High Versus Low Pneumoperitoneum PressUre for Parenchymal Transection in Minimally Invasive Major Liver Surgery (PPULS)

High Versus Low Pneumoperitoneum PressUre for Parenchymal Transection in Minimally Invasive Major Liver Surgery - a Non-inferiority, Multicenter, Randomized, Controlled Trial

Minimally invasive techniques in liver surgery gain popularity as they facilitate postoperative recovery while achieving comparable oncologic outcomes to the open approach. No consensus on the application of pneumoperitoneum pressure in minimal invasive liver resections (MILR) has been reached yet, as prospective clinical studies are scarce. The positive pressure of the CO2 pneumoperitoneum reduces intraoperative blood loss during MILR alongside the development of new transection devices and advancements in inflow control. Low-pressure pneumoperitoneum on the other hand has been shown to decrease postoperative pain scores and analgesic consumption in comparison to standard pneumoperitoneum, and international guidelines recommend the application of "the lowest intra-abdominal pressure allowing adequate exposure of the operative field rather than a routine pressure". Nevertheless, evidence for the application of low-pressure pneumoperitoneum is only moderate to low, requiring additional studies to better define its safety. To address this oxymoron, the investigators conduct a randomized non-inferiority trial to investigate the effect of low in comparison to high-pressure pneumoperitoneum during the transection phase of major MILR on intraoperative blood loss while also evaluating the risk of embolic complications.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Surgery; Minimal Invasive Surgery; Major Liver Resection
• Intervention / Treatment: Procedure: High Pressure Pneumoperitoneum; Procedure: Low Pressure Pneumoperitoneum

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arianeb Mehrabi, Professor; Phone Number: 004962215636223; Email: arianeb.mehrabi@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• age equal or older than 18 years and
• capacity of consent and
• planned elective conventional laparoscopic or da Vinci-assisted major liver resection or resections near the liver hilum or the hepatic venous vasculature. Major liver resections are defined as the resection of 3 liver segments or more (right and left partial hepatectomies, extended right and left hepatectomies, liver resections of 3 or more segments). Right posterior sectionectomies and mesohepatectomies of ≥2 liver segments are considered resections in proximity to the liver hilum or hepatic venous vasculature.

Exclusion Criteria:

• the participation in another trial with interference of intervention and outcome of this study,
• being a woman who is pregnant or breast-feeding or planning to become pregnant,
• American Society of Anesthesiologists (AS) score >3,
• language barrier,
• any contraindication to a minimal invasive surgical approach or intolerance to pneumoperitoneum
• a patent foramen ovale (PFO) or any other structural cardiac defect that facilitates paradoxical gas embolisms,
• diagnosis of neuromuscular disease, heart failure NYHA > class II or chronic obstructive pulmonary disease (COPD)
• being on oral anticoagulation therapy other than Aspirin 100mg daily or any other condition known to increase the risk of bleeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High Pressure Pneumoperitoneum; Intraperitoneal insufflation pressures (IIP) during the parenchymal transection phase of liver resection will be different between the two study groups. Baseline IIP of the surgical procedure will be ≤10 mmHg. IIP will be elevated to ≥14 mmHg in the intervention group during the parenchymal transection phase of liver resection.	Procedure: High Pressure Pneumoperitoneum; The objective of this trial is to determine whether the maintenance of a low intraperitoneal insufflation pressure (IIP) of ≤10 mmHg during the parenchymal transection phase of conventional and robotic-assisted laparoscopic liver resection is non-inferior to a higher IIP of ≥14 mmHg in terms of intraoperative blood loss, gas embolisms, perioperative morbidity, and mortality.
Sham Comparator: Low Pressure Pneumoperitoneum; Intraperitoneal insufflation pressures (IIP) during the parenchymal transection phase of liver resection will be different between the two study groups. Baseline IIP of the surgical procedure will be ≤10 mmHg. IIP will be maintained at ≤10 mmHg in the control group.	Procedure: Low Pressure Pneumoperitoneum; The objective of this trial is to determine whether the maintenance of a low intraperitoneal insufflation pressure (IIP) of ≤10 mmHg during the parenchymal transection phase of conventional and robotic-assisted laparoscopic liver resection is non-inferior to a higher IIP of ≥14 mmHg in terms of intraoperative blood loss, gas embolisms, perioperative morbidity, and mortality.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Intraoperative blood loss	From the time of randomization until the completion of the liver surgery, assessed up to 24 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of CO2 embolisms	Incidence of CO2 embolisms in the right atrioventricular system detected by intraoperative transesophageal echocardiography	intraoperative
Morbidity rate	Postoperative complication rate	90 days postoperative
Mortality rate	Postoperative mortality	90 days postoperative

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Collaborators: University of Ulm; University Hospital Dresden; Groeninge Hospital, Kortrijk, Belgium

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Pneumoperitoneum; intraoperative blood loss; minimal-invasive liver surgery
• Additional Relevant MeSH Terms: Digestive System Diseases; Peritoneal Diseases; Pneumoperitoneum
• Other Study ID Numbers: S-729/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon reasonable request, the data generated by the current research that supports our future article, would be made available as soon as possible, wherever legally and ethically possible.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No