The impact of inhalation versus total intravenous anesthesia on the immune status in patients undergoing breast cancer surgery: a double-blind randomized clinical trial (TeMP)

BackgroundBreast cancer (BC) mortality primarily stems from metastases rather than the primary tumor itself. Perioperative stress, encompassing both surgical and anesthetic factors, profoundly impacts the immune system, leading to alterations in neuroendocrine pathways and immune functions, potentially facilitating tumor progression and metastasis. Understanding the immunomodulatory effects of different anesthesia techniques is crucial for optimizing perioperative care in patients with BC. The neutrophil-to-lymphocyte ratio (NLR) serves as one of the key indicators of perioperative immune response.ObjectiveTo compare the effects of inhalation anesthesia (IA) and total intravenous anesthesia (TIVA) on perioperative immune response in BC surgery patients.MethodsIn this randomized, double-blind clinical trial, BC surgery patients were randomized to receive either TIVA with propofol or IA with sevoflurane. The primary endpoint was NLR assessment. Secondary immune parameters measured included natural killer cells, various T cell subsets, B cells, the immuno-regulatory index [T-helpers (CD3+CD4+)/cytotoxic T-cells (CD3+CD8+)], matrix metallopeptidases (MMP-9), complement components, and immunoglobulins, preoperatively and at 1 and 24 hours postoperatively.ResultsThe study included 98 patients (IA: 48, TIVA: 50). The baseline characteristics exhibited remarkable similarity across the groups. No significant difference in absolute NLR values was found between IA and TIVA groups at any time point (1 hour: p = 0.519, 24 hours: p = 0.333). Decreased IgA and IgM levels post-surgery suggested potential negative impacts of IA on humoral immunity compared to TIVA. CRP levels increased more by 24 hours (p = 0.044) in IA compared to TIVA. No significant differences were observed in natural killer cells, T cell subsets, B cells, MMP-9 levels or complement components between groups. Significant differences in the immuno-regulatory index between the TIVA and IA groups at one hour postoperatively (p = 0.033) were not maintained at 24 hours.ConclusionWhile there were no notable differences in NLR among the types of anesthesia, the observed disparities in immunoglobulin content and C-reactive protein levels between groups suggest that we cannot dismiss the potential immunosuppressive effects of inhalational anesthesia in breast cancer surgeries. Further investigation needed to clarify the impact of various anesthesia methods on immune function and their implications for long-term cancer outcomes

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.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians’ opinions and routine practices to understand the clinicians’ response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to “do you agree” and “do you use”) showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

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