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

NCT04894864 | Recruiting Phase 4

• 1 other identifier: OFA-aneurysm
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Elective Surgical Procedures; Postoperative Pain; Anesthesia; Opioid Use; Abdominal Aortic Aneurysm Without Rupture; Vascular Surgical Procedure; Interleukin 6; Immunomodulators

Keywords

Opioid-free Anesthesia-Analgesia; Cytokines; Opioid-based Anesthesia-Analgesia; Haemodynamic Stability; Open Abdominal Aortic Aneurysm Repair; Immunomodulation; Inflammatory Markers

Outcome Measures

Primary Outcomes (75)

• Surgical Stress Response - IL-6 - Preoperatively

  Inflammatory response and stress response as quantified by IL-6 serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - IL-6 - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by IL-6 serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - IL-6 - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by IL-6 serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - IL-6 - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by IL-6 serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - IL-8 - Preoperatively

  Inflammatory response and stress response as quantified by IL-8 serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - IL-8 - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by IL-8 serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - IL-8 - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by IL-8 serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - IL-8 - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by IL-8 serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - IL-10 - Preoperatively

  Inflammatory response and stress response as quantified by IL-10 serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - IL-10 - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by IL-10 serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - IL-10 - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by IL-10 serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - IL-10 - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by IL-10 serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - AVP - Preoperatively

  Inflammatory response and stress response as quantified by AVP serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - AVP - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by AVP serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - AVP - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by AVP serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - AVP - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by AVP serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - TNF-a - Preoperatively

  Inflammatory response and stress response as quantified by TNF-a serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - TNF-a - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by TNF-a serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - TNF-a - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by TNF-a serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - TNF-a - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by TNF-a serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - Cortisol - Preoperatively

  Inflammatory response and stress response as quantified by cortisol serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - Cortisol - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by cortisol serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - Cortisol - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by cortisol serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - Cortisol - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by cortisol serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - CRP - Preoperatively

  Inflammatory response and stress response as quantified by CRP serum levels. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - CRP - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by CRP serum levels. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - CRP - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by CRP serum levels. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - CRP - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by CRP serum levels. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Surgical Stress Response - WBC - Preoperatively

  Inflammatory response and stress response as quantified by WBC count. Blood sample collection will take place in both study groups.

  1) Preoperatively (as a baseline)

• Surgical Stress Response - WBC - 15 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by WBC count. Blood sample collection will take place in both study groups.

  2) 15 minutes after aortic cross-clamping

• Surgical Stress Response - WBC - 60 minutes after aortic cross-clamp

  Inflammatory response and stress response as quantified by WBC count. Blood sample collection will take place in both study groups.

  3) 60 minutes after aortic cross-clamp release

• Surgical Stress Response - WBC - 24 hours after aortic cross-clamp release

  Inflammatory response and stress response as quantified by WBC count. Blood sample collection will take place in both study groups.

  4) 24 hours after aortic cross-clamp release

• Haemodynamic Stability - Coefficient of Variation PR

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Pulse Rate - PR. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. The Coefficient of variation of the PR values will be reported for each patient, extracted from the collected data.

  Every 20 seconds from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Average Real Variability PR

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Average Real Variability of the PR. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Values will be averaged every minute and the Average Real Variability will be reported for each patient, extracted from the collected data.

  Every minute from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Coefficient of Variation SBP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Systolic Blood Pressure - SBP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. The Coefficient of variation of SBP values will be reported for each patient, extracted from the collected data.

  Every 20 seconds from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Average Real Variability SBP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Average Real Variability of the SBP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Values will be averaged every minute and the Average Real Variability will be reported for each patient, extracted from the collected data.

  Every minute from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Coefficient of Variation DBP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Diastolic Blood Pressure - DBP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. The Coefficient of variation of DBP values will be reported for each patient, extracted from the collected data.

  Every 20 seconds from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Average Real Variability DBP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Average Real Variability of the DBP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Values will be averaged every minute and the Average Real Variability will be reported for each patient, extracted from the collected data.

  Every minute from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Coefficient of Variation MBP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Mean Blood Pressure - MBP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. The Coefficient of variation of MBP values will be reported for each patient, extracted from the collected data.

  Every 20 seconds from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Average Real Variability MBP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Average Real Variability of the MBP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Values will be averaged every minute and the Average Real Variability will be reported for each patient, extracted from the collected data.

  Every minute from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Coefficient of Variation PP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Pulse Pressure. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. The Coefficient of variation of PP values will be reported for each patient, extracted from the collected data.

  Every 20 seconds from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Average Real Variability PP

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Average Real Variability of the PP. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Values will be averaged every minute and the Average Real Variability will be reported for each patient, extracted from the collected data.

  Every minute from anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours.

• Haemodynamic Stability - Tachycardia

  Intraoperative Tachycardia (defined as PR≥ 100 bpm), with episodes lasting ≥1 minute. Data will be reported in as a percentage of the total surgical time in which the participant exhibited tachycardia.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Bradycardia

  Intraoperative Bradycardia (defined as PR≤ 40 bpm), with episodes lasting ≥1 minute. Data will be reported in as a percentage of the total surgical time in which the participant exhibited bradycardia.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Hypotension SBP

  Intraoperative Hypotension (defined as SBP≤90mmHg or ≤80% of preoperative Baseline), with episodes lasting ≥1 minute. All patients will have a 5 minute preoperative SBP baseline, with measurements every 20 seconds. Intraoperative data will be compared to the mean preoperative 5 minute SPB baseline. Data will be reported in as a percentage of the total surgical time in which the participant exhibited hypotension, based on the SBP values.

  Baseline: 5 minutes prior to anaesthesia induction. Intraoperative Hypotension: From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Hypotension MBP

  Intraoperative Hypotension (defined as MBP≤65mmHg or ≤80% of preoperative Baseline), with episodes lasting ≥1 minute. All patients will have a 5 minute preoperative MBP baseline, with measurements every 20 seconds. Intraoperative data will be compared to the mean preoperative 5 minute MPB baseline. Data will be reported in as a percentage of the total surgical time in which the participant exhibited hypotension, based on the MBP values.

  Baseline: 5 minutes prior to anaesthesia induction. Intraoperative Hypotension: From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Hypertension

  Intraoperative Hypertension (defined as SBP ≥120% of preoperative Baseline), with episodes lasting ≥1 minute. All patients will have a 5 minute preoperative SBP baseline, with measurements every 20 seconds. Intraoperative data will be compared to the mean preoperative 5 minute SPB baseline. Data will be reported in as a percentage of the total surgical time in which the participant exhibited hypertension, based on the SBP values.

  Baseline: 5 minutes prior to anaesthesia induction. Intraoperative Hypotension: From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid requirements - Crystalloids - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Crystaloid Fluid Requirements averaged over the total surgical time. Data will be reported in ml/kg\*h.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid requirements - Crystalloids - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Crystaloid Fluid Requirements. Data will be reported in ml/kg\*h.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Fluid requirements - Colloids - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Colloid Fluid Requirements averaged over the total surgical time. Data will be reported in ml/kg\*h.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid requirements - Colloids - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Colloid Fluid Requirements. Data will be reported in ml/kg\*h.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Fluid requirements - Concentrated RBCs - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Concentrated RBC unit Requirements. Data will be reported in ml.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid requirements - Concentrated RBCs - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Concentrated RBC unit Requirements. Data will be reported in ml.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Fluid requirements - Plasma - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Plasma unit Requirements. Data will be reported in ml.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid requirements - Plasma - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Plasma unit Requirements. Data will be reported in ml.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Fluid requirements - Platelets - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Platelet unit Requirements. Data will be reported in ml.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid requirements - Platelets - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Platelet unit Requirements. Data will be reported in ml.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Blood Loss - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Blood Loss. Data will be reported in ml.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Blood Loss - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Blood Loss. Data will be reported in ml.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Fluid Balance - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Fluid Balance averaged over the total surgical time. Data will be reported in ml/kg/h

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Fluid Balance - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Fluid Balance. Data will be reported in ml.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Adrenaline - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Adrenaline requirements. Data will be reported in mg.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Adrenaline - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Adrenaline requirements. Data will be reported in mg.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Noradrenaline - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Noradrenaline requirements. Data will be reported as an averaged intraoperative rate in mcg/kg\*min.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Noradrenaline - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Noradrenaline requirements. Data will be reported as an averaged rate in mcg/kg\*min.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Ephedrine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Ephedrine requirements. Data will be reported in mg.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Ephedrine - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Ephedrine requirements. Data will be reported in mg.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Phenylephrine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Phenylephrine requirements. Data will be reported as an averaged intraoperative rate in mcg/kg\*min.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Phenylephrine - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Phenylephrine requirements.Data will be reported as an averaged rate in mcg/kg\*min.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Dobutamine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Dobutamine requirements. Data will be reported as an averaged intraoperative rate in mcg/kg\*min.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Dobutamine - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Dobutamine requirements. Data will be reported as an averaged rate in mcg/kg\*min.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Dopamine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Dopamine requirements. Data will be reported as an averaged intraoperative rate in mcg/kg\*min.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Dopamine - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Dopamine requirements. Data will be reported as an averaged rate in mcg/kg\*min.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

• Haemodynamic Stability - Vasoactive Requirements - Nitroglycerine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Nitroglycerine requirements. Data will be reported as an averaged intraoperative rate in mcg/kg\*min.

  From anesthesia induction, until the end of surgery (end of placement of last suture/surgical clip on patient), assessed up to 8 hours

• Haemodynamic Stability - Vasoactive Requirements - Nitroglycerine - 24 hours postoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Nitroglycerine requirements. Data will be reported as an averaged rate in mcg/kg\*min.

  From the end of surgery (end of placement of last suture/surgical clip on patient) until 24 hours postoperatively

Secondary Outcomes (71)

• Postoperative pain - Numerical Rating Scale (NRS) - Immediately Postoperatively

  1) Immediately postoperatively (if awakened prior to ICU admission)

• Postoperative pain - Numerical Rating Scale (NRS) - First postoperative day

  2) First postoperative day

• Postoperative pain - Numerical Rating Scale (NRS) - Second postoperative day

  3) Second postoperative day

• Postoperative pain - Numerical Rating Scale (NRS) - Third postoperative day

  4) Third postoperative day

• Postoperative pain - Critical Care Pain Observation Tool (CPOT) - Immediately Postoperatively

  1) Immediately postoperatively (if awakened prior to ICU admission)

Study Arms (2)

Opioid-Based Anesthesia Analgesia

ACTIVE COMPARATOR

Premedication: IM Midazolam 0.05-0.07mg/kg. Anesthesia induction: Midazolam 0.03mg/kg, Propofol 2-3mg/kg, Fentanyl 1-2mcg/kg and Cisatracurium 0.2mg/kg or alternatively Rocuronium 0.6-1.2mg/kg. Anesthesia maintenance: Desflurane set at approximately 1 MAC, Morphine 0.1-0.12mg/kg, Fentanyl 1-2mcg/kg during induction and 50-100mcg prn, Paracetamol 1g +/- Dexketoprofen trometamol 50mg, along with Ondansetron 4mg or Droperidol 0.625mg. Wound infiltration: Ropivacaine 75-150mg. ICU stay sedation: Remifentanil infusion, until removal of the endotracheal tube. Surgical ward: PCA pump with Morphine for the first 3 postoperative days. Additional postoperative analgesia: Paracetamol 1g x3 +/- Dexketoprofen trometamol 50mg x2. Rescue therapy only: Tramadol 50-100mg.

Drug: Opioid-Based Anesthesia-Analgesia Strategy

Opioid-Free Anesthesia Analgesia

ACTIVE COMPARATOR

Premedication: Pregabalin 50-150mg x2, IM Midazolam 0.05-0.07mg/kg. Anesthesia induction: Midazolam 0.03mg/kg, Dexdmedetomidine 0.5-1mcg/kg, Lidocaine 1mg/kg, Propofol 2-3mg/kg, Ketamine 1-1.5mg/kg, Hyoscine 10mg, Cisatracurium 0.2mg/kg or alternatively Rocuronium 0.6-1.2mg/kg, Magnesium sulphate 2.5-5g and Dexamethasone 8-16mg. Anesthesia maintenance: Desflurane set at \~1 MAC, Dexmedetomidine 0.2-1.2mcg/kg/h, Lidocaine 0.5-1mg/kg/h, Ketamine 0.3-0.5mg/kg prn, Paracetamol 1g +/- Dexketoprofen trometamol 50mg, and Ondansetron 4mg or Droperidol 0.625mg. Wound infiltration: Ropivacaine 75-150mg. ICU sedation: Dexmedetomidine + Lidocaine infusions, until removal of the ETT. Surgical ward: PCA pump with Ketamine, Lidocaine, Clonidine and Midazolam for the first 3 postoperative days. Additionally, Pregabalin 50mg per os x1 and 25mg x1, up to x2, Paracetamol 1g x3 +/- Dexketoprofen trometamol 50mg x2. Rescue therapy only: Tramadol 50-100mg.

Drug: Opioid-free Anesthesia-Analgesia Strategy

Interventions

Opioid-Based Anesthesia-Analgesia Strategy DRUG

A perioperative Opioid-Based multimodal Anesthesia-Analgesia strategy will be implemented as described in the Opioid-Based arm of the study.

Also known as: Opioid-Based Anesthesia, OBA-A

Opioid-Based Anesthesia Analgesia

Opioid-free Anesthesia-Analgesia Strategy DRUG

A perioperative Opioid-Free multimodal Anesthesia-Analgesia strategy will be implemented as described in the Opioid-Free arm of the study.

Also known as: Opioid-Free Anesthesia, OFA-A

Opioid-Free Anesthesia Analgesia

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient Consent
• Age between 40 and 85 years old
• Patients undergoing Elective Open Abdominal Aortic Infrarenal Aneurysm Repair

You may not qualify if:

• Immunocompromised patients
• Patients with active infection
• Reoperation on the aorta
• Inflammatory bowel Disease
• Malignancy
• Chronic Inflammatory conditions (e.g. Rheymatoid arthritis, Psoriatic arthritis)
• Chronic corticosteroid or immunosuppressive drug use
• Intraoperative transfusion with \>2 units of packed Red Blood Cells

Sponsors & Collaborators

• University of Crete: lead
• University Hospital of Crete: collaborator

Study Sites (1)

University of Crete

Heraklion, Crete, 71110, Greece

RECRUITING

Related Publications (21)

• Norman PE, Semmens JB, Lawrence-Brown MM. Long-term relative survival following surgery for abdominal aortic aneurysm: a review. Cardiovasc Surg. 2001 Jun;9(3):219-24. doi: 10.1016/s0967-2109(00)00126-5.

  PMID: 11336844 BACKGROUND

• Johal AS, Loftus IM, Boyle JR, Heikkila K, Waton S, Cromwell DA. Long-term survival after endovascular and open repair of unruptured abdominal aortic aneurysm. Br J Surg. 2019 Dec;106(13):1784-1793. doi: 10.1002/bjs.11215.

  PMID: 31747067 BACKGROUND

• Moris DN, Kontos MI, Mantonakis EI, Athanasiou AK, Spartalis ED, Bakoyiannis CN, Chrousos GP, Georgopoulos SE. Concept of the aortic aneurysm repair-related surgical stress: a review of the literature. Int J Clin Exp Med. 2014 Sep 15;7(9):2402-12. eCollection 2014.

  PMID: 25356092 BACKGROUND

• Tsilimigras DI, Sigala F, Karaolanis G, Ntanasis-Stathopoulos I, Spartalis E, Spartalis M, Patelis N, Papalampros A, Long C, Moris D. Cytokines as biomarkers of inflammatory response after open versus endovascular repair of abdominal aortic aneurysms: a systematic review. Acta Pharmacol Sin. 2018 Jul;39(7):1164-1175. doi: 10.1038/aps.2017.212. Epub 2018 May 17.

  PMID: 29770795 BACKGROUND

• Pearson S, Hassen T, Spark JI, Cabot J, Cowled P, Fitridge R. Endovascular repair of abdominal aortic aneurysm reduces intraoperative cortisol and perioperative morbidity. J Vasc Surg. 2005 Jun;41(6):919-25. doi: 10.1016/j.jvs.2005.02.040.

  PMID: 15944585 BACKGROUND

• Wilt TJ, Lederle FA, Macdonald R, Jonk YC, Rector TS, Kane RL. Comparison of endovascular and open surgical repairs for abdominal aortic aneurysm. Evid Rep Technol Assess (Full Rep). 2006 Aug;(144):1-113.

  PMID: 17764213 BACKGROUND

• Moore WS, Kashyap VS, Vescera CL, Quinones-Baldrich WJ. Abdominal aortic aneurysm: a 6-year comparison of endovascular versus transabdominal repair. Ann Surg. 1999 Sep;230(3):298-306; discussion 306-8. doi: 10.1097/00000658-199909000-00003.

  PMID: 10493477 BACKGROUND

• Salartash K, Sternbergh WC 3rd, York JW, Money SR. Comparison of open transabdominal AAA repair with endovascular AAA repair in reduction of postoperative stress response. Ann Vasc Surg. 2001 Jan;15(1):53-9. doi: 10.1007/s100160010014.

  PMID: 11221945 BACKGROUND

• Panaretou V, Siafaka I, Theodorou D, Manouras A, Seretis C, Gourgiotis S, Katsaragakis S, Sigala F, Zografos G, Filis K. Combined general-epidural anesthesia with continuous postoperative epidural analgesia preserves sigmoid colon perfusion in elective infrarenal aortic aneurysm repair. Saudi J Anaesth. 2012 Oct-Dec;6(4):373-9. doi: 10.4103/1658-354X.105870.

  PMID: 23493852 BACKGROUND

• Jessula S, Atkinson L, Casey P, Kwofie K, Stewart S, Lee MS, Smith M, Herman CR. Surgically positioned paravertebral catheters and postoperative analgesia after open abdominal aortic aneurysm repair. J Vasc Surg. 2019 Nov;70(5):1479-1487. doi: 10.1016/j.jvs.2019.02.037. Epub 2019 May 29.

  PMID: 31153699 BACKGROUND

• Panaretou V, Toufektzian L, Siafaka I, Kouroukli I, Sigala F, Vlachopoulos C, Katsaragakis S, Zografos G, Filis K. Postoperative pulmonary function after open abdominal aortic aneurysm repair in patients with chronic obstructive pulmonary disease: epidural versus intravenous analgesia. Ann Vasc Surg. 2012 Feb;26(2):149-55. doi: 10.1016/j.avsg.2011.04.009. Epub 2011 Oct 22.

  PMID: 22018500 BACKGROUND

• Greco KJ, Brovman EY, Nguyen LL, Urman RD. The Impact of Epidural Analgesia on Perioperative Morbidity or Mortality after Open Abdominal Aortic Aneurysm Repair. Ann Vasc Surg. 2020 Jul;66:44-53. doi: 10.1016/j.avsg.2019.10.054. Epub 2019 Oct 28.

  PMID: 31672606 BACKGROUND

• Ammar AS, Mahmoud KM. Comparative effect of propofol versus sevoflurane on renal ischemia/reperfusion injury after elective open abdominal aortic aneurysm repair. Saudi J Anaesth. 2016 Jul-Sep;10(3):301-7. doi: 10.4103/1658-354X.174907.

  PMID: 27375385 BACKGROUND

• Loggi S, Mininno N, Damiani E, Marini B, Adrario E, Scorcella C, Domizi R, Carsetti A, Pantanetti S, Pagliariccio G, Carbonari L, Donati A. Changes in the sublingual microcirculation following aortic surgery under balanced or total intravenous anaesthesia: a prospective observational study. BMC Anesthesiol. 2019 Jan 5;19(1):1. doi: 10.1186/s12871-018-0673-7.

  PMID: 30611197 BACKGROUND

• Giudice V, Lauwick S, Kaba A, Joris J. [Proven and expected benefits of intravenous lidocaine administered during the perioperative period]. Rev Med Liege. 2012 Feb;67(2):81-4. French.

  PMID: 22482237 BACKGROUND

• Liu FL, Chen TL, Chen RM. Mechanisms of ketamine-induced immunosuppression. Acta Anaesthesiol Taiwan. 2012 Dec;50(4):172-7. doi: 10.1016/j.aat.2012.12.001. Epub 2013 Jan 11.

  PMID: 23385040 BACKGROUND

• Mojtahedzadeh M, Chelkeba L, Ranjvar-Shahrivar M, Najafi A, Moini M, Najmeddin F, Sadeghi K, Barkhordari K, Gheymati A, Ahmadi A. Randomized Trial of the Effect of Magnesium Sulfate Continuous Infusion on IL-6 and CRP Serum Levels Following Abdominal Aortic Aneurysm Surgery. Iran J Pharm Res. 2016 Fall;15(4):951-956.

  PMID: 28243294 BACKGROUND

• Marik PE. Propofol: an immunomodulating agent. Pharmacotherapy. 2005 May;25(5 Pt 2):28S-33S. doi: 10.1592/phco.2005.25.5_part_2.28s.

  PMID: 15899746 BACKGROUND

• Roeckel LA, Utard V, Reiss D, Mouheiche J, Maurin H, Robe A, Audouard E, Wood JN, Goumon Y, Simonin F, Gaveriaux-Ruff C. Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide. Sci Rep. 2017 Sep 4;7(1):10406. doi: 10.1038/s41598-017-11120-4.

  PMID: 28871199 BACKGROUND

• Yi P, Pryzbylkowski P. Opioid Induced Hyperalgesia. Pain Med. 2015 Oct;16 Suppl 1:S32-6. doi: 10.1111/pme.12914.

  PMID: 26461074 BACKGROUND

• Mauermann E, Filitz J, Dolder P, Rentsch KM, Bandschapp O, Ruppen W. Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial. Anesthesiology. 2016 Feb;124(2):453-63. doi: 10.1097/ALN.0000000000000976.

  PMID: 26655493 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Vasileia Nyktari, MD,PhD

  University of Crete, Medical School

  STUDY CHAIR

Central Study Contacts

George Papastratigakis, MD

CONTACT

00306979056672; papastratigakisg@gmail.com

Georgios Stefanakis, MD

CONTACT

00306978779726; G_Stefanakis@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Laboratory data analysis collaborators
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Implementation of a multimodal anesthetic opioid-free strategy, that includes the administration of pregabalin, ketamine, dexmedetomidine, lidocaine, dexamethasone, magnesium sulphate, paracetamol and dexketoprofen is anticipated to modulate the inflammatory and stress response, as measured by levels of inflammatory markers and haemodynamic stability, compared to conventional anesthetic opioid-based techniques. Furthermore, a decreased inflammatory and stress response, as expressed by reduced levels of inflammatory biomarkers and hemodynamic stability, is expected to decrease peripheral and central sensitization, contributing to better postoperative analgesia.

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: May 20, 2021
• Study Start: October 8, 2020
• Primary Completion: October 8, 2025
• Study Completion (Estimated): October 8, 2027
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)