Guiding Opioid Administration by Nociception Level Index (NOL) in Patients With Regional Anesthesia

NCT06905340 | Recruiting

• 1 other identifier: TEMP522873-BO-ff
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

General anesthesia consists of a combination of hypnotic drugs to achieve unconsciousness and opioid analgesics to ensure antinociception. An alternative approach to the intraoperative administration of high-potency opioids to achieve antinociception during surgery is combining general anesthesia with regional anesthesia. Modern general anesthesia aims to avoid an overdose of opioid analgesics and reduce side effects of opioid administration. Quality and safety of general anesthesia are of major clinical importance and can be improved by adjusting the opioid analgesics to the optimal individual dose needed. In current clinical practice, opioid dosage is usually determined by clinical judgment. However, different monitoring devices estimating the effect of nociception during unconsciousness have become commercially available. One of the most recent commercially available nociception indices is the Nociception Level Index (NOL). Until today, there is conflicting evidence on whether guiding sufentanil administration by NOL monitoring, which is the intended use of the nociception index, affects postoperative pain level in the postanesthesia care unit (PACU), the amount of postoperatively administered opioids, and the quality of postoperative recovery in patients with a combination of general and regional anesthesia. This study aims to investigate the clinical performance of intraoperative NOL monitoring and determine whether guiding sufentanil administration by NOL monitoring - compared to routine care - reduces either postoperative pain level in the PACU, postoperative opioid consumption in the PACU or postoperative opioid consumption in the first 24 hours after the operation in patients having trauma and orthopedic surgery with combined general and regional anesthesia.

Conditions

Nociceptive Pain; Pain, Postoperative; Analgesia, Postoperative; Anesthesia Recovery Period; Opioid Use

Keywords

General anesthesia; Regional anesthesia; Analgesia Monitoring; Opioids

Outcome Measures

Primary Outcomes (3)

• Postoperative pain level in the PACU

  Compares the proportion of postoperative pain level (NRS=0 vs. NRS\>0) in the postanesthesia care unit (PACU) between the groups.

  1 day

• Postoperative administration of opioids during the PACU stay

  Compares the proportion of postoperative administration of opioids during the PACU stay (none vs. any) between the groups.

  1 day

• Postoperative administration of opioids in the first 24 hours after the operation

  Compares the proportion of postoperative administration of opioids in the first 24 hours after the operation (none vs. any) between the groups.

  2 days

Secondary Outcomes (7)

• Intraoperative sufentanil consumption

  1 day

• Intraoperative norepinephrine consumption

  1 day

• Time to extubation

  1 day

• Postoperative nausea and vomiting (PONV)

  1 day

• PACU stay

  1 day

Study Arms (2)

NOL (Nociception Level Index)

EXPERIMENTAL

Opioid administration (sufentanil) guided by the Nociception Level Index (NOL) derived from photoplethysmography, galvanic skin conductance, and the measurement of skin temperature performed by the device PMD-200 Nociception Monitor from the manufacturer Medasense Biometrics Ltd, Ramat Yishai, Israel. Included in the monitoring system is software that continuously calculates the NOL from normalized heart rate variability, pulse plethysmographic amplitude, skin conductance, and skin temperature derived from a finger sensor. The numerical index ranges from 0 (low sympathetic tone) to 100 (high sympathetic tone). A NOL score between 10 and 25 has been proposed as the target range based on which to guide opioid analgesics dosage. 5 µg sufentanil will be administered if the NOL score exceeds 25 for more than 60 seconds. The sufentanil boluses may be repeated to keep NOL between 10-25 accordingly.

Procedure: NOL (Nociception Level Index)

Control

ACTIVE COMPARATOR

Opioid administration (sufentanil) based on standard clinical practice where attending anesthesiologists are advised to administer 5 µg sufentanil if signs of inadequate anesthesia are present. Given adequate hypnosis (BIS 40-60), these signs include hypertension (MAP\>120% of baseline or \>100mmHg), tachycardia (HR\>120% of baseline or \>90/min), somatic arousal (coughing, chewing, grimacing) and somatic response (purposeful movement). The patient-specific baseline is defined as the average of three consecutive post-induction, pre-surgery MAP and HF values. The time elapsed between 5µg doses of sufentanil is up to the anesthesiologist's discretion.

Other: Control (Standard treatment)

Interventions

NOL (Nociception Level Index) PROCEDURE

Elective surgery in patients having trauma and orthopedic surgery with a combination of general and regional anesthesia. Opioid titration is guided by NOL during general anesthesia in the experimental arm.

NOL (Nociception Level Index)

Control (Standard treatment) OTHER

Opioid administration (sufentanil) guided according to standard clinical practice of the attending anesthesiologist

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients undergoing elective trauma or orthopedic surgery with a combination of general and regional anesthesia

You may not qualify if:

• Preexisting therapy with cardiac glycosides or pacemakers
• Cardiac arrhythmia (atrial fibrillation, atrioventricular block \> I°)
• Chronic opioid misuse
• Intraoperative treatment with ketamine, beta-adrenergic agonists, or clonidine
• Serious peripheral or cardiac autonomic neuropathy
• Inability to specify the postoperative pain level
• Postoperative treatment in an ICU

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg Eppendorf

Hamburg, 20246, Germany

RECRUITING

MeSH Terms

Conditions

Nociceptive Pain; Pain, Postoperative; Agnosia

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Study Officials

• Rainer Nitzschke, MD

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rainer Nitzschke, MD

CONTACT

+4915222815884; r.nitzschke@uke.de

Annika Zoller

CONTACT

+49040741052415; ana-sek@uke.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded to the three primary endpoints (postoperative pain level in the PACU, postoperative opioid consumption in the PACU, and postoperative opioid consumption in the first 24 hours after the operation). Patients are blinded to group allocation. Postoperative outcome parameters are assessed by members of the study team. These outcome assessors are blinded to the group assignment. During the operation, the attending anesthesiologists cannot be blinded to group allocation because the study involves intervention during the intraoperative treatment. As such, the study is only single-blinded regarding the intraoperative secondary endpoints.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: May 12, 2025
• Primary Completion: December 1, 2025
• Study Completion: January 1, 2026
• Last Updated: June 8, 2025

Record last verified: 2025-06

Locations

DE (1)