Trial Outcomes & Findings for Comparison of Metoprolol and Tramadol With Remifentanil in Endoscopic Sinus Surgery (NCT NCT02484859)

Last Updated: 2023-12-20

Results Overview

Intraoperative bleeding score is reported by the surgeon according to Boezaart Surgical Field Grading scale. The scale ranges from 0 to 5. '0' is the best, and '5' is the worst outcome. The scale construct is: 0 No bleeding. 1. Slight bleeding, no suction is required. 2. Slight bleeding, occasional suctioning required. 3. Slight bleeding, frequent suctioning required. Bleeding threatens surgical field a few seconds after suction is removed. 4. Moderate bleeding, frequent suctioning required. Bleeding threatens surgical field as soon as suction is removed. 5. Severe bleeding, constant suctioning required. Bleeding appears faster than suctioning. Thoroughout the intraoperative period, the surgeon is free to report a score at any time he/she sees appropriate.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

88 participants

Primary outcome timeframe

throughout surgery, up to 3 hours

Results posted on

2023-12-20

Participant Flow

Recruitment period started at 27.06.2015. Recruitment was performed by an anaesthesiologist at the outpatient polyclinic for anaesthesiology.

A total of 105 patients were evaluated. Three patients declined to participate in the study. Eleven patients did not meet inclusion criteria. On 29 December 2015, we reached the target number of patients (88). Since patients were matched for severity of sinonasal disease, we evaluated three more patients anticipating possible dropouts.

Participant milestones

Participant milestones
Measure	Remifentanil Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Overall Study STARTED	44	44
Overall Study COMPLETED	44	44
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Metoprolol and Tramadol With Remifentanil in Endoscopic Sinus Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Remifentanil n=44 Participants Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 Participants Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.	Total n=88 Participants Total of all reporting groups
Age, Continuous	37.8 years STANDARD_DEVIATION 10.1 • n=5 Participants	39.3 years STANDARD_DEVIATION 10.6 • n=7 Participants	38.6 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	32 Participants n=7 Participants	60 Participants n=5 Participants
American Society of Anesthesiologists physical status 1	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
American Society of Anesthesiologists physical status 2	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Lund-Mackay score	12 units on a scale n=5 Participants	10 units on a scale n=7 Participants	11 units on a scale n=5 Participants
Prothrombin time	13.1 seconds STANDARD_DEVIATION 0.5 • n=5 Participants	13.4 seconds STANDARD_DEVIATION 0.6 • n=7 Participants	13.3 seconds STANDARD_DEVIATION 0.6 • n=5 Participants
Partial thromboplastin time	30.6 seconds STANDARD_DEVIATION 2.2 • n=5 Participants	29.7 seconds STANDARD_DEVIATION 2.2 • n=7 Participants	30.1 seconds STANDARD_DEVIATION 2.3 • n=5 Participants
International normalized ratio	1.01 international normalized ratio STANDARD_DEVIATION 0.07 • n=5 Participants	1.02 international normalized ratio STANDARD_DEVIATION 0.08 • n=7 Participants	1.01 international normalized ratio STANDARD_DEVIATION 0.07 • n=5 Participants
Haemoglobin	14.1 grams per deciliter STANDARD_DEVIATION 1.3 • n=5 Participants	14.2 grams per deciliter STANDARD_DEVIATION 1.3 • n=7 Participants	14.2 grams per deciliter STANDARD_DEVIATION 1.3 • n=5 Participants
Platelet count	236 10^3 platelets per microliter STANDARD_DEVIATION 69 • n=5 Participants	242 10^3 platelets per microliter STANDARD_DEVIATION 69 • n=7 Participants	239 10^3 platelets per microliter STANDARD_DEVIATION 69 • n=5 Participants

PRIMARY outcome

Timeframe: throughout surgery, up to 3 hours

Outcome measures

Outcome measures
Measure	Remifentanil n=44 Participants Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 Participants Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Intraoperative Bleeding Score	1 units on a scale Interval 1.0 to 1.0	1 units on a scale Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: throughout surgery, up to 20 minutes

The intraoperative bleeding score will be reported by the surgeon throughout surgery. At the start of the surgery, a timer will be used to measure the duration to achieve a bleeding score of 2.

Outcome measures

Outcome measures
Measure	Remifentanil n=44 Participants Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 Participants Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Time to Achieve Intraoperative Bleeding Score < 3	8.3 minutes Standard Deviation 2.1	13.4 minutes Standard Deviation 4.2

SECONDARY outcome

Timeframe: throughout surgery, up to 3 hours

In the end of each surgery, bleeding rate will be calculated as ml/min by dividing total bleeding (amount of blood in the graded suction and sponges minus total irrigation fluid) to the duration of surgery (excluding local anesthetic infiltration, and nasal packing).

Outcome measures

Outcome measures
Measure	Remifentanil n=44 Participants Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 Participants Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Bleeding Rate	0.53 ml/min Standard Deviation 0.2	0.45 ml/min Standard Deviation 0.15

SECONDARY outcome

Timeframe: following extubation, up to 24 hours

Postoperative pain scores on the day of surgery will be evaluated with a visual analog scale (0: no pain, 10: worst pain ever) at the post anaesthetic care unit (PACU), and the surgical ward. The evaluation will begin after the patient arrives at the post anaesthetic care unit, and will continue for 24 hours.

Outcome measures

Outcome measures
Measure	Remifentanil n=44 Participants Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 Participants Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Postoperative Pain VAS at arrival to PACU	3 units on a scale Interval 2.0 to 6.0	3 units on a scale Interval 2.0 to 3.0
Postoperative Pain VAS at discharge from PACU	4 units on a scale Interval 3.0 to 5.0	4 units on a scale Interval 3.0 to 5.0

SECONDARY outcome

Timeframe: following extubation, up to 24 hours

Postoperative nausea, retching, and vomiting on the day of surgery will be evaluated with a four-point ordinal scale (0-none, 1-nausea, 2-retching, 3-vomiting) at the post anaesthetic care unit, and the surgical ward. The evaluation will begin after the patient arrives at the post anaesthetic care unit, and will continue for 24 hours.

Outcome measures

Outcome measures
Measure	Remifentanil n=44 Participants Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 Participants Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Number of Participants With Postoperative Nausea and Vomiting	14 Participants	10 Participants

Adverse Events

Remifentanil

Serious events: 21 serious events

Other events: 0 other events

Deaths: 0 deaths

Tramadol + Metoprolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Remifentanil n=44 participants at risk Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 participants at risk Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Cardiac disorders Intraoperative hypotension	6.8% 3/44 • Number of events 8 • 6 months Adverse event data were collected during the whole study period.	0.00% 0/44 • 6 months Adverse event data were collected during the whole study period.
Cardiac disorders Intraoperative bradycardia	40.9% 18/44 • Number of events 44 • 6 months Adverse event data were collected during the whole study period.	0.00% 0/44 • 6 months Adverse event data were collected during the whole study period.
Blood and lymphatic system disorders Intraoperative bleeding	0.00% 0/44 • 6 months Adverse event data were collected during the whole study period.	0.00% 0/44 • 6 months Adverse event data were collected during the whole study period.

Other adverse events

Other adverse events
Measure	Remifentanil n=44 participants at risk Following an intravenous bolus dose of 0.5 µg/kg remifentanil administered just before the induction of anaesthesia, patients will receive an intravenous infusion of remifentanil at a dose of 0.25-0.5 µg/kg/min throughout the surgery. The rate of infusion will be adjusted to maintain a mean blood pressure within %70-80 of the baseline value. At the end of the surgery, the rate of infusion will be decreased to 0.05 µg/kg/min, and continued until the patient is extubated.	Tramadol + Metoprolol n=44 participants at risk Just before the induction of anaesthesia, an intravenous infusion of 1 mg/kg of tramadol in 100 ml isotonic fluid will be started. The infusion will be completed in 30 minutes using a perfusor. Additionally, following the administration of the neuromuscular blocking agent, 0.1 mg/kg of intravenous metoprolol will be administered within 5 minutes.
Cardiac disorders Adverse hemodynamic event in the surgical ward	0.00% 0/44 • 6 months Adverse event data were collected during the whole study period.	0.00% 0/44 • 6 months Adverse event data were collected during the whole study period.

Additional Information

Dr. Başar Erdivanlı

Recep Tayyip Erdoğan Üniversitesi

Phone: 04642130491

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place