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

Victor Contreras, MSN

Status: Completed

Conditions: Postoperative Pain; Analgesics, Opioid; Allodynia; Nociceptive Pain; Pain, Postoperative; Opioid Use; Anesthesia

Treatments: Drug: fentanyl NOL guided

Study type: Interventional

Funder types: Other

Identifiers

NCT03858621

FONDECYT Iniciacion (Other Grant/Funding Number)

180522017

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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100 participants in 2 patient groups

fentanyl NOL guided

Experimental group

Description:

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.

Treatment:

Drug: fentanyl NOL guided

fentanyl standard analgesia

No Intervention group

Description:

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.