Opioid Free Anesthesia-Analgesia Strategy and Surgical Stress in Elective Open Abdominal Aortic Aneurysm Repair

  • End date
    Oct 8, 2025
  • participants needed
  • sponsor
    University of Crete
Updated on 10 November 2021
pain relieving


Open Abdominal Aortic Aneurysm (AAA) repair is a high-risk surgical procedure accompanied by intense endocrine and metabolic responses to surgical stress, with subsequent activation of the inflammatory cascade, cytokine and acute-phase protein release, and bone marrow activation. There is a proven correlation of surgical stress, which patients undergoing open AAA repair are subjected to, with patient outcome, morbidity/mortality, intensive care unit stay and overall length of stay. Modern general anesthetic techniques have been revised and rely on perioperative multimodal anesthetic and analgesic strategies for improved overall patient outcome. Based on this context of a multimodal anesthetic technique and having taken into consideration the international "opioid-crisis" epidemic, an Opioid Free Anesthesia-Analgesia (OFA-A) strategy started to emerge. It is based on the administration of a variety of anesthetic/analgesic agents with different mechanisms of action, including immunomodulating and anti-inflammatory effects.

Our basic hypothesis is that the implementation of a perioperative multimodal OFA-A strategy, involving the administration of pregabalin, ketamine, dexmedetomidine, lidocaine, dexamethasone, dexketoprofen, paracetamol and magnesium sulphate, will lead to attenuation of surgical stress response compared to a conventional Opioid-Based Anesthesia-Analgesia (OBA-A) strategy. Furthermore, the anticipated attenuation of the inflammatory response, is pressumed to be associated with equal or improved analgesia, compared to a perioperative OBA-A technique.


Open abdominal aortic aneurysm (AAA) repair surgery is a high-risk operation, often performed on high-risk patients. Despite advancements made in diagnosis, management, surgical techniques and treatment of these patients, morbidity and mortality remain high. Mortality after open AAA repair remains higher than the average mortality of the matched population for age and sex. Debate is ongoing as to whether open AAA repair or endovascular aneurysm repair (EVAR) is better in terms of overall long-term survival rate.

Regarding open AAA repair, the very nature of the surgery itself, with surgical trauma, aortic cross clamping and its resulting ischemia-reperfusion injury, and cellular interactions of blood with the biomaterial surface of the graft, causes intense and varied metabolic, endocrine and immunological responses. These surgical stress-related responses are evident as marked increases in inflammatory cytokines such as TNF-a, IL-1a, IL-6, IL-8, IL-10, stimulation of the sympathetic system, and stimulation of the hypothalamic-pituitary-adrenal axis, caused by release of CRH and AVP. High levels of IL-6, peaking at 4-48h after clamp removal, have been associated with serious postoperative complications and its levels reflect the intensity of surgical trauma following AAA repair. Other inflammation markers such as CRP and leukocytes have also been shown to increase postoperatively.

While the surgical technique has been extensively studied as to the role it plays on the control of the surgical stress response, patient outcome, morbidity and overall mortality, fewer studies have been conducted to study the effect of the anesthetic management on these factors. While most of them have been focusing on the comparison of general anesthetic vs regional techniques, only few compare different general anesthetic techniques on patient outcome.

Modern general anesthetic techniques have been revised and rely on a multimodal anesthetic and analgesic perioperative regimen for improved patient outcome. A multimodal regimen requires the administration of at least 2 factors with different mechanisms of action. At least one factor causes inhibition of central sensitization and at least another one inhibits the peripheral sensitization of the nervous system, as a response to painful surgical stimuli, mitigating adverse neuroplasticity. One such example, is an Opioid-Free Anesthetic-Analgesic (OFA-A) strategy, which implements a variety of pharmacological agents, including some with demonstrated immunomodulating and anti-inflammatory effects. Apart from sparing any opioid-related adverse effects, an OFA-A multimodal strategy targets optimal analgesia with a multitude of factors in the lowest possible dose, aiming for additive or synergistic effects. An additional advantage of using an OFA-A technique is the prevention of opioid-induced hyperalgesia.

Our hypothesis is that implementation of a multimodal OFA-A strategy, leads to a decreased sympathetic and inflammatory response, compared to conventional opioid-based anesthetic techniques. A decreased inflammatory and stress response as expressed by reduced levels of IL-6, IL-8, IL-10, TNF-a, CRP, cortisol, arginine vasopressin (AVP), white blood cells count and hemodynamic stability is expected to decrease peripheral and central sensitization, contributing to better postoperative analgesia.

Condition vascular surgical procedures, Post-Surgical Pain, Pain, Interleukin-6, anesthesia procedures, Pain (Pediatric), elective surgeries, Anesthesia (Local), immune mediators, immune modulators, immunotherapy agent, sensory loss, anesthesia for, post-op pain, Abdominal Aortic Aneurysm Without Rupture, interleukin 6, immunomodulator, Narcotic Use, post-operative pain, anaesthesia, Anesthesia, immunomodulators, vascular surgery procedure, immunologic adjuvant, immunomodulatory agent, immune regulators, Vascular surgery, immunomodulating agent, biological response modifier, biological response modifiers, Elective surgery, Opioid Use, elective surgical procedures, immunostimulants, Immunostimulant, immunotherapeutic agent, il-6, Postoperative pain, immunological adjuvant, dental anesthesia
Treatment Opioid-Based Anesthesia-Analgesia Strategy, Opioid-free Anesthesia-Analgesia Strategy
Clinical Study IdentifierNCT04894864
SponsorUniversity of Crete
Last Modified on10 November 2021


Yes No Not Sure

Inclusion Criteria

Patient Consent
Age between 40 and 85 years old
Patients undergoing Elective Open Abdominal Aortic Infrarenal Aneurysm Repair
AAA Diameter 5,0 cm

Exclusion Criteria

Immunocompromised patients
Patients with active infection
Reoperation on the aorta
Inflammatory bowel Disease
Chronic Inflammatory conditions (e.g. Rheymatoid arthritis, Psoriatic arthritis)
Chronic corticosteroid or immunosuppressive drug use
Transfusion with >3 units of packed red blood cells
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note