Remifentanil and Fentanyl in Dental Surgery (REFEDS) (REFEDS)

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Remifentanil; Drug: Fentanyl

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 12462
      • 2nd Department of Anesthesiology, Attikon University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remifentanil; Drug: Remifentanil (Ultiva). Intraoperative intravenous infusion of remifentanil 0.5-1 μg/kg/min for up to 1 h.	Drug: Remifentanil; Intraoperative continuous infusion of remifenatanil. Remifentanil infusion was interrupted upon completion of surgical intervention.; Other Names: Ultiva; Drug: Fentanyl; Fentanyl 50 μg iv bolus at the induction of anesthesia and before the start of surgery.; Other Names: FNT
Active Comparator: Fentanyl; 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; Intraoperative continuous infusion of remifenatanil. Remifentanil infusion was interrupted upon completion of surgical intervention.; Other Names: Ultiva; Drug: Fentanyl; Fentanyl 50 μg iv bolus at the induction of anesthesia and before the start of surgery.; 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

Collaborators and Investigators

• Sponsor: Attikon Hospital
• Collaborators: Asklepieion Voulas General Hospital
• Investigators: Principal Investigator: Eirini A Sklika, Consultant, Asklepeion Voulas General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: November 25, 2015
• First Submitted That Met QC Criteria: November 30, 2015
• First Posted (Estimate): December 2, 2015

Study Record Updates

• Last Update Posted (Estimate): December 2, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: fentanyl; remifentanil; dental surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Remifentanil; Fentanyl
• Other Study ID Numbers: ATT968