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This study evaluates the safety and effectiveness of Ciprofol, a new sedative, in critically ill patients receiving Extracorporeal Membrane Oxygenation (ECMO), a life-support system for heart or lung failure. The investigation aims to:
Assess how Ciprofol affects the oxygenator, a critical ECMO component responsible for adding oxygen to blood.
Compare the safety of Ciprofol to midazolam, a commonly used sedative. Eligibility Criteria Adults aged 18 years or older. Patients receiving ECMO and mechanical ventilation for over 72 hours. Individuals requiring sedation for medical procedures. Study Protocol
Participants will be randomly assigned to one of two groups:
Ciprofol Group: Initial sedation dose of 0.1 mg/kg, adjusted as needed. Midazolam Group: Initial sedation dose of 0.05 mg/kg, adjusted as needed. Both groups will receive pain management with remifentanil. Sedation levels will be adjusted daily by the clinical team to ensure patient safety and comfort.
Outcome Measures Primary: Oxygenator performance (oxygen and carbon dioxide levels) on Days 3 and 7.
Secondary: Changes in blood triglyceride and clotting marker (D-dimer) levels, oxygenator lifespan before replacement, and safety outcomes such as low blood pressure, respiratory issues, or allergic reactions.
Significance ECMO patients often require prolonged sedation, but current sedatives like midazolam may contribute to oxygenator damage. Ciprofol's potential for faster recovery and fewer side effects could improve sedation practices and device longevity in this high-risk population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ciprofol group | Experimental | Patients in this arm will receive Ciprofol, an investigational sedative, administered via continuous intravenous infusion. Dosing Protocol: Initial Dose: 0.1 mg/kg loading dose over 1-2 minutes. Maintenance Dose: 0.05-0.3 mg/kg/h, adjusted hourly based on the Richmond Agitation-Sedation Scale (RASS) score (target range: -3 to 0). Combined Analgesia: All patients will concurrently receive remifentanil (0.05-0.3 μg/kg/min) for pain control. Monitoring & Adjustments: Sedation depth assessed every 30 minutes using RASS and ( Critical-Care Pain Observation Tool) CPOT scores. Dose adjustments made to avoid hypotension (Mean Arterial Pressure) MAP < 65 mmHg or oversedation. Triglyceride levels monitored daily to guide lipid emulsion management. Safety Measures: Rescue protocol for hypotension (e.g., vasopressors) or respiratory depression (e.g., temporary ECMO flow adjustment). |
|
| Midazolam group | Active Comparator | Patients in this arm will receive midazolam, a benzodiazepine sedative commonly used in ECMO patients, administered via continuous intravenous infusion. Dosing Protocol: Initial Dose: 0.05 mg/kg loading dose over 2-5 minutes. Maintenance Dose: 0.02-0.1 mg/kg/h, adjusted hourly based on the RASS score (target range: -3 to 0). Combined Analgesia: All patients will concurrently receive remifentanil (0.05-0.3 μg/kg/min) for pain control, identical to the Ciprofol group. Monitoring & Adjustments: Sedation depth assessed every 30 minutes using RASS and CPOT scores, consistent with the experimental group. Dose adjustments made to avoid hypotension (MAP < 65 mmHg) or oversedation. Daily monitoring of drug accumulation markers (e.g., midazolam plasma levels if available). Safety Measures: Rescue protocol for hypotension (e.g., vasopressors) or respiratory depression (e.g., ventilator support escalation). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ciprofol | Drug | Continuous intravenous infusion (0.05-0.3 mg/kg/h), adjusted hourly based on the RASS score (target range: -3 to 0). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite Oxygenator Dysfunction | Definition: Meeting ≥2 of the following: Post-oxygenator PaO₂/FiO₂ <200 mmHg ΔTransmembrane pressure (ΔdP) ≥20% from baseline or Transmembrane pressure (TMP)>50 mmHg from baseline CO₂ clearance <20% [(Pre-MLCO₂ - Post-MLCO₂)/Pre-MLCO₂] at gas flow ≥10 L/min | At Day 3 and Day 7 of ECMO support |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygenator Transmembrane Pressure (TMP) Gradients | Transmembrane pressure (TMP) will be assessed using continuous inline pressure monitoring via the ECMO circuit's integrated pressure sensors (e.g., pre- and post-oxygenator pressure transducers). TMP is calculated as: TMP (mmHg) = Post-oxygenator Pressure - Pre-oxygenator Pressure | Daily from Day 1 to Day 7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qiancheng Xu | Contact | 86-18297529106 | qianchengxu@wnmc.edu.cn |
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| Midazolam | Drug | Continuous intravenous infusion (0.02-0.1 mg/kg/h), adjusted hourly based on the RASS score (target range: -3 to 0). |
|
| Post-oxygenator Oxygenation Index (PaO₂/FiO₂ Ratio) | The post-oxygenator PaO₂/FiO₂ ratio will be measured daily to evaluate oxygenator efficiency. A value <200 mmHg indicates impaired oxygenation capacity. | Daily from Day 1 to Day 7 |
| Oxygenator Lifespan | Definition: Time (hours) from ECMO initiation to oxygenator replacement. Replacement Criteria: Meeting ≥2 composite dysfunction criteria. | Through ECMO weaning or Day 30, whichever comes first |
| Lipid Profile Changes | Measure: Serum triglycerides (TG) | At 24 hours, 72 hours, and Day 7 |
| Plasma D-dimer Concentration (μg/mL) | Description: Absolute plasma D-dimer levels measured as a biomarker of hypercoagulability and thromboembolic risk. Threshold: >5 μg/mL (defined as high thrombotic risk per International Society on Thrombosis and Haemostasis [ISTH] guidelines). | At 24 hours, 72 hours, and Day 7 post-ECMO initiation. |
| Incidence of delirium | At 24h post-sedation discontinuation |
| ECMO Pump Head Malfunction | Definition: Occurrence of any of the following: Pump head rupture (visible crack or leak) Pump head thrombosis (ultrasound-confirmed thrombus within the pump housing) Mechanical failure (unplanned pump stoppage requiring emergency intervention) | During ECMO support (up to 30 days) |
| Thromboembolic Events | Definition: Radiologically confirmed: Arterial embolism: Cerebral or limb artery occlusion (CT angiography/ultrasound) Venous thrombosis: Lower extremity DVT or pulmonary embolism (CT pulmonary angiography/Doppler) Intracardiac thrombus: Echocardiographic or CT evidence Grading: Major: Life-threatening or requiring intervention (e.g., thrombectomy) Minor: Asymptomatic or managed medically | From ECMO initiation until 48 hours after decannulation |
| ECMO Weaning Success | Definition: Successful decannulation without re-initiation of ECMO within 24 hours. | Through study completion (Day 30) |
| 7-day mortality rate | All-cause death rate at Day 7 post-ECMO initiation. | At Day 7 |
| 28-day mortality rate | All-cause death rate at Day 28 post-ECMO initiation. | At Day 28 |
| ICU Length of Stay (LOS) | Duration from ICU admission to discharge (days). | Through hospital discharge, up to 90 days |
| Duration of Mechanical Ventilation | Measure: Time (hours) from intubation to sustained extubation (48 hours without reintubation). | From ECMO initiation to successful extubation (up to 28 days) |
| ID | Term |
|---|---|
| D055371 | Acute Lung Injury |
| D012770 | Shock, Cardiogenic |
| ID | Term |
|---|---|
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D012769 | Shock |
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| ID | Term |
|---|---|
| C000730795 | (2-(1R)-1-cyclopropyl)ethyl-6-isopropyl-phenol |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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