Sedation in Endoscopic Retrograde Cholangiopancreatography (ERCP) With or Without Opioids

The Effect of Intranasal Fentanyl Versus Remifentanil Infusion on Propofol Requirements During Elective Therapeutic ERCP, as Well on the Recovery, Pain, and Early Cognitive Function: A Randomized Control Trial

Addition of fentanyl or remifentanil to the propofol produced sedation for scheduled ERCP will decrease the propofol requirements for predetermined sedation levels (as shown by Bispectral Index Monitor (BIS) monitor), will be associated with faster recovery monitored by Ramsay's and Observer's Assessment of Alertness/Sedation (OAAS) scores and BIS, less postoperative pain (assessed by Visual Analogue Scale=VAS) and less early cognitive impairment after sedation (as assessed by the MiniMental test).

Study Overview

• Status: Completed
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: Remifentanil; Drug: Fentanyl; Drug: Normal saline

Detailed Description

Patients After obtaining approval from the Institutional Review Board (IRB) adult patients ASA I-III aged between 45 and 75 yrs scheduled for elective therapeutic ERCP are enrolled in the study. All patients are informed and asked to give written informed consent. Those with chronic pain, consuming opioids or other analgesics, sedatives, hypnotics, allergic to the drugs to be used in the study protocol, or patients who refuse to give written informed consent are excluded from the study.

Randomization and blindness Randomization was done by a Research Randomizer program, using 60 sets of numbers and 3 numbers per set for a total of 180 patients, keeping each number in a set to remain unique and without sorting the numbers that are generated. (http://www.randomizer.org/). The remifentanil or placebo solutions as well as the nasal fentanyl or placebo spray are prepared and administered by an independent investigator who is aware of the group randomization and indicated interventions.

Group 1: Receive remifentanil i.v infusion 1 ml/10 kg/h (10 μg/ml) starting 5 minutes before propofol administration and continued throughout the procedure. At the same time intranasal normal saline is given. A bolus dose of propofol 1 mg/kg is followed by propofol infusion and the infusion is titrated to obtain BIS values around 40-70.

Group 2: Receive normal saline i.v. infusion in volume equal to the volume of remifentanil as if he/she were assigned to Group 1, intranasal fentanyl 200 μg, and propofol as in group 1.

Group 3: Receive i.v. normal saline infusion in volume equal to the volume of remifentanil as if he/she were assigned to Group 1, intranasal normal saline, and propofol as in groups 1 and 2.

Anesthetic technique Before opioid/placebo/anesthetic administration all patients receive for 3-5 min 100% oxygen via a face mask from a wall oxygen source by means of a Mapleson C breathing system. Two venous catheters are inserted in peripheral veins and connected via extension tubes to two separate infusion pumps for remifentanil or placebo and for propofol infusion.

Basic monitoring includes pulse oximetry, non-invasive blood pressure (measured in the beginning and at the end of the procedure), heart rate, respiratory rate and ECG. Additional monitoring includes BIS, (BIS VIEW ™ Monitoring System, Aspect Medical Systems, Inc. One Upland Road Norwood, MA 02062 USA). All patients are preoxygenated with 100% oxygen via a face mask before anesthetic administration. During the procedure oxygen (9 l/min) is administered via a nasal catheter. Sedation/anesthesia is maintained with propofol bolus 1 mg/kg to begin with, plus infusion (5-9 mg/kg/h) by means of an electric pump to obtain BIS values around 40-70.

Intraoperative variables to be recorded Baseline values (before starting opioid/placebo) and every 3 min thereafter throughout the procedure BIS, SpO2, HR, RR, and Movement of the patient (Yes/No) are recorded and the propofol infusion is increased accordingly. Systolic and diastolic blood pressure is recorded in the beginning and at the end of the procedure (not to disturb the patient and change the level of consciousness, except for complications during the procedure like bleeding, apnea etc). Also events of desaturation (SpO2 below 90), episodes of apnea (apnea for > than 30s), and other adverse events are recorded. Systolic and diastolic blood pressure is recorded in the beginning and at the end of the procedure (not to disturb the patient and change the level of consciousness, except for complications during the procedure, like bleeding, apnea etc).

At the end of the procedure the total doses of propofol and remifentanil (or the volume of placebo) are recorded.

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11528
    • Department of Anesthesiology, Aretaieio Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients both sexes
• ASA I-III
• aged between 45 and 75 years old
• scheduled for interventional ERCP

Exclusion Criteria:

• patients receiving opioids or other analgesics, sedatives, hypnotics
• allergic to drugs used in the study protocol
• alcoholism
• refuse to sign the informed consent and chronic pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remifentanil; Remifentanil 1 microgram/kg/h along with propofol infusion	Drug: Remifentanil; 1 microgram/kg/h, continuous infusion, 5 min before and during the ERCP; Other Names: Ultiva
Active Comparator: Fentanyl; Fentanyl 200 micrograms intranasally	Drug: Fentanyl; Intranasal fentanyl 200 micrograms 5 min before the ERCP
Placebo Comparator: Normal saline; Normal saline intravenously and intranasally	Drug: Normal saline; Normal saline intravenously and intranasally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Propofol requirements	30 min, 60 min and if not full recovery 120 min

Secondary Outcome Measures

Outcome Measure	Time Frame
Speed of recovery	30, 60 and 120 min
postoperative pain	30, 60, and 120 minutes
early cognitive function	30, 60, and 120 minutes
patient satisfaction	30, 60, and 120 minutes
endoscopist satisfaction	30, 60, and 120 minutes

Collaborators and Investigators

• Sponsor: University of Athens

Publications and helpful links

General Publications

• Fassoulaki A, Iatrelli I, Vezakis A, Polydorou A. Deep sedation for endoscopic cholangiopancreatography with or without pre or intraprocedural opioids: A double-blind randomised controlled trial. Eur J Anaesthesiol. 2015 Sep;32(9):602-8. doi: 10.1097/EJA.0000000000000187.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: February 24, 2011
• First Submitted That Met QC Criteria: February 24, 2011
• First Posted (Estimate): February 25, 2011

Study Record Updates

• Last Update Posted (Estimate): August 5, 2013
• Last Update Submitted That Met QC Criteria: August 2, 2013
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: satisfaction; recovery; fentanyl; ERCP; Propofol; remifentanil; respiratory depression; Quality of sedation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Remifentanil; Fentanyl
• Other Study ID Numbers: M-17, M-18/21-12-2010