Bleeding in Laparoscopic Liver Surgery

NCT04609410 | Terminated

• 1 other identifier: MODELS/22/OSR
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuromuscular Blockade; Intraoperative Bleeding; Hepatic Cancer

Keywords

liver surgery; bleeding; neuromuscular blockade; rocuronium; airway pressure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of blood product units transfused

  Up to hospital discharge, an average of 5 days

• Incidence of surgical revision

  Up to hospital discharge, an average of 5 days

• Airway peak and plateau pressures

  Postoperative day 0

• Quality of surgical field

  Postoperative day 0

• Surgery and hepatic resection time

  Postoperative day 0

Other Outcomes (3)

• 30-day mortality

  day 30

• Pulmonary complications at day 30

  day 30

• 90-day quality of life

  day 90

Study Arms (2)

Deep neuromuscular blockade

EXPERIMENTAL

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

Moderate neuromuscular blockade

ACTIVE COMPARATOR

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

Interventions

Neuromuscular blockade PROCEDURE

Neuromuscular blockade will be achieved via rocuronium intravenous administration and level will be monitored with train of four/post tetanic count monitoring

Deep neuromuscular blockade; Moderate neuromuscular blockade

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (1)

Ospedale San Raffaele

Milan, 20132, Italy

Location

Related Publications (8)

• 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.

  PMID: 16721773 BACKGROUND

• 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.

  PMID: 17382216 BACKGROUND

• 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.

  PMID: 21656309 BACKGROUND

• 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.

  PMID: 27797116 BACKGROUND

• 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.

  PMID: 23269462 BACKGROUND

• 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.

  PMID: 26595124 BACKGROUND

• 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.

  PMID: 25125097 BACKGROUND

• 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.

  PMID: 31013693 BACKGROUND

MeSH Terms

Conditions

Blood Loss, Surgical; Liver Neoplasms; Hemorrhage

Interventions

Neuromuscular Blockade

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Anesthesia and Analgesia; Investigative Techniques

Study Officials

• Alberto Zangrillo, Prof.

  IRCCS San Raffaele Scientific Institute

  STUDY DIRECTOR

• Luigi Beretta, Prof.

  IRCCS San Raffaele Scientific Institute

  STUDY CHAIR

• Raffaella Reineke, MD

  IRCCS San Raffaele Scientific Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Associate Professor

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: October 30, 2020
• Study Start: October 30, 2020
• Primary Completion: September 20, 2023
• Study Completion: September 20, 2023
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

IT (1)