Sedation and analgesia requirements during venovenous extracorporeal membrane oxygenation in acute respiratory distress syndrome patients.

INTRODUCTION: The purpose of this study is to describe sedation and analgesia management, and identify the factors associated with increased demand for medication in acute respiratory distress syndrome (ARDS) patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO). METHODS: This retrospective, single-center study included consecutive adult ARDS patients who received VV-ECMO for at least 24 hours from January 2018 to December 2020 in a comprehensive intensive care unit. The electronic medical records were retrospectively reviewed to collect data. RESULTS: Forty-two adult patients meeting the inclusion criteria were included in the study. Midazolam, sufentanil, and remifentanil were main sedatives and analgesics used in the patient population. The morphine equivalents, representative of the demand for opioids, was 512.9 (IQR, 294.5, 798.2) mg/day. The midazolam equivalents, representative of benzodiazepine requirement, was 279.6 (IQR, 208.8, 384.5) mg/day. The levels of serum creatinine, total bilirubin, lactic acid, SOFA score, and APACHE Ⅱ score at cannulation were found to be associated with opiate or benzodiazepine requirements. Multiple linear regression analysis revealed a linear correlation between midazolam equivalents and morphine equivalents (p < 0.001). In addition, there was a negative linear correlation between Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score and midazolam equivalents (p = 0.024). CONCLUSIONS: The sedation and analgesia requirements of ARDS patients receiving VV-ECMO often increase simultaneously. More large-scale studies are needed to confirm the risk factors for increased sedation and analgesia needs in patients supported on VV-ECMO.

SS-31 Improves Cognitive Function in Sepsis-Associated Encephalopathy by Inhibiting the Drp1-NLRP3 Inflammasome Activation.

Neuroinflammation and microglial activation are involved in the pathogenesis of sepsis-associated encephalopathy (SAE). Mitochondrial dynamics emerged as a new player in the regulation of immunological processes. In this study, we aimed at exploring the effects of mitochondrial-targeted antioxidant peptide SS-31 on cognitive function in mice with SAE. In mice, SS-31 was intraperitoneally administered for seven consecutive days after cecal ligation and puncture surgery. SS-31 improved cognitive performance and survival rate of mice and alleviated hippocampal inflammation, reactive oxygen species production, and excessive mitochondrial fission. The increase of nucleotide-binding oligomerization domain 3 (NLRP3) and phosphorylated dynamin-related protein 1 (Drp1) ser616 in microglia was attenuated by SS-31. In vitro, the microglial cell line BV-2 was pre-treated with SS-31, followed by lipopolysaccharide/adenosine triphosphate induction. SS-31 effectively decreased the activation of NLRP3 inflammasome, mitochondrial translocation of Drp1, excessive mitochondrial fission, and mitochondrial membrane recruitment of gasdermin-D N-terminal (GSDMD-N). Similarly, knockdown of Drp1 inhibited the activation of NLRP3 inflammasome. SS-31 improved survival rate and cognitive functions of mice with SAE, related to mitochondrial fission protein Drp1 to inhibiting activation of NLRP3 inflammasome.

Systematic Review and Meta-analysis: The Effects of Prophylactic Proton Pump Inhibitor Treatment in Patients With Coronary Heart Disease Receiving Dual Antiplatelet Therapy.

Dual antiplatelet therapy (DAPT) and proton pump inhibitors (PPIs) are widely used in clinical treatment. However, the pharmacokinetic interaction between PPIs and DAPT is still unclear in patients with cardiovascular disease. This systematic review and meta-analysis aimed to evaluate the risks and benefits of the combination of PPI and DAPT in patients with coronary heart disease. The PubMed, EMBASE, Cochrane, and Web of Science databases were systematically searched from inception to April 1, 2020, for eligible studies. The outcomes investigated in this study included major adverse cardiovascular events, myocardial infarction, all-cause death, gastrointestinal complications, and platelet function testing. Studies were excluded from the review if other gastrointestinal medication or aspirin or P2Y12 receptor inhibitor monotherapy was administered. The review included 52 studies, and data from 40 studies were extracted for meta-analysis. No association was found between the risk of adverse clinical outcomes and the combination of PPI and DAPT based on the randomized controlled trial data (risk ratio: 0.98; 95% confidence interval: 0.87-1.09; P = 0.877; I2 = 0%). However, an increased risk of adverse clinical outcomes due to the use of PPIs was observed in patients treated with DAPT based on the data from observational studies (risk ratio: 1.259; 95% confidence interval: 1.079-1.468; P = 0.003; I2 = 67.8%), although the heterogeneity of these studies was high. In conclusion, this systematic review and meta-analysis demonstrated that pharmacokinetic interactions between PPI and DAPT do not lead to adverse clinical outcomes.