Evaluating the Predictive Value of the Nociception Level Index NOL

• ClinicalTrials.gov Identifier: NCT03324269
• Recruitment Status: Completed
• First Posted: October 27, 2017
• Last Update Posted: May 2, 2018
• Sponsor: Université Libre de Bruxelles
• Information provided by (Responsible Party): Sarah Saxena, Université Libre de Bruxelles

Tracking Information

• First Submitted Date: October 16, 2017
• First Posted Date: October 27, 2017
• Last Update Posted Date: May 2, 2018
• Actual Study Start Date: October 30, 2017
• Actual Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2017)

Predictive value of NOL [ Time Frame: intra-operative ]

A calibration Tetanus test of 60 mAmp during 30 sec at remifentanil level (Ce) of 4 ng/ml will be done when starting NOL is below 10. According to the NOL response: there will be an increment of 1 ng/ml of RemiCe if NOL gradient ≥ 10 or a decrement of 1 ng/ml of remifentanil Ce NOL gradient < 10. The optimal individual remifentanil level is defined as the level at which the variation of NOL index will be less than 10 units starting at a NOL value below 10. So surgical incision and sternotomy will be done at 'optimal individual remifentanil level' and MAP (mean artrial pressure), HR (heart rhythm), NIBP (non-invasive blood pressure) will be measured (every 3 minutes during thyroid and continuous measurement for cardiac surgery).

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03324269 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluating the Predictive Value of the Nociception Level Index NOL
• Official Title: Evaluating the Predictive Value of the Nociception Level Index NOL in Cardiac and Thyroid Surgery: a Pilot Study

Brief Summary

The evaluation of pain, a conscious response, in the anesthetized patient remains one of the main challenges in anaesthesia.

Opioids remain the cornerstone for perioperative analgesia, albeit frequently associated with side effects. Most of these side-effects are dose-dependent.

Thus intra-operative monitors are necessary to measure the balance between Nociception and Anti-Nociception (NAN balance) by an adequate opioid administration.

Recently the NOL monitor was released.The NoL index ranges from 0 to 100 and is based on a nonlinear combination of nociception-related physiologic variables, specifically heart rate (HR), heart rate variability at the 0.15- to 0.4-Hz band power, photoplethysmograph wave amplitude (PPGA), skin conductance level, number of skin conductance fluctuations, and their time derivatives. The NoL index estimates the nociceptive/antinociceptive state from these component measures using random forest regression.

NOL index has been studied in many types of surgery apart from cardiac surgery. Cardiac surgery has one of the frailest patient populations, in whom hemodynamic stability is of utter importance.

In our institution, a combination of TCI propofol (Schnider model) and remifentanil (Minto model) is used to for most of the anaesthetic procedures, including cardiac anaesthesia. Remifentanil is titrated to prevent an increase in blood pressure and hearth rhythm at noxious stimuli, such as surgical incision, sternotomy and adapted following hemodynamic trend during surgery.

The hypothesis of this study is to develop a calibration test using the NOL index variation to define the individual most appropriate NAN balance using remifentanil TCI before the start of surgery and before a very strong noxious surgical stimulus such as surgical incision in thyroid surgery and sternotomy during cardiac surgery.

Before the start of surgery, the investigators want to titrate in each patient the remifentanil Ce required to abolish the NOL index response to a calibrated noxious tetanic stimulus (Tetanus 60 mamp, 100 Hz, 30 seconds). Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision and sternotomy. NOL and hemodynamic responses will be recorded during the entire duration of thyroid surgery and until the cardiopulmonary bypass during cardiac surgery.

The individual relation between the remifentanil calibration level and the patient's response will be studied.

Detailed Description

The evaluation of pain, a conscious response, in the anesthetized patient remains one of the main challenges in anaesthesia.

Opioids remain the cornerstone for perioperative analgesia, albeit frequently associated with side effects. Most of these side-effects are dose-dependent. The misadministration of opioids contributes to side-effects such as: post-operative nausea and vomiting, respiratory depression and opioid-induced hyperalgesia.

Thus intra-operative monitors are necessary to measure the balance between Nociception and Anti-Nociception (NAN balance) by an adequate opioid administration.

In the past few years, different monitors have been developed such as the Analgesia Nociception index (ANI) based on the heart rate variability and the Surgical Plethysmographic index (SPI) based on the amplitude of the Plethysmogram and the heart rate variation. Pupil dilation has also been proposed (Algiscan, Idmed company, Marseille, France). Each one of these monitors is measuring only one parameter.

Recently the NOL monitor was released.The NoL index ranges from 0 to 100 and is based on a nonlinear combination of nociception-related physiologic variables, specifically heart rate (HR), heart rate variability at the 0.15- to 0.4-Hz band power, photoplethysmograph wave amplitude (PPGA), skin conductance level, number of skin conductance fluctuations, and their time derivatives.The NoL index estimates the nociceptive/antinociceptive state from these component measures using random forest regression.

NOL index has been studied in many types of surgery apart from cardiac surgery. Cardiac surgery has one of the frailest patient populations, in whom hemodynamic stability is of utter importance.

In our institution, a combination of TCI propofol (Schnider model) and remifentanil (Minto model) is used to for most of the anaesthetic procedures, including cardiac anaesthesia. Remifentanil is titrated to prevent an increase in blood pressure and hearth rhythm at noxious stimuli, such as surgical incision, sternotomy and adapted following hemodynamic trend during surgery.

The hypothesis of this study is to develop a calibration test using the NOL index variation to define the individual most appropriate NAN balance using remifentanil TCI before the start of surgery and before a very strong noxious surgical stimulus such as surgical incision in thyroid surgery and sternotomy during cardiac surgery.

Before the start of surgery, the investigators want to titrate in each patient the remifentanil Ce required to abolish the NOL index response to a calibrated noxious tetanic stimulus (Tetanus 60 mamp, 100 Hz, 30 seconds). Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision and sternotomy. NOL and hemodynamic responses will be recorded during the entire duration of thyroid surgery and until the cardiopulmonary bypass during cardiac surgery.

The individual relation between the remifentanil calibration level and the patient's response will be studied.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Intervention Model: Single Group Assignment
Intervention Model Description:

Patients undergoing cardiac surgery and thyroid surgery have NOL monitoring

Masking: None (Open Label)
Masking Description:

All patients wear NOL monitoring and are aware of it. Anesthesiologist can read NOL values.

Primary Purpose: Diagnostic

Condition

• Pain
• Anesthesia

Intervention

Device: NOL

After tracheal intubation, a Tetanus test (60 mAmp,100 Hz) is done during 30 sec at remifentanil level Ce of 4 ng/ml (with starting NOL value <10). According to the NOL response: increment of 1 ng/ml of RemiCe if NOL gradient ≥ 10 / decrement of 1 ng/ml of remifentanil Ce NOL gradient < 10. During the testing period propofol Ce is fixed at the concentration associated with BIS levels between 45-60 during the first calibration.

Upon the incision and 10 minutes after skin incision and sternotomy, Propofol TCI (Schnider model) is adjusted to BIS between 45-60 and remifentanil Ce at which the variation of NOL index variation is less than10 units at a NOL starting value <10. MAP (mean arterial pressure), HR (heart rhythm) and NIBP (non-invasive blood pressure) will be measured.

Study Arms

NOL

After tracheal intubation and before surgical incision, a calibration Tetanus test of 100Hz, 60 mAmp during 30 sec at remifentanil level (Ce) of 4 ng/ml will be done (starting NOL below 10).

According to the NOL response, there will be an increment of 1 ng/ml of RemiCe if NOL gradient ≥ 10 or decrement of 1 ng/ml if NOL gradient < 10. Ideal remifentanil Ce is the remifentanil Ce at which the variation of NOL index will be less than 10 units at a NOL starting value below 10. Thus this individual remifentanil Ce will be the remifentanil level programmed before surgical incision and sternotomy. NOL and hemodynamic responses will be recorded during the entire duration of thyroid surgery and until the cardiopulmonary bypass during cardiac surgery.

Intervention: Device: NOL

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 23, 2017): 20
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 31, 2017
• Actual Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients undergoing cardiac surgery (Coronary Artery Bypass Graft)
• Patients undergoing thyroid surgery
• Knowledge of French, English or Dutch is required.

Exclusion Criteria:

• Pregnancy
• Allergy or contraindications to one of the study drugs
• BMI >30
• History of drug and alcohol abuse,
• preoperative analgesic drug use
• Heart rhythm disturbances (Atrial fibrillation, atrial flutter).
• the use of Alpha-2 adrenergic agonists

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03324269
• Other Study ID Numbers: NOL
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Sarah Saxena, Université Libre de Bruxelles
• Study Sponsor: Université Libre de Bruxelles
• Collaborators: Not Provided

Investigators

• Principal Investigator: Luc Barvais; Université Libre de Bruxelles

• PRS Account: Université Libre de Bruxelles
• Verification Date: April 2018