Optimization of Morphinomimetic Administration Intraoperatively: Evaluation of the Impact of the NOL Index on the Occurrence of Postoperative Adverse Events Related to Morphinomimetics (NOL-Impact)

Optimization of Morphinomimetic Administration Intraoperatively: Evaluation of the Impact of the NOL Index on the Occurrence of Postoperative Adverse Events Related to Morphinomimetics: A Randomized Controlled Trial

Reducing the quantity of morphinomimetics during the operative period reduces the prevalence and intensity of adverse effects.

However, morphinomimetics are indispensable during surgery, as they limit the autonomic nervous system's deleterious reactions to nociception. The administration of these drugs in intravenous boluses during surgery is usually guided by their duration of action and by variations in heart rate and blood pressure. Other events, such as hypovolemia or extreme surgical position, may stimulate the autonomic nervous system outside of nociception. These events, along with routine drug administration, can lead to undue consumption of morphinomimetics.

The Nol index, a multiparametric monitor of nociception, is based on analysis of variations in plethysmography waveform, heart rate and skin conductance. It has been demonstrated that the use of this type of monitor can reduce intraoperative consumption of morphinomimetics and optimize their administration. Does intraoperative morphinomimetic administration optimized by the NOL index have an impact on the occurrence of dose-dependent adverse effects?

Study Overview

• Status: Not yet recruiting
• Conditions: Anesthesia; Intensive Care Medicine
• Intervention / Treatment: Procedure: Nol index

• Study Type: Interventional
• Enrollment (Estimated): 332
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabien ESPITALIER, PU-PH; Phone Number: +33 2 47 47 17 47; Email: fabien.espitalier@univ-tours.fr

Study Locations

• France
  • Angers, France
    • CHU Angers
    • Contact: Sigismond LASOCKI, PH; Phone Number: +33 6 03 16 62 95; Email: SiLasocki@chu-angers.fr
  • Blois, France
    • CH Blois
    • Contact: Thibault CAMOZZI, PH; Phone Number: +33 2 54 55 66 37; Email: thibaultcamozzi@hotmail.com
  • Brest, France
    • CHU Brest
    • Contact: Anaïs CAILLARD, PH; Phone Number: +33 2 98 22 33 33; Email: anais.caillard@chu-brest.fr
  • Nantes, France
    • CHU Nantes
    • Contact: Raphaël CINOTTI, PU-PH; Phone Number: +33 2 40 08 47 31; Email: Raphael.CINOTTI@chu-nantes.fr
  • Tours, France
    • Chru Tours Sar1
    • Contact: Marc LAFFON, PU-PH; Phone Number: +33 2 47 47 38 10; Email: marc.laffon@univ-tours.fr
  • Tours, France
    • Chru Tours Sar2
    • Contact: Fabien ESPITALIER, PU-PH; Phone Number: +33 2 47 47 17 47; Email: fabien.espitalier@univ-tours.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female
• Subject aged ≥ 18 years
• Affiliated with a social security scheme
• Having given written informed consent to participate study
• Admitted for major surgery expected to last more than 2 hours
• Under general anesthesia with tracheal intubation
• For a planned hospital stay of at least 48 hours
• Participant's ability to understand the nature and objectives of the study to comply with study requirements.

Exclusion Criteria:

• Contraindication to one of the drugs used for anesthesia
• Urgent surgery
• Intracranial surgery
• Transplant surgery
• Cardiac surgery
• Surgery with scheduled local anesthesia
• Patient requiring postoperative intubation
• Neuromuscular disease
• Patient chronically using morphinomimetics
• Chronic pain patient
• Patients with a history of sleep apnea
• Conditions likely to interfere with photoplethysmograph signal acquisition or skin conductance (excessive or tremors of the extremities, skin lesions or burns)
• Patients wearing false nails and/or nail polish
• Contraindication to the use of the PMD 200 ™ medical device (including cardiovascular resuscitation and cardioversion/defibrillation);
• Patient with an implanted pacemaker or defibrillator
• Treatment with β-blockers
• Preoperative cardiac arrhythmia
• Pregnant or breast-feeding women. A β-HCG test will be systematically performed prior to inclusion of non-menopausal women menopausal women
• Patients under legal protection (safeguard of justice, curatorship guardianship) or deprived of liberty
• Participation in other interventional research involving an experimental drug or medical device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group NOL; Morphinomimetics will be administered according to NOL Index values.	Procedure: Nol index; Morphinomimetics will be administered according to NOL Index values or according to the usual criteria.
No Intervention: Group control; Morphinomimetics will be administered according to the usual criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite outcome including at least one occurrence of hypoxemia, of nausea-vomiting or of ileus.	occurrence of hypoxemia: at least 1 episode of SpO2 < 95%,; occurrence of nausea-vomiting: at least one episode of nausea requiring antiemetic treatment, or at least one episode of vomiting,; occurrence of ileus: absence of gas or stool.	From enrollment to within 48 hours post-extubation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total consumption of intraoperative morphinomimetics		From intervention to 48 hours after extubation
Total consumption of intraoperative vasoconstrictors	type of vasoconstrictor, amount of vasaoconstrictor used and number of boli of vasoconstrictor will be considered	From induction to extubation, up to 8 hours
Time of extubation	Delay between the end of the hypnotic infusion and the patient becoming conscious and able to breathe freely	From the end of anesthesia administration to extubation, up to 1 hours
Time from extubation to theoretical post-anesthesia care unit discharge time with Aldrete score at 10	Aldrete's score will be assessed every 5 minutes during his stay in the post-anesthesia care unit. Discharge from the post-anesthesia care unit will be possible when the Aldrete score reaches 10.	From extubation to Aldrete score at 10, every 5 minutes, up to 2 hours
Maximum intensity of pain	Numeric rating scale (NRS): Patients rate their pain intensity on a 11-point Numeric Rating Scale (NRS-11), where 0 indicates the absence of pain and 10 means the worst possible pain.	From extubation to 48 hours postoperative
Number of episodes of pain	Numerical scale > 3	From extubation to 48 hours postoperative.
Number of episodes of hypoxemia		From intervention to 48 hours post-extubation
Number of episodes of nausea and vomiting		From intervention to 48 hours post-extubation
Hospital stay length	Time from hospital admission to hospital discharge	From admission to hospital discharge up to 1 month.
Quality of post-operative recovery	The French version of the Quality of Recovery -15 (FQoR-15) is is a validated multidimensional PROM-based questionnaire that measures postoperative quality of recovery. The QoR-15 scale consists of 15 questions, where the patient is asked to quote dimensions of his/her recovery from 0 to 10. After summing all 15 responses, the QoR-15 is presented as a score, ranging from 0 to 150, with 150 corresponding to an ideal health status.	From enrollment to 24 hours and 48 hours after chirurgical intervention
Intensity of chronic pain	Phone contact : DN4 form The DN4 form (douleur neuropathique - neuropathic pain 4) is a form with 10 questions. The results are from 0 to 10. A result greater than 4 is considered positive.	At 3 months, at 6 months and at 12 months (end of the study)
Occurrence of hypoxemia	Occurrence of hypoxemia: at least 1 episode of SpO2 < 95%	From enrollment to 48 hours post-extubation
Occurrence of nausea-vomiting	Occurrence of nausea-vomiting: at least one episode of nausea requiring antiemetictreatment, or at least one episode of vomiting	From enrollment to 48 hours post-extubation
Occurrence of ileus	Occurrence of ileus: absence of gas or stool.	From enrollment to 48 hours post-extubation

Collaborators and Investigators

• Sponsor: University Hospital, Tours

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: DR220248

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