Prophylactic Penehyclidine Inhalation for Prevention of Postoperative Pulmonary Complications in High-risk Patients: A Double-blind Randomized Trial.

BACKGROUND: Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. METHODS: This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. RESULTS: A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. CONCLUSIONS: In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications.

Subanesthetic Dose of Esketamine Improves the Sedative and Analgesic Effects of Dexmedetomidine and Remifentanil in Liposuction Anesthesia: A Prospective, Double-Blinded, Randomized Controlled Trial.

Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration: ChiCTR2400080363.

Estrogen alleviates acute and chronic itch in mice.

Itching is associated with various skin diseases, including atopic dermatitis and allergic dermatitis, and leads to repeated scratching behavior and unpleasant sensation. Although clinical and laboratory research data have shown that estrogen is involved in regulating itch, the molecular and cellular basis of estrogen in itch sensation remains elusive. In the present study, it was found that estrogen-treated mice exhibited reduced scratching bouts when challenged with histamine, chloroquine, the proteinase-activated receptor-2 activating peptide SLIGRL-NH2 (SLIGRL), compound 48/80, and 5-hydroxytryptamine when compared with mice in the placebo group. Moreover, estrogen also suppressed scratching bouts in the mouse model of chronic itch induced by acetone-ether-water treatment. Notably, consistent with the behavioral tests, the present RNA-seq analysis showed that estrogen treatment caused significantly reduced expression levels of itch-related molecules such as Mas-related G-protein coupled receptor member A3, neuromedin B and natriuretic polypeptide b. In addition, estradiol attenuated histamine-induced and chloroquine-induced calcium influx in dorsal root ganglion neurons. Collectively, the data of the present study suggested that estrogen modulates the expression of itch-related molecules and suppresses both acute and chronic itch in mice.

Effects of multiple exposures to general anesthesia on the sleep quality of children after plastic surgery in Beijing, China: a cohort study.

To assess the effects of the number and duration of general anesthesia exposure on the sleep quality of 6-15-year-old school children who underwent plastic surgery. The study was conducted on 688 children who underwent plastic surgery between the ages of 6 and 15 years using the Sleep Disorder Scale for Children (SDSC). The children were divided into two groups according to their exposure to general anesthesia: No General Anesthesia (NGA) and General Anesthesia (GA) groups. The GA group was further divided into three subgroups according to the number of exposures: Single-exposure, Double-exposure, and Multiple-exposure groups. The GA group was also subdivided into two groups according to the cumulative total time of anesthesia exposure: < 3 h and ≥ 3 h groups. Multivariate logistic regression analysis was used to confirm the potential factors that affect children with sleep disturbance (SDSC scores > 39) after general anesthesia exposure. Linear regression was used to analyze the correlation of the factors with the SDSC scores. The SDSC scores were higher in the GA group [35.4 ± 4.3 vs. 34.0 ± 3.6, P < 0.0001] as compared to the NGA group. The number of children with SDSC scores > 39 was also higher in the GA group [80 (17.5%) vs. 17 (7.4%), P < 0.0001]. More anesthesia exposure was correlated with higher total SDSC scores [34.5 ± 4.3 for single exposure vs 35.1 ± 3.9 for double exposure vs 37.5 ± 4.5 for multiple exposures, P < 0.0001] and a higher proportion of SDSC scores > 39 [24 (12.0%) for single exposure vs 24 (15.5%) for double exposure vs 32 (31.1%) for multiple exposures, P < 0.0001]. Longer anesthesia exposure was also correlated with higher total SDSC scores [34.4 ± 4.5 for < 3 h vs. 35.8 ± 4.2 for ≥ 3 h, P = 0.002]. The number of exposures to general anesthesia was a potential factor in sleep disturbance among children, determined based on logistic regression. Children who underwent plastic surgery between the ages of 6 and 15 years with general anesthesia exposure might have worse sleep quality and a higher incidence of sleep disorders. More frequent anesthesia exposure leads to worsened sleep quality and a higher incidence of sleep disorders. This study also confirmed that a longer duration of cumulative anesthesia exposure also leads to worse sleep quality.

Prophylactic penehyclidine inhalation for prevention of postoperative pulmonary complications in high-risk patients: study protocol of a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) are major causes of morbidity, mortality, and prolonged hospital stay in patients after surgery. Using effective strategies to prevent its occurrence is essential to improve outcome. However, despite various efforts, the incidence of PPCs remains elevated in high-risk patients. Anticholinergic inhalation is used to reduce high airway resistance and improve pulmonary function; it may be helpful to decrease the risk of PPCs. Penehyclidine is a long-acting anticholinergic agent which selectively blocks M1 and M3 receptors. We hypothesize that, in high-risk patients, prophylactic penehyclidine inhalation may decrease the incidence of PPCs. METHODS: This is a randomized, double-blind, placebo-controlled trial with two parallel arms. A total of 864 patients at high risk of PPCs will be enrolled and randomized to receive prophylactic inhalation of either penehyclidine or placebo (water for injection). Study drug inhalation will be administered from the night (7 pm) before surgery until the second day after surgery, in an interval of every 12 hours. The primary outcome is the incidence of PPCs within 30 days after surgery. Secondary outcomes include the time to onset of PPCs (from end of surgery to first diagnosis of PPCs), the number of PPCs (indicates the number of diagnosed individual PPCs), the incidence of postoperative extrapulmonary complications, the length of stay in hospital after surgery, and the 30-day all-cause mortality. DISCUSSION: Results of the present study will provide evidence to guide clinical practice in using prophylactic inhalation of an anticholinergic to prevent PPCs in high-risk patients. TRIAL REGISTRATION: The study was registered prospectively in Chinese Clinical Trial Registry ( www.chictr.org.cn , ChiCTR-IPC-15006603 ) on 14 May 2015 and retrospectively in ClinicalTrials.gov ( NCT02644876 ) on 30 December 2015.