Title

Comparison of Metoprolol and Tramadol With Remifentanil in Endoscopic Sinus Surgery
Comparison of Normotensive Anesthesia Using a Combination of Metoprolol and Tramadol With Controlled Hypotension Using Remifentanil in Endoscopic Sinus Surgery
  • Phase

    Phase 4
  • Study Type

    Interventional
  • Study Participants

    88
Functional endoscopic sinus surgery (FESS) is indicated in diseases such as chronic sinusitis refractory to medical treatment, nasal polyposis, mass lesions in the nasal cavity. The purpose of this study is to determine whether tramadol and metoprolol are as effective as remifentanil in providing controlled hypotension during FESS.
This study aims to compare two techniques for controlled hypotension during FESS. In both cases, the patients will be evaluated during the preoperative anesthetic visit, and will be given care by an anesthesiologist during the perioperative period.

Patients who are scheduled for an elective FESS operation will be included in the study. During the preoperative anaesthetic visit, patients who do not meet any of the the exclusion criteria will be offered to participate in hte study. Patients accepting to contribute tot he study will be randomised into one of the two groups via closed envelope technique.

A pilot study with 20 patients resulted in similar means and slightly different standard deviations of mean blood pressure. This pilot study showed that 44 patients in each group are sufficient to obtain 80% power with an alpha error of 0.05 and beta error of 20%. To compensate for missing/inconsistent data, or allow for better matching of the demographic variables, 3-5 additional patients will be recruited.

The anesthesiologist in charge of the patient will not be blinded to the groups, and will be responsible for maintaining the hypotension (and patient safety) with either remifentanil in one group, or tramadol and metoprolol in the other group. Systolic, diastolic, and mean blood pressures, and heart rate will be recorded into a spreadsheet every three minutes during the anaesthetic and surgical period. The data will be recorded via an excel form, which will validate the entries upon entrance. The accuracy and completeness of registry data will be verified by a third investigator, who will compare the registry data to the medical monitor records at the end of each operative day.

The surgeon will be blinded to the groups, and will be responsible for scoring the surgical vision and bleeding with the intraoperative bleeding score. The study drugs will be administered via the same type of infusion pump to facilitate the blinding process.

Any adverse event will be reported in the patient chart and study records.

Statistical analysis will be carried out using R and Statistical Package for the Social Sciences (SPSS) programs. Demographic variables (age, gender, American Society of Anesthesiologists (ASA) score, comorbidities) will be analysed using descriptive statistics. Study variables such as duration of operation, variance of the hemodynamic parameters, amount of bleeding, bleeding score, occurrence of adverse events will be analysed with the appropriate statistical tests.
Study Started
Jul 31
2015
Primary Completion
Dec 31
2015
Study Completion
Feb 29
2016
Results Posted
Sep 10
2019
Last Update
Sep 17
2019

Drug Remifentanil

Remifentanil infusion will be started with a bolus dose of 0.5 µg/kg before the induction, and will be continued throughout the surgery at a dose of 0.25-0.5 µg/kg/min. 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.

  • Other names: Ultiva

Drug Tramadol

1 mg/kg tramadol will be added to 100 ml of isotonic fluid, and will be administered intravenously in exactly 30 minutes via a perfusor. The infusion will be started just before the induction.

  • Other names: Contramal

Drug Metoprolol

0.1 mg/kg of metoprolol will be administered intravenously within 5 minutes following the administration of neuromuscular blocking agent.

  • Other names: Beloc

remifentanil Active Comparator

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 Active Comparator

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.

Criteria

Inclusion Criteria:

diagnosis of rhinosinusitis
indication for functional endoscopic sinus surgery

Exclusion Criteria:

American Society of Anesthesiologists risk score > 2
undertreated hypertension
Haemoglobin A1c test level > 7.5
pregnancy
concurrent surgery
history of drug abuse
history of or new diagnosis of allergy to any of the study drugs
history of post-operative nausea and vomiting

Summary

Remifentanil

Tramadol + Metoprolol

All Events

Event Type Organ System Event Term Remifentanil Tramadol + Metoprolol

Intraoperative Bleeding Score

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. Slight bleeding, no suction is required. Slight bleeding, occasional suctioning required. Slight bleeding, frequent suctioning required. Bleeding threatens surgical field a few seconds after suction is removed. Moderate bleeding, frequent suctioning required. Bleeding threatens surgical field as soon as suction is removed. 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.

Remifentanil

1.0
units on a scale (Median)
Inter-Quartile Range: 1.0 to 1.0

Tramadol + Metoprolol

1.0
units on a scale (Median)
Inter-Quartile Range: 1.0 to 1.0

Time to Achieve Intraoperative Bleeding Score < 3

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.

Remifentanil

8.3
minutes (Mean)
Standard Deviation: 2.1

Tramadol + Metoprolol

13.4
minutes (Mean)
Standard Deviation: 4.2

Bleeding Rate

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).

Remifentanil

0.53
ml/min (Mean)
Standard Deviation: 0.2

Tramadol + Metoprolol

0.45
ml/min (Mean)
Standard Deviation: 0.15

Postoperative Pain

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.

Remifentanil

VAS at arrival to PACU

3.0
units on a scale (Median)
Inter-Quartile Range: 2.0 to 6.0

VAS at discharge from PACU

4.0
units on a scale (Median)
Inter-Quartile Range: 3.0 to 5.0

Tramadol + Metoprolol

VAS at arrival to PACU

3.0
units on a scale (Median)
Inter-Quartile Range: 2.0 to 3.0

VAS at discharge from PACU

4.0
units on a scale (Median)
Inter-Quartile Range: 3.0 to 5.0

Number of Participants With Postoperative Nausea and Vomiting

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.

Remifentanil

Tramadol + Metoprolol

Total

88
Participants

Age, Continuous

38.6
years (Mean)
Standard Deviation: 10.3

Haemoglobin

14.2
grams per deciliter (Mean)
Standard Deviation: 1.3

International normalized ratio

1.01
international normalized ratio (Mean)
Standard Deviation: 0.07

Lund-Mackay score

11
units on a scale (Median)
Inter-Quartile Range: 7.0 to 14.25

Partial thromboplastin time

30.1
seconds (Mean)
Standard Deviation: 2.3

Platelet count

239
10^3 platelets per microliter (Mean)
Standard Deviation: 69

Prothrombin time

13.3
seconds (Mean)
Standard Deviation: 0.6

American Society of Anesthesiologists physical status

Sex: Female, Male

Overall Study

Remifentanil

Tramadol + Metoprolol