Impact of Opioid Free Anesthesia on the Complications After DIEPflap Surgery: A Retrospective Observational Cohort Study.
Conditions: Major and Minor Surgical Complications
Sponsor: AZ Sint-Jan AV

Cover page of doc uploaded for ClinTrials.gov PRS    
study protocol and statistical analysis plan.  Date first loaded up Oct 15. 2019  
local name of study:   2019OSOFADIEPFLAP 
 
full name of study 
Impact of opioid free anesthesia on the complications after DIEPflap surgery: A 
retrospective observational cohort study. 
 
NCT number:    NCT03202134 
 
 
 

Methods  
Patients  
In this cohort study, we included all patients in our hospital database who underwent DIEP 
flap surgery between January 2014 and April 2019. All patients entering our hospital provide 
consent to allow retrospective data analysis without patient identification. The study protocol 
was approved by our institutional review board and registered at http://clinicaltrials.gov 
(registration number: NCT03202134) under the name of Jan Mulier on June 28, 2017. This 
manuscript adheres to the STROBE and CONSORT guidelines.  
At our institution, the possibility of breast reconstruction is discussed with all women 
undergoing mastectomy for established breast cancer or prophylactic as a risk reduction 
strategy, and the decision regarding timing and type of reconstruction is based on each 
patient’s preference and surgical options. Approximately 80% of patients requesting breast 
reconstruction choose a DIEP flap. When adjuvant radiotherapy is required, our breast 
multidisciplinary team policy is to offer delayed autologous tissue reconstruction. Patients 
with a high body mass index (BMI; >30 kg/m2) are advised to lose weight and those who 
smoke are advised to stop smoking at least 4 weeks before surgery; however, neither of these 
characteristics will exclude women from being offered DIEP flap surgery. Hormone therapy, 
when a component of the breast cancer treatment, is stopped one week before surgery and 
continued after discharge. Prior to DIEP flap surgery, all women undergo computed 
tomography angiography (CTA) with three-dimensional (3D) image reconstruction to assess 
the lower abdominal wall perforators and recipient vessels by an experienced radiologist.  
Surgery  
All DIEP flap reconstructions were performed by senior surgeons using a standard technique. 
These surgeons routinely preserve the superior inferior epigastric vein for “supercharging” if 
venous congestion occurs. The internal thoracic vessels at the level of the third or fourth rib 
were the first-choice recipient vessels. End-to-end anastomoses were performed using 9-0 or 
10-0 Nylon (ST&T)®, depending on the vessel caliber.  
Anesthesia  
The choice of OFA or OA was at the discretion of the attending anesthesiologist, only some 
of whom were experienced with OFA. Because the date of surgery for each patient was 
usually determined without knowing which anesthesiologist would be assigned to the 
operating room on a given day, the choice of OFA or OA was random in most cases. OFA 
was defined as the administration of no opioids either pre- or intraoperatively until wound 
closure. Opioids administered after wound closure were considered postoperative opioids. OA 
was defined as the administration of any opioid at any time during the pre- or intraoperative 
period (up to the time of wound closure). Postoperative opioid-free analgesia (OF analgesia) 
was defined as the administration of no opioids from the time of wound closure until 
discharge from the hospital, in patients who received no medium- or long-acting opioids 
either pre- or intraoperatively.  
Most patients received a balanced general anesthetic, which was usually a combination of 0.5 
MAC sevoflurane inhalation and a continuous propofol infusion at 3 mg/kg/h. Neuromuscular 

blockade (NMB) was achieved with rocuronium or cisatracurium in a continuous infusion to 
achieve periods of deep NMB when required.  
The method of OFA has remained unchanged at our institution since 2014. Dexmedetomidine 
was administered as follows: 0.3 mcg/kg 15 minutes before induction, 0.1 mcg/kg at 
induction, and an infusion of 0.1 mcg/kg/h for maintenance. Lidocaine was administered as 1 
mg/kg at induction, followed by an infusion of 1 mg/kg/h for maintenance. Ketamine was 
administered  
as 0.1 mg/kg at induction, 0.7 mg/kg (maximum, 50 mg) before incision, and an infusion of 
0.1 mg/kg/h for maintenance. Postoperative analgesia was further improved by continuing 
very low doses of dexmedetomidine (0.05 mcg/kg/h), ketamine (0.05 mg/kg ideal body 
weight/h), and lidocaine (0.5 mg/kg/h) for the first few hours (maximum, 5 h) after surgery, 
with bolus doses of 10 mg lidocaine, 1 mg ketamine, and 1 mcg dexmedetomidine 
administered every 15 minutes on an as-needed basis.  
OA involved the use of sufentanil or sufentanil combined with remifentanil. Sufentanil was 
administered as 0.1–0.3 mcg/kg at induction, followed by additional 0.1–0.2 mcg/kg doses as 
needed during surgery or by a continuous infusion of remifentanil at 0.20–0.35 mcg/kg/h. 
Since 2014, various adjunct medications (e.g., clonidine, dexmedetomidine, ketamine, 
lidocaine) have been administered as a single dose at induction to reduce the total dose of 
intraoperative opioids. Nevertheless, as long as an opioid was given before wound closure the 
type of anesthesia was still classified as OA.  
All patients undergoing OFA were managed with strict goal-directed fluid therapy, receiving 
approximately 600 to 1,200 mL of intravenous (iv) fluids intraoperatively. Patients 
undergoing OA received more liberal fluid therapy, with usual total intraoperative volumes 
between 3,000 and 5,000 ml.  
Data collection  
The following demographic data were retrieved: age; body mass index (BMI); American 
Society of Anesthesiologists (ASA) physical status class; and history of hypertension, current 
or recent smoking, motion sickness, or previous PONV. We also recorded the total volume of 
intraoperative fluids, duration of surgery, and laterality of the DIEP flap (bilateral or 
unilateral). The simplified Apfel score ii (based on non-smoking status, female sex, history of 
previous PONV or motion sickness, and postoperative opioid use) was calculated for each  
patient, and the presence of nausea or vomiting, as well as the number of antiemetics  
administered before and after PONV, was recorded. We likewise recorded the maximum  
visual analog scale (VAS) pain score and opioid usage during the first 24 hours  
postoperatively. Opioid usage was converted to total iv morphine equivalents as follows: 1  
mg iv morphine = 1 mg iv or subcutaneous piritramide, 10 mg iv tramadol, or 2 mg 
sublingual  
iii  

oxycodone. 
hours after surgery and compared to the temperature of the surrounding skin (reference 
temperature). Hospital length of stay (LOS) was calculated as the number of nights in the 
hospital postoperatively. 
The presence of perioperative complications during the first 1 month postoperatively were  
Postoperative flap skin temperature was measured every hour for the first 24  
iv 
converted to 6 ranks for use in the statistical analysis, with grades 1, 2, 3a, 3b, 4a, and 4b  
graded according to the modified Clavien-Dindo (CD) classification.  
The CD grades were  
being converted to ranks 1, 2, 3, 4, 5, and 6, respectively. 
failure was defined as the need for a revision procedure that failed to preserve the flap, 
thereby requiring another type of flap reconstruction.  
Statistical analysis  
The demographic data and clinical outcome parameters are expressed as means and standard 
deviations and analyzed using Mann-Whitney test or expressed as percentage of cases and 
analyzed using χ2. A linear or logistic regression is used to analyze the independent effect of 
different factors on the outcome parameters. Statistical analysis was performed using 
statistical package (Stata/IC 15.1 for Mac, StataCorp, TX 77845 USA)  
i Rothenberger J, Amr A, Schiefer J, Schaller H, Rahmanian-Schwarz A. A quantitative 
analysis of the venous outflow of the deep inferior epigastric flap (DIEP) based on the 
perforator veins  
Fout! Bladwijzer niet gedefinieerd.  
DIEP flap  
 

 
and the efficiency of superficial inferior epigastric vein (SIEV) supercharging. Journal of 
Plastic, Reconstructive & Aesthetic Surgery 2013;66,67-72. 
ii Apfel C C, Laara E, Koivuranta M, Greim C, Roewer N. A Simplified Risk Score for 
Predicting Postoperative Nausea and Vomiting Anesthesiology 1999; 91:693–700.  
iii Mary Lynn. McPherson. Demystifying opioid conversion calculations: A guide for effective 
dosing. ISBN 978-1-58528-198-5 . 2009 American society of health-system Pharmacists, Inc. 
iv Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindoo classification of Surgical 
complications. Ann Surg 2009;250:187-96.