A Phase 4 interventional study of Fentanyl dosing schemes in Hyperalgesia, Opioid Use and Pain, Postoperative, sponsored by University Hospital, Ghent. Completed at 1 site in Belgium. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-19.
Sponsored by University Hospital, Ghent · Phase 4, Interventional, and Prevention
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.
A prospective, randomized, double-blinded (patient, anesthesiologist, assessor) clinical study. This study will examine three different clinically used application schemes of fentanyl, an opioid used as the standard of care in routine practice. Patients will be randomized to receive one of the following three treatment arms for anesthesia maintenance (pre-sternotomy):
Continuous fentanyl application by Shibutani scheme
This study will include data from 69 adult patients (23 per arm) undergoing first time, elective, on-pump CABG surgery with median sternotomy and central cannulation.
Following randomization by the sealed envelope technique, fentanyl kits will be drawn up by an anesthesiologist not involved in patient care or outcome assessment. Patients with preexisting chronic pain, opioids in the last 30 days, a BMI>36kg/m2, sleep apnoea, renal failure (clearance \<30ml/min), with neuraxial anesthesia, pregnant, with planned wound infiltration, known allergies/intolerance to opioids, and unable to understand pin-prick testing will be excluded.
At induction, all patients will receive a standard 3 µg/kg bolus of fentanyl (not study medication, but rather standard of care). 5 minutes prior to sternotomy, the patient will receive analgesia maintenance (one of the three fentanyl study arms). Clinicians will at all times be able to administer a bolus of fentanyl on a perceived "as needed" basis (not study medication, but rather standard of care).
The primary objective of this trial is to assess whether or not different intraoperative dosing schemes of fentanyl during on-pump CABG surgery influence the area of hyperalgesia as measured by sternal pin-prick testing on the first postoperative day. As the mechanisms causing opioid-induced analgesia are poorly understood but appear to be dosis-related, the investigators will examine 3 clinically used fentanyl application schemes in cardiac surgery: 1) a high-dose bolus group, 2) a low-dose bolus group, and 3) a low-dose continuous infusion group.
[i.e. does fentanyl dosing influence the area of hyperalgesia?]
The secondary objectives of this trial are 1) to explore the intraoperative concentrations of fentanyl in these various dosing schemes during and after extracorporeal circulation (ECC).
[i.e. determine the time course of fentanyl with ECC and its association with hyperalgesia; explorative] 2) to explore a possible association between fentanyl dosing, hyperalgesia, and persisting pain 3, 6, and 12 months after surgery.
[i.e. clinical implication on persistent/chronic pain; explorative]
Exclusion Criteria:
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
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
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
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.
Area of hyperalgesia at 24h
Determination of secondary, wound hyperalgesia by pin prick (256mN von Frey filament)
Time frame: 24 hours after surgery (+/- 3 hours)
Area of hyperalgesia at 48h
Determination of secondary, wound hyperalgesia by pin prick (256mN von Frey filament)
Time frame: 48 hours after surgery (+/- 3 hours)
Area of allodynia at 24h
Determination of allodynia by cotton swab
Time frame: 24 hours after surgery (+/- 3 hours)
Area of allodynia at 48h
Determination of allodynia by cotton swab
Time frame: 48 hours after surgery (+/- 3 hours)
Persistent Pain at 3 months
Validated questionnaire to assess pain after by1) mail and 2) phone follow-up
Time frame: 3 months after surgery (+/- 1 week)
Persistent Pain at 6 months
Validated questionnaire to assess pain after by1) mail and 2) phone follow-up
Time frame: 6 months after surgery (+/- 1 week)
Persistent Pain at 12 months
Validated questionnaire to assess pain after by1) mail and 2) phone follow-up
Time frame: 12 months after surgery (+/- 1 week)
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run as specified by the time frame of this outcome and the following outcomes.
Time frame: 5 min. (+/- 1 min) prior to sternotomy, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 5 min. (+/- 1 min) after fentanyl/placebo bolus, given just prior to sternotomy
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 30 min. (+/- 1 min) after fentanyl/placebo bolus, given just prior to sternotomy
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: just prior (<1min) to start of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 5 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 20 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 40 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 60 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 80 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 100 min. (+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 120 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 140 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 160 min.(+/- 1 min) after begin of pump run, a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: 5 min.(+/- 1 min) after end of pump run,a surgical step
Description of perioperative fentanyl concentrations with on-pump extra corporeal circulation
Fentanyl will be measured from samples taken prior to, during, and after a pump run
Time frame: end of surgery (+/- 5 min)
Plan to share: Undecided
No publications or documents are linked to this record.
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University Hospital, Ghent