Cardiac Output Optimization on Postoperative Complications in Major Hepatic Surgery (OPTILIVER)

Effect of an Individualized Protocol Based on Cardiac Output Optimization Guided by Dynamic Indices of Preload Responsiveness Monitoring on Postoperative Complications in Major Hepatic Surgery for Primary or Secondary Liver Cancer

Major hepatectomies are high-risk surgeries offered more and more frequently for the curative treatment of primary or secondary liver cancer, and for complex cases, representing a real challenge for medical teams. The 1st peroperative phase of "hepatic resection" requires a minimum supply of filling fluids to limit perioperative bleeding (Low Central Venous Pressure). However this strategy exposes the risk of organ hypoperfusion due to low cardiac flow, secondary to hypovolaemia, which may lead to ischemic situations favoring the onset of postoperative complications. On the other hand, the hemodynamic management of the 2nd peroperative phase "post hepatic resection" is marked by the need to correct this hypoperfusion by optimizing cardiac output by suitable vascular filling.

The major challenge is thus to restore cardiac output by refilling without excess, by correcting the hypovolemia that arose during the "post resection of the hepatic parenchyma" phase.

Our hypothesis is that an individualized protocol for optimizing intraoperative cardiac flow by guided vascular filling during the "post hepatic resection" phase is accompanied by a reduction in postoperative complications in patients operated on for major hepatic surgery.

Study Overview

• Status: Recruiting
• Conditions: Primary or Metastatic Hepatic Adenocarcinoma
• Intervention / Treatment: Behavioral: Optimization of cardiac flow by base water-electrolyte supply; Behavioral: Control arm

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carine Feuillet, PhD; Phone Number: +33 4 91 22 34 48; Email: drci.up@ipc.unicancer.fr
• Study Contact Backup: Name: Dominique GENRE, MD; Phone Number: +33 4 91 22 37 78; Email: drci.up@ipc.unicancer.fr

Study Locations

• France
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
    • Contact: GOUARNE Caroline, PhD; Phone Number: + 33 4 91 22 37 78; Email: drci.up@ipc.unicancer.fr
    • Contact: GENRE Dominique, MD; Phone Number: + 33 4 91 22 37 78; Email: drci.up@ipc.unicancer.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years old,
2. Signature of consent,
3. Any patient scheduled for major hepatic surgery (≥ 3 segments) scheduled by laparotomy, for primary hepatic cancer or secondary metastases,
4. Affiliation to the ''National security'' regimen or beneficiary of this regimen.

Exclusion Criteria:

1. Emergency surgery,
2. Cirrhosis: depending on availability of CT and / or MRI imaging results, clinical examination, Biology (PT, Bilirubin) or histological results (preoperative biopsies in healthy liver)
3. Portal hypertension: depending on availability of imaging data, history of esophageal varices
4. Contraindication to fitting a tool for monitoring dynamic hemodynamic indices (case of esophageal varices for esophageal Doppler for example),
5. Benign tumors,
6. Associated procedures programmed at the same operating time (excluding hepatic surgery): programmed associated digestive resection (colorectal or pancreatic),
7. Laparoscopy,
8. Liver transplantation,
9. Woman pregnant or likely to be (without effective contraception) or breastfeeding,
10. Person in an emergency situation, adult person subject to a legal protection measure (adult under guardianship, guardianship or legal protection), or unable to express consent,
11. Inability to undergo medical monitoring of the trial for geographical, social or psychological reasons.

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: Optimization of cardiac flow by base water-electrolyte supply; Optimization of cardiac flow by base water-electrolyte supply of 1 ml / kg / h by Ringer Lactate® and faced with any decrease of more than 10% of the VES compared to the reference VES, achievement of an optimization of the preload by administration of 250 ml of Ringer Lactate® with renewal until correction of the VES.	Behavioral: Optimization of cardiac flow by base water-electrolyte supply; optimization of cardiac flow by base water-electrolyte supply of 1 ml / kg / h by Ringer Lactate® and faced with any decrease of more than 10% of the VES compared to the reference VES, achievement of an optimization of the preload by administration of 250 ml of Ringer Lactate® with renewal until correction of the VES.
Other: Control arm; Increase basic hydro-electrolyte supply of 6 ml / kg / h by Ringer Lactate® and 1: 1 blood loss compensation by crystalloids of the same nature.	Behavioral: Control arm; increase basic hydro-electrolyte supply of 6 ml / kg / h by Ringer Lactate® and 1: 1 blood loss compensation by crystalloids of the same nature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the cardiac output optimization strategy on the occurrence of postoperative complications	Assessment of the impact of an individualized protocol for optimizing perioperative cardiac flow guided by monitoring of dynamic indices of preload dependence during the post-hepatic resection phase on the occurrence of postoperative complications in major hepatic surgery, for primary hepatic cancer or metastatic origin. We retain as the primary endpoint, the percentage of patients with at least one postoperative complication regardless of the grade in the Dindo-Clavien classification.	From Day 1 to Day 30 post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of grade III-IV postoperative complication in the Dindo-Clavien classification	To determine whether the strategy for optimizing cardiac output guided by dynamic dependence preload indices is associated with a difference in the incidence of occurrence of at least one grade III-IV postoperative complication in the Dindo-Clavien classification	From Day 1 to Day 30 post-surgery
Evaluation of length of stay in the hospital	To determine whether the cardiac output optimization strategy guided by the dynamic dependence preload indices is associated with a difference in the length of stay in the Continuing Care Unit, intensive care unit or length of hospital stay or on re-hospitalization rates	From Day 1 to Day 30 post-surgery
Evaluation of mortality	To determine whether the cardiac output optimization strategy guided by the dynamic dependence preload indices is associated with a difference in mortality at D30 and D90	On Day 1, Day 30 and Day 90 post-surgery
Evaluation occurrence of organ failures	To determine whether the cardiac output optimization strategy guided by dynamic dependence preload indices has an impact on the occurrence of organ failures, which will be evaluated by the SOFA score per device from Day 1 to Day 7 postoperatively	From Day 1 to Day 7 post-surgery
Evaluation of hemodynamic parameters	To determine whether the cardiac output optimization strategy guided by dynamic dependence preload indices is associated with a difference on hemodynamic parameters	From Day 0 to Day 1 post-surgery

Collaborators and Investigators

• Sponsor: Institut Paoli-Calmettes
• Investigators: Principal Investigator: Jean-Manuel de Guibert, MD, Institut Paoli-Calmettes

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2022
• Primary Completion (Estimated): March 15, 2026
• Study Completion (Estimated): May 15, 2026

Study Registration Dates

• First Submitted: November 27, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: OPTILIVER TRIAL-IPC 2018-022

Drug and device information, study documents

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