Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis.

BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition. METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane. RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use. CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect.

Treatment strategies for new onset atrial fibrillation in patients treated on an intensive care unit: a systematic scoping review.

BACKGROUND: New-onset atrial fibrillation (NOAF) in patients treated on an intensive care unit (ICU) is common and associated with significant morbidity and mortality. We undertook a systematic scoping review to summarise comparative evidence to inform NOAF management for patients admitted to ICU. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, OpenGrey, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, ISRCTN, ClinicalTrials.gov, EU Clinical Trials register, additional WHO ICTRP trial databases, and NIHR Clinical Trials Gateway in March 2019. We included studies evaluating treatment or prevention strategies for NOAF or acute anticoagulation in general medical, surgical or mixed adult ICUs. We extracted study details, population characteristics, intervention and comparator(s), methods addressing confounding, results, and recommendations for future research onto study-specific forms. RESULTS: Of 3,651 citations, 42 articles were eligible: 25 primary studies, 12 review articles and 5 surveys/opinion papers. Definitions of NOAF varied between NOAF lasting 30 s to NOAF lasting > 24 h. Only one comparative study investigated effects of anticoagulation. Evidence from small RCTs suggests calcium channel blockers (CCBs) result in slower rhythm control than beta blockers (1 study), and more cardiovascular instability than amiodarone (1 study). Evidence from 4 non-randomised studies suggests beta blocker and amiodarone therapy may be equivalent in respect to rhythm control. Beta blockers may be associated with improved survival compared to amiodarone, CCBs, and digoxin, though supporting evidence is subject to confounding. Currently, the limited evidence does not support therapeutic anticoagulation during ICU admission. CONCLUSIONS: From the limited evidence available beta blockers or amiodarone may be superior to CCBs as first line therapy in undifferentiated patients in ICU. The little evidence available does not support therapeutic anticoagulation for NOAF whilst patients are critically ill. Consensus definitions for NOAF, rate and rhythm control are needed.

The cellular mechanisms associated with the anesthetic and neuroprotective properties of xenon: a systematic review of the preclinical literature.

Introduction: Xenon exhibits significant neuroprotection against a wide range of neurological insults in animal models. However, clinical evidence that xenon improves outcomes in human studies of neurological injury remains elusive. Previous reviews of xenon's method of action have not been performed in a systematic manner. The aim of this review is to provide a comprehensive summary of the evidence underlying the cellular interactions responsible for two phenomena associated with xenon administration: anesthesia and neuroprotection. Methods: A systematic review of the preclinical literature was carried out according to the PRISMA guidelines and a review protocol was registered with PROSPERO. The review included both in vitro models of the central nervous system and mammalian in vivo studies. The search was performed on 27th May 2022 in the following databases: Ovid Medline, Ovid Embase, Ovid Emcare, APA PsycInfo, and Web of Science. A risk of bias assessment was performed utilizing the Office of Health Assessment and Translation tool. Given the heterogeneity of the outcome data, a narrative synthesis was performed. Results: The review identified 69 articles describing 638 individual experiments in which a hypothesis was tested regarding the interaction of xenon with cellular targets including: membrane bound proteins, intracellular signaling cascades and transcription factors. Xenon has both common and subtype specific interactions with ionotropic glutamate receptors. Xenon also influences the release of inhibitory neurotransmitters and influences multiple other ligand gated and non-ligand gated membrane bound proteins. The review identified several intracellular signaling pathways and gene transcription factors that are influenced by xenon administration and might contribute to anesthesia and neuroprotection. Discussion: The nature of xenon NMDA receptor antagonism, and its range of additional cellular targets, distinguishes it from other NMDA antagonists such as ketamine and nitrous oxide. This is reflected in the distinct behavioral and electrophysiological characteristics of xenon. Xenon influences multiple overlapping cellular processes, both at the cell membrane and within the cell, that promote cell survival. It is hoped that identification of the underlying cellular targets of xenon might aid the development of potential therapeutics for neurological injury and improve the clinical utilization of xenon. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: 336871.

Managing new-onset atrial fibrillation in critically ill patients: a systematic narrative review.

OBJECTIVES: The aim of this review is to summarise the latest evidence on efficacy and safety of treatments for new-onset atrial fibrillation (NOAF) in critical illness. PARTICIPANTS: Critically ill adult patients who developed NOAF during admission. PRIMARY AND SECONDARY OUTCOMES: Primary outcomes were efficacy in achieving rate or rhythm control, as defined in each study. Secondary outcomes included mortality, stroke, bleeding and adverse events. METHODS: We searched MEDLINE, EMBASE and Web of Knowledge on 11 March 2019 to identify randomised controlled trials (RCTs) and observational studies reporting treatment efficacy for NOAF in critically ill patients. Data were extracted, and quality assessment was performed using the Cochrane Risk of Bias Tool, and an adapted Newcastle-Ottawa Scale. RESULTS: Of 1406 studies identified, 16 remained after full-text screening including two RCTs. Study quality was generally low due to a lack of randomisation, absence of blinding and small cohorts. Amiodarone was the most commonly studied agent (10 studies), followed by beta-blockers (8), calcium channel blockers (6) and magnesium (3). Rates of successful rhythm control using amiodarone varied from 30.0% to 95.2%, beta-blockers from 31.8% to 92.3%, calcium channel blockers from 30.0% to 87.1% and magnesium from 55.2% to 77.8%. Adverse effects of treatment were rarely reported (five studies). CONCLUSION: The reported efficacy of beta-blockers, calcium channel blockers, magnesium and amiodarone for achieving rhythm control was highly varied. As there is currently significant variation in how NOAF is managed in critically ill patients, we recommend future research focuses on comparing the efficacy and safety of amiodarone, beta-blockers and magnesium. Further research is needed to inform the decision surrounding anticoagulant use in this patient group.

Prophylactic use of platelets in critically ill patients with thrombocytopaenia: A retrospective two-centre observational study.

PURPOSE: We report the use and effect of prophylactic platelet transfusions in critically ill thrombocytopaenic patients, comparing patients with or without bone marrow failure as a cause of thrombocytopaenia. METHODS: A retrospective observational study of admissions to three intensive care units (ICU) in the UK. We identified thrombocytopaenic patients who received a platelet transfusion and extracted the platelet count prior and subsequent to platelet transfusion. We grouped patients with or without suspected bone marrow failure, defined by a total white cell count ≤1.0 × 109/L. RESULTS: Of 11,757 admissions, 399 (3.4%) patients received a platelet transfusion for thrombocytopaenia. The median [IQR] platelet count prior to transfusion in patients without bone marrow failure was 42 [28-64] × 109/L versus 14 [7-24] × 109/L (p < .0001) in those with. The median [IQR] increment in platelets following transfusion was lower in patients with marrow failure (12 [-1-23] × 109/L) compared to those without (18 [5-36] × 109/L) (p = .006). CONCLUSIONS: Platelet transfusions were given at a higher median platelet count than suggested by guidelines. Patients with bone marrow failure were transfused at a lower threshold and experienced a smaller increment in platelet count when compared to patients without marrow failure.