Opioid-Sparing Anesthesia Versus Opioid-Free Anesthesia for the Prevention of Postoperative Nausea and Vomiting after Laparoscopic Bariatric Surgery: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Patients who undergo laparoscopic bariatric surgery (LBS) are susceptible to postoperative nausea and vomiting (PONV). Opioid-free anesthesia (OFA) or opioid-sparing anesthesia (OSA) protocols have been proposed as solutions; however, differences between the 2 alternative opioid protocols for anesthesia maintenance in obese patients remain uncertain. A network meta-analysis was conducted to compare the impacts of OFA and OSA on PONV. METHODS: Systematic searches were conducted using Embase, PubMed, MEDLINE, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing OFA and OSA strategies. After screening according to the inclusion and exclusion criteria, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the credibility of the evidence. The main concern of this review was the difference between OFA and OSA in reducing PONV. The primary outcome was any PONV occurrence within 24 hours. Secondary outcomes included postoperative pain intensity, opioid consumption, opioid-related adverse events, and length of hospital stay. RESULTS: Fifteen RCTs involving 1310 patients were identified for a network meta-analysis from 1776 articles that compared OFA, OSA, and traditional opioid-based anesthesia (OBA) strategies in LBS. Twelve RCTs (80%) with 922 participants (70%) were eligible for the occurrence of PONV. These included 199 (22%) patients who received OFA and 476 (52%) and 247 (27%) patients who received OSA and OBA, respectively. OFA was more effective at reducing PONV (relative risks [RR], 0.6, 95% confidence interval [CI], 0.5-0.9, moderate-quality evidence) compared to OSA. No differences were observed in postoperative pain control or opioid consumption between the OFA and OSA strategies (very low-to high-quality evidence). Notably, OFA is associated with a higher risk of bradycardia than OSA (RR, 2.6, 95% CI, 1.2-5.9, moderate-quality evidence). CONCLUSIONS: OFA is more effective than OSA in reducing the occurrence of PONV during the early postoperative period of LBS, although it may associate with an increased risk of bradycardia. Patients who received either opioid-alternative strategy demonstrated similar effects in reducing postoperative opioid consumption and alleviating pain intensity.

Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation.

BACKGROUND: Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. METHODS: Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5-24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. RESULTS: In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. CONCLUSIONS: Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Microarray analysis identifies lncFirre as a potential regulator of obesity-related acute lung injury.

AIMS: The inflammatory response in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is heightened in obesity. The aim of this study was to investigate whether lncRNAs are involved in the effects of obesity on acute lung injury and to find possible effector lncRNAs. MAIN METHODS: Microarray analysis was used to assess the transcriptional profiles of lncRNAs and mRNAs in lung tissues from normal (CON), high-fat diet induced obese (DIO), and obese ALI mice (DIO-ALI). GO and KEGG analyses were employed to explore the biological functions of differentially expressed genes. A lncRNA-mRNA co-expression network was constructed to identify specific lncRNA. Lung tissues and peripheral blood samples from patients with obesity and healthy lean donors were utilized to confirm the expression characteristics of lncFirre through qRT-PCR. lncFirre was knocked down in MH-S macrophages to explore its function. ELISA and Griess reagent kit were used to detect PGE2 and NO. Flow cytometry was used to detect macrophages polarization. KEY FINDINGS: There were 475 lncRNAs and 404 mRNAs differentially expressed between DIO and CON, while 1348 lncRNAs and 1349 mRNAs between DIO-ALI and DIO. Obesity increased lncFirre expression in both mice and patients, and PA elevated lncFirre in MH-S. PA exacerbated the inflammation and proinflammatory polarization of MH-S induced by LPS. LncFirre knockdown inhibited the secretion of PGE2 and NO, M1 differentiation while promoted the M2 differentiation in PA and LPS co-challenged MH-S. SIGNIFICANCE: Interfering with lncFirre effectively inhibit inflammation in MH-S, lncFirre can serve as a promising target for treating obesity-related ALI.