Prevention of Organ Dysfunction and Mortality by Monitoring the Administration of Opioids and Hypnotics in Patients at High Postoperative Risk

Official title

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.

Overview

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.

Interventions

• 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.
• 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

Primary outcome measures

• death [Time frame: Day 30]
• Postoperative acute kidney injury (PO-AKI) [Time frame: Day 30]
• cardiovascular complication [Time frame: Day 30]
• neurological complication [Time frame: Day 30]
• Post-operative delirium (POD) [Time frame: Day 30]

Secondary outcome measures (12)

• doses of hypnotics administered [Time frame: during surgery]
• doses opioids administered; [Time frame: during surgery]
• number and duration of hypotensive periods [Time frame: during surgery]
• time spent within the desired range of sedation: [Time frame: during surgery]
• time spent within the desired range of analgesia: [Time frame: during surgery]
• doses of vasopressive amines (ephedrine or norepinephrine) administered; [Time frame: during surgery]
• pain ≥ 5 as assessed with the Visual Analogic Scale (VAS) [Time frame: At 48 Hours after surgery]
• dose of opioid administered; [Time frame: At 48 Hours after surgery]
• incidence of awareness and recall during anesthesia (explicit memory). [Time frame: At 48 Hours after surgery]
• acute respiratory failure or Acute Respiratory Distress Syndrome (ARDS) [Time frame: Day 30]
• duration of stay in Intensive Care Unit (ICU); [Time frame: Day 30]
• rate of unexpected ICU admission, or readmission [Time frame: Day 30]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

France · 18 centers

• Chu D'Amiens Picardie — Amiens
• Clinique Victor Pauchet — Amiens
• Chru de Besancon — Besançon
• Polyclinique Bordeaux Nord Aquitaine — Bordeaux
• Chu Clermont-Ferrand — Clermont-Ferrand
• Chu de Grenoble — Grenoble
• Chu de Lille — Lille
• APHM - Centre Hôpital Marseille Nord — Marseille
• … and 10 more centers

Identifiers

NCT: NCT05893030 · 20PH283 · ANSM

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗