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1.
Expert Opin Drug Saf ; 19(1): 1-8, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31855607

RESUMO

Introduction: Hypoactive sexual desire disorder (HSDD) is the most prevalent sexual dysfunction in women, previously managed with off-label therapies. Indicated for premenopausal women, flibanserin is the first FDA-approved medication to treat HSDD.Areas covered: This review summarizes flibanserin's pharmacokinetics, proposed mechanism of action, and safety data in clinical trials with a focus on sedation- and hypotension-related adverse events, and drug interactions with alcohol and antidepressants. Sources included peer-reviewed publications and internal data from the manufacturer.Expert opinion: Flibanserin is a well-tolerated and effective treatment that decreases distress and restores sexual desire to a level that is normative for the individual patient with HSDD. Simplification of a risk mitigation program for flibanserin in the US is likely to increase the number of prescribing clinicians if accompanied with educational efforts to clarify flibanserin's risk-benefit profile. As flibanserin is dosed daily and may be used for a decade or more in the typical premenopausal patient, long-term pharmacovigilance data will be essential. Over time, HSDD will be treated by more nonspecialist health care professionals and flibanserin will likely become established as a significant treatment option along with other medications approved for this indication in the context of a holistic biopsychosocial treatment paradigm.


Assuntos
Benzimidazóis/administração & dosagem , Pré-Menopausa , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Benzimidazóis/efeitos adversos , Interações de Medicamentos , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia
2.
N Engl J Med ; 381(22): 2103-2113, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31774955

RESUMO

BACKGROUND: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied. METHODS: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death. RESULTS: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant. CONCLUSIONS: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).


Assuntos
Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Fenitoína/análogos & derivados , Estado Epiléptico/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Benzodiazepinas/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Humanos , Hipotensão/induzido quimicamente , Infusões Intravenosas , Injeções Intramusculares , Levetiracetam/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fenitoína/efeitos adversos , Fenitoína/uso terapêutico , Ácido Valproico/efeitos adversos , Adulto Jovem
3.
Undersea Hyperb Med ; 46(5): 701-707, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31683370

RESUMO

Purpose: To report the successful treatment of postoperative posterior ischemic optic neuropathy (PION) with hyperbaric oxygen therapy and to review the current literature on the pathogenesis and treatment of PION. Observations: During an angiographic procedure at a community hospital, an elderly woman had a transient drop in blood pressure after receiving an intravenous dose of hydralazine. During recovery, the patient experienced bilateral vision loss. She was transferred to our specialty referral center for treatment with hyperbaric oxygen. We followed Table 5 in the U.S. Navy Diving Manual, the protocol for decompression sickness. Our patient's vision improved markedly immediately after the first session and continued to improve throughout the course of treatment to its completion. Follow-up ophthalmology visits found the patient's vision to be close to baseline. Conclusions and importance: PION is a rare condition. It has been difficult to determine a successful therapeutic approach because of the lack of large case-controlled studies. Hyperbaric oxygen has been used to treat other ischemic ophthalmic conditions, but there are only few reports of its use in patients with PION. Systemic steroids and antiplatelet therapy have also been used, with mixed success. In our patient, the combination of hyperbaric oxygen therapy and steroids was successful in restoring vision after postoperative PION.


Assuntos
Oxigenação Hiperbárica , Neuropatia Óptica Isquêmica/terapia , Complicações Pós-Operatórias/terapia , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Feminino , Humanos , Hidralazina/efeitos adversos , Hipotensão/induzido quimicamente , Neuropatia Óptica Isquêmica/etiologia , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica
4.
Neurosurg Rev ; 42(4): 843-852, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617125

RESUMO

To perform a systematic review of the techniques for transient circulatory arrest during intracerebral aneurysm surgery according to the PRISMA guidelines. Search of PubMed and Google Scholar using the following: ("heart arrest" OR "cardiac standstill"[All Fields]) AND ("intracranial aneurysm" OR "intracranial"[All Fields] AND "aneurysm"[All Fields]). A total of 41 original articles were retrieved, of which 17 were excluded (review articles, editorials and single-case reports). A total of 24 separate articles published between 1984 and 2018 were included in the final analysis, where the majority of patients harbored anterior circulation giant or large aneurysms. Adenosine-induced cardiac arrest gave a short, temporary asystole. The method had benefits in aneurysm with a broad neck, a thin wall, in specific localizations with narrow surgical corridors or in case of intraoperative rupture. Rapid ventricular pacing (RVP) allows a longer and more easily controlled hypotension. Its use is largely limited to elective cases. Deep hypothermic circulatory arrest required a complex infrastructure, and fatal procedure complications lead to a 11.5-30% 30-day mortality rate, limiting its application to giant or complex aneurysm of the basilar artery or to residual posterior circulation aneurysm after endovascular treatment. Adenosine and RVP are both effective options to facilitate clipping of complex aneurysms. However, their use in patient with ischemic heart disease and cardiac arrhythmias should be avoided, and their safety in the context of subarachnoid hemorrhage is yet to be determined. Today, deep hypothermic circulatory arrest is almost obsolete due to endovascular alternatives.


Assuntos
Parada Cardíaca Induzida/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adenosina/administração & dosagem , Estimulação Cardíaca Artificial/métodos , Fármacos Cardiovasculares/administração & dosagem , Parada Circulatória Induzida por Hipotermia Profunda , Humanos , Hipotensão/induzido quimicamente , Hipotensão/etiologia
5.
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
6.
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
7.
Molecules ; 24(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505853

RESUMO

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.


Assuntos
Ativação do Complemento/efeitos dos fármacos , Síndrome de Hipersensibilidade a Medicamentos/tratamento farmacológico , Leucocitose/sangue , Lipossomos/farmacologia , Anfotericina B/química , Anfotericina B/farmacologia , Animais , Colesterol/química , Convertases de Complemento C3-C5/química , Convertases de Complemento C3-C5/farmacologia , Proteínas do Sistema Complemento/química , Proteínas do Sistema Complemento/metabolismo , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/patologia , Venenos Elapídicos/química , Venenos Elapídicos/farmacologia , Humanos , Hipotensão/sangue , Hipotensão/induzido quimicamente , Leucocitose/induzido quimicamente , Leucopenia/sangue , Leucopenia/induzido quimicamente , Lipossomos/química , Nanopartículas/química , Polietilenoglicóis/química , Ratos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Zimosan/química , Zimosan/farmacologia
8.
N Engl J Med ; 381(17): 1609-1620, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31475794

RESUMO

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).


Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Neprilisina/antagonistas & inibidores , Tetrazóis/administração & dosagem , Valsartana/administração & dosagem , Idoso , Aminobutiratos/efeitos adversos , Angioedema/induzido quimicamente , Antagonistas de Receptores de Angiotensina/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores Sexuais , Método Simples-Cego , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/efeitos adversos
9.
Medicine (Baltimore) ; 98(33): e16872, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415426

RESUMO

Patients undergoing surgery and taking angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) are susceptible to complications related to intraoperative hypotension. Perioperative continuation of such medications in patients undergoing colorectal surgery may be associated with more harm than benefit, as these patients are often exposed to other risk factors which may contribute to intraoperative hypotension. Our objectives were to assess the incidence and severity of postinduction hypotension as well as the rates of acute kidney injury (AKI), 30-day all-cause mortality, 30-day readmission, and hospital length of stay in adult patients undergoing colorectal surgery who take ACEi/ARB.We performed a retrospective chart review of patients undergoing colorectal surgery of ≥4 hour duration at a tertiary care academic medical center between January 2011 and November 2016. The preoperative and intraoperative characteristics as well as postoperative outcomes were compared between patients taking ACEi/ARB and patients not taking these medications.Of the 1020 patients meeting inclusion criteria, 174 (17%) were taking either ACEi or ARB before surgery. Patients taking these medications were more likely to receive both postinduction and intraoperative phenylephrine and ephedrine. The incidences of postoperative AKI (P = .35), 30-day all-cause mortality (P = .36), 30-day hospital readmission (P = .45), and hospital length of stay (P = .25), were not significantly different between the 2 groups.Our results support the current recommendation that ACEi/ARB use is probably safe within the colorectal surgery population during the perioperative period. Intraoperative hypotension should be expected and treated with vasopressors.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Cirurgia Colorretal/efeitos adversos , Hipotensão/induzido quimicamente , Assistência Perioperatória/métodos , Lesão Renal Aguda/induzido quimicamente , Adulto , Estudos de Casos e Controles , Cirurgia Colorretal/mortalidade , Feminino , Humanos , Hipotensão/tratamento farmacológico , Masculino , Estudos Retrospectivos , Vasoconstritores/uso terapêutico
10.
R I Med J (2013) ; 102(6): 44-46, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398969

RESUMO

We describe a case of disulfiram-ethanol reaction in a patient presenting with altered mental status. The patient was found to be profoundly hypotensive, requiring multiple vasopressor agents. As the symptoms associated with disulfiram reaction are non-specific, it is important to maintain a high level of suspicion for drug reaction when caring for the undifferentiated altered and hypotensive patient.


Assuntos
Dissuasores de Álcool/efeitos adversos , Dissulfiram/efeitos adversos , Etanol/efeitos adversos , Hipotensão/induzido quimicamente , Dissuasores de Álcool/administração & dosagem , Dissulfiram/administração & dosagem , Etanol/administração & dosagem , Feminino , Humanos , Hipotensão/tratamento farmacológico , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Vasoconstritores/uso terapêutico , Vasopressinas/uso terapêutico
11.
BMC Med ; 17(1): 168, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455332

RESUMO

BACKGROUND: The alpha-adrenergic agonist phenylephrine is often used to treat hypotension during anesthesia. In clinical situations, low blood pressure may require prompt intervention by intravenous bolus or infusion. Differences in responsiveness to phenylephrine treatment are commonly observed in clinical practice. Candidate gene studies indicate genetic variants may contribute to this variable response. METHODS: Pharmacological and physiological data were retrospectively extracted from routine clinical anesthetic records. Response to phenylephrine boluses could not be reliably assessed, so infusion rates were used for analysis. Unsupervised k-means clustering was conducted on clean data containing 4130 patients based on phenylephrine infusion rate and blood pressure parameters, to identify potential phenotypic subtypes. Genome-wide association studies (GWAS) were performed against average infusion rates in two cohorts: phase I (n = 1205) and phase II (n = 329). Top genetic variants identified from the meta-analysis were further examined to see if they could differentiate subgroups identified by k-means clustering. RESULTS: Three subgroups of patients with different response to phenylephrine were clustered and characterized: resistant (high infusion rate yet low mean systolic blood pressure (SBP)), intermediate (low infusion rate and low SBP), and sensitive (low infusion rate with high SBP). Differences among clusters were tabulated to assess for possible confounding influences. Comorbidity hierarchical clustering showed the resistant group had a higher prevalence of confounding factors than the intermediate and sensitive groups although overall prevalence is below 6%. Three loci with P < 1 × 10-6 were associated with phenylephrine infusion rate. Only rs11572377 with P = 6.09 × 10-7, a 3'UTR variant of EDN2, encoding a secretory vasoconstricting peptide, could significantly differentiate resistant from sensitive groups (P = 0.015 and 0.018 for phase I and phase II) or resistant from pooled sensitive and intermediate groups (P = 0.047 and 0.018). CONCLUSIONS: Retrospective analysis of electronic anesthetic records data coupled with the genetic data identified genetic variants contributing to variable sensitivity to phenylephrine infusion during anesthesia. Although the identified top gene, EDN2, has robust biological relevance to vasoconstriction by binding to endothelin type A (ETA) receptors on arterial smooth muscle cells, further functional as well as replication studies are necessary to confirm this association.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Anestesia/efeitos adversos , Hipotensão/induzido quimicamente , Hipotensão/genética , Fenilefrina/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Estudo de Associação Genômica Ampla , Humanos , Infusões Intravenosas , Gravidez , Estudos Retrospectivos
12.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373469

RESUMO

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Trióxido de Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/efeitos adversos , Lesão Renal Aguda/terapia , Adulto , Dexametasona/uso terapêutico , Edema/induzido quimicamente , Febre de Causa Desconhecida/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Quimioterapia de Indução/efeitos adversos , Masculino , Diálise Renal , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome
13.
Hypertension ; 74(3): 645-651, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31327266

RESUMO

Alpha-blockers (ABs) are commonly prescribed as part of a multidrug regimen in the management of hypertension. We set out to assess the risk of hypotension and related adverse events with AB use compared with other blood pressure (BP) lowering drugs using a population-based, retrospective cohort study of women (≥66 years) between 1995 and 2015 in Ontario, Canada. Cox proportional hazards examined the association of AB use and hypotension and related events (syncope, fall, and fracture) compared with other BP lowering drugs matched via a high dimensional propensity score. The primary outcome was a composite of hospitalizations for hypotension and related events (syncope, fractures, and falls) within 1 year. From 734 907 eligible women, 14 106 were dispensed an AB (mean age, 75.7; standard deviation 6.9 years, median follow-up 1 year) and matched to 14 106 dispensed other BP lowering agents. The crude incidence rate of hypotension and related events was 95.7 (95% CI [confidence interval], 90.4-101.1, events 1214 [8.6%]) with AB and 79.8 (95% CI, 74.9-84.7 per 1000 person-years, events 1025 [7.3%]) with other BP lowering medications (incident rate ratio, 1.20; 95% CI, 1.10-1.30). The risk was higher for hypotension (hazard ratio, 1.71; 95% CI, 1.33-2.20) and syncope (hazard ratio, 1.44; 95% CI, 1.18-1.75) with no difference in falls, fractures, adverse cardiac events, or all-cause mortality. Treatment of hypertension in women with ABs is associated with a higher risk of hypotension and hypotension-related events compared with other BP lowering agents. Our findings suggest that ABs should be used with caution, even as add on therapy for hypertension.


Assuntos
Antagonistas Adrenérgicos alfa/efeitos adversos , Hipertensão/tratamento farmacológico , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Acidentes por Quedas/estatística & dados numéricos , Antagonistas Adrenérgicos alfa/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Canadá , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Avaliação Geriátrica/métodos , Humanos , Hipertensão/diagnóstico , Hipotensão/fisiopatologia , Incidência , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Síncope/diagnóstico , Síncope/epidemiologia , Resultado do Tratamento
14.
Nutrients ; 11(8)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349678

RESUMO

Postprandial hypotension (PPH) is under-recognised, but common, particularly in the elderly, and is of clear clinical importance due to both the independent association between PPH and an increase in mortality and lack of effective management for this condition. Following health concerns surrounding excessive consumption of sugar, there has been a trend in the use of low- or non-nutritive sweeteners as an alternative. Due to the lack of literature in this area, we conducted a systematic search to identify studies relevant to the effects of different types of sweeteners on postprandial blood pressure (BP). The BP response to ingestion of sweeteners is generally unaffected in healthy young subjects, however in elderly subjects, glucose induces the greatest decrease in postprandial BP, while the response to sucrose is less pronounced. The limited studies investigating other nutritive and non-nutritive sweeteners have demonstrated minimal or no effect on postprandial BP. Dietary modification by replacing high nutritive sweeteners (glucose, fructose, and sucrose) with low nutritive (d-xylose, xylitol, erythritol, maltose, maltodextrin, and tagatose) and non-nutritive sweeteners may be a simple and effective management strategy for PPH.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipotensão/induzido quimicamente , Adoçantes não Calóricos/efeitos adversos , Adoçantes Calóricos/efeitos adversos , Período Pós-Prandial , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
15.
Br J Anaesth ; 123(4): 430-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31255290

RESUMO

BACKGROUND: Vasopressor agents are used to prevent intraoperative hypotension and ensure adequate perfusion. Vasopressors are usually administered as intermittent boluses or manually adjusted infusions, but this practice requires considerable time and attention. We have developed a closed-loop vasopressor (CLV) controller to correct hypotension more efficiently. Here, we conducted a proof-of-concept study to assess the feasibility and performance of CLV control in surgical patients. METHODS: Twenty patients scheduled for elective surgical procedures were included in this study. The goal of the CLV system was to maintain MAP within 5 mm Hg of the target MAP by automatically adjusting the rate of a norepinephrine infusion using MAP values recorded continuously from an arterial catheter. The primary outcome was the percentage of time that patients were hypotensive, as defined by a MAP of 5 mm Hg below the chosen target. Secondary outcomes included the total dose of norepinephrine, percentage of time with hypertension (MAP>5 mm Hg of the chosen target), raw percentage "time in target" and Varvel performance criteria. RESULTS: The 20 subjects (median age: 64 years [52-71]; male (35%)) underwent elective surgery lasting 154 min [124-233]. CLV control maintained MAP within ±5 mm Hg of the target for 91.6% (85.6-93.3) of the intraoperative period. Subjects were hypotensive for 2.6% of the intraoperative period (range, 0-8.4%). Additional performance criteria for the controller included mean absolute performance error of 2.9 (0.8) and mean predictive error of 0.5 (1.0). No subjects experienced major complications. CONCLUSIONS: In this proof of concept study, CLV control minimised perioperative hypotension in subjects undergoing moderate- or high-risk surgery. Further studies to demonstrate efficacy are warranted. TRIAL REGISTRY NUMBER: NCT03515161 (ClinicalTrials.gov).


Assuntos
Infusões Intravenosas/instrumentação , Norepinefrina/administração & dosagem , Procedimentos Cirúrgicos Operatórios/métodos , Vasoconstritores/efeitos adversos , Idoso , Anestesia , Pressão Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Eletivos , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Resultado do Tratamento , Vasoconstritores/uso terapêutico
16.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31356183

RESUMO

High salt (HS) intake can lead to hypertension, probably the result of the predominance of vasoconstrictor reactive oxygen species over vasodilator nitric oxide (NO). We aimed to examine if the supposed NO deficiency and the resultant blood pressure increase could be corrected by supplementation of L-arginine, the substrate, and tetrahydrobiopterin (BH4), a co-factor of NO synthases. Wistar rats without known genetic background of salt sensitivity were exposed to HS diet (4%Na) for 10 or 26 days, without or with supplementation with oral L-arginine, 1.4 mg/kg b.w. daily, alone or together with intraperitoneal BH4, 10 mg/kg daily. Systolic blood pressure (SBP, tail-cuff method) was measured repeatedly and found to increase ~40 mmHg after 26 days; L-arginine and BH4 did not significantly attenuate this increase. At the end of chronic studies, in anaesthetized rats the diet- and treatment-induced changes in renal haemodynamics were assessed. HS diet selectively decreased (-30%, P < 0.03) the inner medullary blood flow (IMBF, laser-Doppler flux) without changing total or cortical renal perfusion. Arginine supplementation tended to raise all renal circulatory parameters, and distinctly increased IMBF, to 61% above the HS diet level (P < 0.05). In conclusion, unlike in confirmed genetically determined salt-dependent hypertension, L-arginine and BH4 supplementation failed to attenuate the SBP increase observed after exposure to HS diet. On the other hand, arginine increased total and regional renal perfusion, especially IMBF. This suggests that the delivery of arginine increased intrarenal NO synthesis, an action of renoprotective potential which presumably countered the harmful influence of the local tissue oxidative stress.


Assuntos
Arginina/farmacologia , Biopterina/análogos & derivados , Pressão Sanguínea/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipotensão/induzido quimicamente , Cloreto de Sódio na Dieta/administração & dosagem , Animais , Arginina/efeitos adversos , Biopterina/efeitos adversos , Biopterina/farmacologia , Suplementos Nutricionais , Hipertensão/metabolismo , Hipotensão/metabolismo , Rim , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Circulação Renal/efeitos dos fármacos
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.
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
19.
J Stroke Cerebrovasc Dis ; 28(8): 2155-2158, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31103551

RESUMO

OBJECTIVE: To determine adherence to nimodipine administration in patients admitted with aneurysmal subarachnoid hemorrhage (aSAH). BACKGROUND: Oral nimodipine (60 mg every 4 hours for 21 days) is recommended by the national guidelines for aSAH. A Cochrane systematic review has determined that nimodipine reduces the risk of cerebral ischemia and is currently the only effective drug for the prevention of vasospasm in aSAH patients. DESIGN/METHODS: We retrospectively analyzed 109 patients with aSAH admitted to the Neurosciences Intensive Care Unit (NICU) at a tertiary care medical center between 2010 and 2013. Nimodipine-prescribing patterns, days of therapy completed, and adverse effects were tabulated. Patients not initiated on nimodipine and reasons for prematurely stopping therapy were noted. RESULTS: One hundred two (93%) patients with aSAH were started on oral nimodipine upon admission to the NICU. Early death (3%) and hypotension (1%) were reasons why patients were not started on nimodipine. Only 36 (33%) patients received nimodipine, 60 mg orally every 4 hours for 21 days. In 26 patients (39%), the dose of nimodipine was reduced because of excessive drops in blood pressure. Transient discontinuation occurred in 2 (2%) patients. Thirty one (47%) patients were discharged from the hospital before 21 days and nimodipine was not ordered to continue at home. CONCLUSION: We found that the majority of patients with aSAH in our practice did not complete 21 days of nimodipine. Hypotension was mostly responsible for dosing change or discontinuation.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Nimodipina/administração & dosagem , Padrões de Prática Médica , Hemorragia Subaracnóidea/tratamento farmacológico , Vasodilatadores/administração & dosagem , Administração Oral , Adulto , Idoso , Bloqueadores dos Canais de Cálcio/efeitos adversos , Esquema de Medicação , Feminino , Fidelidade a Diretrizes , Humanos , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nimodipina/efeitos adversos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversos
20.
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
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