To explore the sedative effect of different loading doses of remimazolam on patients with mechanical ventilation in intensive care unit (ICU) and its influence on respiratory and circulatory system.

A prospective observation was conducted. From January 2021 to September 2021, the patients with mechanical ventilation who needed sedation and met the inclusion and exclusion criteria were enrolled in ICU of Xinyang Central Hospital. They were randomly divided into three groups: A, B and C. Sufentanil was given pre-analgesia; the analgesic target was critical-care pain observation tool (CPOT) score<2. Then, the loading doses of remimazolam (0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg)was pumped at a constant speed within 10 minutes, followed by 0.05-0.5 mg·kg^-1·h^-1 was given intravenously. According to Richmond restlessness-sedation score (RASS), the sedation depth of the target was maintained at -2 to 0 point. The RASS score, heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), and respiratory rate were compared among the three groups at different times before administration (T0) and 5 min(T1), 10 min(T2), 15 min(T3), 45 min(T4), 90 min(T5), 180 min(T6) after administration. Adverse events of respiratory and circulatory system (respiratory depression; hypotension and bradycardia) were recorded.

Totally 98 patients were involved in this study. There was no significant difference in general data such as gender, age, height, weight, acute physiology and chronic health score (APACHEⅡ), respiratory and hemodynamic indexes before medication between three groups. The sedative effective rate (RASS≤1 point) of groups A, B and C in T2 time was 67.7%(21 cases), 87.9%(29 cases) and 100%(34 cases), respectively, and the difference was statistically significant (χ²=14.25, P<0.01). The incidence of sedation insufficiency (RASS ≥2 points) in the three groups was 32.3%(10 cases), 12.1%(4 cases) and 0%(0 cases), respectively, and the difference was statistically significant (P<0.01). The incidence of deep sedation (RASS ≤ -3 points) in the three groups was 3.2%(1 cases), 15.2%(5 cases) and 47.1%(16 cases) respectively, and the difference was statistically significant (χ²=18.99, P<0.01). In the maintenance dose period (T4, T6), about 46.9%(46 cases) patients in the three groups had the maintenance dose lower than 0.1 mg·kg^-1·h^-1, about 34.7%(34 cases) patients was 0.1~ 0.2 mg·kg^-1·h^-1, about 18.4%(18 cases) patients was higher than 0.2 mg·kg^-1·h^-1. HR decreased by 13.8%, 19.6% and 29.7% respectively (T2 vs T0), and HR of the three groups still decreased at 15 min(T3) after administration. Inter-group analysis showed that there were significant differences among groups A and B (T2, T3), groups A and C (T1, T2, T3) and groups B and C (T2, T3) (P<0.05). The mean value of MAP in the three groups also showed a gradual downward trend after administration, and the decrease ranges of MAP were 12.9%, 14.4% and 22.8% respectively after fully pumping the loading dose of remimazolam (T2 compared to T0). Inter-group analysis showed that there were significant differences between group A (T1, T2) and group B (T2) compared with group C (P<0.05). Although the mean RR and mean OI changed after administration, the RR of group C and group A was statistically different only at T2 time (P<0.05), but there was no statistical difference at other time points. There was no significant difference in OI between the three groups at T1~T6 (P>0.05).

In the sedation of ICU patients with mechanical ventilation, the optimal loading dose is 0.15 mg/kg. For some patients with RASS score ≥3, the loading dose can be appropriately increased. High loading dose of remimazolam pumped rapidly should be avoided, which can increase the incidence of adverse events of respiratory and circulatory system.