Postoperative Consequences of Intraoperative NOL Titration

To demonstrate that intraoperative NOL-guided titration of fentanyl improves initial recovery characteristics.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Adverse Effect
• Intervention / Treatment: Drug: Routine opioid management; Device: PMD-200 Nol-guided opioid administration

Detailed Description

Previous work has shown that NOL (Nociception Level) accurately quantifies nociception during general anesthesia.6 Presumably, titrating opioids to NOL will therefore provide individual guidance so that patients will be given about the right amount. Patient given the right amount will presumably awaken quickly when anesthesia is done, and have good initial pain control in the PACU (Post-Anesthesia Care Unit). To the extent that NOL titration facilitates optimal opioid dosing, patients are likely to have better PACU experiences - which would be an important outcome that clinicians and regulators are likely to take seriously.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults having major non-cardiac surgery expected to last ≥2 hours
• American Society of Anesthesiologists physical status 1-3
• Age 21-85 years old
• Planned endotracheal intubation

Exclusion Criteria:

• Planned neuraxial or regional block
• Clinician preference for an opioid other than, or in addition to, fentanyl
• Non-sinus heart
• Neurologic condition that, in the opinion of the investigators, may preclude accurate assessment of postoperative pain and nausea
• Lack of English language fluency
• Routine user of psychoactive drugs other than opioids
• Contraindication to sevoflurane, fentanyl, morphine, or ondansetron.
• Intracranial surgery.
• BMI > 40

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PMD-200 NOL group; Clinicians will titrate fentanyl to keep PMD-200 (Pain Monitoring Device) Nociception level (NOL) under 25 - always using good clinical judgement for individual patients	Device: PMD-200 Nol-guided opioid administration; PMD-200 Nociception level (NOL) values exceeding 25 for more than 30 seconds will typically be treated with boluses of fentanyl 1µg/kg ABW, up to a maximum of 100 µg per boluses, 5-minute intervals. Towards the end of the surgery (approximately 30-45 minutes before end of surgery, based on clinical judgment), the boluses of fentanyl will be reduced to 0.5 µg/kg ABW, up to a maximum of 50 µg per boluses, 5 minutes intervals. The target of a PMD-200 NOL score below 25 will be maintained until surgery ends; Other Names: PMD-200 NOL
Active Comparator: Control Group; Clinicians will be blinded to PMD-200 Nociception level (NOL) monitoring and use clinical judgement to determine how much fentanyl should be given, and when.	Drug: Routine opioid management; Clinical judgement will be according to their standard practice and may include interpretation of blood pressure, heart rate, diaphoresis, tearing, and pupil size. Boluses of fentanyl 1 µg/kg actual body weight (ABW), up to a maximum dose of 100 µg per bolus, can be given per clinical judgement.; Other Names: Fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Scores at 10-minute Intervals for the Initial Hour of Recovery	Pain scores are measured using a Verbal Response Scale (VRS) every 10 minutes in the initial hour of recovery. VRS is a scale from 0 to 10 where 0 signifies no pain and 10 signifies the worst pain ever experienced.	At 10-minute intervals during the first 60 minutes after extubation.
Pain Scores at 10-minute Intervals for the Initial 30 Minutes of Recovery	Pain scores are measured using a Verbal Response Scale (VRS) at 10-minute intervals for the initial 30 minutes of recovery. VRS is a scale from 0 to 10 where 0 signifies no pain and 10 signifies the worst pain ever experienced.	At 10-minute intervals during the first 30 minutes after extubation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Measurements With Pain Score Less Than 5 (vs ≥5) for Initial Hour of Recovery	Binary repeated-measures outcome of pain score will be defined as a pain score less than 5 (vs ≥5). Pain scores will be measured using a Verbal Response Scale (VRS) at 10-minute intervals for the initial hour of recovery. VRS is a scale from 0 to 10 where 0 signifies no pain and 10 signifies the worst pain ever experienced.	At 10-minute intervals during the first 60 minutes after extubation.
Number of Measurements With Pain Score Less Than 5 (vs ≥5) for the Initial 30 Minutes of Recovery	Binary repeated-measures outcome will be defined as a pain score less than 5 (vs ≥5). Pain scores will be measured using a Verbal Response Scale (VRS) at 10-minute intervals for the 30 minutes of recovery. VRS is a scale from 0 to 10 where 0 signifies no pain and 10 signifies the worst pain ever experienced.	At 10-minute intervals during the first 30 minutes after extubation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Analgesic Rescue Boluses	Number of analgesic rescue boluses in the first 60 minutes after extubation.	During the first 60 minutes after extubation.
Ramsay Scores During the First 60 Minutes	Ramsay scores will be measured using Ramsay Sedation Scale every 10 minutes in the initial hour of recovery. Ramsay Sedation Scale: 1 = Patient is anxious and agitated or restless, or both; 2 = Patient is co-operative, oriented, and tranquil; 3 = Patient responds to commands only; 4 = Patient exhibits brisk response to light glabellar tap or loud auditory stimulus; 5 = Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus; 6 = Patient exhibits no response. Frequencies for each score were reported.	At 10-minute intervals during the first 60 minutes after extubation.
Treatment Effect on the Time to Emergence From Anesthesia.	Time to emergence from anesthesia is defined as minutes from discontinuation of sevoflurane anesthesia to extubation	From discontinuation of sevoflurane anesthesia to extubation intraoperatively, assessed up to the timepoint of leaving operation room.

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Kurt Ruetzler, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): December 30, 2022
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Narcotics; Adjuvants, Anesthesia; Fentanyl; Analgesics, Opioid
• Other Study ID Numbers: 19-1646

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes