Comparison of Postoperative Nociception Between NOL-guided and Standard Intraoperative Analgesia Based on Fentanyl (NOLFentanyl)

Comparison of Postoperative Nociception Outcomes Between NOL - Guided and Standard Intraoperative Analgesia Based on Fentanyl in Patients Undergoing Elective Surgery With General Anesthesia

Pain is defined as an unpleasant sensory and emotional conscious experience, associated with actual or potential tissue damage. Nociception is the sympathetic response to noxious stimuli during unconsciousness. The appearance of different forms of chronic pain results from sensitization of both peripheral and central neural circuits of pain, which involves inflammatory mechanisms both at a systemic level and specifically in the peripheric and central nervous system, as observed through elevation of specific neuroinflammatory mediators, such as MCP-1, IL-1, IL-1b, and IL-10. Clinically, this sensitization expresses as hyperalgesia and allodynia, which increase postoperative pain and morbidity, but also induce permanent modifications in the nociceptive system. These effects may be ameliorated by adequately adjusting intraoperative analgesia through use of nociception/analgesia balance monitors, of which Nociception Level Index (NOL) shows convenient characteristics and promising results from previous studies.

Objectives: The goal of our study is to assess the utility of NOL index monitoring against standard care for Fentanyl-based analgesia by measuring postoperative pain, sensorial thresholds and inflammatory markers related to nociception.

Hypothesis: The use of NOL index to guide the intraoperative analgesia will produce less postoperative pain, hyperalgesia, allodynia, and neuroinflammation.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Postoperative Pain; Anesthesia; Opioid Use; Nociceptive Pain; Analgesics, Opioid; Allodynia
• Intervention / Treatment: Drug: fentanyl NOL guided

Detailed Description

Methodology: In this RCT double-blinded study will invite to 100 patients aged between 18 and 50 years admitted for elective surgery that is planned to require general anesthesia, with fentanyl as the opioid of choice for intraoperative analgesia.

Each patient will be randomly allocated to one of two groups: the intervention group will be provided intraoperative analgesia guided by NOL values (n=50), and the control group will be provided standard intraoperative analgesia (n=50). To account for inter-personal variability, the NOL threshold value associated with nociceptive stimulation will be assessed on each patient at baseline condition with the Quantitative Sensory Testing (QST) and neuroinflammatory mediators MCP-1, IL-1, IL-1b, and IL-10 will be measured pre- and post-surgery in both groups. Opioid consumption and AVS will be assessed during the stay at the post-surgical care unit as a measurement of post-operative pain and will follow them until three months after surgery.

Statistical Analysis: Results will be expressed as means (±SD) or numbers (%). When indicated, 95% confidence interval (CI) will be calculated. A p-value < 0.05 will be considered statistically significant.

Differences between groups on post-surgical opioid consumption, Δz-score of QST measurements, and serum biomarkers level will be analyzed with Student's T-test for unpaired samples. For analysis purposes, VAS scores will be grouped into three distinct categories: Mild (0-3), Moderate (4-6) and Severe (7-10) pain. Differences between groups will be analyzed with Chi-square test.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Región Metropolitana
    • Santiago, Región Metropolitana, Chile, 8420525
      • Victor Contreras

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA I-II
• Elective abdominal surgery without a neuraxial block.
• Over 2 horas.
• Body Mass Index 18 - 30 kg/m2

Exclusion Criteria:

• Cardiac surgery
• Cardiopathy
• Arrhythmia or use of pacemakers.
• Chronic Kidney disease (Plasma Crea >1 mg/dL).
• Allergic to drugs of this study.
• Opioids or Non-inflammatory drugs over 5 days for two weeks before surgery.
• Neuropathies and dysautonomias.
• Beta-blockers and other drugs that act at the level of the sympathetic system the month prior to surgery.
• Chemotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: fentanyl NOL guided; A bolus of 2 mcg/kg IV Fentanyl will be given at the induction of the anesthesia. A bolus of 0,5 - 1 mcg/kg IV Fentanyl will be given at the time of incision and during surgery following a predeterminate NOL index + heart rate + mean arterial blood pressure variations.	Drug: fentanyl NOL guided; Intervention is NOL monitoring in this group that will help to guide intravenous administration of fentanyl during surgery.; Other Names: NOL analgesia guided fentanyl administration
NO_INTERVENTION: fentanyl standard analgesia; A bolus of 2 mcg/kg IV Fentanyl will be given at the induction of the anesthesia. A bolus of 0,5 - 1 mcg/kg IV Fentanyl will be given at the time of incision and during surgery following the heart rate and mean arterial blood pressure variations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consumption of IV fentanyl intra-operative in the NOL-guided group compared to the standard group.	Total consumption of fentanyl in mcg.	Intra-operative
Consumption of opioid in the early postoperative in the NOL-guided group compared to the standard group.	Total consumption of morphine in mg.	Postoperative Unit (2 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain measured by Visual Analog Scale (VAS) in the NOL-guided group compared to the standard group.	Visual Analog Scale 0 to 10. 0 = no pain. 10 = worse pain Values to find out is less than 5-6	Postoperative Unit (Every 30 minutes per 2 hours)
Sensorial thresholds in the NOL-guided group compared to the standard group.	QST (Quantitative Sensory Testing) is a valuable method for diagnosing peripheral nervous system disorders.; Thermal Testing; Mechanical test threshold; Mechanical pain threshold; Wind-up phenomenon; Vibration detection threshold; Pressure pain threshold	Postoperative Unit (2 hours)
Pain Management Satisfaction in the NOL-guided group compared to the standard group.	Pain Management Satisfaction Scale 1 to 5. 1 = Not satisfied at all. 5 = Completly satisfied One question	Postoperative Unit (2 hours)
Pain Management Satisfaction in the NOL-guided group compared to the standard group.	Pain Management Satisfaction Scale 1 to 5. 1 = Not satisfied at all. 5 = Completly satisfied One question	Postoperative (6 hours)
Pain Management Satisfaction in the NOL-guided group compared to the standard group.	Pain Management Satisfaction Scale 1 to 5. 1 = Not satisfied at all. 5 = Completly satisfied One question	Postoperative (12 hours)
Inflammatory markers in the NOL-guided group compared to the standard group.	Concentration in plasma of: MCP1 (pg/mL) , IL6 (pg/mL) , IL1b (pg/mL), IL10 (pg/mL)	Postoperative (0 hours)
Inflammatory markers in the NOL-guided group compared to the standard group.	Concentration in plasma of: MCP1 (pg/mL) , IL6 (pg/mL) , IL1b (pg/mL), IL10 (pg/mL)	Postoperative (6 hours)
Inflammatory markers in the NOL-guided group compared to the standard group.	Concentration in plasma of: MCP1 (pg/mL) , IL6 (pg/mL) , IL1b (pg/mL), IL10 (pg/mL)	Postoperative (12 hours)
Persistent pain at three months in the NOL-guided group compared to the standard group.	Brief Pain Inventory by telephone call	3 months after surgery

Collaborators and Investigators

• Sponsor: Victor Contreras, MSN
• Investigators: Study Director: VICTOR CONTRERAS, MSN, Research Profesor

Publications and helpful links

General Publications

• Gandhi K, Heitz JW, Viscusi ER. Challenges in acute pain management. Anesthesiol Clin. 2011 Jun;29(2):291-309. doi: 10.1016/j.anclin.2011.04.009.
• Baliki MN, Apkarian AV. Nociception, Pain, Negative Moods, and Behavior Selection. Neuron. 2015 Aug 5;87(3):474-91. doi: 10.1016/j.neuron.2015.06.005.
• Katz J, Seltzer Z. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert Rev Neurother. 2009 May;9(5):723-44. doi: 10.1586/ern.09.20.
• Argoff CE. Recent management advances in acute postoperative pain. Pain Pract. 2014 Jun;14(5):477-87. doi: 10.1111/papr.12108. Epub 2013 Aug 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 15, 2019
• Primary Completion (ACTUAL): February 23, 2022
• Study Completion (ACTUAL): February 23, 2022

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (ACTUAL): March 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Postoperative Pain; pain; fentanyl; Nociceptive monitoring index
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Pain, Postoperative; Hyperalgesia; Nociceptive Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: 180522017; FONDECYT Iniciacion (OTHER_GRANT: 11180674)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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