Comparison of Pupillometry-guided Anesthesia With Surgical Pleth Index Guided Anesthesia

Study Overview
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Brief Summary
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In this study, the investigators measure a pupil size every 5 minutes during the operation in patients undergoing laparoscopic cholecystectomy under general anesthesia. The investigators would compare the intraoperative opioid consumption and postoperative pain between the group adjusted the anesthetic drug concentration based on the changes of the pupil (Pupil group) and the group based on the changes of a surgical pleth index (SPI group).

Official Title
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Comparison of Pupillometry-guided With Surgical Pleth Index (SPI) Guided General Anesthesia on Perioperative Opioid Consumption and Pain Intensity: a Pilot Study

Conditions
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Cholecystectomy, Laparoscopic, Anesthesia, General, Reflex, Pupillary

Intervention / Treatment
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* Procedure: Pupillometry guided anesthesia
* Procedure: SPI guided anesthesia
* Procedure: Standard management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 20 to 65 yr, American Society of Anesthesiologist Physical status(ASA PS) I to II, scheduled for a laparoscopic cholecystectomy under general anesthesia Exclusion Criteria: Presence of ophthalmologic diseases such as Horner's syndrome or Sjogren's disease. Presence of neurologic or metabolic diseases Medicated that could interfere with the autonomous nervous system (e.g., b- blockers, anticholinergics) History of substance abuse or psychiatric disease with chronic pain or preoperative analgesics with pacemaker or arrhythmia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pupillometry group<br>In this group, anesthesia is performed using Pupillometry guided anesthesia. | Procedure: Pupillometry guided anesthesia<br>* At least 10 min after anesthesia induction by target-controlled infusion of propofol and remifentanil, baseline values for pupillary diameter is recorded before any surgical procedure. During the operation, propofol effect-site target concentration (Ce) is adjusted to maintain the bispectral index (BIS) value between 40 and 60. Remifentanil Ce is adapted every 5 min based on the changes of pupillary diameter. If the pupillary diameter is increased by more than 30% compared to baseline value, remifentanil concentration is increased by 0.5 ng/ml. If the pupillary diameter is maintained between 5 and 30 % change compared with baseline, remifentanil is not modified. In a case of pupillary diameter is decreased less than 5 % change of baseline, remifentanil concentration is decreased by 0.5 ng/ml.<br>* Other names: PUPIL;|
| Active Comparator: SPI group<br>In this group, anesthesia is performed using SPI guided anesthesia. | Procedure: SPI guided anesthesia<br>* During the operation, SPI value should be maintained between 20 and 50 by changing the infusion rate of remifentanil. Even if the SPI is maintained within the target range, the remifentanil infusion rate is increased by 0.5 ng/ml in a case of the SPI value suddenly arises by more than 10.<br>* Other names: SPI;|
| Sham Comparator: Control group<br>In this group, remifentanil concentration is controlled by the discretion of the anesthesiologist in charge of the patients (Standard management). | Procedure: Standard management<br>* During the operation, propofol effect-site target concentration (Ce) is adjusted to maintain the bispectral index (BIS) value between 40 and 60. Remifentanil concentration is controlled by the discretion of the anesthesiologist in charge of the patients.<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative opioid consumption | The amount of remifentanil consumption during the operation is calculated by following equation: Total remifentanil consumption (mcg) / body weight of the patients (kg)/ duration of anesthesia (min) | During the operation period (Within 2 hour after the anesthesia induction) | 
| Peak pain score assessed by numeric rating scale (NRS) in post-anesthesia care unit (PACU) | Patients are asked to rate their pain according to the numeric rating scale (NRS, 0=no pain to 10= extreme pain imaginable) every 10 min after the PACU admission. Peak pain score is the peak NRS during PACU stay. Higher NRS represents a worse outcome. | During the PACU stay (Within 1 hour after the PACU admission) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative propofol consumption | The amount of propofol consumption during the operation | During the operation period (Within 2 hour after the anesthesia induction) | 
| Intraoperative vasopressor or vasodilator consumption | The amount of ephedrine and nicardipine consumption during the operation | During the operation period (Within 2 hour after the anesthesia induction) | 
| PACU stay time | Duration of time interval from PACU admission to discharge. | Approximately within 1 hour after the PACU admission | 
| Postoperative adverse events | Check the postoperative nausea and vomiting, dizziness, desaturation, urinary retention, itching sensation and bradycardia | Approximately within 1 hour after the PACU admission | 
| Remnant sedation degree | Remnant sedation is evaluated by Riker Sedation-Agitation Scale every 10 minutes after the PACU admission. unarousable, minimal or no response to noxious stimuli, does not communicate of follow commands very sedate, arouse to physical stimuli but does not communicate or follow command, may move spontaneously sedate, difficult to arouse but awakens to verbal stimuli or gentle shaking, follows simple commands but drifts off again Calm and cooperative, calm and follows commands agitated, anxious or physically agitated and calms to verbal instructions very agitated, requiring restraint and frequent verbal reminding of limits, biting endotracheal tubes dangerous agitation, pulling at tracheal tube, trying to remove catheters or striking at staff | Approximately within 1 hour after the PACU admission | 
| Total analgesic consumption after PACU discharge | Check the analgesic consumption after PACU discharge including oral, intramuscular and intravenous administration. | During 1 day after the operation | 
| Pain score assessed by numeric rating scale (NRS) 1 day after the operation | Patients are asked to rate their pain according to the numeric rating scale (NRS, 0=no pain to 10= extreme pain imaginable) 1 day after the operation. Higher NRS represents a worse outcome. | On 1 day after the operation | 
| initial Pupillary unrest under ambient light (PUAL) | At room light, the pupil is taken for 8 seconds at a frame rate of 30 frames per second. The pupillometer generates raw data in the format of pupil diameter versus time. We define the PUAL as the area under the curve of power spectral density between 0.23 and 3 Hz. The integral of the area is calculated using the composite Simpson's rule. | Just before the induction of anesthesia | 
| Pupillary unrest under ambient light (PUAL) on PACU arrival | At room light, the pupil is taken for 8 seconds at a frame rate of 30 frames per second. The pupillometer generates raw data in the format of pupil diameter versus time. We define the PUAL as the area under the curve of power spectral density between 0.23 and 3 Hz. The integral of the area is calculated using the composite Simpson's rule. | Approximately within 1 min after the PACU admission |