Purpose: To identify the effectiveness of remimazolam at the end of tonsillectomy and adenoidectomy for preventing emergence delirium in children under sevoflurane anesthesia. Patients and Methods: One hundred and four patients aged 3– 7 years scheduled for tonsillectomy and adenoidectomy under sevoflurane anesthesia were recruited. Patients were randomly assigned to receive either remimazolam 0.2 mg kg^{– 1} (intervention, n=52) or 0.9% normal saline (control, n=52) at the end of the procedure. The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Secondary outcomes were peak PAED score, emergence time, postoperative pain intensity, length of postanesthesia care unit (PACU) stay, parental satisfaction, and postoperative behavior changes three days postoperatively. Results: Emergence delirium occurred in 6 of 51 (12%) patients receiving remimazolam versus 22 of 50 (44%) patients receiving saline (risk difference 32% [95% confidence interval, 16% to 49%], relative risk 0.27 [95% confidence interval, 0.12 to 0.60]; P< 0.001). The peak PAED scores (median [interquartile range]) were lower in the remimazolam group than in the saline group (7 [6– 8] versus 9 [8– 11], P< 0.001). Likewise, parental satisfaction was improved in the remimazolam group compared with the saline group (9 [8– 10] versus 8 [7– 8], P< 0.001). There was no difference between groups concerning postoperative pain scores, length of PACU stay, or postoperative behavior changes. Conclusion: In children undergoing tonsillectomy and adenoidectomy, administration of remimazolam 0.2 mg kg^{– 1} at the end of the surgery, compared with 0.9% saline, resulted in a significantly lower likelihood of emergence delirium after sevoflurane anesthesia.

Purpose: To compare the efficacy of intranasal dexmedetomidine and dexmedetomidine-ketamine premedication in preschool children undergoing tonsillectomy. Patients and Methods: We enrolled 66 children with American Society of Anesthesiologists physical status I or II, aged 3– 7 years undergoing tonsillectomy. Patients were randomly allocated to receive intranasal premedication with either dexmedetomidine 2 μg kg^{− 1} (Group D) or dexmedetomidine 2 μg kg^{− 1} and ketamine 2 mg kg^{− 1} (Group DK). The primary outcome was the sedation level assessed by the Modified Observer’s Assessment of Alertness/Sedation Scale (MOAA/S) 30 min after intervention. The minimal clinically relevant difference in the MOAA/S score was 0.5. Secondary outcomes included sedation onset time, parental separation anxiety, acceptance of mask induction, emergence time, emergence delirium, postoperative pain intensity, length of stay in the post-anesthesia care unit (PACU), and adverse effects. Results: At 30 min after premedication, the MOAA/S score was lower in Group DK than in Group D patients (median: 1.0, interquartile range [IQR]: 1.0– 2.0 vs median: 3.0, IQR: 2.0– 3.0; P< 0.001), with a median difference of 1.0 (95% confidence interval [CI]: 1.0– 2.0, P< 0.001). Patients in Group DK showed considerably faster onset of sedation (15 min, 95% CI: 14.2– 15.8 min) than Group D (24 min, 95% CI: 23.2– 24.8 min), with a median difference of 8.0 min (95% CI: 7.0– 9.0 min, P< 0.001). Both parental separation and facemask acceptance scores were lower in Group DK than in Group D patients (P=0.012 and P=0.001, respectively). There was no significant difference in emergence time, incidence of emergence delirium, postoperative pain scores, and length of stay in the PACU between the two groups. Conclusion: Intranasal premedication with a combination of dexmedetomidine and ketamine produced better sedation for pediatric tonsillectomy than dexmedetomidine alone.

Purpose: Chronic postsurgical pain is a challenging problem after breast cancer surgery. This prospective, randomized, double-blinded, parallel-group, placebo-controlled trial was conducted to evaluate the influence of preoperative ultrasound-guided multilevel paravertebral blocks (PVBs) on chronic pain following mastectomy. Patients and methods: One hundred eighty-four women were randomized to receive ultrasound-guided multilevel (T1–T5) PVBs with 5 mL of ropivacaine 0.5% or normal saline per level. The primary end point was the incidence of chronic pain at 3 months following mastectomy assessed by the brief pain inventory (BPI), while the secondary end points were the acute postoperative pain, the number of patients requiring rescue analgesia, postoperative nausea and vomiting (PONV), side effects, and chronic pain at 6 months after surgery assessed by the BPI. Results: A total of 172 patients completed the study. Ultrasound-guided multilevel PVBs significantly decreased immediate postoperative pain for the first 12 hours (P<0.001). Additionally, fewer patients in the PVB group required rescue analgesia in the first 48 hours postoperatively compared to the control group (5/86 vs 28/86, OR =0.128, 95% CI: 0.047–0.351, P<0.001). No statistically significant difference was tested between the two groups (9.3% vs 17.4%, OR =0.419, 95% CI: 0.162–1.087, P=0.068) in the incidence of PONV. At 3 months, the incidence of chronic pain (BPI average pain score ≥3) was 34.5% and 51.2% (OR =0.511, 95% CI: 0.277–0.944, P=0.031) in the PVB and control groups, respectively, and at 6 months, the incidence was 22.1% and 37.2% (OR =0.479, 95% CI: 0.245–0.936, P=0.03), respectively. No complications occurred during the study. Conclusion: This study indicated that perioperative ultrasound-guided multilevel PVBs with ropivacaine improved acute postoperative pain and decreased postmastectomy chronic pain at 3 and 6 months postoperatively.

Upregulation of vascular endothelial growth factor receptor-1 contributes to sevoflurane preconditioning-mediated cardioprotection Bin Qian,1 Yang Yang,2 Yusheng Yao,3 Yanling Liao,3 Ying Lin3 1Department of Anesthesiology, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 3Department of Anesthesiology, The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China Purpose: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1) is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection.Materials and methods: Myocardial ischemia–reperfusion (I/R) rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated.Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects.Conclusion: Our data have demonstrated that 2.5% sevoflurane preconditioning alleviates heart I/R injury, which is probably mediated by the anti-inflammatory property and upregulation of VEGFR-1. Keywords: sevoflurane, preconditioning, ischemic–reperfusion injury, vascular endothelial growth factor receptor 1, anti-inflammatory

Purpose: Emergence delirium and postoperative negative behavioral changes (PNBC) are common complications in pediatric anesthesia. This study evaluated whether intranasal premedication combining dexmedetomidine and esketamine more effectively reduces these complications compared to either drug alone in children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia. Patients and Methods: This randomized, double-blind trial involved 198 children aged 2− 5 years undergoing tonsillectomy and/or adenoidectomy. Participants received intranasal premedication with either dexmedetomidine (2 μg/kg), esketamine (1 mg/kg), or their combination (dexmedetomidine 1 μg/kg plus esketamine 0.5 mg/kg). The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10. Secondary outcomes included the incidence of PNBC, sedation depth, easiness of separation from parents, acceptance of the mask for induction, emergence time, postoperative pain score, parental satisfaction, and adverse events. Results: The combination premedication significantly reduced emergence delirium incidence (9.4%) compared to esketamine alone (38.1%; relative risk [RR] 0.25, 95% confidence interval [CI] 0.11– 0.57, p < 0.001), but not compared to dexmedetomidine alone (17.2%; RR 0.55, 95% CI 0.21– 1.39, p = 0.193). PNBC incidence at day 7 was lower with the combination (28.1%) versus dexmedetomidine (48.4%; RR 0.58, 95% CI 0.36– 0.93, p = 0.018), but not significantly different from esketamine alone (20.6%; RR 1.38, 95% CI 0.74– 2.58, p = 0.326). The combination also provided significantly superior sedation, improved ease of separation from parents, better acceptance of the mask for induction, shorter emergence time, and higher parental satisfaction than both monotherapies. Conclusion: In children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal dexmedetomidine-esketamine premedication more effectively reduces emergence delirium compared to esketamine alone and PNBC compared to dexmedetomidine alone. This combination also improves sedation, shortens emergence times, and enhances parental satisfaction compared to monotherapy without significant adverse effects. Trial Registration: The Chinese Clinical Trial Registry, ChiCTR2300076709.