas , Tacrolimo/farmacologia , Transplante Homólogo/métodos
11.
Neth J Med ; 77(5): 189-192, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31264585
13.
J Zhejiang Univ Sci B ; 20(7): 598-604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168973

RESUMO

There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α2A-adrenergic receptor (ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 µg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after intravenous infusion of dexmedetomidine.


Assuntos
Bradicardia/induzido quimicamente , Dexmedetomidina/farmacologia , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos alfa 2/genética , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Adulto , Pressão Sanguínea , China , Dexmedetomidina/administração & dosagem , Feminino , Genótipo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Farmacogenética , Análise de Sequência de DNA
15.
Reprod Toxicol ; 87: 140-145, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31199962

RESUMO

Nausea and vomiting of pregnancy (NVP) is the most common medical complaint during pregnancy affecting up to 70% of pregnant women worldwide. Some antiemetic medications (AEM) (droperidol, domperidone, granisetron, metoclopramide and trifluoperazine) used to treat NVP have the unwanted side effect of hERG blockade. The hERG potassium channel is essential for normal heart rhythm in both the adult human and the human and rat embryo. Animal studies show hERG blockade in the embryo causes bradycardia and arrhythmia leading to cardiovascular malformations and other birth defects. Whole rat embryo in vitro culture was used to determine the effect of the above listed AEM and meclizine on the heart rate of Gestational day 13 rat embryos. These embryos are similar in size and heart development to 5-6-week human embryo. The results showed that all of the AEMs caused a concentration-dependent bradycardia. Droperidol had the lowest margin of safety.


Assuntos
Antieméticos/toxicidade , Bradicardia/induzido quimicamente , Coração/efeitos dos fármacos , Animais , Domperidona/toxicidade , Droperidol/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/fisiologia , Granisetron/toxicidade , Coração/embriologia , Coração/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Meclizina/toxicidade , Metoclopramida/toxicidade , Ratos Sprague-Dawley , Trifluoperazina/toxicidade
16.
Indian J Pharmacol ; 51(2): 120-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31142948

RESUMO

Phenytoin is an anticonvulsant which is also a Class IB antiarrhythmic. Its common adverse drug reactions (ADRs) include gastrointestinal symptoms, psychiatric disorders, gingival hyperplasia, and rash. Bradycardia and hypotension following intravenous (IV) phenytoin are rare ADRs. We report the case of a 62-year-old female with subarachnoid hemorrhage and right bundle branch block, who developed sinus bradycardia and hypotension on administration of IV phenytoin. This case report serves as a note for caution on patient selection for the administration of phenytoin and highlights the need for specific guidelines on the same.


Assuntos
Anticonvulsivantes/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Fenitoína/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade
17.
N Engl J Med ; 380(26): 2506-2517, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31112380

RESUMO

BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).


Assuntos
Sedação Consciente , Estado Terminal/terapia , Dexmedetomidina , Hipnóticos e Sedativos , Respiração Artificial , Adulto , Idoso , Bradicardia/induzido quimicamente , Estado Terminal/mortalidade , Dexmedetomidina/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipotensão/induzido quimicamente , Unidades de Terapia Intensiva , Análise de Intenção de Tratamento , Masculino , Midazolam , Pessoa de Meia-Idade , Propofol , Fatores de Tempo , Resultado do Tratamento
18.
Pediatr Cardiol ; 40(5): 925-933, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30929065

RESUMO

OBJECTIVE: To determine the incidence of cardiovascular collapse in children receiving intravenous (IV) amiodarone and to identify the population at risk. DESIGN: A multicenter study of patients ≤ 18 years of age who received intravenous amiodarone between January 2005 and December 2015. A retrospective analysis was performed to identify patients who developed cardiovascular collapse (bradycardia and/or hypotension). RESULTS: Of 456 patients who received amiodarone, cardiovascular collapse occurred in 47 patients (10%). Patient risk factors for collapse in a univariate analysis were as follows: age < 3 months (p = 0.04), depressed cardiac function (p < 0.001), blood pressure below 3rd percentile (p < 0.001), high lactate at baseline (p < 0.001). Administration risk factors included bolus administration (p = 0.04), and bolus administration over ≤ 20 min (p = 0.04). In multivariate analysis, age, baseline blood pressure less than 3rd percentile, and rapid bolus delivery were independent risk factors for cardiovascular collapse in the study group. The mortality rate was significantly higher in the collapse group (28% versus 8%). CONCLUSION: We found an association between IV amiodarone administration and the risk of developing cardiovascular collapse in a significant subset of children. Extreme caution and careful hemodynamic monitoring is recommended when using IV amiodarone in this population, especially in young infants, hemodynamically compromised patients, and in patients receiving rapid amiodarone bolus administration.


Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Taquicardia Ectópica de Junção/induzido quimicamente , Taquicardia Ventricular/induzido quimicamente , Administração Intravenosa , Adolescente , Distribuição por Idade , Amiodarona/administração & dosagem , Amiodarona/farmacologia , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/mortalidade , Criança , Pré-Escolar , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/mortalidade , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Taquicardia Ectópica de Junção/mortalidade , Taquicardia Ventricular/mortalidade
20.
J Pediatr Hematol Oncol ; 41(7): 537-541, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30994505

RESUMO

Systemic corticosteroids are widely used for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. Anecdotal case reports demonstrate bradycardia in patients receiving corticosteroids; however, a more in-depth analysis is lacking. This study aimed to describe the incidence, timing, and outcomes of bradycardia in children with ALL receiving corticosteroids during induction chemotherapy at our center from 2010 to 2016. A total of 153 children were included, with 150 (98%) demonstrating decreased heart rate following steroid administration with a median HR decrease of 23 beats per minute. Bradycardia ≤first percentile for age developed in 90 (59%) patients, with nadir occurring, on average, 7 doses into treatment, corresponding to 79 hours after initiation of therapy. No patient experienced adverse events related to bradycardia. Resolution of bradycardia at outpatient follow-up occurred in 62 of 71 (87%). Examination of nadir heart rate during subsequent hospitalizations in which steroids were not being administered did not demonstrate a significant incidence of bradycardia. Corticosteroid-induced bradycardia is common in children with ALL receiving induction chemotherapy. It was not associated with clinical adverse events and self-resolved without intervention. Therefore, further cardiac assessment may not be warranted in the presence of asymptomatic bradycardia suspected to be secondary to steroid administration.


Assuntos
Corticosteroides/efeitos adversos , Bradicardia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Bradicardia/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Lactente , Masculino , Adulto Jovem
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