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出境医 / 临床实验 / Pupillometry - Future of Objective Pain Reaction Measurement While Unconscious

Pupillometry - Future of Objective Pain Reaction Measurement While Unconscious

Study Description
Brief Summary:
This study aims to assess the usefulness of pupillometry as a nociceptive indicator during elective orotracheal intubation in patients given intravenous lignocaine pre-intubation as compared to a placebo pre-intubation.

Condition or disease Intervention/treatment Phase
Pain Device: Pupil reflex dilation measurement (PRD) Device: PPI (Pupillary Pain Index) Drug: lidocaine Drug: Placebo Device: Bispectral Index (BIS) Device: HR Device: BP Not Applicable

Detailed Description:

Laryngoscopy and tracheal intubation are associated with a sympathetic discharge caused by stimulation of the upper respiratory tract. Venous lidocaine is the agent most used to attenuate the hemodynamic response to laryngoscopy and intubation. Hemodynamic response might be masked by the drugs the patient is taking and its status (ex. sepsis). There's a need for an objective pain assessment method while the patient is unconscious, to maintain a proper level of analgesia and to control the hemodynamic response in order to decrease systemic repercussions.

This single-blind, randomized, single center, prospective study was approved by the Bioethics Committee of the University of Warmia and Mazury under the report number 11/2019 21st of February 2019.

Patients scheduled for elective surgery under general anesthesia with tracheal intubation were divided into three groups:

Group 1: anaesthetic induction with standard doses iv was performed (fentanyl 3mcg/kg, propofol 2mg/kg, rocuronium 0,6mg/kg).

Group 2: same as in group 1 + lidocaine 1,5mg/kg w 100ml 0,9% NaCl 10 min before intubation.

Group 3 (placebo group): same as group 1 + 100ml 0,9% NaCl 10 min before intubation

The values for blood pressure (NIBP), heart rate (HR), Train of four (TOF) and bispectral index (BIS) were measured in all groups during the whole time of the protocol. PRD (Pupillary Reflex Dilation) was measured in the exact time of intubation. Additionally, after intubation PPI (Pupillary Pain Index) was checked.

During the whole protocol BIS value was maintained to be equal to or less than 50, if this value was not reached, a venous increment of 1mg/kg of propofol was administered.

Hypertension was considered when the BP values were 20% above baseline values or if Systolic Blood Pressure (SBP) > 140 mmHg. Hypotension was considered when the Blood Pressure (BP) values were 20% below baseline values or if SBP > 90 mmHg. Tachycardia was considered when the Heart Rate (HR) values were 20% above baseline values or if HR > 100 mmHg. Bradycardia was considered for HR values under 50 bpm.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Diagnostic
Official Title: Pupillometry - Future of Objective Pain Reaction Measurement While Unconscious
Actual Study Start Date : February 25, 2019
Actual Primary Completion Date : November 30, 2019
Actual Study Completion Date : December 31, 2019
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Control C
This group will be given induction anesthesia agents in standard doses (fentanyl 3mcg/kg, propofol 2mg/ kg, rocuronium 0,6mg/kg)
Device: Pupil reflex dilation measurement (PRD)
Pupillary Reflex Dilation (PRD) measured for 60 s during orotracheal intubation using a video pupillometer

Device: PPI (Pupillary Pain Index)
Pupillary Reflex Dilation (PRD) measured using a video pupillometer 5 min after orotracheal intubation

Device: Bispectral Index (BIS)
Bispectral Index will be monitored to assess the depth of anaesthesia

Device: HR
HR in beats/min will be measured by the electrocardiogram monitor

Device: BP
BP will be measured automatically by an occluding upper arm cuff

Experimental: Lignocaine group L
This group will be given additionally 1.5 mg/kg lidocaine/ 100ml 0,9% NaCl iv 10min before intubation
Device: Pupil reflex dilation measurement (PRD)
Pupillary Reflex Dilation (PRD) measured for 60 s during orotracheal intubation using a video pupillometer

Device: PPI (Pupillary Pain Index)
Pupillary Reflex Dilation (PRD) measured using a video pupillometer 5 min after orotracheal intubation

Drug: lidocaine
1.5 mg/kg lidocaine/ 100ml 0,9% NaCl iv 10min before intubation
Other Name: lidocaine, Xylocaine

Device: Bispectral Index (BIS)
Bispectral Index will be monitored to assess the depth of anaesthesia

Device: HR
HR in beats/min will be measured by the electrocardiogram monitor

Device: BP
BP will be measured automatically by an occluding upper arm cuff

Placebo Comparator: Placebo P
This group will be given additionally 100 ml 0,9% NaCl iv 10 min before intubation
Device: Pupil reflex dilation measurement (PRD)
Pupillary Reflex Dilation (PRD) measured for 60 s during orotracheal intubation using a video pupillometer

Device: PPI (Pupillary Pain Index)
Pupillary Reflex Dilation (PRD) measured using a video pupillometer 5 min after orotracheal intubation

Drug: Placebo
100ml 0,9% NaCl iv 10min before intubation
Other Name: 0,9% natrium chloratum, sodium chloride

Device: Bispectral Index (BIS)
Bispectral Index will be monitored to assess the depth of anaesthesia

Device: HR
HR in beats/min will be measured by the electrocardiogram monitor

Device: BP
BP will be measured automatically by an occluding upper arm cuff

Outcome Measures
Primary Outcome Measures :
  1. Usefulness of Pupillary Reflex Dilation (PRD) measured using a video pupillometer in determining the role of lidocaine iv before intubation. [ Time Frame: PRD: during the exact time of intubation (continuous measurement for 60 seconds) ]
    Level of analgesia will be investigated in all groups (placebo, lidocaine, control) basing on the autonomous system activation during intubation by measuring variation of pupil diameter (% and mm).


Secondary Outcome Measures :
  1. The influence of intravenous lidocaine on level of analgesia during orotracheal intubation [ Time Frame: PRD: during the exact time of intubation (continuous measurement for 60 seconds) ]
    Changes that occur in PRD measured using video pupillometer as a response to an analgesic intervention will be investigated in all groups (placebo, lidocaine, control).

  2. The influence of intravenous lidocaine on level of analgesia during orotracheal intubation. [ Time Frame: HR - baseline and 0,1,2,3,4 minutes post-intubation ]
    Level of analgesia will be investigated in all groups (placebo, lidocaine, control) basing on the autonomous system activation during intubation by measuring changes in HR (beats/min)

  3. The influence of intravenous lidocaine on level of analgesia during orotracheal intubation. [ Time Frame: BP - baseline and 0,1,2,3,4 minutes post-intubation ]
    Level of analgesia will be investigated in all groups (placebo, lidocaine, control) basing on the autonomous system activation during intubation by measuring changes in BP (mmHg)

  4. Correlation between PRD and PPI (Pupillary Pain Index) measured using video pupillometer and BIS (Bispectral Index) [ Time Frame: BIS - baseline, during intubation, 0,1,2,3,4,5 minutes post-intubation, PRD: during the exact time of intubation (continuous measurement for 60 seconds), PPI - 5 minutes post-intubation ]
    Changes that occur in PRD and PPI as a response to an analgesic intervention will be investigated in all groups (placebo, lidocaine, control) and correlated to BIS in all groups.

  5. The influence of intravenous lidocaine on PPI [ Time Frame: 5 minutes post-intubation ]
    Changes that occur in PPI measure using video pupillometer as a response to an analgesic intervention will be investigated in all groups (placebo, lidocaine, control).


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Physical State 1 or 2 of the American Society of Anesthesiology (ASA)
  • Electively scheduled for surgery requiring general anesthesia
  • Age >18 years

Exclusion Criteria:

  • Difficult airway
  • Unanticipated difficult airway based on the previous history of difficult intubation
  • Urgently scheduled for surgery requiring general anesthesia
  • Ophthalmologic pathology precluding pupillometry, ex. Horner's syndrome, Sjogrens syndrome
  • Anisocoria
  • History of opioid abuse
  • Subjects who are or may be pregnant
  • Unable to converse in Polish
  • History of psychiatric/cognitive disease
  • Patients who do not give informed consent
  • Patients with contraindications or history of hypersensitivity to lidocaine
  • Patients with coronary ischemic disease
  • Patients with atrioventricular block at any grade
  • Patients with diagnosed cardiac arrhythmias
  • Patients with heart failure
  • Patients who are taking drugs influencing the pupil size
  • Patients with pacemaker
  • Patients younger than 18 years of age
  • History of chronic pain, chronic opioid use (> 3 months)
Contacts and Locations

Locations
Layout table for location information
Poland
Anesthesiology and Intensive Care Clinical Ward, Clinical University Hospital
Olsztyn, Warmian-masurian, Poland, 11-041
Sponsors and Collaborators
University of Warmia and Mazury
Investigators
Layout table for investigator information
Study Chair: Ewa Mayzner-Zawadzka, MD,PhD,Prof Anesthesiology and Intensive Care Clinical Ward, University of Warmia and Mazury
Tracking Information
First Submitted Date  ICMJE May 1, 2019
First Posted Date  ICMJE June 27, 2019
Last Update Posted Date January 22, 2020
Actual Study Start Date  ICMJE February 25, 2019
Actual Primary Completion Date November 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2019)
Usefulness of Pupillary Reflex Dilation (PRD) measured using a video pupillometer in determining the role of lidocaine iv before intubation. [ Time Frame: PRD: during the exact time of intubation (continuous measurement for 60 seconds) ]
Level of analgesia will be investigated in all groups (placebo, lidocaine, control) basing on the autonomous system activation during intubation by measuring variation of pupil diameter (% and mm).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2019)
  • The influence of intravenous lidocaine on level of analgesia during orotracheal intubation [ Time Frame: PRD: during the exact time of intubation (continuous measurement for 60 seconds) ]
    Changes that occur in PRD measured using video pupillometer as a response to an analgesic intervention will be investigated in all groups (placebo, lidocaine, control).
  • The influence of intravenous lidocaine on level of analgesia during orotracheal intubation. [ Time Frame: HR - baseline and 0,1,2,3,4 minutes post-intubation ]
    Level of analgesia will be investigated in all groups (placebo, lidocaine, control) basing on the autonomous system activation during intubation by measuring changes in HR (beats/min)
  • The influence of intravenous lidocaine on level of analgesia during orotracheal intubation. [ Time Frame: BP - baseline and 0,1,2,3,4 minutes post-intubation ]
    Level of analgesia will be investigated in all groups (placebo, lidocaine, control) basing on the autonomous system activation during intubation by measuring changes in BP (mmHg)
  • Correlation between PRD and PPI (Pupillary Pain Index) measured using video pupillometer and BIS (Bispectral Index) [ Time Frame: BIS - baseline, during intubation, 0,1,2,3,4,5 minutes post-intubation, PRD: during the exact time of intubation (continuous measurement for 60 seconds), PPI - 5 minutes post-intubation ]
    Changes that occur in PRD and PPI as a response to an analgesic intervention will be investigated in all groups (placebo, lidocaine, control) and correlated to BIS in all groups.
  • The influence of intravenous lidocaine on PPI [ Time Frame: 5 minutes post-intubation ]
    Changes that occur in PPI measure using video pupillometer as a response to an analgesic intervention will be investigated in all groups (placebo, lidocaine, control).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pupillometry - Future of Objective Pain Reaction Measurement While Unconscious
Official Title  ICMJE Pupillometry - Future of Objective Pain Reaction Measurement While Unconscious
Brief Summary This study aims to assess the usefulness of pupillometry as a nociceptive indicator during elective orotracheal intubation in patients given intravenous lignocaine pre-intubation as compared to a placebo pre-intubation.
Detailed Description

Laryngoscopy and tracheal intubation are associated with a sympathetic discharge caused by stimulation of the upper respiratory tract. Venous lidocaine is the agent most used to attenuate the hemodynamic response to laryngoscopy and intubation. Hemodynamic response might be masked by the drugs the patient is taking and its status (ex. sepsis). There's a need for an objective pain assessment method while the patient is unconscious, to maintain a proper level of analgesia and to control the hemodynamic response in order to decrease systemic repercussions.

This single-blind, randomized, single center, prospective study was approved by the Bioethics Committee of the University of Warmia and Mazury under the report number 11/2019 21st of February 2019.

Patients scheduled for elective surgery under general anesthesia with tracheal intubation were divided into three groups:

Group 1: anaesthetic induction with standard doses iv was performed (fentanyl 3mcg/kg, propofol 2mg/kg, rocuronium 0,6mg/kg).

Group 2: same as in group 1 + lidocaine 1,5mg/kg w 100ml 0,9% NaCl 10 min before intubation.

Group 3 (placebo group): same as group 1 + 100ml 0,9% NaCl 10 min before intubation

The values for blood pressure (NIBP), heart rate (HR), Train of four (TOF) and bispectral index (BIS) were measured in all groups during the whole time of the protocol. PRD (Pupillary Reflex Dilation) was measured in the exact time of intubation. Additionally, after intubation PPI (Pupillary Pain Index) was checked.

During the whole protocol BIS value was maintained to be equal to or less than 50, if this value was not reached, a venous increment of 1mg/kg of propofol was administered.

Hypertension was considered when the BP values were 20% above baseline values or if Systolic Blood Pressure (SBP) > 140 mmHg. Hypotension was considered when the Blood Pressure (BP) values were 20% below baseline values or if SBP > 90 mmHg. Tachycardia was considered when the Heart Rate (HR) values were 20% above baseline values or if HR > 100 mmHg. Bradycardia was considered for HR values under 50 bpm.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Diagnostic
Condition  ICMJE Pain
Intervention  ICMJE
  • Device: Pupil reflex dilation measurement (PRD)
    Pupillary Reflex Dilation (PRD) measured for 60 s during orotracheal intubation using a video pupillometer
  • Device: PPI (Pupillary Pain Index)
    Pupillary Reflex Dilation (PRD) measured using a video pupillometer 5 min after orotracheal intubation
  • Drug: lidocaine
    1.5 mg/kg lidocaine/ 100ml 0,9% NaCl iv 10min before intubation
    Other Name: lidocaine, Xylocaine
  • Drug: Placebo
    100ml 0,9% NaCl iv 10min before intubation
    Other Name: 0,9% natrium chloratum, sodium chloride
  • Device: Bispectral Index (BIS)
    Bispectral Index will be monitored to assess the depth of anaesthesia
  • Device: HR
    HR in beats/min will be measured by the electrocardiogram monitor
  • Device: BP
    BP will be measured automatically by an occluding upper arm cuff
Study Arms  ICMJE
  • Active Comparator: Control C
    This group will be given induction anesthesia agents in standard doses (fentanyl 3mcg/kg, propofol 2mg/ kg, rocuronium 0,6mg/kg)
    Interventions:
    • Device: Pupil reflex dilation measurement (PRD)
    • Device: PPI (Pupillary Pain Index)
    • Device: Bispectral Index (BIS)
    • Device: HR
    • Device: BP
  • Experimental: Lignocaine group L
    This group will be given additionally 1.5 mg/kg lidocaine/ 100ml 0,9% NaCl iv 10min before intubation
    Interventions:
    • Device: Pupil reflex dilation measurement (PRD)
    • Device: PPI (Pupillary Pain Index)
    • Drug: lidocaine
    • Device: Bispectral Index (BIS)
    • Device: HR
    • Device: BP
  • Placebo Comparator: Placebo P
    This group will be given additionally 100 ml 0,9% NaCl iv 10 min before intubation
    Interventions:
    • Device: Pupil reflex dilation measurement (PRD)
    • Device: PPI (Pupillary Pain Index)
    • Drug: Placebo
    • Device: Bispectral Index (BIS)
    • Device: HR
    • Device: BP
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 25, 2019)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date November 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Physical State 1 or 2 of the American Society of Anesthesiology (ASA)
  • Electively scheduled for surgery requiring general anesthesia
  • Age >18 years

Exclusion Criteria:

  • Difficult airway
  • Unanticipated difficult airway based on the previous history of difficult intubation
  • Urgently scheduled for surgery requiring general anesthesia
  • Ophthalmologic pathology precluding pupillometry, ex. Horner's syndrome, Sjogrens syndrome
  • Anisocoria
  • History of opioid abuse
  • Subjects who are or may be pregnant
  • Unable to converse in Polish
  • History of psychiatric/cognitive disease
  • Patients who do not give informed consent
  • Patients with contraindications or history of hypersensitivity to lidocaine
  • Patients with coronary ischemic disease
  • Patients with atrioventricular block at any grade
  • Patients with diagnosed cardiac arrhythmias
  • Patients with heart failure
  • Patients who are taking drugs influencing the pupil size
  • Patients with pacemaker
  • Patients younger than 18 years of age
  • History of chronic pain, chronic opioid use (> 3 months)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04000126
Other Study ID Numbers  ICMJE UWarmiaMazury
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  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified study participants data for all primary and secondary outcome measures.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data will be available within 12 months of study completion
Access Criteria: Data will be made available for researchers who provide a methodologically sound proposal. Proposals should be directed to m.braczkowska@gmail.com . Data access requests will be reviewed by an External Independent Review Panel. To gain access, data requestors will need to sign a data access agreement.
Responsible Party Malgorzata Braczkowska, University of Warmia and Mazury
Study Sponsor  ICMJE University of Warmia and Mazury
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Ewa Mayzner-Zawadzka, MD,PhD,Prof Anesthesiology and Intensive Care Clinical Ward, University of Warmia and Mazury
PRS Account University of Warmia and Mazury
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP