Opioid Free Anaesthesia in Oncologic Gynaecological Surgery: Is There Any Benefit?

Opioid Free Anaesthesia in Oncologic Gynaecological Surgery: Is There Any Benefit? Retrospective Observational Study

Opioid Free Anesthesia (OFA) is a multimodal anesthesia and emerging technique that spares the use of opioids and involve other adjuvant anesthetics, which have demonstrated in vitro influence on immunologic and inflammatory response, as well as in metastatic progression. For these reasons we believe that OFA may positively influence in oncologic patients postoperative recovery and in its disease progression.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Ovarian Cancer; Cervix Cancer; Endometrial Cancer
• Intervention / Treatment: Drug: Opioid

Detailed Description

After Local Ethics Committee approval, consecutive consenting patients scheduled for major gynecologic oncologic surgery were included between February 2019 and January 2020 in this observational retrospective study. We Compared OFA to standard technique used in our institution and assessed its effect on Postoperative Systemic Inflammatory Response (SIRS), hospital stay, postoperative complications in the following 2 months, cancer progression and mortality 6 months and 12 months after surgery. OFA protocol consisted of a Total IntraVenous Anaesthesia of Propofol, a Dexmedetomidine infusion of 0,8-1,0 mcg/kg/h, together with 0,2-0,3 mg/kg ketamine and lidocaine 1,5 mg/kg in the first hour of surgery. The standard anaesthetic protocol included opioids (Fentanyl 2mcg/kg at induction, and remifentanyl infusion 0,1-0,2 mcg/kg/min) and volatile agents (sevoflurane or desflurane). Patients in both groups received a regional block when possible, dexamethasone 8 mg at induction and paracetamol 1g plus dexketoprofen 50mg at the end of surgery. Continuous variables were compared using unpaired t-test (or Mann-Whitney U test) and categorical variables by Chi-square test. Statistical significance was set at p < 0.05

• Study Type: Observational
• Enrollment (Actual): 132

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Julia Albano Polo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 91 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

132 women, aged 20-91 years old and ASA I-IV, who had Major Surgery for gynecologic cancers (cervix, endometrial, ovarian, vaginal, vulvar and breast cancer) under OFA and balanced anesthesia with opioids, both combined with regional anesthesia. They had surgery between February 2019 and February 2020 in Hospital La Paz de Madrid.

Description

Inclusion Criteria:

• Patients who had Major Surgery for gynecologic cancers (cervix, endometrial, ovarian, vaginal, vulvar and breast cancer) under OFA and balanced anesthesia with opioids, both combined with regional anesthesia.

Exclusion Criteria:

• Patients who had Major Surgery for gynecologic cancers (cervix, endometrial, ovarian, vaginal, vulvar and breast cancer) under OFA and balanced anesthesia with opioids, but had later surgery with a different to previous anesthesia technique.
• Patients who had no later follow up during 12 months in the same Hospital, so we cannot register recurrence.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Balanced anesthesia with opioids; Patients who had Major Surgery for gynecologic cancers (cervix, endometrium, ovarian and breast cancer) under balanced anesthesia including opioids between February 2019 and 2020 in Hospital La Paz.	Drug: Opioid; Use of balanced anesthesia including opioids during anesthesia for gynecologic cancer surgery; Other Names: Opioid Free Anesthesia
Opioid Free Anesthesia (OFA); Patients who had Major Surgery for gynecologic cancers (cervix, endometrium, ovarian and breast cancer) under Opioid Free anesthesia between February 2019 and 2020 in Hospital La Paz.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Systemic Inflammatory Response (C-Reactive Protein)	To compare postoperative SIRS (Systemic Inflammatory Response) with C-Reactive Protein plasmatic level	48 hours after surgery
Postoperative Systemic Inflammatory Response (Leucocytes Ratio)	To compare postoperative SIRS (Systemic Inflammatory Response) with Leucocytes Ratio	48 hours after surgery
Postoperative Systemic Inflammatory Response (Platelet Level)	To compare postoperative SIRS (Systemic Inflammatory Response) with Platelet Level	48 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent in the Post-Anesthesia Care Unit (PACU)	To compare recovery time between groups	30 days after surgery
Hospital stay	To compare hospital stay in both groups	30 days after surgery
Rate of later postoperative complications	Complications due to surgery which required hospitalization	3 months after surgery
Number of Participants with Cancer recurrence after surgery	To compare cancer recurrence (local and/or metastatic) 12 months after surgical treatment between groups.	12 months after surgery
Number of patients who Survive 12 months after surgery	To compare cancer survival 12 months after surgical treatment between groups	12 months after surgery

Collaborators and Investigators

• Sponsor: Instituto de Investigación Hospital Universitario La Paz
• Investigators: Principal Investigator: Nicolas Brogly, PhD, Hospital Universitario La Paz

Publications and helpful links

General Publications

• Dubowitz JA, Sloan EK, Riedel BJ. Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis. Clin Exp Metastasis. 2018 Apr;35(4):347-358. doi: 10.1007/s10585-017-9862-x. Epub 2017 Sep 11.
• Malo-Manso A, Raigon-Ponferrada A, Diaz-Crespo J, Escalona-Belmonte JJ, Cruz-Manas J, Guerrero-Orriach JL. Opioid Free Anaesthesia and Cancer. Curr Pharm Des. 2019;25(28):3011-3019. doi: 10.2174/1381612825666190705183754.
• Rossaint J, Zarbock A. Perioperative Inflammation and Its Modulation by Anesthetics. Anesth Analg. 2018 Mar;126(3):1058-1067. doi: 10.1213/ANE.0000000000002484.
• Byrne K, Levins KJ, Buggy DJ. Can anesthetic-analgesic technique during primary cancer surgery affect recurrence or metastasis? Can J Anaesth. 2016 Feb;63(2):184-92. doi: 10.1007/s12630-015-0523-8.
• Brown EN, Pavone KJ, Naranjo M. Multimodal General Anesthesia: Theory and Practice. Anesth Analg. 2018 Nov;127(5):1246-1258. doi: 10.1213/ANE.0000000000003668.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2019
• Primary Completion (Actual): January 30, 2021
• Study Completion (Actual): January 30, 2021

Study Registration Dates

• First Submitted: January 12, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Opioid; Postoperative infection; Opioid Free Anesthesia; SIRS (Systemic Inflammatory Response)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Endometrial Neoplasms; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Narcotics; Analgesics, Opioid
• Other Study ID Numbers: PI-3958

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No