Evaluation of NoL Index and ANI After Nociceptive Stimulation at Different Infusion Rates of Remifentanil Infusion

Evaluation of NoL Index and ANI Variations After Nociceptive Stimulation Under Different Rates of Infusion of Intravenous Remifentanil in Patients Undergoing Laparotomies With Intraoperative Epidural Analgesia

Contrary to "immobility" and, to a lesser extent, to the "hypnosis/unconsciousness" component of general anaesthesia, the monitoring of "analgesia" remains largely elusive, evaluated mainly through poorly sensitive and potentially undesirable changes in patients' vital signs. This has led the industry to pursue the development of various devices and indices based on other physiological parameters such as heart rate variability (HRV), electroencephalogram (EEG), skin conductance, to name only a few. To the best of the knowledge, none of these parameters on its own has shown sufficient capacity in detecting different degrees of pain/analgesia balance to gain wide clinical use.

The purpose of this prospective observational study is to evaluate the response of a single-parameter index (the Analgesia Nociception Index [ANI]) and a multi-parameter index (the Nociception Level [NoL] Index) when patients under combined general anaesthesia/epidural anaesthesia for laparotomies are subjected to a standardized painful stimulus (a tetanic stimulation over the ulnar nerve at 70 mA, 100 Hz for 30 seconds) at different doses of remifentanil infusion at steady state (0,005 mcg/kg/min; 0,05 mcg/kg/min; 0,1 mcg/kg/min; 0,15 mcg/kg/min). With the painful stimulus held constant but the analgesia provided gradually increased, it is expected to characterize the response of these two indices to different levels of nociception/anti-nociception balance.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Other: Tetanic stimulation

Detailed Description

Patients scheduled for elective abdominal surgery by laparotomy (general surgery or gynaecological surgery) will receive a thoracic epidural (around T9-T10/T10-T11) and general anesthesia. Apart from standard monitoring, the ANI (derived from the EKG) and the NoL index (obtained via a finger probe) will be recorded. The epidural catheter will be injected with 6-10 ml of lidocaine 2% with epinephrine 5 mcg/ml to produce anesthetic level of neuraxial blocade and then be perfused with the same solution at 4-8 ml/hour. After incision and confirmation of adequate blocade with the epidural local anesthetic, the patient will receive a series of painful electric stimulation with a standard nerve stimulator applied over the ulnar nerve in tetanic mode for 30 seconds at 100 Hz and 70mA. Each stimulation will occur at a different rate of infusion of IV remifentanil at steady state (0,005 mcg/kg/min; 0,05 mcg/kg/min; 0,1 mcg/kg/min; 0,15 mcg/kg/min). A stimulation at 0,005 mcg/kg/min will be done before and after epidural loading with local anesthetics to look for altered variations in analysed parameters. The variation and the kinetic of the variations after stimulations will be observed for heart rate, mean blood pressure, BIS, ANI and NoL index.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Hôpital Maisonneuve-Rosemont

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients scheduled for elective abdominal surgery by laparotomy (general surgery or gynaecological surgery) who will receive a thoracic epidural (around T9-T10/T10-T11) and general anesthesia.

Description

Inclusion Criteria:

• ASA status I, II or III
• Elective abdominal surgery with median laparotomy under general anaesthesia and epidural analgesia.

Exclusion Criteria:

• Coronary artery disease
• Serious cardiac arrhythmias (including atrial fibrillation)
• Patient refusal
• History of substance abuse
• Chronic use of psychotropic and/or opioid drugs
• Use of drugs that act on the autonomic nervous system (including β-blockers)
• History of psychiatric diseases or psychological problems
• Contraindications to epidural analgesia
• Allergy to remifentanil
• Unexpected difficult airway requesting excessive, possibly painful airway manipulations.
• Dural puncture during epidural catheter installation
• Failure of epidural analgesia
• Surgical unexpected complications requiring strong haemodynamic support (transfusions, vasopressors, inotropes)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tetanic stimulation; Single arm study. See Study description for a through description of the intervention.	Other: Tetanic stimulation; Standard Tetanic stimulation will be used as the stimulus to evaluate responses of the intraoperative pain indexes (ANI and NoL) at different concentration of i.v. remifentanil during anesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between NoL index responses to electrical stimulus and the i.v. doses of remifentanil infusion given during anesthesia. The n of patients (40 in this study) is calculated on this primary outcome.	The electrical stimulus will be applied on the forearm of the asleep patient at different doses of iv remifentanil (0.005mcg/kg/min to a maximum of 0.15 mcg/kg.min during anesthesia for abdominal surgery with active intraoperative epidural pain management). It will be evaluated whether or not exists a correlation between the doses of iv remifentanil and the responses of the Nol index after electrical stimulus.	At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NoL index changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion	Measure the NoL changes after a nociceptive stimulus at various intravenous remifentanil infusion doses.	At time of surgery
ANI index changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion	Measure the ANI changes after a nociceptive stimulus at various intravenous remifentanil infusion doses. ANI being another uniparametric pain index.	At time of surgery
Heart rate changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion	Measure the changes of Heart Rate after a nociceptive stimulus at various intravenous remifentanil infusion doses.	At time of surgery
Mean Blood Pressure changes after a standardized electrical stimulus at 4 different concentrations of iv remifentanil infusion	Measure the changes of Heart Rate after a nociceptive stimulus at various intravenous remifentanil infusion doses.	At time of surgery
Sensitivity and specificity of NoL index, ANI index, Heart Rate and Mean blood Pressure in detecting a painful stimulus such as intubation as well as standardized electrical stimulus at remifentanil infusion of 0.005 msg/kg/min	Measure the sensitivity and specificity of these 4 criteria in detecting a painful stimulus such as intubation and standardized electrical stimulus	At time of surgery

Collaborators and Investigators

• Sponsor: Maisonneuve-Rosemont Hospital
• Collaborators: Medasense Biometrics Ltd
• Investigators: Principal Investigator: Philippe Richebé, M.D. PhD, Maisonneuve-Rosemont Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: October 25, 2015
• First Submitted That Met QC Criteria: November 9, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Remifentanil; Pain; Monitoring; Analgesia Nociception Index; NoL; Nociception Level
• Other Study ID Numbers: HMR14090

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