Clinical trial NCT03858621: Comparison of Postoperative Nociception Between NOL-guided and Standard Intraoperative Analgesia Based on Fentanyl
Official title: Comparison of Postoperative Nociception Outcomes Between NOL - Guided and Standard Intraoperative Analgesia Based on Fentanyl in Patients Undergoing Elective Surgery With General Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain, Postoperative
Opioid Use
Nociceptive Pain
Postoperative Pain
Anesthesia
Allodynia
Analgesics, Opioid
Keywords: pain
Postoperative Pain
fentanyl
Nociceptive monitoring index
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2019-03-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Consumption of IV fentanyl intra-operative in the NOL-guided group compared to the standard group.
timeFrame: Intra-operative
measure: Consumption of opioid in the early postoperative in the NOL-guided group compared to the standard group.
timeFrame: Postoperative Unit (2 hours)
Secondary outcomes:
measure: Pain measured by Visual Analog Scale (VAS) in the NOL-guided group compared to the standard group.
timeFrame: Postoperative Unit (Every 30 minutes per 2 hours)
measure: Sensorial thresholds in the NOL-guided group compared to the standard group.
timeFrame: Postoperative Unit (2 hours)
measure: Pain Management Satisfaction in the NOL-guided group compared to the standard group.
timeFrame: Postoperative Unit (2 hours)
measure: Pain Management Satisfaction in the NOL-guided group compared to the standard group.
timeFrame: Postoperative (6 hours)
measure: Pain Management Satisfaction in the NOL-guided group compared to the standard group.
timeFrame: Postoperative (12 hours)
measure: Inflammatory markers in the NOL-guided group compared to the standard group.
timeFrame: Postoperative (0 hours)
measure: Inflammatory markers in the NOL-guided group compared to the standard group.
timeFrame: Postoperative (6 hours)
measure: Inflammatory markers in the NOL-guided group compared to the standard group.
timeFrame: Postoperative (12 hours)
measure: Persistent pain at three months in the NOL-guided group compared to the standard group.
timeFrame: 3 months after surgery
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Victor Contreras
state: Región Metropolitana
Study officials:
affiliation: Research Profesor
name: VICTOR CONTRERAS, MSN
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.