Anesthesia/surgery activate MMP9 leading to blood-brain barrier disruption, triggering neuroinflammation and POD-like behavior in aged mice.

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Analgesic Effects of Different Local Infiltration Anesthesia Techniques Combined with Femoral Nerve Block in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Clinical Trial.

Objective: Pain after total knee arthroplasty (TKA) remains an unresolved problem. Femoral nerve block (FNB) could relieve pain; however, it alone is insufficient. The local infiltration anesthesia technique (LIA) has been suggested as a supplement to FNB. This study aimed to evaluate the analgesic effects of different LIA combined with FNB in TKA patients. Methods: The femoral nerve was blocked with 0.375% ropivacaine 20mL, and all patients routinely received general anesthesia. The primary indicator was the proportion of patients who did not receive post-operative remedial analgesia. Seventy-eight patients were randomly assigned to PAI (periarticular injection combined with FNB), IAI (intra-articular injection combined with FNB), or control (FNB alone) groups. All patients underwent FNB under general anesthesia. The primary outcome was the proportion of patients who did not receive additional postoperative analgesia within the first 48 h after surgery. Results: Compared with the PAI and control groups, the IAI group had a higher proportion (69.23%) of patients who did not receive remedial analgesia within 48 hours after surgery (P = 0.009; P = 0.009), a lower consumption of diclofenac sodium lidocaine (P = 0.021; P < 0.001), and an earlier time of walking with a walker (P < 0.001; P < 0.001). The time of first need for remedial analgesia postoperatively in IAI group was longer than the PAI group (P = 0.008) and IAI group has a shorter hospital stay than the control group (P = 0.008). The maximum NRS during the first 48 hours postoperatively and NRS 24 hours after surgery in the IAI group were lower than those in the control and PAI groups. The incidences of POD and PONV were similar among the three groups (P = 0.610; P = 0.264). Conclusion: When combined with FNB, intra-articular injection offers a superior analgesic effect and favorable recovery compared to periarticular injection and separate application of FNB.