Bleeding in Laparoscopic Liver Surgery (MODELS)

Bleeding in Moderate Versus Deep Neuro Muscular Blockade for Laparoscopic Liver Surgery

Blood loss during liver resection surgery affects patients morbidity, short and long-term mortality. Among non-surgical interventions to minimize intraoperative blood loss and perioperative blood products transfusion, maintaining conditions of low central venous pressure is considered as standard of care. In animals undergoing laparoscopic hepatectomy, reducing airway pressures represents a minimally invasive measure to reduce central venous pressure and therefore bleeding from the hepatic vein. Neuromuscular blocking agents are usually administered during anesthesia to facilitate endotracheal intubation and to improve surgical conditions: a deep level of neuromuscular blockade has already been shown to reduce peak airway pressures and plateau airway pressures in non-abdominal procedures. Such airway pressures reduction can potentially limit bleeding from hepatic veins during transection phase in liver surgery. The aim of the present study is to evaluate the impact of deep neuromuscular blockade on bleeding (as a consequence of reduced airway peak pressure and plateau pressure) in hepatic laparoscopic resections. Patients undergoing laparoscopic liver resection will be randomized to achieve, using intravenous Rocuronium, either a deep neuromuscular blockade (post-tetanic count = 0 and/or = 1 and train of four count = 0) or moderate neuromuscular blockade (train of four count ≥ 1 and/or post-tetanic count > 5) during surgery. Neuromuscular blockade measurements will be performed every 15 minutes. The primary endpoint is to assess the total blood loss at the end of the resection phase.

Study Overview

• Status: Terminated
• Conditions: Neuromuscular Blockade; Hepatic Cancer; Intraoperative Bleeding
• Intervention / Treatment: Procedure: Neuromuscular blockade

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients undergoing laparoscopic liver resection
• Patients ≥ 18 years old
• Patients willing to participate to the study and able to validly sign informed consent.

Exclusion Criteria:

• Patients presenting a pre-operative platelet count < 50 x 109/L and/or patients with active pre-operative bleeding
• Patients with planned requirement of continuous neuromuscular blockade monitoring (upon clinical judgement)
• Known hypersensitivity / previous allergic reactions to study medications
• Planned total intra-venous anesthesia technique
• Pregnant or breastfeeding patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deep neuromuscular blockade; During surgery, deep neuromuscular blockade will be achieved with the use of train of four (TOF) monitoring, aiming for a Post-Tetanic Count (PTC) = 0 or PTC = 1 and Train of Four Count (TOFC) = 0. TOF and PTC measurements will be performed every 15 minutes. Boluses of 0,1 mg/kg Rocuronium will be administered if monitored PTC is > 1. Complete neuromuscular blockade reversal at the end of surgery will be achieved with an i.v. bolus of Sugammadex (variable dose according to depth of residual blockade) if TOF ratio is ≤ 0.9. If TOF ratio is > 0.9, pharmacological neuromuscular blockade reversal can be avoided.	Procedure: Neuromuscular blockade; Neuromuscular blockade will be achieved via rocuronium intravenous administration and level will be monitored with train of four/post tetanic count monitoring
Active Comparator: Moderate neuromuscular blockade; During surgery, a moderate neuromuscular blockade will be achieved with the use of train of four (TOF) monitoring. TOF and Post-Tetanic Count (PTC) measurements will be performed every 15 minutes. Boluses of 0,1 mg/kg Rocuronium will be administered if monitored TOF count is ≥ 1 and/or PTC > 5. Complete neuromuscular blockade reversal at the end of surgery will be achieved with an i.v. bolus of Sugammadex (variable dose according to depth of residual blockade) if TOF ratio is ≤ 0.9. If TOF ratio is > 0.9, pharmacological neuromuscular blockade reversal can be avoided.	Procedure: Neuromuscular blockade; Neuromuscular blockade will be achieved via rocuronium intravenous administration and level will be monitored with train of four/post tetanic count monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total intra-operative blood loss	total blood loss at the end of surgery, measured in milliliters (ml) of blood inside the aspirator canister	Postoperative day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of blood product units transfused	number of blood product units transfused from the experimental intervention until hospital discharge	Up to hospital discharge, an average of 5 days
Incidence of surgical revision	incidence of surgical revision	Up to hospital discharge, an average of 5 days
Airway peak and plateau pressures	airway pressures, as indicated by ventilator peak pressure (mmHg) and plateau pressure (mmHg) during surgery	Postoperative day 0
Quality of surgical field	quality of surgical field as assessed by the surgeon with Leiden-Surgical Rating Scale (L-SRS), ranging from 1 (extremely poor conditions) to 5 (optimal conditions), higher scores meaning better outcome	Postoperative day 0
Surgery and hepatic resection time	surgery and hepatic resection time	Postoperative day 0

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day mortality	mortality	day 30
Pulmonary complications at day 30	rate of pulmonary complications	day 30
90-day quality of life	quality of life measured with Euro-Quality of Life - 5 Dimensions scale (EQ-5D-5L), composed of: the EQ-5D-5L descriptive system comprising 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Each level corresponds to 1-digit number expressing the level selected for that dimension; the EQ VAS corresponding to a 20 cm vertical, visual analogue scale ranging from 'the best health you can imagine' to 'the worst health you can imagine'	day 90

Collaborators and Investigators

• Sponsor: Università Vita-Salute San Raffaele
• Investigators: Study Director: Alberto Zangrillo, Prof., IRCCS San Raffaele Scientific Institute; Study Chair: Luigi Beretta, Prof., IRCCS San Raffaele Scientific Institute; Principal Investigator: Raffaella Reineke, MD, IRCCS San Raffaele Scientific Institute

Publications and helpful links

General Publications

• Blobner M, Frick CG, Stauble RB, Feussner H, Schaller SJ, Unterbuchner C, Lingg C, Geisler M, Fink H. Neuromuscular blockade improves surgical conditions (NISCO). Surg Endosc. 2015 Mar;29(3):627-36. doi: 10.1007/s00464-014-3711-7. Epub 2014 Aug 15.
• Ibrahim S, Chen CL, Lin CC, Yang CH, Wang CC, Wang SH, Liu YW, Yong CC, Concejero A, Jawan B, Cheng YF. Intraoperative blood loss is a risk factor for complications in donors after living donor hepatectomy. Liver Transpl. 2006 Jun;12(6):950-7. doi: 10.1002/lt.20746.
• Taketomi A, Kitagawa D, Itoh S, Harimoto N, Yamashita Y, Gion T, Shirabe K, Shimada M, Maehara Y. Trends in morbidity and mortality after hepatic resection for hepatocellular carcinoma: an institute's experience with 625 patients. J Am Coll Surg. 2007 Apr;204(4):580-7. doi: 10.1016/j.jamcollsurg.2007.01.035.
• Yang T, Zhang J, Lu JH, Yang GS, Wu MC, Yu WF. Risk factors influencing postoperative outcomes of major hepatic resection of hepatocellular carcinoma for patients with underlying liver diseases. World J Surg. 2011 Sep;35(9):2073-82. doi: 10.1007/s00268-011-1161-0.
• Moggia E, Rouse B, Simillis C, Li T, Vaughan J, Davidson BR, Gurusamy KS. Methods to decrease blood loss during liver resection: a network meta-analysis. Cochrane Database Syst Rev. 2016 Oct 31;10(10):CD010683. doi: 10.1002/14651858.CD010683.pub3.
• Honda G, Kurata M, Okuda Y, Kobayashi S, Tadano S, Yamaguchi T, Matsumoto H, Nakano D, Takahashi K. Totally laparoscopic hepatectomy exposing the major vessels. J Hepatobiliary Pancreat Sci. 2013 Apr;20(4):435-40. doi: 10.1007/s00534-012-0586-7.
• Kobayashi S, Honda G, Kurata M, Tadano S, Sakamoto K, Okuda Y, Abe K. An Experimental Study on the Relationship Among Airway Pressure, Pneumoperitoneum Pressure, and Central Venous Pressure in Pure Laparoscopic Hepatectomy. Ann Surg. 2016 Jun;263(6):1159-63. doi: 10.1097/SLA.0000000000001482.
• Oh SK, Kwon WK, Park S, Ji SG, Kim JH, Park YK, Lee SY, Lim BG. Comparison of Operating Conditions, Postoperative Pain and Recovery, and Overall Satisfaction of Surgeons with Deep vs. No Neuromuscular Blockade for Spinal Surgery under General Anesthesia: A Prospective Randomized Controlled Trial. J Clin Med. 2019 Apr 12;8(4):498. doi: 10.3390/jcm8040498.

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2020
• Primary Completion (Actual): September 20, 2023
• Study Completion (Actual): September 20, 2023

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 25, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: bleeding; rocuronium; neuromuscular blockade; liver surgery; airway pressure
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intraoperative Complications; Liver Neoplasms; Hemorrhage; Blood Loss, Surgical
• Other Study ID Numbers: MODELS/22/OSR

Drug and device information, study documents

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