Comparison of Postoperative Nociception Between NOL-guided and Standard Intraoperative Analgesia Based on Fentanyl
Condition: Pain, Postoperative; Opioid Use; Nociceptive Pain; Postoperative Pain; Anesthesia; Allodynia; Analgesics, Opioid
MeSH terms: Hyperalgesia; Pain, Postoperative; Nociceptive Pain
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): fentanyl NOL guided
Intervention type(s): Drug
Intervention description(s): Intervention is NOL monitoring in this group that will help to guide intravenous administration of fentanyl during surgery.
Other intervention name(s): NOL analgesia guided fentanyl administration
Intervention MeSH terms: Fentanyl
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 2 groups of patients. Randomization into group fentanyl NOL-guided vs fentanyl standard according to randomization list for a total number of 100 patients.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Prevention
Keywords: pain; Postoperative Pain; fentanyl; Nociceptive monitoring index