Comparison of the Skin Conductance Algesimeter and the Nociception Level Index in the Paediatric Population. An Observational Study.

Study Overview
=================
Brief Summary
-----------------
Evaluation and comparison of the skin conductance algesimeter(SCA) and the nociception level index(NOL) in the paediatric population (1-12 years) during surgery with general anaesthesia with bispectral index(BIS) in a tertiary hospital in The Netherlands.

Detailed Description
-----------------
Intraoperative non-invasive monitors designed to detect nociception during surgery have seen a considerable development over the past few years. There are multiple commercial monitoring devices available of which most have not been extensively evaluated in the pediatric population. Adequate levels of perioperative analgesia are important as they lead to less intraoperative nociception and less post-operative pain and post-operative complications and thereby leads to improved patient recovery. Monitoring the nociceptive state of a patient by monitoring the autonomic peripheral sympathetic pathways during surgery with these monitoring methods might lead to earlier detection of nociception and therefore less nociception and perioperative pain. Most monitoring devices have not been extensively evaluated in the pediatric population and have not yet demonstrated large clinical implications such as a decrease in post-operative pain or a decrease in opioid usage by using monitor guided analgesia administration. One of the nociception monitoring methods that has not been studied extensively in the pediatric population is the Nociception level index(NOL, Medasense, Ramat Gan, Israel). This monitor is a multi-parametric non-invasive monitoring method that measures heartrate, heartrate variability, skin temperature, photoplethysmographic amplitude, skin conductance and fluctuations in skin conductance using a non-invasive finger probe. These parameters are combined in an algorithm that provides an index from 0-100 with an abstract unit. With 0 indicating no nociception and 100 indicating severe nociception. A first study in the paediatric population with the NOL monitor showed that the NOL index was able to significantly detect first incision and significantly respond to opioid administration during surgery in children 1 to 5 years of age. Another more recent study demonstrated that the NOL index can quantify nociceptive stimuli in children aged 1 to 12. Other more commonly used monitoring methods for nociception such as fluctuations in mean arterial blood pressure(MAP), heartrate(HR) and respiratory rate(RR) did not show a significant change during first incision or during opioid administration in this study, indicating that the NOL monitor might be a better method to assess and respond to intraoperative nociception than fluctuations in MAP, HR and RR alone. Another nociception monitoring method is the skin conduction algesimeter(SCA, Medstorm, Oslo, Norway. This is a single parameter nociception monitoring device that uses three electrodes that are fixed to the skin to measure fluctuations in skin conductance in order to detect nociception. It measures the amount of bursts in the skin sympatetic nerves in peaks per second. This contrasts with the multiparametric design of the NOL monitor with an algorithm and an abstract index of 0-100. The SCA monitor system doesn't utilize heartrate and photoplethysmographic amplitude. Hypothetically making the device less susceptible to interference of intraoperative hemodynamic changes and intraoperative vasoactive medication administration in comparison with the NOL monitor which does utilizes these variables in its system and algorithm. Furthermore as the SCA monitor measures the direct burst of the palmary or plantary sympathetic nerves this could mean that it responds faster than the NOL index to nociceptive stimuli. The SCA monitor has already been studied in the unanesthetized and the sedated pediatric and neonatal population. But has not seen extensive validation during surgery under general anaesthesia. One small pilot study in the pediatric population under general anaesthesia has been performed. In this study only 12 patients were included, and these patients had a broad age range (8.4 ± 5 years) and received perioperative analgesia through means of continuous infusion of remifentanil. Furthermore the studies researchers did not use the recommended threshold value for the SCA monitor. Both monitors use different proprietary owned algorithms with the same aim of detecting nociception. Therefore, the primary goal of this study is to evaluate the SCA in the pediatric population during general anaesthesia. As more extensive evaluation of the SCA in the pediatric population is imperative in order to assess if it the SCA can detect nociceptive stimuli during general anesthesia. Another primary objective of this study will be to compare the SCA with the NOL index during general anesthesia. Evaluation of SCA through this feasibility study and comparison with the NOL monitor at the same time, may answer the question of which monitor can better predict and monitor nociceptive stimulation in the perioperative period. This will be the basis for future interventional randomized studies to assess if perioperative monitoring of the analgesia level leads to improved post-operative outcomes. We hypothesize that the NOL monitor and SCA monitor will both be able to quantify nociceptive stimuli, and that the SCA monitor responds faster than the NOL monitor. Another secondary aim of the current study is the comparison of the BIS to the algesimeters awakening index. Previous studies have demonstrated that fluctuations in skin conductance with an increase of area under the skin conductance peaks curve while awakening from general anesthesia performs similar to the bispectral index (BIS) in the adult population during nociceptive stimuli. Primary Objectives: Evaluate if the SCA can detect nociceptive stimuli in children undergoing surgery with general anaesthesia. Compare the response of the SCA to the response of the NOL monitor during surgery with general anaesthesia. Secondary Objective(s): Evaluate the response of the SCA and NOL to intraoperative opioid administration. Evaluate the response of the SCA and NOL index to intraoperative administration of vasoactive medication. Evaluate the response of the SCA and NOL to changes in mean arterial blood pressure (MAP, heartrate (HR) and respiratory rate (RR) Comparison of the SCA awakening index to the BIS. Comparison of the peak(maximum) values for NOL and SCA across both selected age groups (1-4 and 5-12) Comparison of the reaction time of both monitors after nociceptive stimulation. Compare the functionality of the NOL index and SCA monitor during general anesthesia and usage of localregional anesthesia.

Official Title
-----------------
Comparison of the Skin Conductance Algesimeter and the Nociception Level Index in the Paediatric Population. An Observational Study.

Conditions
-----------------
Nociceptive Pain, Anesthesia, Pain

Intervention / Treatment
-----------------
* Device: Connecting patients to both non-invasive monitors to observe and compare the monitor's capabilities.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female ASA I, ASA II and ASA III Aged 1 to 12 years old Scheduled to undergo elective surgery with general anaesthesia Written informed consent obtained from subject or/and subject's legal representatives. Exclusion Criteria: Known allergy to the adhesive tape used in the sensors. Patients that do not meet the inclusion criteria will be excluded. No free available limb to attach the probes to.

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients aged 1 to 4 years of age<br>Patients will be connected to the NOL monitor and the SCA monitor during surgery with general anaesthesia. | Device: Connecting patients to both non-invasive monitors to observe and compare the monitor's capabilities.<br>* All patients will be connected to the NOL monitor and the SCA monitor during general anesthesia.<br>|
| Patients aged 5 to 12 years of age<br>Patients will be connected to the NOL monitor and the SCA monitor during surgery with general anaesthesia. | Device: Connecting patients to both non-invasive monitors to observe and compare the monitor's capabilities.<br>* All patients will be connected to the NOL monitor and the SCA monitor during general anesthesia.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the SCA prior to and during a nociceptive event during the intraoperative period. | The pre stimulation values for SCA will be estimated by taking the peak(maximum) value -30 to 0 seconds before the occurrence of the nociceptive event. Post stimulation values for SCA will be estimated by taking the peak (maximum) value +0 to +30 seconds after the nociceptive event. The SCA monitor records skin conductance in peaks per second. Varying from 0.00 peaks per second to 0,40 or more peaks per second. These peaks per second correlate with the pain index according to the manufacturer. With 0.00-0.06 peaks per second equalling pain index of zero and 0,40 or more peaks per second equalling a pain index of ten during surgical stimuli. | Through study completion, an average of 1 year | 
| Changes in the NOL index prior to and during a nociceptive event during the intraoperative period. | The pre stimulation values for NOL will be estimated by taking the peak(maximum) value -30 to 0 seconds before the occurrence of the nociceptive event. Post stimulation values for NOL will be estimated by taking the peak (maximum) value +0 to +30 seconds after the nociceptive event. The NOL index ranges from 0 to 100. With 0 indicating absence of nociception and 100 indicating severe nociception. The NOL index values are registered at a 5 second interval. | Through study completion, an average of 1 year | 
| Correlation between changes in SCA and changes in NOL index during nociceptive events in the intraoperative period. | The pre stimulation values for SCA and NOL will be estimated by taking the peak(maximum) value -30 to 0 seconds before the occurrence of the nociceptive event. Post stimulation values for NOL and SCA will be estimated by taking the peak (maximum) value +0 to +30 seconds after the nociceptive event. To compare the diagnostic performance of the SCA and the NOL index we will display data of the SCA and NOL index response to nociception stimuli in a scatterplot and we will perform an intraclass correlation coefficient calculation in order to assess if the response of the patients to the monitors correlate with each other. The NOL index ranges from 0 to 100. With 0 indicating absence of nociception and 100 indicating severe nociception. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCA response to opioid administration. | Response of the SCA to opioids administration is measured by comparing the peak (maximum) -20 to 0 seconds SCA value prior to fentanyl administration to the estimated peak (maximum) value +0-10 to 120-240 seconds after fentanyl administration. This is in accordance with known fentanyl pharmacokinetics in literature that states a maximum time to onset of 90 seconds | Through study completion, an average of 1 year. | 
| NOL response to opioid administration. | Response of the NOL index to opioids administration is measured by comparing the peak (maximum) -20 to 0 seconds NOL index value prior to fentanyl administration to the estimated peak (maximum) value +0-10 to 120-240 seconds after fentanyl administration. This is in accordance with known fentanyl pharmacokinetics in literature that states a maximum time to onset of 90 seconds. | Through study completion, an average of 1 year. | 
| SCA response to vasoactive medication administration. | The pre vasoactive medication values for SCA will be estimated by taking the peak(maximum) value -30 to 0 seconds before the occurrence of the nociceptive event. Post vasocative medication values for SCA will be estimated by taking the peak(maximum) value +0 to +30 seconds after the nociceptive event. | Through study completion, an average of 1 year. | 
| NOL response to vasoactive medication administration. | The pre vasoactive medication values for NOL will be estimated by taking the peak(maximum) value -30 to 0 seconds before the occurrence of the nociceptive event. Post vasocative medication values for NOL will be estimated by taking the peak(maximum) value +0 to +30 seconds after the nociceptive event. | Through study completion, an average of 1 year. | 
| Correlation between changes in the SCA compared to other predictors of nociception. | being heartrate, respiratory rate and non-invasive blood pressure data collected during nociceptive events. Data on non-invasive blood pressure is registered at a five-minute interval by the Intellivue Philips monitor (Koninklijke Philips N.V., 2004 - 2022). Data on respiratory rate is registered at a 1-minute interval by the Intellivue Philips monitor. Data on heartrate is registered at a 5 second interval by the PMD-200 monitor. | Through study completion, an average of 1 year. | 
| Correlation between changes in the NOL index compared to other predictors of nociception | being heartrate, respiratory rate and non-invasive blood pressure data collected during nociceptive events. Data on non-invasive blood pressure is registered at a five-minute interval by the Intellivue Philips monitor (Koninklijke Philips N.V., 2004 - 2022). Data on respiratory rate is registered at a 1-minute interval by the Intellivue Philips monitor. Data on heartrate is registered at a 5 second interval by the PMD-200 monitor. | Through study completion, an average of 1 year. | 
| BIS monitor response to intraoperative nociceptive stimuli | During intra-operative nociceptive events SCA awakening index and BIS will be compared in order to assess their similarity when assessing awakening from nociceptive stimuli. Appropriate statistical analysis will be performed according to the distribution of data regarding BIS and SCA awakening index. BIS values range from 0 to 100. A value of 0 represents the absence of brain activity, and 100 represents the awake state. | Through study completion, an average of 1 year. | 
| SCA awakening index response to intraoperative nociceptive stimuli | During intra-operative nociceptive events SCA awakening index and BIS will be compared in order to assess their similarity when assessing awakening from nociceptive stimuli. Appropriate statistical analysis will be performed according to the distribution of data regarding BIS and SCA awakening index. | Through study completion, an average of 1 year. | 
| Peak values for NOL and SCA for age group 1-4 years | Pre stimulus peak values (-30 to 0+) will be compared to post stimulus peak values (0+ to 30+). | Through study completion, an average of 1 year. | 
| Peak values for NOL and SCA for age group 5-12 years | Pre stimulus peak values (-30 to 0+) will be compared to post stimulus peak values (0+ to 30+). | Through study completion, an average of 1 year. | 
| Reaction time NOL and SCA | Comparison of average reaction time in seconds of NOL and SCA after nociceptive stimuli/event. measured in seconds. | Through study completion, an average of 1 year. | 
| NOL and SCA reaction during locoregional anaesthesia technique | Pre stimulus peak values (-30 to 0+) will be compared to post stimulus peak values (0+ to 30+) for both NOL and SCA for nociceptive stimuli placed inside area of the skin covered bij locoregional blockade. | Through study completion, an average of 1 year. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nociception monitoring, Pediatric population