The SOMNUS Study: Sedative Optimization Via Monitoring Neurological Status

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.

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.