Nociception and BIS Level Monitoring in COVID-19 Patients in the Intensive Care Unit (NEMO)

Pain (nociception), stress and discomfort are difficult to detect in sedated and intubated patients during mechanical ventilation. In order to improve this several nociception level monitors (NOL) were developed that objectively track nociception in sedated or anesthetized patients. Earlier studies showed that for sedated and intubated patients in the operating room, using such monitors is beneficial in reducing stress hormones and post operative pain scores. In this study the investigators aim to observe whether the NOL could be equally beneficial in managing nociception in sedated and intubated ICU patients.

Study Overview

• Status: Recruiting
• Conditions: Nociceptive Pain
• Intervention / Treatment: Device: Nociception Level Monitor (NOL) by Medasense Biometrics Ltd., Israel; Device: Bispectral index (BIS); Other: Questionnaire perception of the nurse on pain patient

Detailed Description

To date it remains challenging to adequately titrate analgesic medication in sedated and anesthetized patients. Recently, nociception monitoring was introduced to guide analgesic treatment in sedated and anesthetized surgical patients. One such monitor is the Nociception Level (NOL; Medasense Biometrics Ltd., Israel). The NOL combines various measurements such as, skin conductance, heart rate, heart rate variability and photoplethysmograph amplitude, and translates these inputs into a single index ranging from 0 (no nociception) to 100 (maximal nociception). Earlier studies have shown that during surgery, the NOL-guided opioid treatment resulted in improved hemodynamics and reduced postoperative pain.

In the COVID-19 pandemic, patients admitted in the Intensive Care Unit (ICU), needed excessive amounts of sedatives, analgesics and muscle relaxants during mechanical ventilation. To determine its value in the ICU, the investigators measured NOL values in COVID and non-COVID ICU patients in an earlier study. The aim of the investigators was to verify the assumption that COVID-19 patients were overdosed on opioids. Since the investigators indeed did observe lower NOL values in COVID-19 patients than in non-COVID patients in an earlier study, the investigators expanded the study to determine whether sedatives were equally overdosed, by also measuring the bispectral index (BIS). With this extra information the investigators also hope to determine whether it is feasible to use the NOL in the ICU.

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

Contacts and Locations

• Study Contact: Name: Imeen van der Wal, MD, Msc; Phone Number: +3175296867; Email: l.i.van_der_wal@lumc.nl
• Study Contact Backup: Name: Albert Dahan, MD, PhD; Phone Number: +31715262301; Email: A.Dahan@lumc.nl

Study Locations

• Netherlands
  • Zuid-holland
    • Leiden, Zuid-holland, Netherlands, 2333ZA
      • Recruiting
      • Leiden University Medical Centre
      • Contact: Imeen van der Wal, MD, Msc; Phone Number: +3175296867; Email: l.i.van_der_wal@lumc.nl
      • Contact: Albert Dahan, MD, PhD; Phone Number: +3175262301; Email: A.Dahan@lumc.nl

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: Probability Sample

Study Population

Patients admitted to the ICU meeting the above mentioned selection criteria can be included in the study. Only half of the included patients will have proven COVID-19 disease by PCR of nose- or airway sample. The Control patients (without COVID-19) will be randomly selected. There will be no matching.

Description

Inclusion Criteria:

• aged 18 years or older
• mechanical ventilation for any reason
• deemed suitable by the investigators

Exclusion Criteria:

• aged 17 years or younger
• severe peripheral edema
• veno-arterial (VA) and veno-venous (VV) exctracorporeal membrane oxygenation (ECMO)
• heart rate below 35
• abdominal position
• not deemed suitable by the investigators

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Covid-19 patients; Mechanically ventilated and sedated adult patients with proven COVID-19 infection by PCR of nose- or airway sample. The nociception of this patient will be monitored by the nociception level monitor for 8 hours.	Device: Nociception Level Monitor (NOL) by Medasense Biometrics Ltd., Israel; The NOL monitor measures various parameters via a sensor in a finger probe that is attached to the patient. These parameters are: Temperature; Galvanic skin response; Accelerometer; Photoplethysmograph (pulse rate, pulse rate variability, photoplethysmograph amplitude) All this data is combined in an algorithm which produces a number between 0-100. Between 10-25 indicates adequate analgesia, below 10 too much analgesia, above 25 too little analgesia. No actions are taken based on this measurement.; Device: Bispectral index (BIS); The BIS processes EEG information to provide a direct measurement of the patient's level of consciousness and insight into the effects of anesthesia on the brain.; Other: Questionnaire perception of the nurse on pain patient; The investigators developed a questionnaire with 7-questions regarding the perception of the responsible nurse on the pain of the patient. When the investigators measured for 8 hours with the BIS and the NOL they will ask the nurse what his or her perception was of the pain of the patient. Eventually the investigators will compare the answers of this questionnaire with the NOL and BIS values that they observed, whether the information corresponds or not.
non-COVID-19 patients; Mechanically ventilated and sedated adult patients not infected with COVID-19 infection. The nociception of this patient will be monitored by the nociception level monitor for 8 hours.	Device: Nociception Level Monitor (NOL) by Medasense Biometrics Ltd., Israel; The NOL monitor measures various parameters via a sensor in a finger probe that is attached to the patient. These parameters are: Temperature; Galvanic skin response; Accelerometer; Photoplethysmograph (pulse rate, pulse rate variability, photoplethysmograph amplitude) All this data is combined in an algorithm which produces a number between 0-100. Between 10-25 indicates adequate analgesia, below 10 too much analgesia, above 25 too little analgesia. No actions are taken based on this measurement.; Device: Bispectral index (BIS); The BIS processes EEG information to provide a direct measurement of the patient's level of consciousness and insight into the effects of anesthesia on the brain.; Other: Questionnaire perception of the nurse on pain patient; The investigators developed a questionnaire with 7-questions regarding the perception of the responsible nurse on the pain of the patient. When the investigators measured for 8 hours with the BIS and the NOL they will ask the nurse what his or her perception was of the pain of the patient. Eventually the investigators will compare the answers of this questionnaire with the NOL and BIS values that they observed, whether the information corresponds or not.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BIS and NOL values over time	The observation of the BIS and NOL values over time	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Propofol and opioid dosage	Propofol and opioid dosage will be monitored during 8 hours	8 hours
Feasibility of using the NOL in the ICU	Is it possible to use the NOL on ICU patients and does it monitor correctly	8 hours

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Anticipated): December 8, 2022
• Study Completion (Anticipated): December 8, 2022

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nociceptive Pain
• Other Study ID Numbers: CoCo 2021-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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