Clinical trial NCT02884778: Observational Evaluation of the Last Version of the PMD200TM
Official title: Evaluation of the Last Version of the PMD200TM and Its NoL Index in Patients Undergoing Laparotomies With Intraoperative Epidural Analgesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pain Monitor During Anesthesia
Keywords: pain
monitoring
anesthesia
Lead sponsor: Maisonneuve-Rosemont Hospital
Sponsor class: OTHER
Collaborators: name: Medasense Biometrics Ltd
First posted: 2016-08-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Title: Evaluation of the last version of the PMD200TM and its NoL index in patients undergoing laparotomies with intraoperative epidural analgesia Objectives: Measure NoL Index changes after a standardized nociceptive electrical stimulus at various intravenous remifentanil infusion rates (0.005, 0.05, 0.1 mcg/kg/min) and also after clinical stimuli such as intubation.

Study Design: Prospective observational study Subject Population: Adults scheduled to undergo elective abdominal surgery with laparotomy under general anesthesia and epidural analgesia Sample Size: 30 patients Study Duration: Starts April 2016 - Ends November 2016 Study Center: Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada Adverse Events: None expected

Detailed description: The motivation behind the actual observational proposed study is to validate the ability of the new PMD-200TM system to accurately detect a nociceptive stimulus that occur during anesthesia (e.g. laryngoscopy for tracheal intubation, standardized electrical stimulations). The NoL index will also be recorded during period of time without any stimulation and called baseline values of NoL under standard anesthesia.

The PMD100TM was an early prototype of the pain monitor device developed by Medasense Biometrics Ltd (Ramat Yishai, Israel), which was used in our center in Montreal in a recently completed clinical trial. This device is based on a software that was integrated into a computer to analyze the different criteria with a multi-parametric index named NoL which estimates the nociception level during general anesthesia and incorporates heart rate, heart rate variability (0.15-0.4 Hz band power), plethysmograph wave amplitude, skin conductance level, number of skin conductance fluctuations (NSCF), and their time derivatives, using a non-linear regression technique. The rationale for the use of skin conductance and NSCF is that the presence of a physical stressor leads to a sympathetic-mediated filling of the palmar sweat glands, thus changing the ion concentration and the skin conductance. It has been shown to correlate with clinical stress score during intubation and to be less reactive to a tetanic stimulation when remifentanil was perfused. With the Medasense device PMD100TM, these five variables are obtained through a single non-invasive finger probe connecting the finger of the patient to the computer. Only signals from the patient are recorded. No signal is sent to the patient by the PMD100TM. The NoL Index obtained and displayed on the Medasense PMD200™ device is a single number from 0 to 100, with a lower score proposed to represent less painful stimulation.

The PMD-200TM system is an advanced configuration product in the final stages of development, with the introduction of several enhancements related to the Hardware (HW) and the Software (SW) platform:

1. Enhanced finger probe - which include 4 new sensors (slightly different from the sensors used in PMD-100 and more efficient in terms of quality of signals)
2. Improvement in the signal acquisition board - a HW module which converts the analog signals from all sensors to digital data
3. All in one system - enables integrated viewing of the recorded signals and NoL index through a touch based user interface (the previous interface for the PMD100 was on a computer screen)
4. A new Graphic user interface for the user The purpose of this new prospective observational study with the finalized PMD200TM device is to evaluate the responses of a multi-parameter index (the Nociception Level \[NoL\] Index) when patients under combined general anesthesia/epidural anesthesia for laparotomies are subjected to standard painful stimuli (laryngoscopy for intubation). Also during surgery, standardized electrical stimulations over the ulnar nerve (70 mA, 100 Hz for 30 seconds) at different doses of remifentanil steady state infusion (0.005 mcg/kg/min; 0.05 mcg/kg/min; 0.1 mcg/kg/min) will be performed as we did in our previous study at HMR after Scientific and Ethic Committee approval in 2015.

Studying the effect of different doses of infused remifentanil on the new and finalized version of the NoL Index from the PMD200TM device in patients subjected to a standardized painful stimulus under general anaesthesia would help validating this final version and to compare results to the prototype used in our center in a previous study.

Primary Aim: Establish a correlation between the NoL Index changes and the infused dose of remifentanil at the time the stimulation was applied. It is expected to see a strong correlation meaning that when the remifentanil infusion is high, the NoL response to the standardized electrical stimulation might be low.

Secondary Aims: NoL changes at different times of the surgery. Heart rate and blood Pressure and BISpectral index changes after clinical stimulus such as intubation, incision, and standardized electrical stimulations at different concentrations/infusions of remifentanil (0.005, 0.05, 0.1 msg/kg/min). Measure the sensitivity and specificity of the study criteria (NoL, BIS, Heart Rate and Mean Blood Pressure) in detecting a painful stimulus such as intubation and electrical stimulus at remifentanil 0.005mcg/kg/min if infusion.

Also, at the end of the surgery, we will still record the NoL index from the PMD200TM device. And we will also record the first pain score when the patient is extubated in PACU. This will be done in an observational manner. We will evaluate whether the last NoL index recorded under general anesthesia at the end of the surgical procedure (last stiches) with patient still under controlled ventilation does correlate with the first pain scores in PACU.

Eligibility criteria: Inclusion Criteria:

* ASA status I, II or III
* Age 18 years or older
* Elective abdominal surgery with median laparotomy under general anesthesia 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

Primary outcomes:
measure: Correlation between NoL index absolute values after electrical stimulus and the doses of remifentanil infused at the time of the stimulation.
timeFrame: Day of surgery during anesthesia
Secondary outcomes:
measure: NoL index peak absolute value after painful stimulus: intubation, electrical stimulations, no pain period, end of surgery
timeFrame: Day of surgery during anesthesia
measure: Heart Rate peak absolute value after painful stimulus: intubation and electrical stimulations, no pain period, end of surgery
timeFrame: Day of surgery during anesthesia
measure: Mean Arterial Blood Pressure (MABP) peak absolute value after painful stimulus: intubation and electrical stimulations, no pain period, end of surgery
timeFrame: Day of surgery during anesthesia
measure: BISpectral index peak absolute value after painful stimulus: intubation and electrical stimulations, no pain period, end of surgery
timeFrame: Day of surgery during anesthesia
measure: Correlation between the NoL index values (ranging from 0 to 100) and i.v. remifentanil infusion rate at the time of the electrical stimulation
timeFrame: Day of surgery intraoperative during anesthesia
measure: Correlation between the Heart Rate values and i.v. remifentanil infusion rate at the time of the electrical stimulation
timeFrame: Day of surgery intraoperative during anesthesia
measure: Correlation between the Mean Arterial Blood Pressure (MABP) values and i.v. remifentanil infusion rate at the time of the electrical stimulation
timeFrame: Day of surgery intraoperative during anesthesia
measure: Correlation between the Bispectral index values and i.v. remifentanil infusion rate at the time of the electrical stimulation
timeFrame: Day of surgery intraoperative during anesthesia
measure: Sensitivity and specificity of NoL index, Heart Rate, Mean Blood Pressure and BIS index to detect stimulus under anesthesia during surgery
timeFrame: Intraoperative, day of surgery
Other outcomes:
measure: Correlation between end of surgery NoL value at the time of wound dressing and postoperative NRS pain scores (0-10) in PACU
timeFrame: Intraoperative day of surgery and day of surgery in PACU
Locations:
city: Montreal
country: Canada
facility: Hopital Maisonneuve Rosemont, CIUSSS de l'Est de l'Ile de Montreal
state: Quebec
Study officials:
affiliation: Hopital Maisonneuve Rosemont, CIUSSS de l'Est de l'Ile de Montreal, University of Montreal
name: Philippe Richebe, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Renaud-Roy E, Stockle PA, Maximos S, Brulotte V, Sideris L, Dube P, Drolet P, Tanoubi I, Issa R, Verdonck O, Fortier LP, Richebe P. Correlation between incremental remifentanil doses and the Nociception Level (NOL) index response after intraoperative noxious stimuli. Can J Anaesth. 2019 Sep;66(9):1049-1061. doi: 10.1007/s12630-019-01372-1. Epub 2019 Apr 17.