Idiopathic pulmonary fibrosis (IPF) carries a poor prognosis, and existing treatments merely delay disease progression, leaving a significant unmet need for safe and effective therapeutic agents. This study aims to explore the anti-IPF effect of dexmedetomidine (Dex) and its underlying mechanism.

A total of 50 male C57BL/6J mice (8 weeks old, 20±2 g) were used. In the first cohort, 30 mice were randomly assigned to Control, bleomycin (BLM), and BLM+Dex groups (n=10). The second cohort of 20 mice was randomized to BLM+Dex and BLM+Atip (atipamezole) groups (n=10). Pulmonary fibrosis was induced by a single intratracheal instillation of BLM (1.2 mg/kg in 50 µL saline) in all groups except the Control group, which received an equal volume of saline. One hour after modeling, mice in the Control and BLM groups received intraperitoneal injections of 100 µL saline; the BLM+Dex group received Dex (25 µg/kg in 100 µL); and the BLM+Atip group received Atip (250 µg/kg) combined with Dex at the same dose. All treatments were administered once daily for 7 consecutive days. Both cohorts were followed for 4 weeks, during which survival was recorded daily. At the end of the experiment, noninvasive pulmonary function tests were performed, and lung tissues were collected for HE and Masson’s staining, hydroxyproline quantification, and immunofluorescence staining to assess the extent of fibrosis.

Compared with the BLM group, Dex increased the survival rate from 50% to 80% and prevented body weight loss (P=0.0030), reduced the area fraction of collagen fibers (P=0.0014), decreased hydroxyproline content (P=0.0161), and downregulated the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in lung tissue (P=0.0004, P<0.0001). Nevertheless, all the above improvements of Dex were reversed following Atip pretreatment.

Early intervention with Dex can ameliorate BLM-induced pulmonary fibrosis in mice, and its protective mechanism may be related to the activation of α2AR.

To investigate the independent influencing factors for delayed discharge from the post-anesthesia care unit (PACU) in elderly patients undergoing non-cardiac surgery under general anesthesia, encompassing preoperative status, intraoperative management, and innovative circadian rhythm dimensions, to provide references for optimizing perioperative management.

This study adopted a retrospective case-control design. A total of 1469 elderly patients (aged≥60 years) who underwent noncardiac surgery under general anesthesia and were admitted to the PACU for recovery at our department between January 2021 and December 2023 were enrolled. Based on whether the time from PACU admission to achieving a modified Aldrete score≥9 exceeded 120 min, patients were divided into a delayed group (n=709) and a non-delayed group (n=760). Data on demographic characteristics, preoperative comorbidities, American Society of Anesthesiologists (ASA) physical status classification, intraoperative management indicators, postoperative monitoring indicators, PACU admission-related indicators and surgery/PACU admission time rhythm data were collected via the Hospital Inpatient Management System and the Anesthesia Clinical Information System. Univariate comparisons of various indicators between the 2 groups were performed using the Chi-square test or binary logistic regression. Subsequently, variables with P<0.05 in the univariate analysis were included in a binary logistic stepwise regression model to analyze the independent factors influencing delayed PACU discharge.

Univariate analysis showed that the delayed group had significantly higher rates of male sex, ASA class Ⅲ-Ⅳ, preoperative respiratory disease, intraoperative use of vasoactive drugs and colloids, total intraoperative fluid intake and output, intraoperative blood loss, postoperative use of intravenous and nerve block analgesia, surgery and anesthesia duration, and body temperature upon PACU admission compared to the non-delayed group (P<0.05). Conversely, the delayed group had a significantly lower rate of using the neuromuscular reversal agent neostigmine and lower postoperative hemoglobin levels (P<0.05). Regarding circadian rhythm, significant differences were found between the 2 groups in the distribution of surgery start time and PACU admission time (P<0.001). Multivariate analysis revealed that preoperative respiratory disease (β =0.616, P<0.001), ASA class Ⅲ-Ⅳ (β =0.501, P=0.002), intraoperative colloid use (β =0.626, P<0.001), increased total intraoperative fluid intake (β=0.001, P<0.001), surgery initiation during the Si period (9:00-11:00) (β=0.353, P=0.005), and PACU admission during the Shen period (15:00-17:00) (β=0.660, P<0.001) were independent risk factors for delayed discharge. In contrast, the use of the neuromuscular reversal agent neostigmine (β =-0.327, P=0.007) and PACU admission during the Xu period (19:00-21:00) (β=-0.468, P=0.042) were independent protective factors.

Delayed discharge from the PACU after general anesthesia in elderly patients is jointly influenced by multiple factors, including preoperative patient status, intraoperative management, recovery-phase interventions, and surgical timing rhythm. Implementing individualized anesthesia and fluid management for high-risk elderly patients, using neuromuscular reversal agents, and considering the time rhythm effects in surgical scheduling and PACU resource allocation may reduce the incidence of delayed PACU discharge after general anesthesia.

To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index (BMI), overweight BMI, and different CYP3A4/5 enzyme genotypes.

The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study. Before the operation, the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit. Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes, the patients were divided into groups Ⅰ (3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation), Ⅱ (3A4 heterozygous mutation + 3A5 heterozygous mutation), and Ⅲ (3A4 wild type or 3A4 heterozygous mutation + 3A5 wild type). According to their BMI, they were also assigned into a normal body weight group (18.5~24.0 kg/m²) and an overweight group (24~<28 kg/m²), and the differences in drug metabolism parameters were statistically analyze between the 2 groups. After routine general anesthesia induction (sufentanil 0.5 μg/kg), venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.

Among the 90 participants completing the blood drug concentration test, 8 patients had their blood samples contaminated (including 1 case with an anesthesia duration of <2 h), and 3 were excluded due to low weight or overweight. Eventually, 79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group. Compared with the normal body weight group, the central compartment volume of distribution in the overweight group was significantly reduced (p<0.05), while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution, total clearance rate, peripheral compartment clearance rate, distribution half-life, clearance halflife, and area under the blood concentration-time curve. In group Ⅰ (n=26), the overweight patients (n=13) had significantly reduced central compartment volume of distribution, peripheral compartment volume of distribution, and peripheral compartment clearance rate when compared with the normal body weight patients (n=13) (P<0.05), while no differences were observed in other pharmacokinetic parameters. In groups Ⅱ (n=25) and Ⅲ (n=28), the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.

Among the patients with the same genotype combination of CYP3A4/5 mutations, there was no difference in the metabolism of sufentanil between the overweight and normal weight patients. Additionally, in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation, the overweight patients have smaller peripheral distribution range of sufentanil, and weakened metabolic process.