Procedural sedative effect of remimazolam in ICU patients on invasive mechanical ventilation: a randomised, prospective study

Abstract

Background: Invasive procedures and environmental factors in the intensive care unit (ICU) may cause anxiety and discomfort in patients, who often require sedation therapy. The aim of this study was to assess the safety of remimazolam tosilate for procedural sedation in ICU patients receiving mechanical ventilation following endotracheal intubation. Eighty patients from a single centre were randomly assigned to either the propofol group or the remimazolam group. Blood tests were conducted to evaluate changes in lactate, blood lipids, liver and kidney function, and inflammatory markers, and patients' vital signs were observed over several periods. This study compared the incidence of delirium, the impact on liver and kidney function, circulatory effects, and changes in blood lipids between the two groups. These findings have optimised the selection of medications, providing ICU patients with more options for sedation therapy.

Methods: In this single-centre randomised controlled trial, intubated patients were randomly assigned to the remimazolam group or the propofol group. Under the same analgesic regimen, the two groups received remimazolam and propofol for procedural sedation.

Results: Our primary outcome was the mean arterial pressure (MAP), which significantly differed on Days 4 and 7 (P = 0.021, control group vs. experimental group = 85.23 ± 11.24 vs. 94.36 ± 13.18, P = 0.023, 83.55 ± 8.94 vs. 92.66 ± 7.02). With respect to liver and kidney function, the ∆AST value in the remimazolam group was significantly lower than that in the control group on Day 7 (P = 0.023). There were significant differences in triglyceride (TG) levels on Days 4 and 7 (P = 0.020) and in the ∆LDL on Day 7 (P = 0.027). Furthermore, the rates of dyslipidaemia and delirium in the remimazolam group were lower than those in the propofol group (85.0%, n = 40 vs. 90.0%, n = 40; 27.5%, n = 40 vs. 55%, n = 40).

Conclusion: Remimazolam is a novel benzodiazepine that has demonstrated promising applications in general anaesthesia and procedural sedation; however, its use in ICU sedation is still in the early stages of research. Current evidence suggests that remimazolam is a safe sedative that is particularly well suited for patients with haemodynamic instability. Large sample-size randomised clinical trials are warranted.

Keywords: Analgesia and sedation; Intensive care unit; Propofol; Remimazolam.

Fig. 1

Flow chart of the study

Fig. 2

Comparison of the MAP (A) and Lac (B) between the remimazolam group and the propofol group. There were significant differences between the remimazolam group and the propofol group on Days 4 (P = 0.021) and 7 (P = 0.023). Abbreviations: MAP, artery pressure; Lac, lactic acid

Fig. 3

The ratio of liver(A-B) and renal(C-E) function between the remimazolam group and the propofol group. (B)The remimazolam group had a significantly lower ΔAST on day 7 (P = 0.023). Abbreviations: AST, aspartate transaminase; ALT, alanine aminotransferase; Δ Difference between Day 1, Day 4, Day 7, and the day of enrolment

Fig. 4

Ratio of blood lipids including TG（A-B）LDL（C-D）HDL(E-F) in the remimazolam group and propofol group. (A)There were statistically significant differences in TG levels between the remimazolam group and the propofol group on the 4th and 7th days (P = 0.020, P = 0.036), and (D)there were also significant differences in ΔLDL on the 7th day (P = 0.027). Abbreviations: TG, triglyceride; LDL, low-density lipoprotein; HDL, high-density lipoprotein; D4Δ, difference between the 4th day and the 1st day; D7Δ, difference between the 7th day and the 1st day

Fig. 5

A: Total mechanical ventilation time; B: time from ventilator to tracheal intubation; C: 20-day mortality in the hospital; D: length of stay in the ICU; E: sedative cost; F: average daily dose. (E-F) Compared with the propofol group, the remimazolam group presented significantly lower average sedation costs and daily drug doses (P < 0.001, P < 0.001). There was no significant difference in the other variables