Nasal Polyps
Conditions
Keywords
Drug: remifentanil, Drug: tramadol, Drug: metoprolol, Functional endoscopic sinus surgery, Controlled hypotension
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.
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.
Interventions
DRUGRemifentanil
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.
DRUGTramadol
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.
DRUGMetoprolol
0.1 mg/kg of metoprolol will be administered intravenously within 5 minutes following the administration of neuromuscular blocking agent.
Sponsors
Recep Tayyip Erdogan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative Bleeding Score | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieve Intraoperative Bleeding Score < 3 | 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. |
| Bleeding Rate | 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). |
| Postoperative Pain | 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. |
| Number of Participants With Postoperative Nausea and Vomiting | 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. |
Countries
Turkey (Türkiye)
Participant flow
Recruitment details
Recruitment period started at 27.06.2015. Recruitment was performed by an anaesthesiologist at the outpatient polyclinic for anaesthesiology.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 44 |
| 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. | 44 |
| Total | 88 |
Baseline characteristics
| Characteristic | Remifentanil | Total | Tramadol + Metoprolol |
|---|---|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 10.1 | 38.6 years STANDARD_DEVIATION 10.3 | 39.3 years STANDARD_DEVIATION 10.6 |
| American Society of Anesthesiologists physical status 1 | 24 Participants | 49 Participants | 25 Participants |
| American Society of Anesthesiologists physical status 2 | 20 Participants | 39 Participants | 19 Participants |
| Haemoglobin | 14.1 grams per deciliter STANDARD_DEVIATION 1.3 | 14.2 grams per deciliter STANDARD_DEVIATION 1.3 | 14.2 grams per deciliter STANDARD_DEVIATION 1.3 |
| International normalized ratio | 1.01 international normalized ratio STANDARD_DEVIATION 0.07 | 1.01 international normalized ratio STANDARD_DEVIATION 0.07 | 1.02 international normalized ratio STANDARD_DEVIATION 0.08 |
| Lund-Mackay score | 12 units on a scale | 11 units on a scale | 10 units on a scale |
| Partial thromboplastin time | 30.6 seconds STANDARD_DEVIATION 2.2 | 30.1 seconds STANDARD_DEVIATION 2.3 | 29.7 seconds STANDARD_DEVIATION 2.2 |
| Platelet count | 236 10^3 platelets per microliter STANDARD_DEVIATION 69 | 239 10^3 platelets per microliter STANDARD_DEVIATION 69 | 242 10^3 platelets per microliter STANDARD_DEVIATION 69 |
| Prothrombin time | 13.1 seconds STANDARD_DEVIATION 0.5 | 13.3 seconds STANDARD_DEVIATION 0.6 | 13.4 seconds STANDARD_DEVIATION 0.6 |
| Sex: Female, Male Female | 16 Participants | 28 Participants | 12 Participants |
| Sex: Female, Male Male | 28 Participants | 60 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 44 | 0 / 44 |
| serious Total, serious adverse events | 21 / 44 | 0 / 44 |
Outcome results
Primary
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. 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.
Time frame: throughout surgery, up to 3 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remifentanil | Intraoperative Bleeding Score | 1 units on a scale |
| Tramadol + Metoprolol | Intraoperative Bleeding Score | 1 units on a scale |
Comparison: Median intraoperative bleeding scores were compared with Wilcoxon test. In this pilot study the power analysis showed that a sample size of 44 patients in each group was sufficient to detect a difference of 0.2 in the mean (standard deviation of 0.4) with an 80% power with an alpha error of 0.05 and a beta error of 20%. The Shapiro-Wilk test was used to test the distribution of data.p-value: >0.69Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: throughout surgery, up to 3 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Bleeding Rate | 0.53 ml/min | Standard Deviation 0.2 |
| Tramadol + Metoprolol | Bleeding Rate | 0.45 ml/min | Standard Deviation 0.15 |
p-value: 0.052t-test, 2 sided
Secondary
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.
Time frame: following extubation, up to 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remifentanil | Number of Participants With Postoperative Nausea and Vomiting | 14 Participants |
| Tramadol + Metoprolol | Number of Participants With Postoperative Nausea and Vomiting | 10 Participants |
p-value: 0.47Chi-squared
Secondary
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.
Time frame: following extubation, up to 24 hours
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remifentanil | Postoperative Pain | VAS at arrival to PACU | 3 units on a scale |
| Remifentanil | Postoperative Pain | VAS at discharge from PACU | 4 units on a scale |
| Tramadol + Metoprolol | Postoperative Pain | VAS at arrival to PACU | 3 units on a scale |
| Tramadol + Metoprolol | Postoperative Pain | VAS at discharge from PACU | 4 units on a scale |
Comparison: Null hypothesis was that the visual analog pain scores (VAS) of patients at arrrival to post anesthetic care unit (PACU) were similar.p-value: 0.05Chi-squared
Comparison: Null hypothesis was that the visual analog pain scores (VAS) of patients at discharge from post anesthetic care unit (PACU) were similar.p-value: 0.55Chi-squared
Secondary
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.
Time frame: throughout surgery, up to 20 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Time to Achieve Intraoperative Bleeding Score < 3 | 8.3 minutes | Standard Deviation 2.1 |
| Tramadol + Metoprolol | Time to Achieve Intraoperative Bleeding Score < 3 | 13.4 minutes | Standard Deviation 4.2 |
p-value: <0.001t-test, 2 sided