Remifentanil and Fentanyl in Dental Surgery (REFEDS)

Study Overview
=================
Brief Summary
-----------------
This study was a prospective comparative study. The purpose of this study was to investigate the hypothesis whether remifentanil compared to fentanyl can induce less inflammatory and stress response to the day-case dental surgery in Persons with special needs (PSN). Secondary aims were to investigate comparatively their effect on patients intraoperative hemodynamic response and postoperative analgesia.

Detailed Description
-----------------
The study included 46 adult patients with cognitive impairment who underwent day-case dental surgery under general anesthesia with propofol aiming to keep a BIS-values range between 40-45. Nasal tracheal intubation was performed in all patients while neuromuscular blockade was achieved by rocuronium 0.6 mg/kg iv and repetitive doses of rocuronium of 10 mg iv, if needed. Patients were randomly allocated receive for intraoperative analgesia either fentanyl 50 μg iv bolus (group F, n=23) or continuous infusion of remifentanil 0.5-1 μg/kg/min (group R, n=23). Randomization was performed using using a computer-generated randomization schedule. Intraoperatively, patients in both groups received IV granisetron 3 mg, methylprednisolone 125 mg and clindamycin 600 mg, while atropine 0.02 mg/kg and neostigmine (0.05 mg/kg) was administered to to reverse neuromuscular blockade. Intraoperative monitoring included non-invasive measurement of arterial blood pressure, electrocardiogram, pulse oxymetry, capnography and Bispectral Sedation Index (BIS®). Postoperatively, patients remained under surveillance in the post-anesthesia care unit [PACU] for 3 h. Postoperative pain was assessed for the first 12 postoperative hours, at 30 min time-intervals for the first 3 hours, and every 3 hours thereafter by an independent observer, blinded to the study group, using the Wong-Baker faces pain rating scale (0-6). If pain scores were ≥3 a rescue dose of paracetamol 12.5 mg/kg iv was administered. Inflammation markers and stress hormones [cortisol, Tumor necrosis factor (TNF-a), substance-P, melatonin and β-endorphin] were measured in each patient before induction of anesthesia, after tracheal intubation and at the end of operation. Statistical Analysis was performed using Kolmogorov-Smirnov test, Student's unpaired t-test or Repeated Measures ANOVA with Holm's post-hoc analysis appropriately. A p value less than 0.05 was considered statistically significant.

Official Title
-----------------
Remifentanil vs Fentanyl During Day Case Dental Surgery in Persons With Special Needs: a Comparative Study of Their Effect on Stress Response and Postoperative Pain

Conditions
-----------------
Postoperative Pain

Intervention / Treatment
-----------------
* Drug: Remifentanil
* Drug: Fentanyl


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with cognitive impairment of category II according to the American Society of Anesthesiology (ASA) classification scheduled for elective dental surgery with short duration Exclusion Criteria: Patients of more than category II of American Society of Anesthesiology (ASA) classification Prolonged duration of surgery (>1 hour)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remifentanil<br>Drug: Remifentanil (Ultiva). Intraoperative intravenous infusion of remifentanil 0.5-1 μg/kg/min for up to 1 h. | Drug: Remifentanil<br>* Intraoperative continuous infusion of remifenatanil. Remifentanil infusion was interrupted upon completion of surgical intervention.<br>* Other names: Ultiva;Drug: Fentanyl<br>* Fentanyl 50 μg iv bolus at the induction of anesthesia and before the start of surgery.<br>* Other names: FNT;|
| Active Comparator: Fentanyl<br>Drug: Fentanyl (FNT). Intraoperative administration of fentanyl given as one single bolus dose of 50 μg at the time of induction of anesthesia. | Drug: Remifentanil<br>* Intraoperative continuous infusion of remifenatanil. Remifentanil infusion was interrupted upon completion of surgical intervention.<br>* Other names: Ultiva;Drug: Fentanyl<br>* Fentanyl 50 μg iv bolus at the induction of anesthesia and before the start of surgery.<br>* Other names: FNT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline plasma cortisol values at 1 hour | Plasma cortisol values were measured with an ELISA kit as mg/dl | At 1 hour after the induction of anesthesia and surgery | 
| Change from baseline plasma tumor necrosis factor-α (TNF-α) values at 1 hour | Tumor necrosis factor-α (TNF-α) measurement was performed with Elisa immunoenzyme assay as pg/ml | At 1 hour after the induction of anesthesia and surgery | 
| Change from baseline plasma substance-P values at 1 hour | Substance-P measurement was performed with Elisa immunoenzyme assay as ng/ml | At 1 hour after the induction of anesthesia and surgery | 
| Change from baseline plasma melatonin values at 1 hour | Melatonin measurement was performed with Elisa immunoenzyme assay as pg/ml | At 1 hour after the induction of anesthesia and surgery | 
| Change from baseline plasma β-endorphin values at 1 hour | β-endorphin was measured with Elisa immunoenzyme assay as ng/ml | At 1 hour after the induction of anesthesia and surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in intraoperative systolic arterial blood pressure values (mm Hg) between the two study groups | Measurements before the induction of anesthesia (baseline values) and at and 60 min (1 hour) after the induction of anesthesia | 1 hour | 
| Differences in intraoperative heart rate values (bmp) between the two study groups | Measurements before the induction of anesthesia (baseline values) and at 60 min (1 hour) after the induction of anesthesia | 1 hour | 
| Differences in postoperative pain scores scores between the two study groups | Pain was assessed using the Wong-Baker faces pain rating scale (0-6) at 12 postoperative hours | Up to 12 postoperative hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
remifentanil, fentanyl, dental surgery