Ability of Pupillometry to Reduce Sufentanil Consumption in Planned Cardiac Surgery: Randomized, Controlled, Single-center Clinical Superiority Trial (PUCCAR)

The objective of general anesthesia is to obtain a loss of consciousness, stillness, and sufficient analgesia to allow surgery. Thus, general anesthesia has two components: hypnosis and analgesia. Combining these two components, with parallel use of a hypnotic agent and a morphine agent makes major surgery possible by limiting the stress on the body. In clinical practice, hypnosis can be assessed by a monitor of the depth of BIS®-type anesthesia, based on a simplified measurement of the patient's spontaneous cortical electroencephalographic activity. However, BIS® type monitors do not specifically judge analgesia.

Traditionally, analgesia is assessed on the basis of hemodynamic changes (blood pressure, heart rate) in relation to a nociceptive stimulus. There is an interaction between pain and cardiovascular control that is mediated by the baroreflex system. But not all hemodynamic changes during general anesthesia are necessarily secondary to nociceptive stimulation. For example, hypovolemia may be responsible for tachycardia without causing pain; opening the pericardium during cardiac surgery may increase blood pressure by increasing cardiac output.... On the other hand, a decrease in hemodynamic response can be observed in relation to the depressant effect of anesthetic agents, despite a lack of analgesia. Similarly, patients' disease-modifying treatments may mask hemodynamic responses (e.g. beta blocker). Thus, the appearance of tachycardia or high blood pressure during surgery does not necessarily reflect a nociceptive process. Currently, the available data do not allow the anaesthetist to differentiate between real hemodynamic changes related to nociception and sympathicotonia. This leads to typical management consisting of an increase in the dosage of morphine.

Pupillometry (monitoring the pupillary dilation reflex) is a simple and sensitive clinical approach that can be done during general anesthesia to specifically monitor the nociceptive component. The main objective of monitoring is to achieve a more rational use of opioids. This means optimizing opioid dosing, ensuring safety by monitoring the lowering of opioid dosages intraoperatively without the risk of waking up, and reducing postoperative hyperalgesia. In the context of cardiac surgery, the interpretation of hemodynamic changes could be facilitated by nociception monitoring coupled with anesthesia monitoring (BIS). Reducing opiod doses without changing other clinical parameters could ensure better hemodynamic stability in increasingly fragile patients.

Study Overview

• Status: Completed
• Conditions: Patients Undergoing Cardiac Surgery; Patients With Coronary Artery Bypass Surgery With CEC
• Intervention / Treatment: Drug: Induction and maintenance of anesthesia; Drug: Adaptation of sufentanil doses according to the usual protocol; Drug: Adjustment of sufentanil doses according to pupillometry

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Dijon, France, 2100
    • Chu Dijon Bourgogne

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Person who has given written consent
• Adult patient
• Patient undergoing coronary artery bypass surgery with CEC, with or without valve surgery, by sternotomy.
• ASA <4.

Exclusion Criteria:

• Person not affiliated to the national health insurance system
• Person subject to legal protection (curatorship, guardianship)
• Person who has been deemed mentally incompetent
• Pregnant, parturient or breastfeeding woman
• Adult unable or unwilling to provide consent
• Patient with preoperative cognitive dysfunction (MMS <13) (APPENDIX 6),
• Patient with morphine intolerance,
• Patient on long-term opioid treatment,
• Emergency surgery,
• Eye disease, corneal injury, or wearing contact lenses, a neurological disease that can influence the pupillary reflex,
• Refusal to participate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard group	Drug: Induction and maintenance of anesthesia; The hypnotic agent used is Propofol and the morphine agent used is Sufentanil.; Drug: Adaptation of sufentanil doses according to the usual protocol; At induction the target concentration of sufentanil is 0.5 ng/ml. The sufentanil dose is decided by the anaesthetist, taking into account the operating times (induction, TIO, incision, opening and sternal spacing, CEC, closure), the usual data provided by the monitoring: heart rate, blood pressure, BIS, EtCO2, modification of insufflation pressures.
Experimental: Pupillometry group	Drug: Induction and maintenance of anesthesia; The hypnotic agent used is Propofol and the morphine agent used is Sufentanil.; Drug: Adjustment of sufentanil doses according to pupillometry; At induction, the target concentration of sufentanil is 0.5 ng/ml. The dose of sufentanil is then adjusted according to the dilation reflex obtained with the PPI (Pain Pupillary Index) at predefined times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total dose of sufentanil required per operation	Total dose of sufentanil expressed in µg	Through study completion an average of 2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Publications and helpful links

General Publications

• Berthoud V, Nguyen M, Appriou A, Ellouze O, Radhouani M, Constandache T, Grosjean S, Durand B, Gounot I, Bahr PA, Martin A, Nowobilski N, Bouhemad B, Guinot PG. Pupillometry pain index decreases intraoperative sufentanyl administration in cardiac surgery: a prospective randomized study. Sci Rep. 2020 Dec 3;10(1):21056. doi: 10.1038/s41598-020-78221-5.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2019
• Primary Completion (Actual): October 22, 2019
• Study Completion (Actual): October 22, 2019

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 4, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Actual): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Sufentanil; Dsuvia
• Other Study ID Numbers: BERTHOUD 2018

Drug and device information, study documents

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