BIS-Guided Sedation in Critically Ill Patients Under Deep Sedation

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate the effectiveness of sedation guided by the bispectral index (BIS) in reducing the incidence of delirium and the doses of sedative drugs used in critical patients who require deep sedation. The main questions this study aims to answer are: Does sedation guided by BIS lead to higher delirium and coma-free days compared to clinical monitoring? Does sedation guided by BIS result in reduced doses of sedative drugs compared to clinical monitoring? Participants in this study will be randomly assigned to one of two groups: Clinical Monitoring Group: Participants in this group will receive sedation based on clinical scales. These participants will also be fitted with a BIS sensor, but the sensor will be covered. Sedation Guided by BIS Group: Participants in this group will receive sedation guided by the bispectral index. The study will be conducted as a prospective, controlled, blind intervention trial with random distribution and intention to treat. The primary outcomes to be evaluated include: Delirium and coma-free days after the end of deep sedation using the Confusion Assessment Method for the ICU (CAM-ICU) scale. Total dose of sedative drugs administered. BIS values Researchers will compare the two groups to determine if sedation guided by BIS is associated with a higher number of delirium and coma-free days, reduced sedative drug doses, and higher values of BIS compared to clinical monitoring.

Detailed Description
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A Phase 4, randomized (1:1), controlled, double-blind, unicenter clinical trial aims to assess the effectiveness of sedation guided by the Bispectral Index (BIS) compared to sedation guided by clinical scales in critically ill patients under deep sedation. The primary objective is to investigate whether BIS-guided sedation can reduce the incidence of delirium and decrease the doses of sedative drugs administered.

Official Title
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Effect of Bispectral Index (BIS)-Guided Sedation on Delirium and Sedative Drug Requirements in Critically Ill Patients Under Deep Sedation

Conditions
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Delirium, Sedative Overdose

Intervention / Treatment
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* Device: Monitorization of sedation by Bispectral Index


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years. Under mechanical ventilation in the intensive care unit Indication of deep sedation (RASS objective -4, -5) Admission to the ICU or indication of deep sedation up to 8 hours prior to randomization. Exclusion Criteria: Patients with end-of-life care. Family refusal to participate in the study. Impossibility to place the BIS sensor (burns, extensive lesions on the forehead, prone position, etc.). Patients with intracranial hypertension or convulsive status, in whom sedation has the objective of suppressing electroencephalographic waves. Patients who, following a decrease in sedation, have a coma, vegetative state or a state of minimal consciousness.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be assigned according to the randomization to clinical monitoring groups or Bispectral Index (BIS) monitoring group. The ranzomization will be stratified randomization by neuromuscular bloquers.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Sedation guided by Clinical Scales<br>Sedative guided by RASS (Richmond Agitation-Sedation Scale) score. Target RASS: -4 / -5. | |
| Experimental: Sedation guided by Bispectral Index<br>Sedation guided by the Bispectral Index (BIS). Target BIS between 40 to 60. | Device: Monitorization of sedation by Bispectral Index<br>* The sedative dose administered through a continuous infusion pump will be adjusted based on the BIS value to maintain a target range of 40 to 60. If the BIS value is below the target range, the dose will be increased, and if it exceeds the range, the dose will be decreased, aiming to keep the BIS within the desired range.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare delirium and coma free days until 14 days after end of deep sedation | To compare the number of Delirium and Coma-Free Days until day 14 after the cessation of deep sedation in patients receiving sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales. Delirium will be assessed using the CAM-ICU scale (Ely EW et al.) by non-ICU researchers who are blinded to the randomization allocation. The delirium evaluation will begin when the patient reaches a Richmond Agitation-Sedation Scale (RASS) score of > -3. | Up to 14 days post end of deep sedation | 
| Compare the doses of sedative drugs received | To compare the total doses of Propofol, Midazolam, and Remifentanil (calculated in mg/kg) received during the period of deep sedation | From date of randomization until the date of end of deep sedation or date of death from any cause, whichever came first, assessed up to 90 days | 
| Compare values of BIS | To compare the values of Bispectral Index (BIS) in patients receiving sedation guided by the Bispectral Index (BIS) versus sedation guided by clinical scales. This outcome will assess the BIS values recorded during the period of deep sedation and compare them between the two groups | From date of randomization until the date of end of deep sedation or date of death from any cause, whichever came first, assessed up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time with values of BIS less than 40 | To compare the number of hours that patients receiving sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales had registered Bispectral Index (BIS) values below 40 during the period of deep sedation. The duration of time with BIS values below 40 will be recorded for each patient. | From date of randomization until the date of end of deep sedation or date of death from any cause, whichever came first, assessed up to 90 days | 
| Compare days alive and free of the ICU | To compare the effect of sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales on days alive and free of the ICU | From date of randomization until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 120 days | 
| Compare days alive and free of the hospital | To compare the effect of sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales on days alive and free of the hospital | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 120 days | 
| Compare days alive and free of mechanical ventilation through Study Day 30 | To compare the effect of sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales on the number of days alive and free of mechanical ventilation through Study Day 30 | From date of randomization until the date of end of mechanical ventilation or date of death from any cause, whichever came first, assessed up to 30 days | 
| Compare days alive and free of mechanical ventilation through Study Day 60 | To compare the effect of sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales on the number of days alive and free of mechanical ventilation through Study Day 60 | From date of randomization until the date of end of mechanical ventilation or date of death from any cause, whichever came first, assessed up to 60 days | 
| Compare delirium and coma free days until 14 days after end of deep sedation in patients who had more than 24 hours of deep sedation | To compare the number of Delirium and Coma-Free Days until day 14 after the cessation of deep sedation in patients receiving sedation guided by the Bispectral Index (BIS) vs. sedation guided by clinical scales. Delirium will be assessed using the CAM-ICU scale (Ely EW et al.) by non-ICU researchers who are blinded to the randomization allocation. The delirium evaluation will begin when the patient reaches a Richmond Agitation-Sedation Scale (RASS) score of > -3, in patients who had more than 24 hours of deep sedation | Up to 14 days post end of deep sedation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bispectral index, Deep Sedation, Critical care patients, Delirium, Sedatives