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Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

ABSTRACT: Background: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that can potentially be a safe and effective sedative in intensive care units. This study aims to assess whether remimazolam besylate is not inferior to propofol in maintaining mild-to-moderate sedation in critically ill patients receiving long-term mechanical ventilation. Methods and analysis: This is a multicenter, randomized, single-blind, propofol-controlled, non-inferiority study. Eligible patients are randomly assigned to receive remimazolam besylate or propofol in a 1:1 ratio to maintain a Richmond Agitation-Sedation Scale score between -3 and 0. When patients are under-sedated, rescue sedation of dexmedetomidine is added. The primary outcome is the percentage of time in the target sedation range. The secondary outcomes are hours free from the invasive ventilator in 7 days, successful extubation in 7 days, and weaning time, the length of intensive care unit stay, the length of hospital stay, and mortality in 28 days. Modified intention-to-treat and safety analysis is performed. Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT05555667.

SUBMITTER: Yang X

PROVIDER: S-EPMC10416620 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

Yang Xiaobo X Tang Yun Y Du Ruofei R Yu Yuan Y Xu Jiqian J Zhang Jiancheng J Liu Hong H Zou Xiaojing X Ren Lehao L Yuan Shiying S Shang You Y

Frontiers in pharmacology 20230728

<b>Background:</b> Remimazolam besylate is a novel ultra-short-acting benzodiazepine that can potentially be a safe and effective sedative in intensive care units. This study aims to assess whether remimazolam besylate is not inferior to propofol in maintaining mild-to-moderate sedation in critically ill patients receiving long-term mechanical ventilation. <b>Methods and analysis:</b> This is a multicenter, randomized, single-blind, propofol-controlled, non-inferiority study. Eligible patients a ...[more]

PMID: 37576823

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Project description:ObjectivesIn mechanically ventilated patients, deep sedation is often assumed to induce "respirolysis," that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure.DesignProspective cohort study.SettingPatients were enrolled during 2 month-long periods in 2016-2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital.PatientsEligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded.InterventionsRespiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days.Measurements and main resultsFifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0-1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (RSpearman, 0.02; 95% CI, -0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2-1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65-0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48-0.70; p < 0.01).ConclusionsSedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.

Project description:ObjectiveRemimazolam besylate and Ciprofol are newer sedatives used in minor surgeries. Propofol is a classic drug mainly used for short surgeries. This trial was conducted to compare the efficacy and safety of remimazolam besylate, ciprofol, and propofol during hysteroscopic surgeries.MethodsPatients undergoing hysteroscopy were randomly assigned to receive remimazolam besylate (Group R), ciprofol (Group C), or propofol (Group P). A total of 194 patients were assessed for eligibility. One patient in Group P was excluded because the operation had timed out of 60 min. Patients all in Group R、Group C and Group P received an induction dose of 0.2 mg/kg remimazolam besylate、0.4 mg/kg ciprofol、2.0 mg/kg propofol seperately over 30 s. A corresponding dosage of 1 mg/kg/h、0.6-1.2 mg/kg/h and 3.0-6.0 mg/kg/h was given by continuous intravenous infusion to maintain a BIS of 40-60 till the end of the surgery. The incidence rates of body movement, respiratory depression, and adverse effects were compared among the groups.ResultsThe incidence of injection pain was much higher in Group P (64.1%) than that in Group R (3.4%) and Group C (3.2%, both P < 0.001). The onset time was significantly shorter in Group P than that in Group R and Group C (both P < 0.01). The awakening time (MOAA/S score = 3) was longest in Group R, followed by Groups C and Group P (P < 0.01). The time to complete recovery (MOAA/S score = 5) has no significantly difference between Group C and Group P, whereas the onset time was significantly shorter in Group R (P < 0.01). The number of body movements was significantly higher in Group R than that in Group C and Group P (P < 0.01). The incidence of hypotension was significantly lower in Group R than that in Group C and Group P (both P < 0.01). The rate of respiratory inhibition was significantly lower in Group R and Group C than that in Group P (both P < 0.05).ConclusionConsidering jointly the safety and efficacy, ciprofol seems to be the best choice for sedation.

Project description:BackgroundThrough many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients.Methods/designThe non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%).DiscussionThe trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients.Trial registerClinicalTrials.gov NCT0196768, 09.01.2014.

Dataset Information

Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

Publications

Long-term sedation with remimazolam besylate versus propofol in critically ill patients during invasive mechanical ventilation: a study protocol for a multicenter randomized non-inferior trial.

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