Optimal Sedation Analgesia In Upper Gastrointestinal Endoscopic Interventions Determination and Comparison of Median Effective Target Concentration of Propofol In Combination With Fentanyl versus Remifentanil PERFS

Background and purpose

Endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic ultrasound (EUS) are complex and time consuming procedures that require optimal sedation and analgesia. Propofol target controlled infusion (TCI) is commonly used at our institution in combination with either fentanyl bolus or remifentanil TCI. However, there is a paucity in literature regarding the median effective effect site concentration (EC50, Ce) of propofol for sedation in such time consuming endoscopic procedures, especially when used with remifentanil TCI. This study is being proposed to compare propofol fentanyl and propofol remifentanil regimens when used via TCI at the predetermined median effective target

concentration (EC50) of propofol. The study will be done in two parts. Part 1 will determine the EC50 and EC95 of propofol with fentanyl and remifentanil combinations. Part 2 of the study will compare the two regimens in terms of efficacy of sedation and incidence of sedation related adverse effects.

Methodology

The study will be done in two parts

Part 1 Determination of EC50 and EC90 of propofol

Participants will be randomly allotted to one of two groups:

Group F Fentanyl bolus of 0.5 mcg/kg

Group R Remifentanil TCI at Ce of 2 ng/mL

The EC50 and EC90 of propofol will be determined for both groups using the Dixon up and down sequential allocation method. The first participant in both will receive an initial effect site concentration (Ce) of 2 mcg/ml. The subsequent participants initial starting Ce will be determined based on the response of the previous participant. Propofol Ce will be increased in step size of 0.5 mcg/mL for rescue in case of unsuccessful sedation.

In case of unsuccessful sedation or positive response, the starting Ce of Propofol will be increased by a step size of 0.5 mcg/mL in the subsequent patient. In case of successful sedation or negative response, the starting Ce of Propofol will be decreased by 0.5 mcg/mL in the subsequent patient.

Successful sedation is defined as

MOASS score 2

Patient does not exhibit gag, cough, purposeful bodily movement throughout the procedure.

Part 2

Randomised controlled trial between the two groups at the determined EC90 of propofol.

Participants will be randomly allotted to one of two groups

Group F Fentanyl bolus of 0.5 mcg/kg

Group R Remifentanil TCI at Ce of 2 ng/mL

Both groups of participants will receive propofol TCI at the determined EC90. The primary outcome is the incidence of adverse effects. The secondary outcome will be

Recovery Time - Time to regain MOASS  5 after stopping TCI.

Endoscopist satisfaction (4 point Likert scale -  excellent, good, acceptable and poor)

Patient satisfaction (4 point Likert scale -  excellent, good, acceptable and poor)

Mean total propofol consumption - in mg/kg.