Infrared Pupillometry During General Anesthesia to Predict Pain

Intraoperative Use of Infrared Pupillometry During General Anesthesia to Predict Pain and Quality of Regional Anesthesia After Surgery

The study comprises of a series of pupillary measurements using infrared pupillometry in patients undergoing arthroscopic knee surgery of any type.

Infrared pupillometry will be used to assess whether a painful stimulus results in pupillary reflex dilation (PRD). The extend of the PRD may be an indicator how painful a stimulus is. This may help to predict the amount of discomfort a patient will be experiencing after emergence from general anesthesia.

In addition to measuring the pupillary reflex dilation, we will also measure oscillations of pupil size before and after indiction of anesthesia, as well as during recovery. These spontaneously occuring oscillations in pupil size, also called hippus, appear to be sensitive to anesthetics and opioids. However, the effect of these drugs on hippus has not been systematically addressed.

The aim of the study is

1. to identify whether regional anesthesia techniques such as femoral and sciatic nerve blocks will block the PRD. This would allow assessment of block success in the anesthetized patient.
2. to correlate the extent of the pupillary reflex dilation and hippus in the anesthetized patient during and at the end of surgery with early postoperative pain scores and subsequent analgesia requirements. Such correlation would allow to predict the amount of postoperative pain before the patients emerge from general anesthesia.

Study Overview

• Status: Terminated
• Conditions: Postoperative Pain; Objective Assessment of Sedation
• Intervention / Treatment: Drug: Anesthesia Premedication, Induction and Maintenance; Procedure: Pupillometry after administration of anesthetic drugs

Detailed Description

The planned study is a prospective cohort study.

Patients undergoing arthroscopic knee surgery of any type (debridements, repair of anterior (ACL) or posterior cruciform ligaments (PCL), meniscectomies, medial (MCL) or lateral collateral ligament (LCL) repair, as well as microfracture surgery will be enrolled.

During anesthesia, infrared pupillometry will be used to assess whether a painful stimulus results in pupillary reflex dilation (PRD). The extend of the PRD may be an indicator how painful a stimulus is. The PRD is measurable under general anesthesia in spite of the fact that the patient does not "feel" or experience the painful stimulus.

The aim of the study is

1. to identify whether regional anesthesia techniques such as femoral and sciatic nerve blocks (performed before the start of anesthesia) will block the PRD evoked by a painful stimulus such electrical stimulation before procedure start. This would allow assessment of block success in the anesthetized patient.
2. to correlate the extent of the pupillary reflex dilation and hippus in the anesthetized patient during and at the end of surgery with early postoperative pain scores and subsequent analgesia requirements. Such correlation would allow to predict the amount of postoperative pain before the patients emerge from general anesthesia.

Knee arthroscopies are routinely performed under general anesthesia with or without regional anesthesia, depending on the anticipated extent of surgery and the preferences of the anesthesiologist and surgeon. The assessment of the PRD and/or hipppus before emergence would identify those patients who would benefit from an additional nerve block before emergence to achieve better pain control immediately postoperatively and to reduce the demand for postoperative analgesics.

The planned investigation tries to achieve two novel findings. First, the measurement of the PRD at the start of surgery will demonstrate whether a nerve block successfully blocks the initial surgical stimulus. There is currently no method available that can assess block success in the anesthetized patient. Secondly, the measurement at the end of the surgery tries to predict the amount of pain following emergence from surgery. Pain may be experienced by patients without nerve blocks as well as with nerve blocks, as the latter may have failed or incomplete blocks, or may had a more extensive procedure that cannot be completely covered by the block administered preoperatively. Identifying these patients may allow treatment to minimize discomfort following emergence.

Pupillary reflex dilation describes the dilation of the pupil following a painful stimulus. The dilation last several seconds. Pupillometry using an infrared pupillometer allows the quantification of the reflex dilation. The PRD can be given a numerical value that reflects the extent of the dilation. A recently published study demonstrated the correlation of the extend of the PRD with pain scores and opioid requirements postoperatively. However, this study was done in awake patients following surgery. The aim of this study is to predict analgesia requirements in patients still under general anesthesia, before they experience postoperative pain. We expect that infrared pupillometry during general anesthesia can predict pain following surgery. Once this has been established, this knowledge and its application would allow the anesthesiologist to initiate pain-relieving interventions such as additional nerve blocks or administration of analgesics before emergence of the patients from general anesthesia.

In addition to measuring the pupillary reflex dilation, we will also measure oscillations of pupil size before and after induction of anesthesia, as well as during recovery. These spontaneously occurring oscillations in pupil size, also called hippus, appear to be sensitive to anesthetics and opioids. However, the effect of these drugs on hippus has not been systematically addressed.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Orthopedic Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients older than 18 years undergoing arthroscopic knee surgery of any type

Exclusion Criteria:

• Blindness
• Anisocoria
• History of opioid abuse
• Chronic pain patients
• Gastric Reflux Disease (due to the use of laryngeal masks in the study)
• Non english speaking patients
• Cognitive impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Intervention Group; all enrolled patients undergo the same protocol/ treatment: Anesthesia Premedication, Induction and Maintenance Pupillometry after administration of anesthetic drugs

Drug: Anesthesia Premedication, Induction and Maintenance; The enrolled patients receive standard of care general anesthesia for knee arthroscopy. No additional pharmacological interventions are performed in study participants. The administered drugs, as outlined in the arms section, are midazolam, fentanyl, propofol, and sevoflurane. Study patients receive analgesic drugs as needed in the recovery room if they experience pain.; Procedure: Pupillometry after administration of anesthetic drugs; All study patients receive the standard of anesthetic care. Every time a anesthetic drug has been administered, changes in pupillary oscillations will be recorded. Assessment of pupil size and movements by shining infrared light into the eye and measuring the reflection over a 20 s period The administered drugs are: Midazolam 1-2 mg iv, Fentanyl 1mcg/kg body weight, Propofol for anesthesia induction 2-2.5 mg/kg body weight, Sevoflurane as needed for maintenance of general anesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain in Recovery Room	Pain as assessed by visual analogue score at arrival of the patient in the recovery room Scale goes from 0-10, with 10 indicating the worst pain possible	at arrival in recovery room

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients we Were Able to Elicit a PLR Under Stable Experimental Conditions	Pupillary Reflex Dilation is measured intraoperatively at incision and at the end of the case as a possible indicator of success of regional anesthesia. Measurement of this requires stable experimental conditions, most notably sufficient depth of anesthesia.	measurements were taken at two time points during surgery. Each measurement took 30 seconds

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippus	We assess the effects of various anesthetic drugs on pupillary unrest (hippus). More specifically, we record pupil diameters over 20 seconds and then perform a Fourier Analysis of the diameter changes. The endpoint variable is power of the oscillations over certain predefined frequency bins.	Before anesthesia start (baseline measurement) until discharge of the patient (on average 1-2 hours after arrival in the recovery room)

Collaborators and Investigators

• Sponsor: University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2012
• Primary Completion (ACTUAL): November 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 7, 2014
• First Posted (ESTIMATE): February 10, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: Pupillometry and Analgesia