Influence of Intraoperative Nociception Guided Analgesia on Perioperative Total Analgesic Requirement Endometriosis (ENDONOL)

Influence of Intraoperative Nociception Guided Analgesia on Perioperative Analgesia Consumption in Patients Undergoing Laparoscopic Resection of Endometriosis

Adequate analgesia in the perioperative setting is one of the most important pillars of anesthesiology. It is generally understood that poorly managed acute postoperative pain correlates with increased morbidity, prolonged recovery periods, extended opioid utilization, and serves as a predictor for chronic pain onset . On the other hand, the overuse of opioid-based analgesics during surgery may evoke respiratory depression, constipation, nausea, sedation, and opioid-induced hyperalgesia . Thus far, the lack of an objective intraoperative pain monitor has constrained anesthesia practitioners to rely on the interpretation of physiological cues such as tachycardia, hypertonia, and lacrimation as surrogate markers of pain (3). Variability in the educational background and clinical experience among providers may predispose to either excessive or inadequate administration of analgesics, consequently allowing for unfavorable postoperative outcomes. However, recent advancements have introduced novel devices for nociception measurement. Thus, a quantifiable assessment of nociception has become feasible. The most widely approved device is the Nociception Level (NOL®) index developed by Medasense in Israel. This index operates by discerning various sympathetic responses of the body to nociceptive stimuli and has been thoroughly tested on opioid-based analgesic regimens. The NOL® index uses a multiparametric approach including a random forest algorithm to measure the balance between sympathetic and parasympathetic system activity. Recently, a strong correlation has been reported between the response of the NOL® index and analgesia during surgery.

Patients being scheduled for endometriosis surgery do have a significant history of chronic pain thus being more prone to postoperative complications and therefore will benefit the most from a tailored analgesic regimen.

Study Overview

• Status: Completed
• Conditions: Perioperative Analgesia in Endometriosis
• Intervention / Treatment: Device: nociception guided treatment

Detailed Description

Adequate analgesia in the perioperative setting is one of the most important pillars of anaesthesiology. It is generally understood that poorly managed acute postoperative pain correlates with increased morbidity, prolonged recovery periods, extended opioid utilization, and serves as a predictor for chronic pain onset. On the other hand, the overuse of opioid-based analgesics during surgery may evoke respiratory depression, constipation, nausea, sedation, and opioid-induced hyperalgesia. Thus far, the lack of an objective intraoperative pain monitor has constrained anaesthesia practitioners to rely on the interpretation of physiological cues such as tachycardia, hypertonia, and lacrimation as surrogate markers of pain. Variability in the educational background and clinical experience among providers may predispose to either excessive or inadequate administration of analgesics, consequently allowing for unfavorable postoperative outcomes. However, recent advancements have introduced novel devices for nociception measurement. Thus, a quantifiable assessment of nociception has become feasible. The most widely approved device is the Nociception Level (NOL®) index developed by Medasense in Israel. This index operates by discerning various sympathetic responses of the body to nociceptive stimuli and has been thoroughly tested on opioid-based analgesic regimens. The NOL® index uses a multiparametric approach including a random forest algorithm to measure the balance between sympathetic and parasympathetic system activity. Recently, a strong correlation has been reported between the response of the NOL® index and analgesia during surgery.

Patients being scheduled for endometriosis surgery do have a significant history of chronic pain thus being more prone to postoperative complications and therefore will benefit the most from a tailored analgesic regimen. Patients' existing analgesic regimen, typically comprising Paracetamol, NSAIDs, and Metamizol, will be carefully documented during preoperative anesthetic consultations and taken into account in the study protocols.

Preoperatively, patients will be staged by their gynecologists using the ENZIAN classification. The ENZIAN classification is a diagnostic system for endometriosis that covers various localizations and forms of the disease. It enables a standardized assessment for both non-invasive and invasive diagnostic procedures. The classification considers specific compartments and uses standardized coding for the severity and location of lesions. The classification is performed preoperatively using ultrasound diagnostics as well as intraoperatively and is annotated with the lower-case letters: (s)= Surgical, (u)= Ultrasound (Keckstein J, 2021). Thereby, a comprehensive picture of the disease is obtained. Deeply infiltrating endometriosis requires a more invasive procedure, a longer operating time and a higher consumption of analgesics.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Zurich
    • Schlieren, Canton of Zurich, Switzerland, 8952
      • Spital Limmattal

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Premenopausal females
• Undergoes any type of laparoscopic surgery for suspected endometriosis or adenomyosis (diagnostic/therapeutic and/or hysterectomy)

Exclusion Criteria:

• Age < 18 years
• Patients with contraindications for opioids and/or ketamine/clonidine (standard medications)
• Pregnant or breastfeeding women
• Lack of ability to follow the study procedure, e.g. due to severe language barriers, mental disorders, dementia
• Patients requiring preoperative or postoperative treatment in the intensive care unit
• Patients with conditions precluding the use of the NOL® sensor, such as neuromuscular deficits affecting hand function
• Regular consumption of opioids (Mankoski Score ≥6)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; The control group will undergo standard treatment for laparoscopic endometriosis/adenomyosis surgery at Spital Limmattal. Although the control group will not be using NOL®-monitoring to guide analgesic requirement, the monitor will be installed with a blinded screen to investigate whether our multimodal anesthesia model is in coherence with values between 10 and 25. The anesthesia care team will not be able to see the values during surgery in order to tailor analgesic requirement only by conventional clinical judgement.
Experimental: nociception guided treatment; For the nociception level-guided group the same standard narcosis will be applied whilst ensuring that the NOL® level value will be maintained between 10 and 25.	Device: nociception guided treatment; For the nociception level-guided group the same standard narcosis will be applied whilst ensuring that the NOL® level value will be maintained between 10 and 25.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total analgestic requirement	Total analgesic requirement. Intra- and postoperative medication administration will be systematically documented throughout until two hours after arrival at the recovery room or until the patient has been discharged from the recovery room.	Start of anaesthesia until discharge from the recovery room (max. lenghth of stay in the recovery 2 hours)..

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Numeric Rating Scale (NRS) scores in PACU	Postoperative Numeric Rating Scale (NRS) scores. The NRS icludes values from 0 to 10 (indicating no pain at 0 and maximized pain at 10, which is a worse outcome). The NRS score will be assessed every 15 minutes starting with arrival at the recovery room until 2 hours after admission or until the patient has been discharged from the recovery room.	Start Start at arrival in the recovery room until discharge from the recovery room (max. lenghth of stay in the recovery 2 hours)
Total length of Stay in the PACU (min)		Start at arrival in the recovery room until discharge from the recovery room (max. lenghth of stay in the recovery 2 hours)
Postoperative Numeric Rating Scale (NRS) scores at discharge	Postoperative Numeric Rating Scale (NRS) scores at discharge (indicating no pain at 0 and maximized pain at 10, which is a worse outcome) will be assessed every 15 minutes starting with arrival at the recovery room until 2 hours after admission or until the patient has been discharged from the recovery room. One more NRS assessement will be made at discharge.	Immediately postoperatively until discharge (1-3 days).

Collaborators and Investigators

• Sponsor: Prof Urs Zingg
• Investigators: Principal Investigator: Isabel Marcolino, Dr. med., Spital STS AG

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2024
• Primary Completion (Actual): September 5, 2025
• Study Completion (Actual): September 5, 2025

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: perioperative analgesia; endometriosis surgery
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neurologic Manifestations; Nervous System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neurobehavioral Manifestations; Genital Diseases, Female; Perceptual Disorders; Endometriosis; Agnosia
• Other Study ID Numbers: 2024-00822

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