Intraoperative electroencephalogram patterns as predictors of postoperative delirium in older patients: a systematic review and meta-analysis

BackgroundPostoperative delirium (POD) significantly affects patient outcomes after surgery, leading to increased morbidity, extended hospital stays, and potential long-term cognitive decline. This study assessed the predictive value of intraoperative electroencephalography (EEG) patterns for POD in adults.MethodsThis systematic review and meta-analysis followed the PRISMA and Cochrane Handbook guidelines. A thorough literature search was conducted using PubMed, Medline, and CENTRAL databases focusing on intraoperative native EEG signal analysis in adult patients. The primary outcome was the relationship between the burst suppression EEG pattern and POD development.ResultsFrom the initial 435 articles identified, 19 studies with a total of 7,229 patients were included in the systematic review, with 10 included in the meta-analysis (3,705 patients). In patients exhibiting burst suppression, the POD incidence was 22.1% vs. 13.4% in those without this EEG pattern (p=0.015). Furthermore, an extended burst suppression duration associated with a higher likelihood of POD occurrence (p = 0.016). Interestingly, the burst suppression ratio showed no significant association with POD.ConclusionsThis study revealed a 41% increase in the relative risk of developing POD in cases where a burst suppression pattern was present. These results underscore the clinical relevance of intraoperative EEG monitoring in predicting POD in older patients, suggesting its potential role in preventive strategies.Systematic Review RegistrationThis study was registered on International Platform for Registered Protocols for Systematic Reviews and Meta-Analyses: INPLASY202420001, https://doi.org/10.37766/inplasy2024.2.0001

Периоперационные предикторы неблагоприятного исхода сосудистых вмешательств

Concurrent cardiac failure is an universally accepted risk factor in surgical patients undergoiing cardiac or non-cardiac surgery.The aim of this study was to search for and identify factors or markers, which would permit to predict early (up to 30 days) or late (up to 1 year) adverse outcomes in patients with acute heart failure (AHF) in the vascular surgery.Materials and Methods. A randomized, multicenter, prospective — retrospective study was performed. 89 patients who had signed the Informed Consent Form were randomized. Throughout the four stages of the study, the cardiac index (CI) and the left ventricle ejection fraction (LVEF) values were recorded. At the same stages, blood was sampled to be tested for the NT-proBNP level. The TnT level was tested only at the 3rd stage of the study. The required stay in the intensive care unit (ICU) and in the in-patient hospital, the incidence of infarctions and strokes during the early postoperative period (up to 30 days), the 30&day and one-year mortality rates were recorded.Results. Different AHF prevention methods were used in patients included into this study in the postoperative period. Predictors of adverse events were studied in a combined population. The incidence of acute myocardial infarction (AMI) was 12% and that of stroke was 2%. The in-hospital mortality rate in the combined group was 2%; the one-year mortality was 10%. Patients stayed in the intensive care unit for 3 (2—4) days; the hospital stay was 11 (10—13) days; the composite adverse outcome of the surgical treatment was registered in 15% of patients. As a result, the Troponin T level was the only significant prognostic factor during the first 24 hours of the postoperative period. A study of the prognostic significance of different parameters in relation to their effect on the one-year mortality rate demonstrated a similar result. Vasoactive Inotropes Score (VIS) turned out to be the most significant criterion for prediction of possible treatment duration.Conclusion. The study results confirmed the predictive value of early determination of TnT levels after reparative vascular surgeries in patients with decreased left ventricular ejection fraction. The diagnostic value of the VIS calculation needs further confirmation. Сопутствующая сердечная недостаточность является общепризнанным фактором риска у хирургических пациентов в кардиальной, так и в некардиальной хирургии.Цель работы состояла в поиске и выделении факторов или маркеров, позволяющих прогнозировать ранний (до 30 дней) и поздний (до 1 года) неблагоприятный исход у пациентов с острой сердечной недостаточностью (ОСН) в сосудистой хирургии.Материалы и методы. Провели рандомизированное, мультицентровое, ретроспективно — проспективное исследование, рандомизировали 89 пациентов, подписавших информированное согласие. На 4&х эта& пах проводимого исследования фиксировали значения сердечного индекса (СИ), фракцию изгнания левого желудочка (ФИлж), брали пробу крови для определения содержания NT-proBNP. Содержание Тропанина Т (TnT) определяли только на 3&ем этапе исследования. Фиксировали необходимое время пребывания в палате отделения анестезиологии-реаниматологии (ПИТ) и в стационаре, частоту развития инфарктов и инсультов в ранние (до 30 суток) сроки после перенесенной операции, 30&ти дневную и годовую летальность.Результаты. Предикторы неблагоприятных событий изучали в смешанной группе больных, для которых использовали различные методы профилактики ОСН в периоперационном периоде. Частота развития острого инфаркта миокарда (ОИМ) составила 12%; инсульта 2%. Госпитальная летальность составила 2%; годовая летальность — 10%. Пациенты провели в палате интенсивной терапии 3 (2—4) дня; время пребывания в стационаре составило 11 (10—13) дней, неблагоприятный композитный исход оперативного лечения отметили у 15% пациентов. Единственным значимым предиктором оказалось содержание тропонина Т в 1-е сутки постопрерационного периода. При изучении прогностической значимости различных показателей годовой летальности получили сходный результат. Для прогнозирования возможных сроков лечения наиболее значимым критерием оказался Vasoactive Inotropes Score (VIS).Заключение. Подтвердили прогностическую значимость определения ТнТ в ранние сроки после выполнения реконструктивных сосудистых операций у пациентов со сниженной фракцией изгнания левого желудочка. Диагностическая ценность расчета VIS требует дальнейшего подтверждения.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, setting, and participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main outcomes and measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial registration: ClinicalTrials.gov Identifier: NCT03452839

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies

INTRODUCTION: Severe COVID-19 cases have a detrimental hyper-inflammatory host response and different cytokine-blocking biologic agents were explored to improve outcomes. Anakinra blocks the activity of both IL-1alpha and IL\u20111beta and is approved for different autoinflammatory disorders, but it is used off-label for conditions characterized by an excess of cytokine production. Several studies on anakinra in COVID-19 patients reported positive effects. We performed a meta-analysis of all published evidence on the use of anakinra in COVID19 to investigate its effect on survival and need for mechanical ventilation.METHODS: We searched for any study performed on adult patients with acute hypoxemic failure related to 2019-nCoV infection, receiving anakinra versus any comparator. Primary endpoint was mortality at the longest available follow-up. Adverse effects, need for mechanical ventilation and discharge at home with no limitations were also analysed.RESULTS: Four observational studies involving 184 patients were included. Overall mortality of patients treated with anakinra was significantly lower than mortality in the control group (95% CI 0.14-0.48, p<0.0001). Moreover, patients treated with anakinra had a significantly lower risk of need for mechanical ventilation than controls (95% CI 0.250.74, p=0.002). No difference in adverse events and discharge at home with no limitations was observed. The Trial Sequential Analysis z-cumulative line reached the monitoring boundary for benefit and the required sample size.CONCLUSIONS: Administration of anakinra in COVID-19 patients was safe and might be associated with reductions in both mortality and need for mechanical ventilation. Randomized clinical trials are warranted to confirm these findings

Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial

Objective: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population. Design: Post hoc analysis of a multicenter randomized trial. Setting: Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries. Participants:: The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate < 60 mL/min/ 1.73 m(2) and perioperative myocardial dysfunction. Interventions: Patients were assigned randomly to receive levosimendan (0.025-0.2 mu g/kg/min) or placebo in addition to standard inotropic treatment. Measurements and Main Results: Forty-six patients were assigned to receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14 (30%) patients in the levosimendan group versus 23 (52%) in the placebo group (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035). The incidence of major complications also was lower (18 [39%]) in the levosimendan group versus that in the placebo group (29 [66%]) (absolute difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum creatinine at intensive care unit discharge was observed in the levosimendan group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76] mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07). Conclusions: Levosimendan may improve renal outcome in cardiac surgery patients with chronic kidney disease undergoing mitral valve surgery who develop perioperative myocardial dysfunction. Results of this exploratory analysis should be investigated in future properly designed randomized controlled trials. (C) 2018 Elsevier Inc. All rights reserved

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, setting, and participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main outcomes and measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial registration: ClinicalTrials.gov Identifier: NCT03452839