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

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.

Study Overview

• Status: Completed
• Conditions: Nasal Polyps
• Intervention / Treatment: Drug: Remifentanil; Drug: Tramadol; Drug: Metoprolol

Detailed Description

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 Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey
  • Eastern Blacksea
    • Rize, Eastern Blacksea, Turkey, 53100
      • Recep Tayyip Erdogan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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
Active Comparator: 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	throughout surgery, up to 3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	throughout surgery, up to 20 minutes
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).	throughout surgery, up to 3 hours
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.	following extubation, up to 24 hours
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.	following extubation, up to 24 hours

Collaborators and Investigators

• Sponsor: Recep Tayyip Erdogan University
• Investigators: Principal Investigator: Başar Erdivanlı, Asst. Prof., Recep Tayyip Erdogan University, Medical Faculty, Department of Anesthesiology

Publications and helpful links

General Publications

• Hosemann W, Draf C. Danger points, complications and medico-legal aspects in endoscopic sinus surgery. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2013 Dec 13;12:Doc06. doi: 10.3205/cto000098.
• Cincikas D, Ivaskevicius J, Martinkenas JL, Balseris S. A role of anesthesiologist in reducing surgical bleeding in endoscopic sinus surgery. Medicina (Kaunas). 2010;46(11):730-4.
• Lin D, Dalgorf D, Witterick IJ. Predictors of unexpected hospital admissions after outpatient endoscopic sinus surgery: retrospective review. J Otolaryngol Head Neck Surg. 2008 Jun;37(3):309-11.
• Komatsu R, Turan AM, Orhan-Sungur M, McGuire J, Radke OC, Apfel CC. Remifentanil for general anaesthesia: a systematic review. Anaesthesia. 2007 Dec;62(12):1266-80. doi: 10.1111/j.1365-2044.2007.05221.x.
• Rathjen T, Bockmuhl U, Greim CA. [Modern anesthesiologic concepts supporting paranasal sinus surgery]. Laryngorhinootologie. 2006 Jan;85(1):20-3. doi: 10.1055/s-2005-870562. German.
• Khalil HS, Nunez DA. Functional endoscopic sinus surgery for chronic rhinosinusitis. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004458. doi: 10.1002/14651858.CD004458.pub2.
• Sartcaoglu F, Celiker V, Basgul E, Yapakci O, Aypar U. The effect of hypotensive anaesthesia on cognitive functions and recovery at endoscopic sinus surgery. Eur J Anaesthesiol. 2005 Feb;22(2):157-9. doi: 10.1017/s0265021505230284. No abstract available.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: June 19, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimated): June 30, 2015

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Functional endoscopic sinus surgery; Drug: remifentanil; Drug: tramadol; Drug: metoprolol; Controlled hypotension
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Polyps; Nasal Polyps; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Remifentanil; Tramadol; Metoprolol
• Other Study ID Numbers: 2015/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are still evaluating the guideline of the Medical Research Council (MRC) Hubs for Trials Methodology Research (HTMR) for individual participant data sharing.