Prevention of Organ Dysfunction and Mortality by Monitoring the Administration of Opioids and Hypnotics in Patients at High Postoperative Risk (OPTI-TWO)

Prevention of Organ Dysfunction and Mortality by Monitoring the Administration of Opioids and Hypnotics in Patients at High Postoperative Risk: the Opti-Two Study. A Multi-center Controlled Randomized Study.

Intraoperative hypotension is a common situation. It increases postoperative morbidity and mortality, especially in patients at high postoperative risk undergoing high-risk surgery. Intraoperative hypotension is partly related to anesthesia, and mainly to the combined, dose-dependent, synergistic effect of hypnotics and opioids. Monitoring sedation and monitoring analgesia reduce intraoperative consumption of each anesthetic agent. To date, the beneficial effect of combined sedation and analgesia monitoring on the reduction of intraoperative hypotension has only been found in one study, involving major abdominal surgery. Up to now, no study has been designed to demonstrate the benefit of monitoring the two components of anesthesia on postoperative organ dysfunction and mortality.

The study propose to evaluate the relevance of a combined optimization of hypnotic and opioid agents on the most frequently encountered dysfunctions related to intraoperative hypotension.

Study Overview

• Status: Recruiting
• Conditions: Sedation and Analgesia Monitoring
• Intervention / Treatment: Procedure: anesthesia guided by sedation and analgesia monitoring; Procedure: anesthesia performed according only to the clinical judgment of the anesthetist as usual practice

• Study Type: Interventional
• Enrollment (Estimated): 1132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David CHARIER, MD, PhD; Phone Number: +33.4.77.82.85.65; Email: david.charier@chu-st-etienne.fr
• Study Contact Backup: Name: Marlène BONNEFOI, CRA; Phone Number: +33 (0)477828822; Email: marlene.bonnefoi@chu-st-etienne.fr

Study Locations

• France
  • Amiens, France, 80090
    • Recruiting
    • Clinique Victor Pauchet
    • Principal Investigator: Pierre HUETTE, MD
  • Amiens, France, 80054
    • Recruiting
    • CHU d'Amiens Picardie
    • Principal Investigator: Hervé DUPONT, MD PhD
  • Besançon, France, 25030
    • Not yet recruiting
    • CHRU De Besancon
    • Principal Investigator: Guillaume BESCH, MD PhD
  • Bordeaux, France, 33300
    • Recruiting
    • Polyclinique Bordeaux Nord Aquitaine
    • Principal Investigator: Philippe RICHEBE, MD, PhD
  • Clermont-Ferrand, France, 63000
    • Not yet recruiting
    • CHU Clermont-Ferrand
    • Principal Investigator: Bertille PAQUETTE, MD
  • Grenoble, France, 38700
    • Not yet recruiting
    • CHU de Grenoble
    • Principal Investigator: Pierre BOUZAT, MD PhD
  • Lille, France, 59037
    • Recruiting
    • CHU de LILLE
    • Principal Investigator: Gilles LEBUFFE, MD PhD
  • Marseille, France, 13015
    • Not yet recruiting
    • APHM - Centre Hôpital Marseille Nord
    • Principal Investigator: Marc LEONE, MD PhD
  • Nantes, France, 44093
    • Not yet recruiting
    • CHU de Nantes
    • Principal Investigator: Raphaël CINOTTI, MD PhD
  • Nîmes, France, 30000
    • Recruiting
    • CHU de Nîmes
    • Sub-Investigator: Yann GRICOURT, MD
    • Principal Investigator: Philippe CUVILLON, MD PhD
  • Paris, France, 75018
    • Recruiting
    • Hopital Bichat Claude Bernard
    • Principal Investigator: Aurélie GOUEL, MD
  • Pierre-Bénite, France, 69495
    • Recruiting
    • CHU Lyon Sud
    • Principal Investigator: Arnaud FRIGGERI, MD, PhD
  • Poitiers, France, 86000
    • Recruiting
    • CHU de Poitiers
    • Principal Investigator: Matthieu BOISSON, MD
  • Saint-Dié, France, 88100
    • Not yet recruiting
    • Hôpital Saint Charles
    • Principal Investigator: Claude MEISTELMAN, MD, PhD
  • Saint-Etienne, France, 42100
    • Recruiting
    • CHU St-Etienne
    • Sub-Investigator: Serge MOLLIEX, MD, PhD
    • Principal Investigator: David CHARIER, MD, PhD
  • Toulouse, France, 31059
    • Recruiting
    • CHU de Toulouse
    • Principal Investigator: Fabrice FERRE, MD PhD
  • Villejuif, France, 94800
    • Not yet recruiting
    • Institut Gustave Roussy
    • Principal Investigator: Cyrus MOTAMED, MD
  • Villeurbanne, France, 69100
    • Recruiting
    • Médipole Lyon Villeurbanne
    • Principal Investigator: Vincent COLLANGE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients affiliated to the French Social Security;
• informed and signed consent to participating in the study;
• planned postoperative hospitalization > 48 hours;

• patients over 75 years of age with at least one of the following postoperative risk factors:

  • ischemic coronary disease;
  • history of compensated or prior heart failure;
  • stroke;
  • significant arrhythmias: fibrillation or auricular flutter with ventricular response > 100/minute, multiform QRS complex) or cardiac conduction abnormalities (trifascicular block, auriculoventricular block of the second or third degree);
  • peripheral vascular disease;
  • chronic obstructive pulmonary disease;
  • chronic respiratory failure;
  • renal insufficiency, defined by a creatinine > 175 µmol.l-1 (2 mg.dl-1);
  • insulin therapy for diabetes;
  • active cancer;
  • chronic alcohol abuse;
  • dementia.
• elective or emergency high-risk surgery under general anesthesia with a combination of hypnotic and opioid, and intubation or placement of a supraglottic airway control device

Non inclusion criteria:

• Patients who meet one or more of the preoperative following criteria will not be included:
• acute heart failure or acute myocardial infarction;
• complete arrhythmia due to atrial fibrillation;
• acute respiratory failure or pneumonia;
• septic shock;
• acute stroke;
• cardiac surgery;
• open chest surgery;
• opioid free anesthesia;
• intraoperative ketamine at a dose > 0.25 mg.kg-1; > 0.25 mg/kg or or intravenous electric syringe
• lidocaine or dexmedetomidine by continuous infusion;
• refusal to participate in the study;
• patient under guardianship, conservatorship, or unable to understand the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group	Procedure: anesthesia guided by sedation and analgesia monitoring; Anesthesia guided by sedation and analgesia monitoring The level of sedation will be monitored by; Monitoring System BIS™ : Bispectral index (BIS) between 45 and 60 AND Suppression Ratio (SR) at 0;; or SedLine® Sedation Monitor : Patient State Index (PSi) between 25 and 50;; or Entropy Sensor™: State entropy (SE) between 45 and 60 AND Burst Suppression Ratio (BSR) at 0; and the level of nociception by : Nociception monitor PMD-200® : Nociception Level (NoL) between 10 and 25.
Placebo Comparator: Control Group	Procedure: anesthesia performed according only to the clinical judgment of the anesthetist as usual practice; Administration of anesthesia will be performed according to the clinical judgment of the anesthetist as usual practice without sedation and analgesia monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death		Day 30
Postoperative acute kidney injury (PO-AKI)	The PO-AKI will be defined as an increase to 1.5 times the reference level, or as more than 0.3 mg.dl-1 (i.e. 26.5 µmol.l-1) between the last preoperative value and the maximal value observed after surgery, or urine volume < 0.5 ml.kg-1.h-1 for 6 hours, according to the recommendations of the Acute Kidney Injury Network	Day 30
cardiovascular complication	postoperative myocardial infarction, acute heart failure, acute/non pre-existing atrial fibrillation or flutter, cardiac arrest with successful resuscitation, coronary revascularisation	Day 30
neurological complication	Stroke or transient ischemic attack	Day 30
Post-operative delirium (POD)	Post-operative delirium (POD) will be evaluated using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM), appropriated and validated for the assessment of delirium in the postoperative period, or the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) for the intubated patients.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
doses of hypnotics administered		during surgery
doses opioids administered;		during surgery
number and duration of hypotensive periods	an hypotensive event will be defined as a Mean Arterial Pressure (MAP) ≤ 65 mmHg.	during surgery
time spent within the desired range of sedation:	Monitoring System BIS™ : Bispectral index (BIS) between 45 and 60 AND Suppression Ratio (SR) at 0 or SedLine® Sedation Monitor : Patient State Index (PSI) between 25 and 50 AND Suppression Ratio (SR) at 0 or Entropy Sensor™: State entropy (SE) between 45 and 60 AND Burst Suppression Ratio (BSR) at 0 The anesthetist will have access to the value of sedation monitoring in the "intervention" group; these data will be recorded but not available to the anesthetist in the "control" group: they will be analyzed at the end of the study to answer this point.	during surgery
time spent within the desired range of analgesia:	Nociception monitor PMD-200® : Nociception Level (NOL) between 10 and 25. The anesthetist will have access to the value of sedation and analgesia monitoring in the "intervention" group; these data will be recorded but not available to the anesthetist in the "control" group: they will be analyzed at the end of the study to answer this point.	during surgery
doses of vasopressive amines (ephedrine or norepinephrine) administered;		during surgery
pain ≥ 5 as assessed with the Visual Analogic Scale (VAS)	VAS 0 to 10 [0 corresponds to no pain - 10 corresponds to maximum pain]	At 48 Hours after surgery
dose of opioid administered;		At 48 Hours after surgery
incidence of awareness and recall during anesthesia (explicit memory).		At 48 Hours after surgery
acute respiratory failure or Acute Respiratory Distress Syndrome (ARDS)		Day 30
duration of stay in Intensive Care Unit (ICU);		Day 30
rate of unexpected ICU admission, or readmission		Day 30
duration of hospital stay;		Day 30
early hospital readmission rate		Day 30

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Direction Générale de l'Offre de Soins
• Investigators: Principal Investigator: David CHARIER, MD, PhD, CHU de Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 7, 2023

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 20PH283; ANSM (Other Identifier: 2026-A00172-49)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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