Effects of different doses of esketamine intervention on postpartum depressive symptoms in cesarean section women: A randomized, double-blind, controlled clinical study.

BACKGROUND: The optimal dosage and method of esketamine for postpartum depressive symptoms (PDS) are unclear. We conducted a randomized controlled trial (RCT) to investigate the effect of different doses of esketamine on PDS in women undergoing cesarean section, with evidence of prenatal depression. METHODS: The three groups were high- (2 mg kg-1) and low-dose (1 mg kg-1) esketamine via patient controlled intravenous analgesia (PCIA), following an initial intravenous infusion of 0.25 mg kg-1 esketamine, compared to placebo (0.9 % saline infusion). All groups also received the sufentanil (2.2 µg kg-1). The primary outcome was the incidence of PDS at 7 and 42 days postpartum. The secondary outcomes were: the remission from depression and total EPDS scores at 7 days and 42 days postpartum; mean change from baseline in the EPDS score; postoperative analgesia. RESULTS: i). 0.25 mg kg-1 of esketamine intravenous infusion combined with 1 mg kg-1 (n = 99) or 2 mg kg-1 (n = 99) esketamine PCIA reduces PDS incidence at 7 days postpartum (p < 0.05), with high-dose esketamine PCIA also reduces PDS incidence 42 days postpartum (p < 0.05), compared to placebo (n = 97). ii). Low- and high-dose esketamine PCIA lowers NRS scores at rest within 48 h postoperatively (p < 0.01), with high-dose esketamine also reducing the NRS score during movement at 48 h postoperatively (p = 0.018). iii). Neither high- nor low-dose esketamine PCIA increased postoperative adverse reactions (p > 0.05). CONCLUSIONS: Esketamine (0.25 mg kg-1) intravenous infusion combined with 1 mg kg-1 or 2 mg kg-1 esketamine PCIA seems safe and with few adverse effects in the management of PDS and pain in women undergoing cesarean section. LIMITATIONS: The tolerability and safety of esketamine requires further investigation based on more specific scales; the transient side effects of esketamine could have biased the staff and patients. TRIAL REGISTRATION: ChiCTR-ROC-2000039069.

Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Safety, Pharmacokinetics/Pharmacodynamics, and Absolute Bioavailability of Dexmedetomidine Hydrochloride Nasal Spray in Healthy Subjects: A Randomized, Parallel, Escalating Dose Study.

Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children. Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-µg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 µg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 µg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 µg and 100 µg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3. Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 µg, whereas the Fabs was tolerated to only 28.9%-32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%-89.0%. A severe adverse event was found in Part 2. In Part 3 (100 µg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly. Conclusion: Using the optimized nasal spray method, a single dose of 20/100 µg of the test drug was safe and tolerable, and 100 µg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.

The IDO genetic polymorphisms and postpartum depressive symptoms: an association study in Chinese parturients who underwent cesarean section.

Postpartum depressive symptoms (PDS) are not an uncommon mood disorder in postpartum women. Our previous research indicated a role for increased tryptophan (TRP) metabolism along the kynurenine pathway (KP) in the pathogenesis of PDS. Accordingly, this study was going to investigate the association of indoleamine-2,3-dioxygenase (IDO, a key enzyme of KP) genetic polymorphisms with PDS. Seven hundred twenty-five women receiving cesarean section were enrolled in this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13. Subsequently, 48 parturients with PDS and 48 parturients without PDS were selected for investigation of perinatal serum concentrations of TRP, kynurenine (KYN), and KYN/TRP ratio, the latter is the representative of IDO activity. In addition, seven single nucleotide polymorphisms of the IDO gene were examined. Following this genotyping, 50 parturients carrying the IDO rs10108662 AA genotype and 50 parturients carrying the IDO rs10108662 AC + CC genotype were selected for comparisons of TRP, KYN, and KYN/TRP ratio levels. This study showed the PDS incidence of 6.9% in the Chinese population, with PDS characterized by increased IDO activity (p < 0.05), versus women without PDS. We also found that the variations of IDO1 gene rs10108662 were significantly related to PDS incidence (p < 0.05). Furthermore, there was a significant difference in IDO activity between the IDO rs10108662 CA + AA, versus CC, genotypes. Our findings indicate a role of the kynurenine pathway in the development of PDS, rs10108662 genetic polymorphism resulting in changes of IDO activity might contribute to PDS pathogenesis.