Comparison of the Efficacy and Safety of Ciprofol Versus Propofol for Sedation in ICU Patients Undergoing Non-Invasive Ventilation

Sedation is frequently required in critically ill patients admitted to the intensive care unit (ICU), including those receiving non-invasive respiratory support such as high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or conventional oxygen therapy. Anxiety, agitation, dyspnea, and poor tolerance of respiratory support may compromise treatment adherence and increase the risk of respiratory deterioration and endotracheal intubation. Appropriate sedation may improve patient comfort, facilitate respiratory support, and reduce complications. However, sedation in non-mechanically ventilated ICU patients remains challenging because excessive sedation may lead to respiratory depression or hemodynamic instability. Propofol is commonly used for ICU sedation because of its rapid onset and controllable depth of sedation. Nevertheless, propofol is associated with several adverse effects, including respiratory depression, hypotension, and injection pain, which may limit its use in patients without invasive mechanical ventilation. Ciprofol is a novel short-acting intravenous sedative that acts as a gamma-aminobutyric acid type A (GABA-A) receptor agonist and is structurally related to propofol. Previous studies have demonstrated that ciprofol has rapid onset, predictable sedation, less injection pain, and a potentially lower incidence of respiratory depression and hemodynamic instability compared with propofol. Clinical studies have shown favorable safety and efficacy profiles of ciprofol in procedural sedation, anesthesia induction, and sedation in mechanically ventilated ICU patients. However, evidence regarding its use in ICU patients receiving non-mechanical ventilation is still limited. This study aims to compare the effectiveness and safety of ciprofol versus propofol for sedation in adult ICU patients who are not receiving invasive mechanical ventilation. The study will be conducted as a multicenter retrospective cohort study involving approximately 30 tertiary hospitals in China. Adult ICU patients treated between January 1, 2022 and July 30, 2024 who received intravenous sedation with either ciprofol or propofol while receiving non-invasive respiratory support (including NIV, HFNC, or conventional oxygen therapy) will be included. The primary outcomes are sedation success rate and the incidence of respiratory depression. Sedation success is defined as maintaining the Richmond Agitation-Sedation Scale (RASS) within the target range of -2 to +1 for at least two consecutive hours without discontinuation of the sedation regimen or switching to another sedative. Respiratory depression will be defined based on predefined criteria including severe hypoxemia, markedly reduced respiratory rate, abnormal end-tidal carbon dioxide levels, or apnea. Secondary outcomes include endotracheal intubation rate during the sedation period, ICU length of stay, ICU mortality, and the requirement for vasoactive agents. Propensity score matching and multivariable statistical models will be used to adjust for baseline differences and potential confounders between treatment groups. This real-world study aims to provide evidence regarding the clinical effectiveness and respiratory safety of ciprofol compared with propofol for sedation in ICU patients without invasive mechanical ventilation. The findings may help optimize sedation strategies in critically ill patients receiving non-invasive respiratory support and provide evidence to support future prospective clinical trials.

Background Sedation is commonly required in critically ill patients admitted to the intensive care unit (ICU). In addition to patients receiving invasive mechanical ventilation, many ICU patients who are not intubated may also require sedation during treatment. These patients may receive various forms of non-invasive respiratory support, including high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or conventional oxygen therapy. Anxiety, agitation, dyspnea, and discomfort are common in these patients and may interfere with essential treatments. For example, agitation can reduce tolerance to non-invasive respiratory support, increase oxygen consumption, and potentially worsen respiratory failure. Appropriate sedation can help improve patient comfort, enhance tolerance to respiratory support, and facilitate clinical procedures and monitoring. However, sedation in patients without invasive mechanical ventilation is particularly challenging. Because these patients maintain spontaneous breathing without the protection of an artificial airway, excessive sedation may increase the risk of respiratory depression, hypoxemia, airway obstruction, or the need for emergency endotracheal intubation. Therefore, selecting sedative medications with a favorable balance between effective sedation and respiratory safety is essential in this population. Currently, several sedative agents are used in ICU practice. Benzodiazepines such as midazolam have historically been widely used, but they are associated with delayed awakening, accumulation in patients with organ dysfunction, and an increased risk of delirium. Dexmedetomidine provides lighter sedation and has minimal respiratory depression, but it may cause bradycardia and hypotension and may not always achieve the desired depth of sedation. Propofol is another commonly used sedative in the ICU. It has a rapid onset of action, short duration, and easily adjustable sedation depth, which makes it attractive for clinical use. However, propofol is also associated with several adverse effects, including respiratory depression, hypotension, and injection-site pain. These effects can limit its use in patients who are not mechanically ventilated. Ciprofol is a novel intravenous anesthetic and sedative agent that acts as a gamma-aminobutyric acid type A (GABA-A) receptor agonist. Structurally related to propofol, ciprofol has been developed to improve pharmacologic properties while maintaining similar sedative effects. Previous clinical studies have shown that ciprofol provides rapid onset of sedation and stable sedation depth with potentially fewer adverse effects. In particular, several studies have suggested that ciprofol may be associated with less respiratory depression, lower incidence of hypotension, and less injection pain compared with propofol. Ciprofol has been evaluated in a variety of clinical settings, including procedural sedation for gastrointestinal endoscopy, anesthesia induction for surger trial.show_full_description

Inclusion Criteria Age: * Age ≥18 years * Admitted to the intensive care unit (ICU) between January 1, 2022 and July 30, 2024 * Received intravenous sedation with either ciprofol or propofol during ICU stay * Total duration of ciprofol or propofol administration ≥2 hours * Sedation initiated while the patient was not receiving invasive mechanical ventilation * Receiving non-invasive respiratory support or oxygen therapy at the time sedation was started, including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), nasal cannula, or face mask oxygen therapy * Availability of complete electronic medical records including sedation assessment using the Richmond Agitation-Sedation Scale (RASS) * Availability of continuous vital sign monitoring records including respiratory rate, oxygen saturation, blood pressure, and heart rate Exclusion Criteria: * Age \<18 years * Pregnancy or breastfeeding * Use of other primary sedative agents during the observation period, including midazolam or dexmedetomidine * Total exposure time to ciprofol or propofol \<2 hours * Known allergy or hypersensitivity to ciprofol, propofol, or their formulation components * Initiation of invasive mechanical ventilation before sedation * Missing key clinical data required for outcome evaluation, including sedation score, vital signs, or drug administration records * Participation in other interventional clinical trials that may interfere with outcome assessment * Severe visual or hearing impairment preventing accurate sedation assessment * Coma or conditions that prevent reliable evaluation using the Richmond Agitation-Sedation Scale (RASS) * Any condition that the investigators consider inappropriate for inclusion in the study