Effect of Bispectral Index (BIS) Titrated Propofol Sedation on Lower Esophageal Sphincter Pressures and Esophageal Function in Intensive Care Patients

Not Applicable

Terminated

• Conditions: Respiration, Artificial
• Interventions: Other: BIS 70 maintained; Other: BIS level 50; Other: BIS 35

• Registration Number: NCT01173263
• Lead Sponsor: The Cleveland Clinic

Brief Summary

Eligible patients will be allocated to receive propofol sedation titrated to 3 different Bispectral Index (BIS) levels in a random order. Primary hypothesis: Deepening propofol sedation - as determined by BIS - lowers esophageal pressure in critical care patients.

Detailed Description

Patient will be selected from the ICU, based on the defined inclusion and exclusion criteria. Potential study subjects will be screened by the research fellow or the on-site study co-investigator. Eligible patients will be allocated to receive propofol sedation titrated to 3 different BIS levels in a random order. BIS XP monitors (Aspect Medical Systems, Norwood, MA, USA) will be used which are relatively resistant to EMG artifact; a BIS sensor will be position on forehead of the patient after the skin is degreased and gently abraded. Esophageal pressure monitoring will be performed by a catheter inserted from the nose to the esophagus and left there trough the study period.

If patients are on sedation they will be placed on propofol sedation for a washout period. Each patient will receive propofol sedation by continuous infusion titrated to a different levels of BIS in a randomized fashion according to a computer-generated random-number sequence;

1. BIS levels of 70, will be targeted (Anxiolysis/high-frequency EEG activity, beta-augmentation);

2. BIS levels of 50 will be targeted, (Low frequency EEG activity, theta-delta activity);

3. BIS levels of 35 will be targeted (low frequency EEG activity). A propofol infusion will be titrated by the investigators to the designated BIS target according to randomization. Clinical personnel will not be blinded to the study, and if patient has clinically significant change in hemodynamic parameters study will be interrupted. Each BIS target level will be kept as constant as possible for at least one hour; thereafter, lower esophageal pressures will be recorded for 15 minutes using high resolution esophageal manometry. Studies will be done in supine position \[Most ICU patients are now kept head-up.\], and the manometric assembly will be positioned to record from the hypopharynx to the stomach with 4-6 of the sensors positioned in the stomach.

All patients will otherwise receive routine ICU care and medications without interruption of standard clinical care.

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-07-21
• Study First Submitted QC: 2010-07-30
• Study First Posted: 2010-08-02
• Primary Completion: 2011-03
• Study Completion: 2011-03
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-04
• Last Update Posted: 2014-03-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• 18-80 years of age
• Written informed consent from relatives
• Clinically stable
• Mechanically ventilated < 2days
• Require sedation and expected to be given propofol

Exclusion Criteria

• Recent injury or other pathologic condition of the esophagus
• Major bronchopleural fistula
• History of liver failure
• History of renal failure
• History of major neuromuscular disease
• Multiple trauma
• Upper motor nerve injury
• Hypersensitivity to propofol
• Recent gastrointestinal surgery
• Patients with a diagnosed or suspected condition that may give false results in BIS monitoring.
• Tracheostomized patients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIS 70	BIS 70 maintained	BIS levels of 70, will be targeted (Anxiolysis/high-frequency EEG activity, beta-augmentation);
BIS 50	BIS level 50	BIS levels of 50 will be targeted, (Low frequency EEG activity, theta-delta activity)
BIS 35	BIS 35	BIS levels of 35 will be targeted (low frequency EEG activity)

Primary Outcome Measures

Name	Time	Method
Deepening propofol sedation - as determined by BIS - lowers esophageal pressure in critical care patients.	for 15 minutes after assigned BIS level has been maintained for one hour, while in the ICU	Sedation will also be evaluated with the bispectral index of the electroencephalogram. BIS of the EEG data will be acquired with 4 BIS-sensor electrodes and a BIS XP monitor. The BIS will be recorded electronically at one-minute intervals. Heart rate, blood pressures (diastolic and systolic), respiratory rate, core temperature and oxygen saturation will be recorded every 5 minutes during the measurement period of the study.

Secondary Outcome Measures

Name	Time	Method
Deepening propofol sedation - as measured by Sedation Agitation Scale, Richmond Agitation Scale Score, and Ramsay sedation scale - lowers esophageal pressure in critical care patients.	every 10 minutes, while sedated in the ICU	The SAS uses a 1 to 7 point scale to make a determination of the patient's level of agitation and sedation from a rating of 7 dangerously agitated to a rating of 1 unarousable (Table 1). Clinical sedation assessments using SAS and RASS scales will be measured every 10 minutes through the study period.
There is an association between ventilator associated pneumonia and baseline lower esophageal and barrier pressure.	daily, until hospital discharge	Patients will be followed for their stay in the hospital for occurrence of ventilator associated pneumonia.
Modifying the target level of BIS titration affects upper esophageal pressures and esophageal peristalsis.	for 15 minutes after assigned BIS level has been maintained for one hour, while in the ICU	Upper esophageal sphincter pressures, transient LES relaxations, and regurgitations will be evaluated by the GI team from recorded data from high resolution manometry.

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States