Hyperalgesia, Persistent Pain, and Fentanyl Dosing in On-Pump Coronary Artery Bypass Grafting

NCT03450161 | Completed Phase 4 DMC

• 2 other identifiers: AGO/2017/0052017-003278-15
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, double-blinded, three arm study in adult patients undergoing first time coronary artery bypass grafting (CABG) surgery with median sternotomy. The investigators will examine the effects of three fentanyl dosing schemes (high-dose bolus, low-dose bolus, continuous dose) on the area of hyperalgesia and allodynia at 24 and 48h as well as on persisting pain at 3, 6, and 12 months. Additionally, the investigators will measure fentanyl concentrations throughout anesthesia.

Conditions

Hyperalgesia; Opioid Use; Pain, Postoperative; Pain, Chronic

Outcome Measures

Primary Outcomes (1)

• Area of hyperalgesia at 24h

  Determination of secondary, wound hyperalgesia by pin prick (256mN von Frey filament)

  24 hours after surgery (+/- 3 hours)

Secondary Outcomes (21)

• Area of hyperalgesia at 48h

  48 hours after surgery (+/- 3 hours)

• Area of allodynia at 24h

  24 hours after surgery (+/- 3 hours)

• Area of allodynia at 48h

  48 hours after surgery (+/- 3 hours)

• Persistent Pain at 3 months

  3 months after surgery (+/- 1 week)

• Persistent Pain at 6 months

  6 months after surgery (+/- 1 week)

Study Arms (3)

High-Dose Bolus of Fentanyl

EXPERIMENTAL

5 minutes prior to sternotomy, patients will receive a fentanyl bolus of 20 mcg/kg BW (verum) and a perfusion pump with sodium chloride (NaCl 0.9%; placebo) will be begun according to the Shibutani dosing scheme. As in the other arms, patients will be induced with 3mcg/kg BW fentanyl and the treating physician may administer boli on an "as needed" basis.

Drug: Fentanyl dosing schemes

Low-Dose Bolus of Fentanyl

EXPERIMENTAL

5 minutes prior to sternotomy, patients will receive a fentanyl bolus of 3 mcg/kg BW (verum) and a perfusion pump with sodium chloride (NaCl 0.9%; placebo) will be begun according to the Shibutani dosing scheme. As in the other arms, patients will be induced with 3mcg/kg BW fentanyl and the treating physician may administer boli on an "as needed" basis.

Drug: Fentanyl dosing schemes

Continuous Dose of Fentanyl

EXPERIMENTAL

5 minutes prior to sternotomy, patients will receive a NaCl 0.9% bolus (placebo) and a perfusion pump with fentanyl (verum) will be begun according to the Shibutani dosing scheme. As in the other arms, patients will be induced with 3mcg/kg BW fentanyl and the treating physician may administer boli on an "as needed" basis.

Drug: Fentanyl dosing schemes

Interventions

Fentanyl dosing schemes DRUG

We routinely use fentanyl as the opioid of choice in CABG surgery. However, how much and whether or not to apply it in boli or continuously remain uncertain. We will apply 3 routinely used fentanyl dosing schemes in our hospital. To blind care-givers and patients, in each of the arms a bolus and a continous injection will occur, as delineated in the treatment arms.

Continuous Dose of Fentanyl; High-Dose Bolus of Fentanyl; Low-Dose Bolus of Fentanyl

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Consenting patients aged ≥18 years
• Undergoing first-time, elective, on-pump CABG surgery with median sternotomy and central cannulation.

You may not qualify if:

• Documentation of preexisting chronic pain as per electronic record
• Use of opioids in the last 30 days or history/documentation of opioid abuse as per electronic record
• BMI \> 35kg/m2 or history of obstructive sleep apnea syndrome
• Patients with renal failure (clearance \< 30 ml/min)
• Neuraxial anesthesia
• Pregnancy
• Planned wound infiltration with local anesthetics
• Known drug allergies or intolerance to fentanyl or other opioids
• Expected to be unable to understand pinprick/allodynia testing / follow-up questions

Sponsors & Collaborators

• University Hospital, Ghent: lead
• University Hospital, Basel, Switzerland: collaborator

Study Sites (1)

University Hospital Ghent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

MeSH Terms

Conditions

Hyperalgesia; Pain, Postoperative; Chronic Pain

Condition Hierarchy (Ancestors)

Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes; Pain

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Only an otherwise uninvolved anesthesiologist will know dosing schemes.
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, double-blinded, three arm study

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: March 1, 2018
• Study Start: May 14, 2018
• Primary Completion: February 1, 2020
• Study Completion: January 9, 2021
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

BE (1)