The SOMNUS Study: Sedative Optimization Via Monitoring Neurological Status - Full Text View

Purpose

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.

Condition	Intervention	Phase
Delirium Cognitive Impairment Critically Ill	Device: RASS Targeting plus BIS Monitoring Other: RASS Targeted	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	A Randomized Control Trial Using the BIS Monitor to Avoid Over Sedation and Prolonged Neuropsychological Deficits in Mechanically Ventilated ICU Patients

Resource links provided by NLM:

MedlinePlus related topics: Coma Delirium

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Number of ventilator free hours and days [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of delirium and coma free days [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Incidence of subacute cognitive dysfunction [ Time Frame: 3 years ] [ Designated as safety issue: No ]
ICU length of stay [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Hospital length of stay [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Six month mortality [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Biomarkers for neurological injury and inflammation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
sleep quality [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	June 2007
Estimated Study Completion Date:	December 2013
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Sedation RASS Targeted Patient sedation utilizing standard of care methods (RASS Targeted)	Other: RASS Targeted Patient sedation utilizing standard of care methods (RASS targeted)
Active Comparator: RASS Targeting plus BIS Monitoring Providing patient sedation utilizing standard of care methods (RASS) plus BIS monitoring.	Device: RASS Targeting plus BIS Monitoring Providing patient sedation utilizing standard of care methods (RASS) plus BIS monitoring

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 tremens.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469482

Locations

United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University

Covidien

Investigators

Principal Investigator:

Paula L. Watson, MD

Vanderbilt Universtiy

More Information

Additional Information:

This is an educational website about ICU delirium. This link exits the ClinicalTrials.gov site

Publications:

Marcantonio ER, Juarez G, Goldman L, Mangione CM, Ludwig LE, Lind L, Katz N, Cook EF, Orav EJ, Lee TH. The relationship of postoperative delirium with psychoactive medications. JAMA. 1994 Nov 16;272(19):1518-22.

Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6.

Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73. Review.

Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001 Aug;27(8):1297-304.

Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996 Mar 20;275(11):852-7.

Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. Epub 2001 Nov 08.

Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62.

Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW. Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004 Apr;32(4):955-62.

Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev. 2004 Jun;14(2):87-98. Review.

Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. No abstract available. Erratum in: Crit Care Med 2002 Mar;30(3):726.

Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998 Aug;114(2):541-8.

Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000 May 18;342(20):1471-7.

Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care. Br Med J (Clin Res Ed). 1985 Apr 6;290(6474):1029-32.

Cooper AB, Thornley KS, Young GB, Slutsky AS, Stewart TE, Hanly PJ. Sleep in critically ill patients requiring mechanical ventilation. Chest. 2000 Mar;117(3):809-18. Erratum in: Chest 2001 Mar;119(3):993.

Sleigh JW, Andrzejowski J, Steyn-Ross A, Steyn-Ross M. The bispectral index: a measure of depth of sleep? Anesth Analg. 1999 Mar;88(3):659-61.

Grocott HP, Newman MF, El-Moalem H, Bainbridge D, Butler A, Laskowitz DT. Apolipoprotein E genotype differentially influences the proinflammatory and anti-inflammatory response to cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2001 Sep;122(3):622-3. No abstract available.

Weigand MA, Volkmann M, Schmidt H, Martin E, Bohrer H, Bardenheuer HJ. Neuron-specific enolase as a marker of fatal outcome in patients with severe sepsis or septic shock. Anesthesiology. 2000 Mar;92(3):905-7. No abstract available.

Hopkins RO, Weaver LK, Pope D, Orme JF, Bigler ED, Larson-LOHR V. Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999 Jul;160(1):50-6.

Norris PR, Dawant BM. Closing the loop in ICU decision support: physiologic event detection, alerts, and documentation. Proc AMIA Symp. 2001;:498-502.

Responsible Party:	Paula Watson, Assitant Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00469482 History of Changes
Other Study ID Numbers:	061218, SOMNUS
Study First Received:	May 3, 2007
Last Updated:	December 20, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

Delirium
Cognitive Impairment
Sleep
Polysomnography

Sedation
Mechanical Ventilation
Critical Illness

Additional relevant MeSH terms:

Critical Illness
Delirium
Cognition Disorders
Disease Attributes
Pathologic Processes
Confusion

Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on May 23, 2013