Opioid Free Anaesthesia-Analgesia Strategy on Surgical Stress and Immunomodulation in Elective VATS-Lobectomy for NSCLC

NCT05172739 | Recruiting Phase 4

• 1 other identifier: OFA-Thoracic
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Lobectomy is a major, high-risk surgical procedure that in addition to one-lung ventilation (OLV) exerts a potent surgical stress response. An overwhelming immune cell recruitment may lead to excessive tissue damage, peripheral organ injury and immunoparesis. The effect of anesthesia on the immune system is modest, compared to the effects induced by major surgery. However, to an immunocompromised patient, due to cancer and/or other comorbidities, the immunosuppressive effects of anesthesia may increase the incidence of post-operative infections, morbidity, and mortality. Exogenous opioids have been correlated with immunosuppression, opioid-induced hyperalgesia, and respiratory depression, with deleterious outcomes. An Opioid-Free Anaesthesia-Analgesia (OFA-A) strategy is based on the administration of a variety of anaesthetic/analgesic and other pharmacological 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, will lead to an attenuated surgical stress response and attenuated immunosuppression, compared to a conventional Opioid-Based Anaesthesia-Analgesia (OBA-A) strategy. The aforementioned effects, are presumed to be associated with equal or improved analgesia and decreased incidence of postoperative infections compared to a perioperative OBA-A technique.

Conditions

Systemic Inflammatory Response Syndrome; Postoperative Pain, Acute; Postoperative Pain, Chronic; Infections Postoperative; Opioid Use; Anesthesia; Non-small Cell Lung Cancer

Keywords

Opioid-free Anesthesia-Analgesia; Opioid-based Anesthesia-Analgesia; Cytokines; NSCLC; Hemodynamic stability; Immunomodulation; Inflammatory markers; Acute postoperative pain; Chronic postoperative pain

Outcome Measures

Primary Outcomes (101)

• Neutrophil to Lymphocyte ratio (NLR)

  Neutrophil to Lymphocyte ratio (NLR) is a prognostic index that predicts patients' overall survival. Higher NLR has been correlated with worse outcome.

  Preoperatively

• Platelet to Lymphocyte ratio (PLR)

  Platelet to Lymphocyte ratio (PLR) is a prognostic index that predicts patients' overall survival. Higher PLR has been correlated with worse outcome.

  Preoperatively

• Lymphocyte to monocyte ratio (LMR)

  Lymphocyte to monocyte ratio (LMR) is a prognostic index that predicts patients' overall survival. Lower LMR has been correlated with worse outcome.

  Preoperatively

• Advanced Lung Cancer Inflammation Index (ALI)

  Advanced Lung Cancer Inflammation Index (ALI) is a prognostic index that predicts patients' recurrence-free survival and overall survival. ALI is calculated as (BMI x Alb / NLR) where BMI = body mass index, Alb = serum albumin, NLR (neutrophil lymphocyte ratio, a marker of systemic inflammation). Higher ALI scores have been correlated with worse outcome.

  Preoperatively

• Systemic Immune Inflammation Index (SII)

  Systemic Immune Inflammation Index (SII) is a prognostic index that predicts patients' overall survival. SII is calculated as follows: SII = platelet count × neutrophil/lymphocyte count. Higher SII scores have been correlated with worse outcome.

  Preoperatively

• Prognostic Nutritional Index (PNI)

  Prognostic Nutritional Index (PNI) is a prognostic index that predicts patients' overall survival. PNI is calculated as follows: PNI = 10 × serum albumin value (g/dL) + 0.005 × total lymphocyte count (per mm3) in the peripheral blood. Higher PNI scores have been correlated with worse outcome.

  Preoperatively

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - IL-6 - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - IL-6 - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - IL-8 - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - IL-8 - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - IL-10 - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - IL-10 - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - TNF-a - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - TNF-a - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - CRP - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - CRP - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - WBC - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - WBC - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - AVP - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - AVP - 24 hours after the end of surgery

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

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

• 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

  Preoperatively (as a baseline)

• Surgical Stress Response - cortisol - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - cortisol - 24 hours after the end of surgery

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

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

• Surgical Stress Response - HIF-1α- preoperatively

  Inflammatory response and stress response as quantified by HIF-1α serum levels. Blood sample collection will take place in both study groups

  Preoperatively (as a baseline)

• Surgical Stress Response - HIF-1α - end of surgery

  Inflammatory response and stress response as quantified by HIF-1α serum levels. Blood sample collection will take place in both study groups

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - HIF-1α - 24 hours after the end of surgery

  Inflammatory response and stress response as quantified by HIF-1α serum levels. Blood sample collection will take place in both study groups

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

• Surgical Stress Response - VEGF- preoperatively

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

  Preoperatively (as a baseline)

• Surgical Stress Response - VEGF- end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - VEGF - 24 hours after the end of surgery

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

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

• Surgical Stress Response - NF-κB - preoperatively

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

  Preoperatively (as a baseline)

• Surgical Stress Response - NF-κB - end of surgery

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

  End of surgery (end of placement of last suture/ surgical clip on patient)

• Surgical Stress Response - NF-κB - 24 hours after the end of surgery

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

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

• Haemodynamic Stability - Mean 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. Mean PR 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 - Minimum 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. Minimum PR 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 - Maximum 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. Maximum PR 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 - Standard Deviation 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. Standard Deviation PR 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 - PR Change Induction

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Pulse Rate change 1 minute after anesthesia induction, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after anesthesia induction, compared to 1 minute prior

• Haemodynamic Stability - PR Change Incision

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Pulse Rate change 1 minute after surgical incision, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after surgical incision, compared to 1 minute prior

• Haemodynamic Stability - Mean 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. Mean SBP 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 - Minimum 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. Minimum SBP 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 - Maximum 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. Maximum SBP 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 - Standard Deviation 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. Standard Deviation SBP 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 - SBP Change Induction

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Systolic Blood Pressure change 1 minute after anesthesia induction, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after anesthesia induction, compared to 1 minute prior

• Haemodynamic Stability - SBP Change Incision

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Systolic Blood Pressure change 1 minute after surgical incision, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after surgical incision, compared to 1 minute prior

• Haemodynamic Stability - Mean 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. Mean DBP 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 - Minimum 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. Minimum DBP 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 - Maximum 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. Maximum DBP 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 - Standard Deviation 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. Standard Deviation DBP 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 - DBP change induction

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Diastolic Blood Pressure change 1 minute after anesthesia induction, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after anesthesia induction, compared to 1 minute prior

• Haemodynamic Stability - DBP change incision

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Diastolic Blood Pressure change 1 minute after surgical incision, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after surgical incision, compared to 1 minute prior

• Haemodynamic Stability - Mean 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. Mean MBP 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 - Minimum 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. Minimum MBP 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 - Maximum 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. Maximum MBP 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 - Standard Deviation 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. Standard Deviation MBP 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 - MBP change induction

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Mean Blood Pressure change 1 minute after anesthesia induction, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after anesthesia induction, compared to 1 minute prior

• Haemodynamic Stability - MBP change incision

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Mean Blood Pressure change 1 minute after surgical incision, compared to 1 minute prior. Data will be collected from a pulse contour analysis monitor.

  1 minute after surgical incision, compared to 1 minute prior

• Haemodynamic Stability - Mean CO

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Output - CO. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Mean CO 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 - Minimum CO

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Output - CO. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Minimum CO 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 - Maximum CO

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Output - CO. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Maximum CO 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 - Standard Deviation CO

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Output - CO. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Standard Deviation CO 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 - Mean CI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Index - CI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Mean CI 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 - Minimum CI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Index - CI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Minimum CI 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 - Maximum CI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Index - CI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Maximum CI 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 - Standard Deviation CI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Cardiac Index - CI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Standard Deviation CI 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 - Mean SV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume - SV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Mean SV 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 - Minimum SV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume - SV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Minimum SV 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 - Maximum SV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume - SV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Maximum SV 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 - Standard Deviation SV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume - SV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Standard Deviation SV 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 - Mean SVV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Variation - SVV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Mean SVV 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 - Minimum SVV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Variation - SVV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Minimum SVV 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 - Maximum SVV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Variation - SVV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Maximum SVV 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 - Standard Deviation SVV

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Variation - SVV. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Standard Deviation SVV 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 - Mean SVI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Index - SVI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Mean SVI 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 - Minimum SVI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Index - SVI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Minimum SVI 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 - Maximum SVI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Index - SVI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Maximum SVI 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 - Standard Deviation SVI

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Stroke Volume Index - SVI. Data will be collected from a pulse contour analysis monitor, and values will be collected every 20 seconds. Standard Deviation SVI 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 - Tachycardia

  Intraoperative Tachycardia (defined as PR≥ 100 bpm), with episodes lasting ≥1 minute. Data will be reported in total seconds of intraoperative tachycardia.

  Intraoperatively, assessed up to 4 hours.

• Haemodynamic Stability - Bradycardia

  Intraoperative Bradycardia (defined as PR≤ 60 bpm), with episodes lasting ≥1 minute. Data will be reported in total seconds of intraoperative bradycardia.

  Intraoperatively, assessed up to 4 hours.

• Haemodynamic Stability - Hypotension

  Intraoperative Hypotension (defined as SBP≤100mmHg or ≤70% 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 total seconds of intraoperative hypotension.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Hypertension

  Intraoperative Hypertension (defined as SBP ≥130% 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 total seconds of intraoperative hypertension.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Fluid requirements - Crystalloids - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Crystalloid Fluid Requirements.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Fluid requirements - Colloids - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Colloid Fluid Requirements.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Fluid requirements - Concentrated RBCs - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Concentrated Red Blood Cell unit Requirements.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Fluid requirements - Plasma - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Plasma unit Requirements.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Fluid requirements - Platelets - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Platelet unit Requirements.

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Blood Loss - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Blood Loss

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Fluid Balance - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Fluid Balance

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Adrenaline - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Adrenaline requirements

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Noradrenaline - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Noradrenaline requirements

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Ephedrine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Ephedrine requirements

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Phenylephrine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Phenylephrine requirements

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Dopamine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Dopamine requirements

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Dobutamine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Dobutamine requirements

  Intraoperatively, assessed up to 6 hours.

• Haemodynamic Stability - Vasoactive Requirements - Nitroglycerine - Intraoperatively

  Haemodynamic Stability as quantified by hemodynamic markers, specifically Nitroglycerine requirements

  Intraoperatively, assessed up to 6 hours.

Secondary Outcomes (77)

• Acute postoperative pain - Numerical Rating Scale (NRS) - Immediately Postoperatively

  Immediately postoperatively

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

  First postoperative day

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

  Second postoperative day

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

  Third postoperative day

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

  Immediately postoperatively

Study Arms (2)

Opioid-Based Anaesthesia 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. Surgical ward: PCA pump with Morphine for the first 3 postoperative days. Additional postoperative analgesia: Paracetamol 1g 1x3 +/- Dexketoprofen trometamol 50mg 1x2. Rescue therapy only: Tramadol 50-100mg.

Drug: Opioid-Based Anesthesia-Analgesia Strategy

Opioid-Free Anesthesia Analgesia

ACTIVE COMPARATOR

Premedication: Pregabalin 150mg 1x2, IM Midazolam 0.05-0.07mg/kg. Anesthesia induction: Midazolam 0.03mg/kg, Dexmedetomidine 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 0.5-1.2mcg/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. Surgical ward: PCA pump with Ketamine, Lidocaine, Clonidine, Droperidol and Midazolam for the first 3 postoperative days. Additionally, Pregabalin 50mg per os 1x1 and 25mg 1x1, Paracetamol 1g 1x3 +/- Dexketoprofen trometamol 50mg 1x2. 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 that incorporates the following pharmacological agents: Premedication: Midazolam, Anaesthesia induction \& maintenance: Midazolam, Propofol, Fentanyl, Cisatracurium or alternatively Rocuronium, Desflurane, Morphine, Paracetamol, Dexketoprofen trometamol, Ondansetron or Droperidol, Ropivacaine Surgical ward: Morphine, Paracetamol, Dexketoprofen trometamol Rescue therapy only: Tramadol

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

Opioid-Based Anaesthesia Analgesia

Opioid-free Anesthesia-Analgesia Strategy DRUG

A perioperative Opioid-Based multimodal Anesthesia- Analgesia strategy will be implemented that incorporates the following pharmacological agents: Premedication: Pregabalin, Midazolam, Anesthesia induction \& maintenance: Midazolam, Dexmedetomidine, Lidocaine, Propofol, Ketamine, Hyoscine, Cisatracurium or alternatively Rocuronium, Magnesium sulphate, Dexamethasone, Desflurane, Paracetamol, Dexketoprofen trometamol, Ondansetron or Droperidol, Ropivacaine, Surgical ward: Ketamine, Lidocaine, Clonidine, Droperidol and Midazolam, Pregabalin, Paracetamol, Dexketoprofen trometamol Rescue therapy only: Tramadol

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

Opioid-Free Anesthesia Analgesia

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients undergoing elective VATS lobectomy
• early stage NSCLC (up to T3N1M0)

You may not qualify if:

• Immunocompromised patients
• previous lung surgery
• preoperative corticosteroid or immunosuppressive drug use
• uncontrolled Diabetes Mellitus
• cardiac failure (NYHA 3 and 4)
• preoperative infection (CRP \>5mg/ml, WBC \>10x10\^9/L)
• preoperative anemia (Hb\<12g/dl)
• chronic inflammatory diseases
• inflammatory bowel disease
• OFA-Α: perioperative opioid administration, within the study period
• OBA-Α: perioperative dexmedetomidine or lidocaine infusion, ketamine, gabapentinoid or corticosteroid administration within the study period

Sponsors & Collaborators

• University of Crete: lead

Study Sites (1)

University of Crete

Heraklion, Crete, 71110, Greece

RECRUITING

Related Publications (13)

• Sanchez-Pedrosa G, Vara Ameigeiras E, Casanova Barea J, Rancan L, Simon Adiego CM, Garutti Martinez I. Role of surgical manipulation in lung inflammatory response in a model of lung resection surgery. Interact Cardiovasc Thorac Surg. 2018 Dec 1;27(6):870-877. doi: 10.1093/icvts/ivy198.

  PMID: 29945217 BACKGROUND

• Schneemilch CE, Hachenberg T, Ansorge S, Ittenson A, Bank U. Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005 Aug;22(8):616-23. doi: 10.1017/s0265021505001031.

  PMID: 16119599 BACKGROUND

• Homburger JA, Meiler SE. Anesthesia drugs, immunity, and long-term outcome. Curr Opin Anaesthesiol. 2006 Aug;19(4):423-8. doi: 10.1097/01.aco.0000236143.61593.14.

  PMID: 16829725 BACKGROUND

• Kurosawa S, Kato M. Anesthetics, immune cells, and immune responses. J Anesth. 2008;22(3):263-77. doi: 10.1007/s00540-008-0626-2. Epub 2008 Aug 7.

  PMID: 18685933 BACKGROUND

• Calogero AE, Norton JA, Sheppard BC, Listwak SJ, Cromack DT, Wall R, Jensen RT, Chrousos GP. Pulsatile activation of the hypothalamic-pituitary-adrenal axis during major surgery. Metabolism. 1992 Aug;41(8):839-45. doi: 10.1016/0026-0495(92)90164-6.

  PMID: 1640860 BACKGROUND

• Ninkovic J, Roy S. Role of the mu-opioid receptor in opioid modulation of immune function. Amino Acids. 2013 Jul;45(1):9-24. doi: 10.1007/s00726-011-1163-0. Epub 2011 Dec 15.

  PMID: 22170499 BACKGROUND

• Kosciuczuk U, Knapp P, Lotowska-Cwiklewska AM. Opioid-induced immunosuppression and carcinogenesis promotion theories create the newest trend in acute and chronic pain pharmacotherapy. Clinics (Sao Paulo). 2020 Mar 23;75:e1554. doi: 10.6061/clinics/2020/e1554. eCollection 2020.

  PMID: 32215455 BACKGROUND

• Plein LM, Rittner HL. Opioids and the immune system - friend or foe. Br J Pharmacol. 2018 Jul;175(14):2717-2725. doi: 10.1111/bph.13750. Epub 2017 Mar 23.

  PMID: 28213891 BACKGROUND

• Vallejo R, de Leon-Casasola O, Benyamin R. Opioid therapy and immunosuppression: a review. Am J Ther. 2004 Sep-Oct;11(5):354-65. doi: 10.1097/01.mjt.0000132250.95650.85.

  PMID: 15356431 BACKGROUND

• Finley MJ, Happel CM, Kaminsky DE, Rogers TJ. Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Cell Immunol. 2008 Mar-Apr;252(1-2):146-54. doi: 10.1016/j.cellimm.2007.09.008. Epub 2008 Feb 14.

  PMID: 18279847 BACKGROUND

• Parkhill AL, Bidlack JM. Reduction of lipopolysaccharide-induced interleukin-6 production by the kappa opioid U50,488 in a mouse monocyte-like cell line. Int Immunopharmacol. 2006 Jun;6(6):1013-9. doi: 10.1016/j.intimp.2006.01.012. Epub 2006 Feb 17.

  PMID: 16644488 BACKGROUND

• Busch-Dienstfertig M, Stein C. Opioid receptors and opioid peptide-producing leukocytes in inflammatory pain--basic and therapeutic aspects. Brain Behav Immun. 2010 Jul;24(5):683-94. doi: 10.1016/j.bbi.2009.10.013. Epub 2009 Oct 29.

  PMID: 19879349 BACKGROUND

• Stein C, Kuchler S. Non-analgesic effects of opioids: peripheral opioid effects on inflammation and wound healing. Curr Pharm Des. 2012;18(37):6053-69. doi: 10.2174/138161212803582513.

  PMID: 22747536 BACKGROUND

MeSH Terms

Conditions

Systemic Inflammatory Response Syndrome; Pain, Postoperative; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Postoperative Complications; Pain; Neurologic Manifestations; Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Vasileia Nyktari, MD, PhD

  University of Crete, Medical school

  STUDY CHAIR

Central Study Contacts

Periklis Vasilos, MD

CONTACT

00306978702023; p.vassilos@gmail.com

Georgios Stefanakis, MD, PhD

CONTACT

00306978779726; G_Stefanakis@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Administration of a multimodal anaesthetic opioid-free strategy that includes pregabalin, ketamine, dexmedetomidine, lidocaine, dexamethasone, magnesium sulphate, paracetamol and dexketoprofen is expected to affect the inflammatory and stress response, measured by levels of inflammatory markers and haemodynamic stability, when compared to conventional opioid based techniques. An Opioid-Free Anaesthesia-Analgesia strategy, is expected to also lead to an attenuated immunosuppression, due to the avoidance of opioids, whose administration has been corelated with immunosuppressive effects. An overall 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: November 13, 2021
• First Posted: December 29, 2021
• Study Start: October 1, 2021
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 29, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)