| Part Ⅰ Remimazolam versus traditional sedatives for endoscopic sedation:a systematic review and meta-analysis of efficacy and safety outcomesObjective:To evaluate the efficacy and safety of remimazolam and traditional sedatives for patients undergoing endoscopic sedation.Methods:We systematically searched Cochrane Library,Embase,Pub Med,Web of Science and Clinical Trials.gov for randomized controlled trials of endoscopic sedation performed with remimazolam versus traditional sedatives.Data from the eligible studies were combined to calculate pooled risk ratio(RR)or standardized mean difference(SMD).Results:Eleven studies of 2356 patients met the inclusion criteria.The results showed that remimazolam was associated with a higher procedure success rate(RR:1.28,95%CI:1.07 to 1.52,p=0.006;I~2=99%),a shorter duration of recovery after procedure(SMD:-0.56,95%CI:-0.98,-0.14,p=0.009;I~2=89%),and an earlier patient discharge after procedure(SMD:-0.37,95%CI:-0.49,-0.25,p<0.00001;I~2=0%)in comparison with traditional sedatives.There were no statistically significant differences in onset time,procedure time,and cognitive recovery between remimazolam and traditional sedatives groups.Remimazolam significantly decreased the rate of bradycardia(RR:0.65,95%CI:0.43,0.97,p=0.04;I~2=0%),hypotension(RR:0.57,95%CI:0.40,0.80,p=0.001;I~2=80%),and respiratory depression/hypoxia(RR:0.46,95%CI:0.25,0.83,p=0.01;I~2=61%)compared to traditional sedatives.Conclusions:Remimazolam is a safe and effective sedative for endoscopic sedation on account of a higher success procedure rate,shorter recovery and discharge times,and a superior safety profile in comparison with traditional sedatives.Larger sample-sized and well-designed clinical trials are needed to verify our finding.Part Ⅱ Remimazolam besylate for sedation of postoperative patients in intensive care units: a dose-finding studyObjective: To investigate the infusion doses of remimazolam besylate that provide a light to moderate level of sedation in mechanically ventilated patients after noncardiac surgeries in intensive care units(ICU).Methods: Patients included were sequentially enrolled into 1 of the 6 possible treatment groups with 12 patients each.Remimazolam besylate was given with a loading dose of0.05 mg/kg followed by a continuous infusion according to their grouping: 0.1,0.125,0.15,0.175,0.2,and 0.225 mg/kg/h,respectively.Propofol provided rescue sedation if adequate sedation was not achieved.The primary end point was at least 9 patients did not need rescue propofol in both two consecutive groups.Results: The predefined end point was reached,when in both 0.125 mg/kg/h group and0.15 mg/kg/h group,9 of 12 patients did not need rescue propofol,so that 36 patients were included.The onset of sedation was rapid.Except for one patient experienced oversedation,other patients were well-maintained at light and moderate sedation levels during the study period.Mean arterial pressure dropped significantly when giving a loading dose of remimazolam besylate(97.3±15.0 mm Hg vs 90.0±17.3 mm Hg,p<0.05)and followed by a moderate decrease during the infusion,while heart rate remained stable(p > 0.05).Hypotension was the most frequently reported adverse events,which could resolve spontaneously or with administration of fluids or small doses of vasopressors.There were no serious adverse events.Conclusions: On the basis of adequate analgesia with sufentanil,continuous infusion of remimazolam besylate between 0.125 and 0.15 mg/kg/h provides a light to moderate level of sedation in mechanically ventilated ICU patients after noncardiac surgeries.Remimazolam appeared to be an effective and safe agent for short-term postoperative sedation in ICUs.Part Ⅲ Remimazolam besylate versus propofol for long-term sedation during invasive mechanical ventilation: a pilot studyObjective: To evaluate the efficacy and safety of remimazolam besylate compared with propofol in maintaining mild to moderate sedation in patients receiving long-term mechanical ventilation.Methods: In this single-centered randomized pilot study,critically ill adult patients expected to be ventilated for more than 24 hours were randomized to receive remimazolam besylate or propofol.The target sedation range was-3 to 0 on the Richmond Agitation-Sedation Scale(RASS).The primary outcome was the percentage of time in the target sedation range without rescue sedation.The Secondary outcomes were ventilator-free days at day 7,the length of ICU stay,28-day mortality and adverse events.Results: Thirty patients were assigned to each group.The median duration of remimazolam besylate infusion was 55.0(28.3,102.0)h,and the median dose was 0.18(0.15,0.22)mg/kg/h.The median duration of propofol infusion was 41.0(24.8,74.3)h,and the median dose was 1.98(1.40,2.91)mg/kg/h.The median percentage of time in the target RASS range without rescue sedation was similar in remimazolam and propofol groups [73.2%(41.5%,97.3%)vs 82.8%(65.6%,100%),p=0.269].No differences were identified between the two groups in term of ventilator-free days at day 7 [0.0(0.0,80.3)h vs 62.0(0.0,122.0)h,p=0.054],length of ICU stay [14.0(5.5,28.0)h vs 6.5(3.0,15.8)h,p=0.143] and 28-day mortality [6(20.0%)vs 3(10.0%),p=0.472].Hypotension was the most frequently reported adverse events.There were no differences between the two groups in the incidence of adverse events,or the proportions of patients requiring interventions(p>0.05).Conclusions: This pilot study suggested that remimazolam besylate was effective and safe for long-term sedation in mechanically ventilated patients compared with propofol.Part Ⅳ Remimazolam besylate versus propofol for deep sedation in critically ill patients: a pilot studyObjective: To evaluate the efficacy and safety of remimazolam besylate compared with propofol for deep sedation in critically ill patients.Methods: In this single-centered randomized pilot study,critically ill adult patients requiring deep sedation were randomized to receive remimazolam besylate or propofol.Clinical assessment of the patients’ level of sedation was performed by means of RASS and Narcotrend Index(NI).Sedation was titrated to RASS score-4 to-5 and NI 13 to 64.The primary outcome was the percentage of time in the target sedation range without rescue sedation.The Secondary outcomes were ventilator-free days at day 7,successful extubation at day 7 and adverse events.Results: Twenty patients were assigned to each group.The median duration of remimazolam besylate infusion was 45.0(19.8,48.0)h,and the median dose was 0.60(0.45,0.96)mg/kg/h.The median duration of propofol infusion was 33.5(23.5,48.0)h,and the median dose was 2.53(1.73,2.88)mg/kg/h.The median percentage of time in the target NI without rescue sedation was similar in remimazolam and propofol groups[97.5%(86.0%,100%)vs 98.4%(84.3%,99.8%),p=0.989].The median percentage of time in the target RASS range without rescue sedation were 100%(100%,100%)in both groups(p=0.583).The number of patients who were successfully extubated at day 7 were significantly more in the remimazolam group than in the propofol group [9(45.0%)vs 3(15.0%),p=0.038].There were no differences between the two groups in terms of ventilator-free days at day 7 [0.0(0.0,29.4)vs 0.0(0.0,0.0),p=0.253],the incidence of adverse events,or the proportions of patients requiring interventions.Conclusions: This pilot study suggested that remimazolam besylate was effective and safe for deep sedation in critically ill patients compared with propofol. |
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