Pupillometry - Future of Objective Pain Reaction Measurement While Unconscious

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Device: Pupil reflex dilation measurement (PRD); Device: PPI (Pupillary Pain Index); Device: Bispectral Index (BIS); Device: HR; Device: BP; Drug: lidocaine; Drug: Placebo

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: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Warmian-masurian
    • Olsztyn, Warmian-masurian, Poland, 11-041
      • Anesthesiology and Intensive Care Clinical Ward, Clinical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / 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; 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; Drug: lidocaine; 1.5 mg/kg lidocaine/ 100ml 0,9% NaCl iv 10min before intubation; Other Names: lidocaine, Xylocaine
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; 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; Drug: Placebo; 100ml 0,9% NaCl iv 10min before intubation; Other Names: 0,9% natrium chloratum, sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Usefulness of Pupillary Reflex Dilation (PRD) measured using a video pupillometer in determining the role of lidocaine iv before intubation.	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).	PRD: during the exact time of intubation (continuous measurement for 60 seconds)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The influence of intravenous lidocaine on level of analgesia during orotracheal intubation	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).	PRD: during the exact time of intubation (continuous measurement for 60 seconds)
The influence of intravenous lidocaine on level of analgesia during orotracheal 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)	HR - baseline and 0,1,2,3,4 minutes post-intubation
The influence of intravenous lidocaine on level of analgesia during orotracheal 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)	BP - baseline and 0,1,2,3,4 minutes post-intubation
Correlation between PRD and PPI (Pupillary Pain Index) measured using video pupillometer and BIS (Bispectral Index)	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.	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
The influence of intravenous lidocaine on PPI	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).	5 minutes post-intubation

Collaborators and Investigators

• Sponsor: University of Warmia and Mazury
• Investigators: Study Chair: Ewa Mayzner-Zawadzka, MD,PhD,Prof, Anesthesiology and Intensive Care Clinical Ward, University of Warmia and Mazury

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): November 30, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): January 22, 2020
• Last Update Submitted That Met QC Criteria: January 17, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: pain; lidocaine; general anesthesia; analgesia; intubation; pupillometry; hemodynamic response; reflex; pupillary monitoring; intraoperative
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Consciousness Disorders; Unconsciousness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: UWarmiaMazury

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified study participants data for all primary and secondary outcome measures.
• IPD Sharing Time Frame: Data will be available within 12 months of study completion
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

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