BIS-Guided Sedation in Critically Ill Patients Under Deep Sedation

NCT03840577 | Unknown DMC FDA Device

• 1 other identifier: 3880
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Delirium; Sedative Overdose

Keywords

Deep Sedation; Bispectral index; Critical care patients; Delirium; Sedatives

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Time with values of BIS less than 40

  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

  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

  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

  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

  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

Other Outcomes (1)

• Compare mortality at 60 days after randomization

  Until 60 days after randomization

Study Arms (2)

Sedation guided by Clinical Scales

NO INTERVENTION

Sedative guided by RASS (Richmond Agitation-Sedation Scale) score. Target RASS: -4 / -5.

Sedation guided by Bispectral Index

EXPERIMENTAL

Sedation guided by the Bispectral Index (BIS). Target BIS between 40 to 60.

Device: Monitorization of sedation by Bispectral Index

Interventions

Monitorization of sedation by Bispectral Index DEVICE

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.

Sedation guided by Bispectral Index

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (1)

Hospital Italiano de Buenos Aires

Capital Federal, 1173, Argentina

Location

Related Publications (7)

• MacKenzie KK, Britt-Spells AM, Sands LP, Leung JM. Processed Electroencephalogram Monitoring and Postoperative Delirium: A Systematic Review and Meta-analysis. Anesthesiology. 2018 Sep;129(3):417-427. doi: 10.1097/ALN.0000000000002323.

  PMID: 29912008 BACKGROUND

• Salluh JI, Soares M, Teles JM, Ceraso D, Raimondi N, Nava VS, Blasquez P, Ugarte S, Ibanez-Guzman C, Centeno JV, Laca M, Grecco G, Jimenez E, Arias-Rivera S, Duenas C, Rocha MG; Delirium Epidemiology in Critical Care Study Group. Delirium epidemiology in critical care (DECCA): an international study. Crit Care. 2010;14(6):R210. doi: 10.1186/cc9333. Epub 2010 Nov 23.

  PMID: 21092264 BACKGROUND

• Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR, Inouye SK. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001 Jul;29(7):1370-9. doi: 10.1097/00003246-200107000-00012.

  PMID: 11445689 BACKGROUND

• Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.

  PMID: 30113379 BACKGROUND

• Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138.

  PMID: 12421743 BACKGROUND

• Shetty RM, Bellini A, Wijayatilake DS, Hamilton MA, Jain R, Karanth S, Namachivayam A. BIS monitoring versus clinical assessment for sedation in mechanically ventilated adults in the intensive care unit and its impact on clinical outcomes and resource utilization. Cochrane Database Syst Rev. 2018 Feb 21;2(2):CD011240. doi: 10.1002/14651858.CD011240.pub2.

  PMID: 29464690 BACKGROUND

• Huespe I, Giunta D, Acosta K, Avila D, Prado E, Sanghavi D, Bisso IC, Giannasi S, Carini FC. Comparing Bispectral Index Monitoring vs Clinical Assessment for Deep Sedation in the ICU: Effects on Delirium Reduction and Sedative Drug Doses-A Randomized Trial. Chest. 2024 Oct;166(4):733-742. doi: 10.1016/j.chest.2024.05.031. Epub 2024 Jun 18.

  PMID: 38901489 DERIVED

MeSH Terms

Conditions

Delirium

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Sergio Giannasi, MD

  Hospital Italiano de Buenos Aires

  STUDY CHAIR

• Federico Carini, MD

  Hospital Italiano de Buenos Aires

  STUDY DIRECTOR

• Ivan A. Huespe, MD

  Hospital Italiano de Buenos Aires

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The primary outcome "Compare delirium and coma-free days until 14 days after the end of deep sedation" will be assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale. The evaluations will be conducted by blinded evaluators who are unaware of the patient's assigned sedation management group
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: February 3, 2019
• First Posted: February 15, 2019
• Study Start: April 1, 2019
• Primary Completion: April 22, 2022
• Study Completion: January 1, 2024
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: The data will be made available at the end of the study, in 2024.
• Access Criteria: All data requirements will be evaluated by the principal investigator and the local Institutional Review Board to ensure compliance with ethical and regulatory guidelines regarding data access and protection

Locations

AR (1)