The SOMNUS Study: Sedative Optimization Via Monitoring Neurological Status

Study Overview
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Brief Summary
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A combined strategy of Richmond Agitation and Sedation Scale (RASS) clinical targeting plus bispectral index (BIS) guided sedation in mechanically ventilated, critically ill patients will decrease time on mechanical ventilation, decrease the duration of intensive care unit (ICU) delirium and coma, and will improve subacute neurocognitive function when compared to sedation guided by RASS targeting alone.

Detailed Description
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Sedatives and analgesics are used to maintain comfort in almost all mechanically ventilated patients. Unfortunately, these medications also have many deleterious effects. Sedatives increase time on mechanical ventilation, have adverse hemodynamic effects, disturb sleep architecture, and have been determined to be an independent risk factor for ICU delirium. Delirium is an independent determinant of longer hospital stay, higher costs, and higher mortality, and the presence of delirium is highly predictive of long-term neurocognitive deficits. In consideration of these facts, better methods are needed to guide sedation, avoid oversedation, and possibly reduce delirium. Current guidelines recommend titration of sedation to a goal level based on bedside evaluation using a validated assessment tool, e.g. the Richmond Agitation and Sedation Scale. These assessment tools, however, are underused and many ICU patients are oversedated with well described consequences. A practical method by which to determine where a patient lies may prove beneficial in optimizing our delivery of sedatives and improving patient outcomes. While conventional EEG monitoring is not practical in the ICU, bispectral index (BIS) monitoring may be easily used in this clinical setting. BIS monitoring may provide a means to assess sedation level in unresponsive or paralyzed ICU patients and to decrease the total amount of sedatives/analgesics administered. Additional benefits of a combined clinical sedation scale and BIS-monitoring approach could include a decreased incidence and/or duration of delirium as well as a decreased incidence and severity of ICU-associated prolonged neurocognitive deficits. The specific aims of this study are as follows: Aim 1: To determine if sedative and analgesic medication delivery guided by clinical sedation scales and BIS monitor parameters of over-sedation will decrease time on mechanical ventilation. Aim 2: To determine if sedative and analgesic medication delivery guided by clinical sedation scales and BIS monitor parameters of over-sedation will decrease the duration of delirium and coma when compared to the use of clinical sedations scales alone. Aim 3: To determine if sedative and analgesic medication delivery guided by clinical sedation scales and BIS monitor parameters of over-sedation will decrease the incidence and severity of subacute cognitive impairment when compared to the use of clinical sedation scales alone. Aim 4: To characterize polysomnography findings in critically ill patients at various BIS levels. Aim 5: To determine if poor sleep quality is a factor in post critical illness neurocognitive dysfunction.

Official Title
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A Randomized Control Trial Using the BIS Monitor to Avoid Over Sedation and Prolonged Neuropsychological Deficits in Mechanically Ventilated ICU Patients

Conditions
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Delirium, Cognitive Impairment, Critically Ill

Intervention / Treatment
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* Other: Sedation,RASS Targeted plus BIS Monitoring
* Other: Sedation, RASS Targeted


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult patients admitted to the ICU for critical illnesses requiring mechanical ventilation with expectation of being mechanically ventilated for greater than 24 hours. Subjects must have an actual or a target RASS of -3 or deeper with 48 hours of initiation of mechanical ventilation. Exclusion Criteria: Subjects who are less than 18 years old. Inability to obtain informed consent from the patient or his/her surrogate. Subjects admitted with alcohol or drug overdoses, suicide attempts, or alcohol/delirium with tremors. Subjects with documented moderate to severe dementia. Subjects with anoxic brain injuries, strokes, neurotrauma, or neuromuscular disorders such as myasthenia gravis or Guillain Barre syndrome. Subjects whose family and/or physician have not committed to aggressive support for 72 hours or who are likely to withdraw within 72 hours. Subjects who are moribund or are not expected to survive hospital discharge due to preexisting uncorrectable medical condition. Subjects who have either Child-Pugh Class B or C cirrhosis.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sedation, RASS Targeted<br>Patient sedation utilizing standard of care methods (RASS Targeted) | Other: Sedation, RASS Targeted<br>* Patient sedation utilizing standard of care methods (RASS targeted)<br>|
| Active Comparator: Sedation,RASS Targeted plus BIS Monitoring<br>Providing patient sedation utilizing standard of care methods (RASS) plus BIS monitoring. | Other: Sedation,RASS Targeted plus BIS Monitoring<br>* Providing patient sedation utilizing standard of care methods (RASS) plus BIS monitoring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of ventilator free hours and days |  | while in ICU, appoximately 3-7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of delirium and coma free days |  | while in ICU, appoximately 3-7 days) | 
| Incidence of subacute cognitive dysfunction using RBANS- Repeatable Battery for the Assessment of Neuropsychological Status, |  | 3 months | 
| Incidence of subacute cognitive dysfunction using TRAILS A&B |  | 3 months | 
| Incidence of subacute cognitive dysfunction using SF-36 - Short Form Health Survey |  | 3 months | 
| Incidence of subacute cognitive dysfunction using MMSE - Mini Mental State Examination |  | 3 months | 
| Incidence of subacute cognitive dysfunction using IADLs - instrumental activities of daily living |  | 3 months | 
| Incidence of subacute cognitive dysfunction using AD8- ADL - activities of daily living |  | 3 months | 
| Incidence of subacute cognitive dysfunction using APACHE II - Acute Physiologic and Chronic Health Evaluation II score |  | 3 months | 
| ICU length of stay |  | while in ICU, appoximately 3-7 days | 
| Hospital length of stay |  | while in hospital, usually 5-10 days | 
| Six month mortality |  | 6 months | 
| Biomarkers for neurological injury and inflammation, Neuron-Specific Enolase (NSE) |  | Baseline, Day 3 and at Ventilator removal (appoximately day 3-7) | 
| Biomarkers for neurological injury and inflammation, S100 |  | Baseline, Day 3 and at Ventilator removal (appoximately day 3-7) | 
| Biomarkers for neurological injury and inflammation, IL-6 |  | Baseline, Day 3 and at Ventilator removal (appoximately day 3-7) | 
| Biomarkers for neurological injury and inflammation, C Reactive Protein (CRP) |  | Baseline, Day 3 and at Ventilator removal (appoximately day 3-7) | 
| sleep quality | measured with continuous polysomnography | within 24 hours of enrollment through day 3-7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delirium, Cognitive Impairment, Sleep, Polysomnography, Sedation, Mechanical Ventilation, Critical Illness