Background Cardiac surgery is associated with a high risk of cardiovascular and other complications that translate into increased mortality and healthcare costs. This retrospective study was designed to determine whether the perioperative use of dexmedetomidine could reduce the incidence of complications and mortality following cardiac surgery. Methods and Results 1,134 patients who underwent CABG and CABG plus valvular and/or other procedures were included. 568 received intravenous dexmedetomidine infusion and 566 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes measured included mortality and postoperative major adverse cardiocerebral events (MACE: stroke, coma, perioperative myocardial infarction, heart block or cardiac arrest). Secondary outcomes included renal failure, sepsis, delirium, postoperative ventilation hours, length of hospital stay and 30-day readmission. Dexmedetomidine use significantly reduced postoperative in-hospital [1.23% vs. 4.59%; adjusted odds ratio (OR), 0.34; 95% confidence intervals (CI), 0.192 to 0.614; P < 0.0001], 30-day (1.76% vs. 5.12%; adjusted OR, 0.39; 95% CI, 0.226 to 0.655; P <0.0001) and 1-year (3.17% vs. 7.95%; adjusted OR, 0.47; 95% CI, 0.312 to 0.701; P = 0.0002) mortalities. Perioperative dexmedetomidine therapy also reduced the risk of overall complications (47.18 vs. 54.06%; adjusted OR, 0.80, 95% CI, 0.68 to 0.96; p= 0.0136) and delirium (5.46% vs. 7.42%; adjusted OR, 0.53; 95% CI, 0.37 to 0.75; p=0.0030). Conclusions Perioperative dexmedetomidine use was associated with a decrease in postoperative mortality up to one year and decreased incidence of postoperative complications and delirium in patients undergoing cardiac surgery.

Background and Aim Remimazolam tosilate (RT) is a new short‐acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. Methods This positive‐controlled, non‐inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. Results The success rate of sedation in the RT group was non‐inferior to that in the propofol group (97.34% vs 100.00%; difference in rate −2.66%, 95% CI −4.96 to −0.36, meeting criteria for non‐inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment‐related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). Conclusion This trial established non‐inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

The current results are affected by substantial heterogeneity, which makes it difficult to predict significant differences in postoperative pain control between propofol anesthesia and inhalational anesthesia. Further large, randomized controlled trials are needed to corroborate these results and to detect differences (if any) between propofol and inhalational anesthesia on postoperative pain.

AimsTo investigate whether dexmedetomidine (DEX) preconditioning could alleviate the inflammation caused by myocardial ischemia/reperfusion (I/R) injury by reducing HMGB1-TLR4-MyD88-NF-кB signaling.MethodsSeventy rats were randomly assigned into five groups: sham group, myocardial I/R group (I/R), DEX+I/R group (DEX), DEX+yohimbine+I/R group (DEX/YOH), and yohimbine+I/R group (YOH). Animals were subjected to 30 min of ischemia induced by occluding the left anterior descending artery followed by 120 min of reperfusion. Myocardial infarct size and histological scores were evaluated. The levels of IL-6 and TNF-α in serum and myocardium were quantified by enzyme-linked immunosorbent assay, and expression of HMGB1, TLR4, MyD88, IκB and NF-κB in the myocardial I/R area were determined with Western blot and immunocytochemistry.ResultsMyocardial infarct sizes, histological scores, levels of circulating and myocardial IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly increased in the I/R group compared with the sham group (P<0.01). DEX preconditioning significantly reduced the myocardial infarct size and histological scores (P<0.01 vs. I/R group). Similarly, the serum and myocardial levels of IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly reduced in the DEX group (P<0.01 vs. I/R group). These effects were partly reversed by yohimbine, a selective α2-adrenergic receptor antagonist, while yohimbine alone had no significant effect on any of the above indicators.ConclusionDEX preconditioning reduces myocardial I/R injury in part by attenuating inflammation, which may be attributed to the downregulation of the HMGB1-TLR4-MyD88-NF-кB signaling pathway mediated by the α2-adrenergic receptor activation.

Premedication is important in pediatric anesthesia. This meta-analysis aimed to investigate the role of dexmedetomidine as a premedicant for pediatric patients.A systematic literature search was conducted to identify randomized controlled trials comparing dexmedetomidine premedication with midazolam or ketamine premedication or placebo in children. Two reviewers independently performed the study selection, quality assessment and data extraction. The original data were pooled for the meta-analysis with Review Manager 5. The main parameters investigated included satisfactory separation from parents, satisfactory mask induction, postoperative rescue analgesia, emergence agitation and postoperative nausea and vomiting.Thirteen randomized controlled trials involving 1190 patients were included. When compared with midazolam, premedication with dexmedetomidine resulted in an increase in satisfactory separation from parents (RD = 0.18, 95% CI: 0.06 to 0.30, p = 0.003) and a decrease in the use of postoperative rescue analgesia (RD = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003). Children treated with dexmedetomidine had a lower heart rate before induction. The incidence of satisfactory mask induction, emergence agitation and PONV did not differ between the groups. Dexmedetomidine was superior in providing satisfactory intravenous cannulation compared to placebo.This meta-analysis suggests that dexmedetomidine is superior to midazolam premedication because it resulted in enhanced preoperative sedation and decreased postoperative pain. Additional studies are needed to evaluate the dosing schemes and long-term outcomes of dexmedetomidine premedication in pediatric anesthesia.

These data suggest that an opioid-DEX combination is a safe and effective strategy for postoperative intravenous PCA.

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BackgroundPrevious studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed activation of spinal cells and the ERK/MAPK pathway in a rat model of bone cancer pain.ResultsA Sprague Dawley rat model of bone cancer pain was established and the model was evaluated by a series of tests. Moreover, fluorocitrate (reversible glial metabolic inhibitor) and U0126 (a MEK inhibitor) was administered intrathecally. Western blots and double immunofluorescence were used to detect the expression and location of phosphorylation of ERK (p-ERK). Our studies on pain behavior show that the time between day 6 and day 18 is a reasonable period ("time window" as the remaining stages) to investigate bone cancer pain mechanisms and to research analgesic drugs. Double-labeling immunofluorescence revealed that p-ERK was sequentially expressed in neurons, microglia, and astrocytes in the L4-5 superficial spinal cord following inoculation of Walker 256 cells. Phosphorylation of ERK (p-ERK) and the transcription factor cAMP response element-binding protein (p-CREB) increased in the spinal cord of CIBP rats, which was attenuated by intrathecal injection of fluorocitrate or U0126.ConclusionsThe ERK inhibitors could have a useful role in CIBP management, because the same target is expressed in various cells at different times.