ABSTRACT
Objective: This study aimed to compare the direct medication costs and clinical effectiveness of using remimazolam versus midazolam for goal-guided sedation therapy in the ICU patients. Methods: This randomized controlled study was conducted in the ICU of People's Hospital Affiliated to Shandong First Medical University. Eighty adult patients admitted to the ICU and requiring sedation were enrolled and randomly assigned in a 1:1 ratio to receive either remimazolam-based sedation (study group, n=40) or midazolam-based sedation (control group, n=40). The inclusion criteria for patient selection were age 18-80 years, requirement for mechanical ventilation, and an expected ICU stay of at least 24 hours. Patients with significant liver or kidney dysfunction, neurological disorders, or contraindications to the study drugs were excluded. The target sedation depth for both groups was a Ramsay Sedation Scale score of 3-4, which was maintained by titrating the infusion rates of remimazolam or midazolam as needed. Vital signs, sedation scores, and respiratory parameters were closely monitored throughout the sedation period. Results: The time to onset of sedation, time to reach the target sedation depth, time to awakening, and length of ICU stay were all significantly shorter in the remimazolam group compared to the midazolam group (P < .05 for all). The remimazolam group had a mean time to onset of 5.2 ± 1.8 minutes versus 8.9 ± 2.4 minutes in the midazolam group. The mean time to reach the target Ramsay Sedation Scale score of 3-4 was 12.6 ± 3.1 minutes in the remimazolam group compared to 18.4 ± 4.2 minutes in the midazolam group. The mean time to awakening was 10.2 ± 2.7 minutes in the remimazolam group versus 16.5 ± 3.9 minutes in the midazolam group. The remimazolam group also had a significantly shorter mean ICU length of stay of 5.1 ± 1.3 days compared to 7.8 ± 2.1 days in the midazolam group (P < .01). The remimazolam group had a significantly higher metabolic clearance rate compared to the midazolam group (P < .001). The Ramsay sedation scores and Wong-Baker FACES pain scores were also significantly lower in the remimazolam group throughout the sedation period (P < .01). There were no significant differences in heart rate between the two groups at any timepoint. However, the overall incidence of adverse events was significantly lower in the remimazolam group compared to the midazolam group (P < .05). Conclusion: This study demonstrated that the use of remimazolam-based goal-directed sedation in the ICU setting resulted in significantly faster onset of action, quicker achievement of the target sedation depth, shorter time to awakening, and shorter ICU length of stay compared to midazolam-based sedation. The remimazolam group also had a higher metabolic clearance rate, lower sedation and pain scores, and a lower incidence of adverse events.These findings suggest that remimazolam may provide advantages over midazolam for ICU sedation, potentially leading to improved patient comfort, more efficient utilization of ICU resources, and potentially better clinical outcomes. The rapid onset, titratability, and favorable safety profile of remimazolam make it a promising sedative agent that could help optimize sedation practices in the critical care setting. Further research is warranted to fully evaluate the impact of remimazolam on long-term patient-centered outcomes and overall healthcare costs in the ICU.
ABSTRACT
BACKGROUND: Viral pneumonias, such as SARS and MERS, have been a recurrent challenge for the public healthcare system. COVID-19 posed an unprecedented global crisis. The primary impact of viral pneumonia is pathologic changes of lung tissue. However, the effect of SP-B site gene polymorphism on alveolar surface tension in viral pneumonia remains unexplored. OBJECTIVE: To explore the molecular mechanism of how the gene polymorphism at SP-B 1580 site regulates the pulmonary surfactant tension of viral pneumonia through the cellular pyroptosis signaling pathway using an in vivo animal experiment and a clinical trial. METHODS: We constructed a genetically modified mouse model of viral pneumonia and administered H5N1 influenza virus through intratracheal injection. After 48 hours, the survival rate of each mouse group was evaluated. Lung tissue, blood, and bronchoalveolar lavage fluid samples were collected for histopathologic analysis. Inflammatory factor concentrations were measured using ELISA. The level of apoptosis was determined using TUNEL assay. Changes in the expression of cell death-related factors were assessed using qRT-PCR and protein blotting. Additionally, blood samples from patients with viral pneumonia were analyzed to detect single nucleotide polymorphisms and explore their correlation with disease severity, inflammatory factor levels, and pulmonary surfactant protein expression. RESULTS: Following H5N1 infection of mice, the model group and hSP-B-C group showed high mortality rates within 24 hours. The survival rates in the blank control group, virus model group, hSP-B-C group, and hSP-B-T group were 100%, 50%, 37.5%, and 75%, respectively. Histologic analysis revealed significant lung tissue damage, congestion, alveolar destruction, and thickened alveolar septa in the model and hSP-B-C groups. However, these pulmonary lesions were significantly alleviated in the hSP-B-T group. Inflammatory factor levels were elevated in the model and hSP-B-C groups but reduced in the hSP-B-T group. TUNEL assay demonstrated a decrease in apoptotic cells in the lungs of the hSP-B-T group. Furthermore, the expression of SP-B and cell death-related proteins was downregulated in all three groups, with the lowest expression observed in the hSP-B-C group. The clinical trial found that patients with severe viral pneumonia exhibited a higher frequency of CC genotype and C allele in, along with increased inflammatory factor levels and decreased SP-B expression compared to those with mild-to-moderate viral pneumonia. CONCLUSION: SP-B polymorphism at the 1580 site regulates lung surfactant tension through the cell pyroptosis signaling pathway, thus affecting the progression of viral pneumonia.
ABSTRACT
We investigated the characteristics of plant species diversity in tree and shurb layers and the main influencing factors in different slope positions of a shady slope of degraded tiankeng talus. The results showed that there were 21 species in 17 genera and 13 families in the tree layer, and 20 species in 20 genera and 14 families in shrub layer in the south side of the Shenxiantang. Plant communities were subtropical moist coniferous and broad-leaved mixed forest. Micro-climate led to obvious vegetation variation between the pit and the pit slope at the tiankeng. The secondary collapse over the talus with mid-slope could conserve more water, which supported the water-demanding species in a high-quality niche. All the α diversity indices including Margalef (3.58), Shannon (2.47), Simpson (0.79) and Pielou (0.86) reached the maximum at the pit bottom edge with slight variability, and the maximum coefficient of variation was only 0.226. The ß diversity index fluctuated greatly among the pit-pit, slope-pit, bottom edge. The Routledge and Whilson-Shmida indices showed the trends of decrease-increase-decrease, with the maximum values of 15.95 and 1.20, respectively. Species turnover demonstrated the upward trend overall, and the number of co-species was decreased. Plant diversity on each slope position was mainly related to the contents of total nitrogen, total phosphorus, available phosphorus and organic carbon in soil. Soil was the most important factor leading to the difference among slope positions.
