Comparison of Metoprolol and Tramadol With Remifentanil in Endoscopic Sinus Surgery

• ClinicalTrials.gov Identifier: NCT02484859
• Recruitment Status: Completed
• First Posted: June 30, 2015
• Results First Posted: September 10, 2019
• Last Update Posted: September 17, 2019
• Sponsor: Rize Üniversitesi
• Information provided by (Responsible Party): Başar Erdivanlı, Rize Üniversitesi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Nasal Polyps	Drug: Remifentanil; Drug: Tramadol; Drug: Metoprolol	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Comparison of Normotensive Anesthesia Using a Combination of Metoprolol and Tramadol With Controlled Hypotension Using Remifentanil in Endoscopic Sinus Surgery
• Study Start Date: July 2015
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: February 2016

Arms and Interventions

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 Name: 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 Name: Contramal; Drug: Metoprolol; 0.1 mg/kg of metoprolol will be administered intravenously within 5 minutes following the administration of neuromuscular blocking agent.; Other Name: Beloc

Outcome Measures

Primary Outcome Measures :

1. Intraoperative Bleeding Score [ Time Frame: throughout surgery, up to 3 hours ]

   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.

Secondary Outcome Measures :

1. Time to Achieve Intraoperative Bleeding Score < 3 [ Time Frame: 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.
2. Bleeding Rate [ Time Frame: 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).
3. Postoperative Pain [ Time Frame: 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.
4. Number of Participants With Postoperative Nausea and Vomiting [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Turkey

Recep Tayyip Erdogan University

Rize, Eastern Blacksea, Turkey, 53100

Sponsors and Collaborators

Rize Üniversitesi

Investigators

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

More Information

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.

• Responsible Party: Başar Erdivanlı, Asst. Prof., Rize Üniversitesi
• ClinicalTrials.gov Identifier: NCT02484859
• Other Study ID Numbers: 2015/14
• First Posted: June 30, 2015
• Results First Posted: September 10, 2019
• Last Update Posted: September 17, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

Keywords provided by Başar Erdivanlı, Rize Üniversitesi:

Drug: remifentanil; Drug: tramadol; Drug: metoprolol; Functional endoscopic sinus surgery; Controlled hypotension

Additional relevant MeSH terms:

Nasal Polyps; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Metoprolol; Remifentanil; Tramadol; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action