CClinicalTrials.gg
CompletedNCT03202134DIEPflapUpdated Feb 23, 2021Results posted

Impact of Opioid Free Anesthesia on Outcome After DIEPflap Surgery

An observational study in Major and Minor Surgical Complications, sponsored by AZ Sint-Jan AV. Completed at 1 site in Belgium. Open to female participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-02-23.

Sponsored by AZ Sint-Jan AV · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
204
Ages
18 Years to 75 Years
Sex
Female
01

Study summary

The Deep Inferior Epigastric Perforator free flap (DIEPflap) involves the transfer of abdominal tissue to the breast using microsurgery. Flap failure is rare today, but is devastating.

Blood flow in a DIEPflap decreases during the first hours. Many anesthetic factors like low cardiac output, hypothermia and surgical stress cause vasoconstriction or thrombosis.

A stable anesthesia during these long procedures improves flap perfusion. Postoperative nausea and vomiting (PONV) is frequent and might have an impact.

Opioid free anesthesia (OFA) reduces PONV. The anti-inflammatory and vasodilator effects of the drugs dexmedetomidine and lidocaine might improve free flap perfusion.

The primary outcome counted all complications. The secondary outcomes were PONV, pain, opioid consumption, skin flap temperature and length of hospital stay.

Patients get according to attending anesthesiologist an opioid or opioid free anesthesia without any randomization but based on availability of competence.

Read the detailed description

The investigators included all patients in the hospital database.belgium who underwent DIEPflap surgery between Jan 2014 and April 2019. All patients entering the hospital provided consent to allow retrospective data analysis without patient identification.

Because patient assignment to an operating day was determined without knowing who would perform the anesthesia on a few exceptions, the choice of opioid free anesthesia (OFA) or opioid anesthesia (OA) in most cases was random. Patients were classified as receiving OFA when no opioids were given pre- or intra- operatively until wound closure. Opioids given after wound closure were counted as post-operative opioids. Patients who received a lower dose of intra-operative opioids by using additives were still classified as OA. Post-operative opioid free analgesia was classified as receiving no opioids after wound closure until discharge from hospital in patients not receiving medium- or long-acting opioids, pre- or intra-operatively.

The method of reaching OFA remained stable since 2014. Dexmedetomidine was given in a first loading dose of 0.3 mcg/kg 15 minutes before induction, a second loading dose of 0.1 mcg/kg at induction followed by an infusion of 0.1 mcg/kg/h for maintenance. Lidocaine is given as a loading dose of 1 mg/kg at induction followed by 1 mg/kg/h for maintenance. A Ketamine loading dose of 0.1 mg/kg is given at induction with an extra bolus of 0.7 mg/kg (or max 50 mg) before incision followed by an infusion of 0.1mg/kg/h.

Post-operative analgesia was further improved by continuing very low doses of dexmedetomidine (0.05 mcg/kg/h), ketamine (0.05 mg/kg/h), and lidocaine (0.5 mg/kg/h) for the first hours (maximum 5 hours) with the possibility of giving a bolus of 10 mg lidocaine, 1 mg ketamine and 1 mcg dexmedetomidine every 15 minutes.

OA was induced with sufentanil (0.1 - 0.3 mcg/kg) and continued with extra boli (0.1 - 0.2 mcg/kg) or a continuous infusion of remifentanil (0.20 - 0.35 mcg/kg/h). Since 2014 more and more additives like clonidine, dexmedetomidine, ketamine and lidocaine were given as a single additive at the induction to reduce the total dose of intraoperative opioid use. Nevertheless these patients were still counted as OA.

All patients getting OFA got a strict goal directed fluid therapy with an average amount of fluids between 600 and 1200 ml. Patients on OA got a more liberal fluid therapy resulting in total amounts between 3000 and 5000 ml. For each patient the total amount of fluids given intra operative and the duration of the surgical procedure is calculated.

Following demographic data was retrieved: age, body mass index (BMI), American society of anesthesiology (ASA) score, incidence of hypertension, smoking or history of recent smoking, motion sickness or previous PONV. A bilateral DIEPflap is noted as bilat versus unilat and depending on the use of opioids postoperative an Apfel score is calculated. The number of anti emetic drugs given before any PONV took place and the number given after PONV is calculated, the incidence of nausea and the incidence of vomiting is measured. The maximum visual analog score (VAS) during the first 24 hours and the total equivalent dose of morphine used in the first 24 hours is measured.

Postoperative flap skin temperature was measured every hour in the first 24 hours and compared to a reference skin temperature close by.

Perioperative complications during the first post-operative month were graded according to a score (CLAVIEN), (DINDOO).

DIEPflap failure was defined as the need for a revision procedure that fails in preserving the flap and requires a new or other flap procedure.

The investigators calculated length of hospital stay (LOS) as the total number of nights in hospital after surgery.

The investigators retrieved all measured factors potentially related to complications of grade I to grade V or healthcare utilization outcomes from the database and medical records. Post-operative opioids were defined as the total dose of opioids used during the first 24 hours post-operatively, calculated as iv morphine equivalents. The following were considered equivalent to 1 mg iv morphine: 1 mg iv or subcutaneous piritramide, 10 mg iv tramadol, or 2 mg sublingual oxycodone.

02

Conditions studied

  • Major and Minor Surgical Complications
03

In context

Lead sponsor

AZ Sint-Jan AV is the lead sponsor of 58 studies on the registry; 14 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
Female
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

woman who are admitted for breast reconstruction using the diepflap (free flap)

Eligibility criteria

Inclusion Criteria: DIEPflap unilat or bilat woman between 18 and 60 years old-

Exclusion Criteria: none

  • allergy to any of the drugs used in anesthesia
05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
204 participants (actual)
Target follow-up
1 Month
Patient registry
Yes

Groups and cohorts

  • opioid free anesthesia (OFA)

    The method of reaching OFA: Dexmedetomidine was given in a first loading dose 15 minutes before induction, a second loading dose at induction followed by an infusion for maintenance. Lidocaine is given as a loading dose at induction followed by infusion for maintenance. A Ketamine loading dose is given at induction with an extra bolus before incision followed by an infusion.

    Other: opioid free anesthesia

  • opioid anesthesia (OA)

    OA was induced with sufentanil and continued with extra boli or a continuous infusion of remifentanil.

Interventions

  • Otheropioid free anesthesia

    general anesthesia blocking reflexes without using an opioid

06

What researchers measure

Primary outcomes

  1. Number of Patients With One or More Complications

    number of minor and major complications (CLAVIEN) (DINDOO)

    Time frame: One month postoperative

Secondary outcomes

  1. Number of Patients With Post Operative Nausea or Vomiting

    number of patients having Post operative nausea or vomiting (PONV)

    Time frame: 24 hours postoperative

  2. Postoperative Pain: Visual Analog Scale

    postoperative Pain measured by visual analog scale: 0: no pain. 10 max pain

    Time frame: 24 hours postoperative

  3. Morphine Used

    morphine consumed in mg

    Time frame: 24 hours postoperative

  4. Skin Temperature

    temperature difference between free flap skin and central patient skin

    Time frame: 24 hours post operative

  5. Length of Hospital Stay

    length of hospital stay in days

    Time frame: up to two weeks

07

Results

Posted Feb 23, 2021

Participant flow

Participant flow — Overall Study
MilestoneOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Started55149
Completed55149
Not completed00

Outcome measures

PrimaryNumber of Patients With One or More Complications

number of minor and major complications (CLAVIEN) (DINDOO)

Time frame:
One month postoperative
Reported as:
Count of participants · Participants
Number of Patients With One or More Complications
ParticipantsOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Number of Patients With One or More Complications1085
Statistical analysis
  • Opioid Free Anesthesia (OFA) vs Opioid Anesthesia (OA) · Chi-squared · p = <0.001
SecondaryNumber of Patients With Post Operative Nausea or Vomiting

number of patients having Post operative nausea or vomiting (PONV)

Time frame:
24 hours postoperative
Reported as:
Count of participants · Participants
Number of Patients With Post Operative Nausea or Vomiting
ParticipantsOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Number of Patients With Post Operative Nausea or Vomiting765
Statistical analysis
  • Opioid Free Anesthesia (OFA) vs Opioid Anesthesia (OA) · Chi-squared · p = <0.001
SecondaryPostoperative Pain: Visual Analog Scale

postoperative Pain measured by visual analog scale: 0: no pain. 10 max pain

Time frame:
24 hours postoperative
Reported as:
Mean · score on a scale
Postoperative Pain: Visual Analog Scale
score on a scaleOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Postoperative Pain: Visual Analog Scale1.87 ± 0.654.94 ± 0.54
Statistical analysis
  • Opioid Free Anesthesia (OFA) vs Opioid Anesthesia (OA) · Wilcoxon (Mann-Whitney) · p = <0.001
SecondaryMorphine Used

morphine consumed in mg

Time frame:
24 hours postoperative
Reported as:
Mean · milligram
Morphine Used
milligramOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Morphine Used1.95 ± 0.844.94 ± 0.54
Statistical analysis
  • Opioid Free Anesthesia (OFA) vs Opioid Anesthesia (OA) · Wilcoxon (Mann-Whitney) · p = <0.001
SecondarySkin Temperature

temperature difference between free flap skin and central patient skin

Time frame:
24 hours post operative
Reported as:
Mean · degrees Celsius
Skin Temperature
degrees CelsiusOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Skin Temperature1.04 ± 0.251.41 ± 0.21
Statistical analysis
  • Opioid Free Anesthesia (OFA) vs Opioid Anesthesia (OA) · Wilcoxon (Mann-Whitney) · p = 0.048
SecondaryLength of Hospital Stay

length of hospital stay in days

Time frame:
up to two weeks
Reported as:
Mean · days
Length of Hospital Stay
daysOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Length of Hospital Stay6.82 ± 0.267.52 ± 0.28

Adverse events

Collected over 1 month. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Opioid Free Anesthesia (OFA)0/55 (0%)1/55 (1.8%)9/55 (16.4%)
Opioid Anesthesia (OA)0/149 (0%)9/149 (6%)67/149 (45%)
Most frequent serious events
Most frequent serious events
EventOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Revision surgerySurgical and medical procedures1/559/149
Most frequent other events
Most frequent other events
EventOpioid Free Anesthesia (OFA)Opioid Anesthesia (OA)
Post operative nausea and vomitingSurgical and medical procedures9/5567/149

Baseline characteristics

Age, Continuous
Age, Continuous(years)Opioid Free Anesthesia (OFA)Opioid Anesthesia (OA)Total
Mean53.9 ± 2.850.3 ± 1.751.6 ± 1.4
Sex/Gender, Customized
Sex/Gender, Customized(Participants)Opioid Free Anesthesia (OFA)Opioid Anesthesia (OA)Total
Sex:Female55149204
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Opioid Free Anesthesia (OFA)Opioid Anesthesia (OA)Total
Count of participants——0
history of nausea after anesthesia
history of nausea after anesthesia(Participants)Opioid Free Anesthesia (OFA)Opioid Anesthesia (OA)Total
Count of participants61925
08

Study locations

1 site
  • Azsintjan
    Brugge, 8000, Belgium
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Oct 15, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 23, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03202134
Lead sponsor
AZ Sint-Jan AV
Responsible party
Jan Mulier (chairman dep anesthesiology & Reanimation, AZ Sint-Jan AV) — Principal investigator
First posted
Jun 28, 2017
Start date
Jan 2014
Primary completion
Nov 15, 2019
Completion
Nov 15, 2019
Results posted
Feb 23, 2021
Last update
Feb 23, 2021

Study contacts

Jan Paul Mulier
principal investigator · AZSint Jan AV

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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