Identification of the risk factors in perioperative respiratory adverse events in children under general anesthesia and the development of a predictive model.

BACKGROUND: This study explored the risk factors of perioperative respiratory adverse events in children under 12 years old undergoing general anesthesia surgery. A prediction model was constructed according to the related risk factors to provide a basis for timely clinical intervention and decision-making. METHODS: Children under 12 years old who underwent general anesthesia in our hospital between January 2016 and December 2020 were included in this study. The clinical data, including age, gender, weight, American Society of Anesthesiologists (ASA) grade classification, operation season, preoperative hospital stay, anesthesia time, and postoperative pain score, were collated. Continuous variables were converted to categorical variables. Logistic regression analysis was used to screen independent risk factors and a nomogram was constructed to predict the probability of adverse events. Fitting curves and receiver operating characteristic (ROC) curves were utilized to verify the model. RESULTS: Logistic regression analyses demonstrated that age [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.08 to 1.49], body weight (OR =1.49, 95% CI: 1.21 to 1.84), anesthesia time (OR =1.61, 95% CI: 1.32 to 1.78), and surgery season (OR =1.12, 95% CI: 1.07 to 1.39) were independent risk factors for respiratory adverse events in children undergoing general anesthesia (P<0.05). The risk of respiratory-related adverse events increased in children with grade II ASA classification compared to children with grade I ASA classification (P<0.05). Similarly, the risk of respiratory adverse events increased in children with level III pain scores compared to children with level I pain scores (P<0.05). The calibration curve showed that the predicted curve was consistent with the actual curve. The area under the ROC curve (AUC) was 0.707, indicating that model showed great predictive ability. CONCLUSIONS: Age, weight, anesthesia time, operation season, ASA grade, and pain score were identified as independent risk factors for respiratory adverse events in children undergoing general anesthesia. Using the above risk factors, a nomogram was established to predict the risk of respiratory system-related adverse events. The predicted results were highly consistent with the actual risk, and the false positive rate was within a reasonable range.

VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund's Adjuvant.

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund's adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.

Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2.

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1ß and tumor-necrosis factor-αin the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

Nalbuphine for analgesia after fracture surgery and its effect on circulating inflammatory factors.

The present study evaluated the use of nalbuphine for analgesia after fraction reduction surgery. Eighty lower limb fracture patients needing open reduction and internal fixation were selected in the First People's Hospital of Jingzhou from January 2015 to December 2015. Patients were randomly divided into observation and control groups (with 40 cases in each). After surgery, the patients in the observation group were treated with nalbuphine (2 mg/kg) for patient-controlled intravenous analgesia (PCIA), while sufentanil (2.5 µg/kg) was used for patients in the control group. The analgesia treatment lasted for 48 h after surgery. Changes in inflammatory factors and catecholamine hormones during the observation period were determined and compared between the groups. Pain, sedation scores and the number of times the analgesia pump was used were recorded at different time-points. Additionally, the life and sleep qualities and any adverse reactions were also recorded. Our results showed that after the operation, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), high-sensitivity CRP (hs-CRP) cortisol, adrenaline epinephrine (AD) and norepinephrine (NE) were significantly lower in the observation group than in the control group (P<0.05). Pain and sedation scores of patients in the observation group were better than those in the control group at all time-points after operation (P<0.05). Life and sleep qualities of patients in the observation group were also better than those in the control group (P<0.05). Finally, the rates of nausea, vomiting, dizziness, lethargy, urinary retention, skin itch and constipation were significantly lower in the observation group than in control group (P<0.05). Based on our findings, the application of nalbuphine for analgesia in patients with fracture surgeries can reduce the levels of inflammatory cytokines, improve the analgesic effect, bring beneficial sedative effects and reduce the occurrence of adverse reactions.