Nociception Level During Opioid-sparing Anaesthesia Versus Conventional Opioid-based Anaesthesia (NOL_Basel)

Nociception Level During Opioid-sparing Anaesthesia Versus Conventional Opioid-based Anaesthesia: a Randomised Controlled Non-inferiority Trial

The aim of this double blind, randomised controlled non-inferiority trial is to compare the antinociceptive efficiency of an opioid-sparing and a conventional opioid-based anaesthesia protocol with the help of the CEcertificated Pain Monitoring Device (PMD-200).

Study Overview

• Status: Recruiting
• Conditions: Analgesia
• Intervention / Treatment: Drug: opioid-sparing group; Drug: conventional opioid-based group

Detailed Description

Opioids have been an integral part of general anaesthesia. They are effective in preventing perception of noxious stimuli and ensure intraoperative haemodynamic stability. However, opioids are associated with a number of unwanted side effects (e.g. nausea and vomiting, sedation, ileus, respiratory depression, increased postoperative pain and morphine consumption and hyperalgesia). To minimise these side effects, there has been an interest in developing opioid-sparing anaesthesia protocols. Recently, analgesia nociception monitoring devices have become available. The aim of this double blind, randomised controlled non-inferiority trial is to compare the antinociceptive efficiency of an opioid-sparing and a conventional opioid-based anaesthesia protocol with the help of the CEcertificated Pain Monitoring Device (PMD-200). Patients scheduled to receive general surgical, gynaecological or urological laparoscopic surgery will be randomised into one of the two study groups. Study group A will be anaesthetised with an opioid-sparing protocol and study group B will be anaesthetised with a conventional opioid-based protocol. Intraoperative nociception will be evaluated with PMD-200. Postoperative visits will take place in recovery, 4-5h after surgery and then twice a day. In recovery, the amount of opioids and ketamine needed, pain, postoperative nausea and vomiting (PONV) and the time until the patient is fit for discharge according to the Aldrete score will be assessed. At the 4-5h postoperative visit, the amount of opioids and ketamine needed, maximum pain at rest and at mobilisation, incidence of PONV, mobilisation, micturition and sedation level will be assessed. At the twice daily follow up visits, amount of opioids and other analgesic drugs needed, pain at rest and at mobilisation, gastrointestinal function, quality of night's sleep, incidence of PONV, level of sedation and fitness for discharge home will be assessed. On day one after surgery, the perceived quality of recovery will be assessed with the QoR40 questionnaire.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Oliver Bandschapp; Phone Number: +41 61 328 6513; Email: oliver.bandschapp@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Department of Anaesthesiology, University Hospital Basel
    • Contact: Oliver Bandschapp, PD Dr. med.; Phone Number: +41 61 328 6513; Email: oliver.bandschapp@usb.ch
    • Principal Investigator: Oliver Bandschapp, PD Dr. med.
    • Sub-Investigator: Luzius Steiner, Prof. Dr. med.
    • Sub-Investigator: Ann-Kathrin Popp
    • Sub-Investigator: Bigna Buddeberg, Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Age older than 18 years
• Ability to give informed consent
• Undergoing scheduled general surgical, gynaecological or urological laparoscopic surgery
• American Society of Anesthesiology Score (ASA) status I, II, III

Exclusion Criteria:

• Inability to give informed consent
• ASA status IV and V
• Pregnant or breastfeeding women
• Allergy to one of the study drugs
• Urgent surgery
• Surgery with planned regional anaesthesia
• Outpatient surgery
• Atrioventricular block, intraventricular or sinoatrial block
• Atrial fibrillation
• Sinus bradycardia
• Cardiac insufficiency with a reduced left ventricular ejection fraction of below 40%
• Coronary artery disease
• Epilepsy
• Liver cirrhosis
• Chronic kidney disease (Clearance < 50ml/h)
• Chronic opioid therapy
• Chronic pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Opioid-sparing: Lidocaine, Ketamine, Magnesium, Clonidine, Fentanyl, Remifentanil, Propofol; Ketamine: started at 5mg/h; continued until 30min before end of surgery, then reduced to 1mg/h until discharge from recovery. Fentanyl: bolus of 50mcg before skin incision (in case of insufficient analgesia further boluses of 25mcg, upper limit is 100mcg). Lidocaine: bolus of 1.5mg/kg of ideal body weight (IBW),(maximum 100mg) at induction of anaesthesia, then continuous infusion of 1.5mg/kg IBW/h (maximum 100mg/h) until discharge from recovery. Magnesium: infusion of 2g/h for a maximum of 2h after induction of anaesthesia (maximum dose 4g). In case of bradycardia or hypotension, rate is reduced to 1g/h. Clonidine: bolus of 15mcg if needed. Maximum amount 150mcg. Remifentanil: started at time of induction of anaesthesia until end of surgery.	Drug: opioid-sparing group; In addition to propofol as a hypnotic and rocuronium as a muscle relaxant, patients in the opioid-sparing group will receive Ketamine, Fentanyl, Lidocaine, Magnesium, Clonidine, Remifentanil
ACTIVE_COMPARATOR: Conventional group: Fentanyl, Remifentanil, Propofol; Control Intervention: Remifentanil: Remifentanil is given as a target controlled infusion using the Minto-model. It is started at the timepoint of induction of anaesthesia and given until the end of surgery. Fentanyl: 2mcg/kg i.v. is given at the time of induction of anaesthesia and another 1-2mcg/kg is given prior to incision. Further fentanyl boluses (1-2mcg/kg boluses) are given in case there seems to be insufficient analgesia.	Drug: conventional opioid-based group; In addition to propofol as a hypnotic and rocuronium as a muscle relaxant, patients in the conventional opioid-based group will receive the following drugs: Remifentanil and Fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean of the nociception level as measured by the PMD-200	The PMD-200 device consists of a finger probe which continuously assesses pulse rate, pulse rate variability, pulse wave amplitude, skin conductance level, skin conductance fluctuations, skin temperature, and finger motion. A value of 0 corresponds to no pain and a value of 100 to maximal pain. A value will be measured every minute from the timepoint of skin incision until skin closure.	From the timepoint of skin incision until skin closure (within 1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Aldrete score	Fitness for discharge to ward is checked every 15 minutes with the Aldrete score. The Aldrete score assigned a number of 0, 1, or 2 to 5 variables: activity, respiration, circulation, consciousness, and color. A score of 9 out of 10 is considered adequate for discharge from the recovery.	Every 15 minutes in recovery until patient discharge to the ward (within 1 day)
Amount of morphine needed	Amount of morphine needed	From the stay in recovery before discharge from the ward (average of 1 week)
Amount of ketamine needed	Amount of ketamine needed	From the stay in recovery before discharge from the ward (average of 1 week)
Change in pain score at rest by numeric rating scale	Change in pain score at rest by numeric rating scale (to assess pain severity using a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable)	From the stay in recovery before discharge from the ward (average of 1 week)
Change in pain score at movement by numeric rating scale	Change in pain score at movement by numeric rating scale (to assess pain severity using a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable)	From the stay in recovery before discharge from the ward (average of 1 week)
Quality of night's sleep	Quality of night's sleep assessed with a verbal numerical scale from 0 (very poor quality of sleep) to 10 (excellent quality of sleep)	From the first postoperative day until discharge from ward (average of 1 week)
Occurrence of nausea and vomiting	Occurrence of postoperative nausea and vomiting (PONV)	From the stay in recovery before discharge from the ward (average of 1 week)
Change in level of sedation	Change in level of sedation	At 4 hours and then twice daily until discharge from the ward (average of 1 week)
Perceived quality of recovery by QoR40 questionnaire	40-item questionnaire that provides a global score and subscores across five dimensions: patient support, comfort, emotions, physical independence, and pain	At the first postoperative day
Time to return of gastrointestinal function	Time to return of gastrointestinal function as defined as the time from the end of surgery to the first passage of flatus and to the first bowel movement	From the stay in recovery before discharge from the ward (average of 1 week)
Time to return of spontaneous micturition	Time to return of spontaneous micturition	From the stay in recovery before discharge from the ward (average of 1 week)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Study Director: Thierry Girard, Prof. Dr. med., Department of Anaesthesiology, University Hospital Basel; Principal Investigator: Oliver Bandschapp, PD Dr. med., Department of Anaesthesiology, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 17, 2022
• Primary Completion (ANTICIPATED): August 1, 2023
• Study Completion (ANTICIPATED): August 1, 2023

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (ACTUAL): August 3, 2022

Study Record Updates

• Last Update Posted (ACTUAL): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 18, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: analgesia nociception; opioid-sparing anaesthesia; conventional opioid-based anaesthesia; Pain Monitoring Device (PMD-200); intraoperative nociceptive levels; Post operative nausea and vomiting (PONV)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Narcotics; Analgesics, Opioid
• Other Study ID Numbers: 2022-00283; qu20Bandschapp

Drug and device information, study documents

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