Daily Anesthesiology Research Analysis

BACKGROUND: General anesthetics may substantially influence endothelium function, potentially affecting outcomes of surgical patients, but their effects are unclear. Here, the authors studied a commonly used inhaled anesthetic, sevoflurane, and an intravenous anesthetic, propofol, on vascular endothelial permeability using multiple in vitro assays and a mouse model. METHODS: Human umbilical vein endothelial cells and mouse pulmonary endothelial cells (MPECs) were used for in vitro models to test the effect of anesthetics on endothelial permeability. The effect of anesthetics on pulmonary vascular leakage was analyzed using AngioSense 750 (PerkinElmer, USA) fluorescent tracer and rhodamine-labeled 3-kD dextran in a mouse model. Downstream targets were identified using RNA sequencing and confirmed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: Sevoflurane at clinically relevant concentrations disrupted the endothelial monolayer formed by human umbilical vein endothelial cells and MPECs in transwell permeability models. Sevoflurane, but not propofol, induced a 1.8-fold increase of AngioSense dye accumulation in mouse lung over control, indicating pulmonary vascular leakage in the sevoflurane group. RNA sequencing analysis, quantitative real-time polymerase chain reaction, and Western blot analysis revealed that sevoflurane induced the expression and activation of hypoxia-inducible factor 1α (HIF-1α) in vitro and in vivo . The activation of HIF-1α led to the increased expression of its downstream vascular endothelial growth factor (VEGF). The knockdown of HIF-1α restored the change of endothelial permeability and abolished the increase of VEGF induced by sevoflurane in MPECs. CONCLUSIONS: The authors' results demonstrate that sevoflurane increased endothelial and pulmonary vascular permeability via HIF-1α and VEGF. Propofol had no significant effect on the permeability of endothelium.

INTRODUCTION: With an estimated 2.1 million hip and knee replacements performed annually in developed countries, orthopedic surgeries can result in complications such as postoperative pain and cognitive dysfunctions. Dexmedetomidine shows potential for reducing pain and opioid use and improving cognitive outcomes, but its efficacy in orthopedic settings needs further evaluation. METHODS: A comprehensive literature search was performed across electronic databases (e.g., PubMed) up to 1 June 2024 to identify relevant randomized controlled trials (RCTs) investigating the use of dexmedetomidine for orthopedic surgeries. The primary outcomes included visual analog scale (VAS), opioid consumption, incidence of postoperative cognitive dysfunction (POCD), and postoperative delirium (POD). Meta-analysis was conducted using RevMan 5.3 and Stata 16.0, with statistical significance set at P < 0.05. Sensitivity analyses, along with trial sequential analysis (TSA), were used to evaluate the robustness of the findings. RESULTS: The meta-analysis included 59 RCTs with 7713 participants and demonstrated that dexmedetomidine significantly reduced postoperative VAS score (mean difference [MD] -0.50, P = 0.0003) and opioid consumption (MD -11.91, P < 0.0001) and decreased the incidence of POCD (risk ratio [RR] 0.59, P = 0.006) and POD (RR 0.49, P < 0.0001). Dexmedetomidine also prolonged motor (MD: 1.70, P < 0.0001) and sensory block durations (MD: 1.80, P < 0.0001) and delayed the time to first rescue analgesics (MD: 1.51, P < 0.0001). TSA and sensitivity analysis confirmed the robustness and reliability of the results, whereas meta-regression revealed no significant effect of variables on primary outcomes. CONCLUSION: Our study demonstrates that intravenous dexmedetomidine significantly improved postoperative pain and neurocognitive functions in orthopedic surgery patients.

BACKGROUND: Complex regional pain syndrome is a chronic pain syndrome typically affecting a limb. It is characterized by severe spontaneous and evoked pain, along with vasomotor, autonomic, and motor signs and symptoms. Although dysregulation in several physiologic systems has been suggested in complex regional pain syndrome (CRPS), including aberrant inflammatory and immune responses, vasomotor dysfunction, and nervous system changes, the pathophysiologic mechanisms underlying the syndrome remain elusive. Effective treatment options are also limited. Previous research has highlighted the role of the gut microbiome in chronic pain, prompting us to investigate the composition and function of the gut microbiome in CRPS. METHODS: The gut microbiomes of individuals with CRPS to age-, sex-, and ethnicity-matched pain-free control participants were compared using 16S rRNA gene amplification. To minimize environmental confounders, participants were recruited from two geographically independent regions. To explore potential changes in gut bacteria-derived metabolites, targeted metabolomic analysis of feces and plasma was performed. Finally, machine learning algorithms were trained to identify the gut microbiome composition specific to CRPS patients and were tested on a validation cohort. RESULTS: In this study, differential abundance analysis revealed significant differences in several bacterial taxa when comparing 53 CRPS patients to 52 unrelated controls, including alterations in short-chain fatty acid-metabolizing species. Targeted stool and plasma metabolite analysis confirmed differences in fecal and plasma short-chain fatty acid levels between CRPS patients and controls. Notably, the microbiome composition alone allowed accurate classification of patients and controls in a geographically independent test cohort. CONCLUSIONS: These findings highlight unique compositional and functional changes in the gut microbiome of individuals with CRPS, thus contributing to the growing body of evidence supporting the role of the gut microbiome in chronic pain syndromes. Furthermore, they pave the way for further studies elucidating the pathophysiology of CRPS and exploring new diagnostic aids and treatment modalities.