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1.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804129

RESUMO

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

2.
J Neurosurg Anesthesiol ; 33(2): 100-106, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33660699

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.


Assuntos
/prevenção & controle , Neurociências/métodos , Pesquisa , Consenso , Humanos , Pandemias , Sociedades Médicas
3.
Artigo em Inglês | MEDLINE | ID: mdl-33637420

RESUMO

OBJECTIVE: Cardiac surgery for repair of congenital heart defects poses unique hazards to the developing brain. Deep hypothermic circulatory arrest (DHCA) is a simple and effective method for facilitating a bloodless surgical field during congenital heart defect repair. There are, however, some concerns that prolonged DHCA increases the risk of nervous system injury. The electroencephalogram (EEG) is used in adult and, to a lesser extent, pediatric cardiac procedures as a neuromonitoring method. The present study was performed to assess outcomes following DHCA with EEG monitoring in the pediatric population. DESIGN: In this systematic review and meta-analysis, the PubMed, Cochrane Central Register of Controlled Trials, Scopus, Institute of Science Index, and Embase databases were searched from inception for relevant articles. A fixed- or random-effects model, as appropriate, was used. SETTING: Surgical setting. PARTICIPANTS: Pediatric population (≤18 y old). INTERVENTIONS: DHCA (18°C) with EEG monitoring. MEASUREMENTS AND MAIN RESULTS: Nineteen articles with 1,267 pediatric patients ≤18 years were included. The event rate of clinical and EEG seizures among patients who underwent DHCA was 12.9% and 14.9%, respectively. Mortality was found to have a 6.3% prevalence. A longer duration of DHCA was associated with a higher risk of EEG seizure and neurologic abnormalities. In addition, seizures were associated with increased neurologic abnormalities and neurodevelopmental delay. CONCLUSIONS: EEG and neurologic abnormalities were common after DHCA. A longer duration of DHCA was found to lead to more EEG seizure and neurologic abnormalities. Moreover, EEG seizures were more common than clinical seizures. Seizures were found to be associated with increased neurologic abnormalities and neurodevelopmental delay.

4.
Anesth Analg ; 130(3): e95-e96, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-33034979
5.
Br J Anaesth ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33039122

RESUMO

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common, mostly silent, and a strong predictor of postoperative mortality. MINS appears to result from myocardial supply-demand mismatch. Recent data support restrictive perioperative transfusion strategies that can result in low postoperative haemoglobin concentrations. Whether low postoperative haemoglobin is associated with myocardial injury remains unknown. We therefore tested the hypothesis that anaemia is associated with an increased risk of myocardial injury in adults having noncardiac surgery. METHODS: We conducted a retrospective analysis of adults ≥45 yr old who had routine postoperative troponin T (TnT) monitoring after noncardiac surgery at the Cleverland Clinic (including those enrolled in the PeriOperative ISchemic Evaluation-2 Trial [POISE-2], the Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery [ENIGMA-II], Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study [VISION], and Anaesthetic Depth and Complications After Major Surgery [BALANCED] trial). Patients with baseline increase in TnT and non-ischaemic aetiologies for TnT increase were excluded. The association between postoperative haemoglobin concentration during the 3 initial postoperative days and the incidence of MINS (fourth-generation TnT ≥0.03 ng ml-1 judged as attributable to ischaemia) was assessed using a time-varying covariate Cox proportional hazards survival analysis. RESULTS: Among 6141 patients, 4480 were analysed. The incidence of MINS was 155/4480 (3.5%), ranging from 0/345 (0%) among patients whose lowest postoperative haemoglobin exceeded 13 g dl-1 to 52/611 (8.5%) in patients whose minimum postoperative haemoglobin was <8 g dl-1. The confounder-adjusted hazard ratio [95% confidence interval] for having MINS was 1.29 [1.16-1.42] for every 1 g dl-1 decrease in postoperative haemoglobin in a time-varying covariate analysis. Similar associations were identified in sensitivity analyses. CONCLUSION: Lower postoperative haemoglobin values are associated with MINS. Whether this association is modifiable by prevention or treatment of, anaemia remains to be determined.

7.
Anesth Analg ; 131(4): 1281-1290, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925349

RESUMO

BACKGROUND: Catheter-related thrombosis (CRT) is a serious complication of vascular catheters. Retrograde catheter insertion has been shown to decrease pericatheter hemostasis and thrombosis, but it is technically challenging. The current in silico trial is an analytical approach to evaluating different approaches to designing retrograde flow into a vascular catheter. METHODS: The novel catheter design aims to provide antistasis retrograde flow (ASRF) of fluid through multiple backward-directed side openings, with a self-closing terminal opening to facilitate standard insertion. Four different models of the catheter were evaluated by computational fluid dynamic studies, with retrograde-angled openings of 15°, 30°, 45°, and 60° to the long axis of the catheter. RESULTS: ASRF successfully reduced the areas of fluid stagnation in models with 15° and 30° openings. Models with 45° and 60° did not significantly reduce stagnation. ASRF is reversed by the main bloodstream after a few millimeters. The novel catheter design achieved a slightly higher saline flow rate compared with the standard catheter (89.75, 91.72, 94.13, and 94.26 mL/min for 15°, 30°, 45°, and 60° designs, respectively, versus 86.93 mL/min for the standard catheter). CONCLUSIONS: The novel ASRF vascular catheter reduces pericatheter fluid stasis and has the potential to reduce CRT. Further in vitro and in vivo trials are warranted to validate these findings and evaluate clinical efficacy.


Assuntos
Trombose/prevenção & controle , Dispositivos de Acesso Vascular , Cateteres de Demora , Simulação por Computador , Desenho de Equipamento , Hemostasia , Humanos , Hidrodinâmica , Trombose/etiologia , Dispositivos de Acesso Vascular/efeitos adversos
9.
Anesthesiology ; 133(1): 119-132, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32349070

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed. METHODS: The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer's disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed. RESULTS: The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001). CONCLUSIONS: Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Delírio do Despertar/induzido quimicamente , Delírio do Despertar/epidemiologia , Idoso , Benzodiazepinas/efeitos adversos , Estudos de Coortes , Confusão/etiologia , Confusão/psicologia , Cuidados Críticos , Delírio do Despertar/prevenção & controle , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Resultados Negativos , Pontuação de Propensão
10.
Crit Care Med ; 48(2): 233-240, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939793

RESUMO

OBJECTIVES: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation. DATA SOURCES: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching. STUDY SELECTION: Studies in mechanically ventilated children that compared early with late tracheostomy were included. DATA EXTRACTION: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis. CONCLUSIONS: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.


Assuntos
Respiração Artificial/estatística & dados numéricos , Traqueostomia/métodos , Adolescente , Criança , Pré-Escolar , Cuidados Críticos , Estado Terminal , Humanos , Lactente , Unidades de Terapia Intensiva , Tempo de Internação , Estudos Retrospectivos , Fatores de Tempo , Traqueostomia/mortalidade
11.
Anesth Analg ; 130(3): 636-643, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31725024

RESUMO

BACKGROUND: Postoperative delirium is common in critically ill patients, with a reported incidence of 11%-43%, and is associated with significant morbidity and cost. Perioperative hypotension and consequent brain hypoperfusion may contribute. We, therefore, tested the hypotheses that intraoperative and postoperative hypotension are associated with critical care delirium. METHODS: We included 1083 postoperative patients who were admitted directly from an operating room to the surgical intensive care unit. Delirium was assessed with the Confusion Assessment Method for Intensive Care Unit patients at 12-hour intervals. We used a confounder-adjusted Cox proportional hazard survival model to assess the association between the amount of intraoperative hypotension, which was measured as the time-weighted average of mean arterial pressure <65 mm Hg, and delirium while in critical care. Thereafter, we used a Cox model with the lowest mean arterial pressure on each intensive care day as a time-varying covariate to assess the relationship between critical care hypotension and delirium, adjusted for confounders and amount of intraoperative hypotension. RESULTS: Three hundred seventy-seven (35%) patients had delirium within the first 5 postoperative days in the surgical intensive care unit. Intraoperative hypotension was moderately associated with higher odds of postoperative delirium. The adjusted hazard ratio associated with 1 mm Hg increase in time-weighted average of mean arterial pressure <65 mm Hg was 1.11 (95% confidence interval [CI], 1.03-1.20; P = .008). Postoperatively, a 10 mm Hg reduction in the lowest mean pressure on each day in the critical care unit was significantly associated with a higher hazard of delirium, with an adjusted hazard ratio 1.12 (95% CI, 1.04-1.20; P = .003). CONCLUSIONS: Both intraoperative and postoperative hypotension are associated with delirium in postoperative critical care patients. The extent to which these relationships are causal remains unknown, but to the extent that they are, hypotension prevention may help reduce delirium and should be studied in prospective clinical trials.


Assuntos
Pressão Arterial , Delírio/epidemiologia , Hipotensão/epidemiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Idoso , Estado Terminal , Delírio/diagnóstico , Delírio/psicologia , Feminino , Humanos , Hipotensão/diagnóstico , Hipotensão/fisiopatologia , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Período Perioperatório , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
14.
Anesth Analg ; 129(3): 896-904, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31425235

RESUMO

BACKGROUND: Hypotension is associated with acute kidney injury, but vasopressors used to treat hypotension may also compromise renal function. We therefore tested the hypothesis that vasopressor infusion during complex spine surgery is not associated with impaired renal function. METHODS: In this retrospective cohort analysis, we considered adults who had complex spine surgery between January 2005 and September 2014 at the Cleveland Clinic Main Campus. Our primary outcome was postoperative estimated glomerular filtration rate. Secondarily, we evaluated renal function using Acute Kidney Injury Network criteria. We obtained data for 1814 surgeries, including 689 patients (38%) who were given intraoperative vasopressors infusion for ≥30 minutes and 1125 patients (62%) who were not. Five hundred forty patients with and 540 patients without vasopressor infusions were well matched across 32 potential confounding variables. RESULTS: In matched patients, vasopressor infusions lasted an average of 173 ± 100 minutes (SD) and were given a median dose (1st quintile, 3rd quintile) of 3.4-mg (1.5, 6.7 mg) phenylephrine equivalents. Mean arterial pressure and the amounts of hypotension were similar in each matched group. The postoperative difference in mean estimated glomerular filtration rate in patients with and without vasopressor infusions was only 0.8 mL/min/1.73 m (95% CI, -0.6 to 2.2 mL/min/1.73 m) (P = .28). Intraoperative vasopressor infusion was also not associated with increased odds of augmented acute kidney injury stage. CONCLUSIONS: Clinicians should not avoid typical perioperative doses of vasopressors for fear of promoting kidney injury. Tolerating hypotension to avoid vasopressor use would probably be a poor strategy.


Assuntos
Lesão Renal Aguda/diagnóstico , Pressão Sanguínea/efeitos dos fármacos , Posicionamento do Paciente/métodos , Decúbito Ventral , Vasoconstritores/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/fisiopatologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Estudos de Coortes , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Decúbito Ventral/fisiologia , Estudos Retrospectivos , Vasoconstritores/efeitos adversos
15.
Curr Pharm Des ; 25(19): 2123-2132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31298146

RESUMO

Multimodal, non-opioid based analgesia has become the cornerstone of ERAS protocols for effective analgesia after spinal surgery. Opioid side effects, dependence and legislation restricting long term opioid use has led to a resurgence in interest in opioid sparing techniques. The increasing array of multimodal opioid sparing analgesics available for spinal surgery targeting novel receptors, transmitters, and altering epigenetics can help provide an optimal perioperative experience with less opioid side effects and long-term dependence. Epigenetic mechanisms of pain may enhance or suppress gene expression, without altering the genome itself. Such mechanisms are complex, dynamic and responsive to environment. Alterations that occur can affect the pathophysiology of pain management at a DNA level, modifying perceived pain relief. In this review, we provide a brief overview of epigenetics of pain, systemic local anesthetics and neuraxial techniques that continue to remain useful for spinal surgery, neuropathic agents, as well as other common and less common target receptors for a truly multimodal approach to perioperative pain management.


Assuntos
Analgesia/métodos , Manejo da Dor , Coluna Vertebral/cirurgia , Analgésicos Opioides , Anestésicos Locais , Humanos , Dor Pós-Operatória
18.
Anesthesiology ; 130(1): 72-82, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30312182

RESUMO

BACKGROUND: Triple-low events (mean arterial pressure less than 75 mmHg, Bispectral Index less than 45, and minimum alveolar fraction less than 0.8) are associated with mortality but may not be causal. This study tested the hypothesis that providing triple-low alerts to clinicians reduces 90-day mortality. METHODS: Adults having noncardiac surgery with volatile anesthesia and Bispectral Index monitoring were electronically screened for triple-low events. Patients having triple-low events were randomized in real time, with clinicians either receiving an alert, "consider hemodynamic support," or not. Patients were blinded to treatment. Helpful responses to triple-low events were defined by administration of a vasopressor within 5 min or a 20% reduction in end-tidal volatile anesthetic concentration within 15 min. RESULTS: Of the qualifying patients, 7,569 of 36,670 (20%) had triple-low events and were randomized. All 7,569 were included in the primary analysis. Ninety-day mortality was 8.3% in the alert group and 7.3% in the nonalert group. The hazard ratio (95% CI) for alert versus nonalert was 1.14 (0.96, 1.35); P = 0.12, crossing a prespecified futility boundary. Clinical responses were helpful in about half the patients in each group, with 51% of alert patients and 47% of nonalert patients receiving vasopressors or having anesthetics lowered after start of triple low (P < 0.001). There was no relationship between the response to triple-low events and adjusted 90-day mortality. CONCLUSIONS: Real-time alerts to triple-low events did not lead to a reduction in 90-day mortality, and there were fewer responses to alerts than expected. However, similar mortality with and without responses suggests that there is no strong relationship between responses to triple-low events and mortality.


Assuntos
Pressão Arterial/fisiologia , Monitores de Consciência/estatística & dados numéricos , Hipotensão/diagnóstico , Hipotensão/mortalidade , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/mortalidade , Monitorização Intraoperatória/métodos , Feminino , Humanos , Hipotensão/fisiopatologia , Complicações Intraoperatórias/fisiopatologia , Masculino , Pessoa de Meia-Idade
20.
Ochsner J ; 17(3): 224-232, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29026353

RESUMO

BACKGROUND: Whether the deleterious effects of carbon dioxide pneumoperitoneum on the kidneys are exacerbated in the obese population remains unknown. We hypothesized that increased body mass index (BMI) is associated with an increased incidence of postoperative acute kidney injury (AKI) in patients undergoing noncardiac laparoscopic surgery. METHODS: Following institutional review board approval, we analyzed data on 8,543 adult patients with American Society of Anesthesiologists physical status scores of I-IV who had inpatient noncardiac laparoscopic surgery from 2005-2014. Because the exposure (current BMI) is a chronic condition, we a priori assumed that diabetes mellitus, hypertension, coronary artery disease, and chronic obstructive pulmonary disease might mediate the effect of obesity on outcome. Our primary analysis was a proportional odds logistic regression model with current BMI as a predictor and AKI as an ordinal outcome. RESULTS: After controlling for potential confounding variables, the odds of developing a more serious level of AKI was 7% (95% CI 0%, 15%) greater with a 5-unit increase in BMI (P=0.05). When the analysis was adjusted for the a priori mediators in an attempt to estimate the pure effect of BMI on AKI, the result was no longer significant (Wald test P=0.35), with the residual effect of BMI of 3% (95% CI -4%, 11%). CONCLUSION: We found a marginal association between BMI and an increased risk of developing AKI in adult patients after having noncardiac laparoscopic surgery. The BMI effect became insignificant when potential mediator variables were considered. The association of BMI and AKI after noncardiac laparoscopic surgery is likely mediated through components of the metabolic syndrome.

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