Bleeding in Laparoscopic Liver Surgery (MODELS)

• ClinicalTrials.gov Identifier: NCT04609410
• Recruitment Status: Recruiting
• First Posted: October 30, 2020
• Last Update Posted: December 22, 2021
• Sponsor: Università Vita-Salute San Raffaele
• Information provided by (Responsible Party): Giovanni Landoni, Università Vita-Salute San Raffaele

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neuromuscular Blockade; Intraoperative Bleeding; Hepatic Cancer	Procedure: Neuromuscular blockade	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Bleeding in Moderate Versus Deep Neuro Muscular Blockade for Laparoscopic Liver Surgery
• Actual Study Start Date: October 30, 2020
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Total intra-operative blood loss [ Time Frame: Postoperative day 0 ]
   total blood loss at the end of surgery, measured in milliliters (ml) of blood inside the aspirator canister

Secondary Outcome Measures :

1. Number of blood product units transfused [ Time Frame: Up to hospital discharge, an average of 5 days ]
   number of blood product units transfused from the experimental intervention until hospital discharge
2. Incidence of surgical revision [ Time Frame: Up to hospital discharge, an average of 5 days ]
   incidence of surgical revision
3. Airway peak and plateau pressures [ Time Frame: Postoperative day 0 ]
   airway pressures, as indicated by ventilator peak pressure (mmHg) and plateau pressure (mmHg) during surgery
4. Quality of surgical field [ Time Frame: Postoperative day 0 ]
   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
5. Surgery and hepatic resection time [ Time Frame: Postoperative day 0 ]
   surgery and hepatic resection time

Other Outcome Measures:

1. 30-day mortality [ Time Frame: day 30 ]
   mortality
2. Pulmonary complications at day 30 [ Time Frame: day 30 ]
   rate of pulmonary complications
3. 90-day quality of life [ Time Frame: day 90 ]

   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'

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Giovanni Landoni, Prof.; +39022643 ext 6158; landoni.giovanni@hsr.it

Locations

Italy

Ospedale San Raffaele; Recruiting

Milano, Italy, 20132

Contact: Giovanni Landoni, Prof +39022643 ext 6151 landoni.giovanni@hsr.it

Principal Investigator: Giovanni Landoni, Prof.

Principal Investigator: Luigi Beretta, Prof.

Principal Investigator: Alberto Zangrillo, Prof.

Sub-Investigator: Roberta Meroni, MD

Sub-Investigator: Matteo Marzaroli, MD

Principal Investigator: Raffaella Reineke, MD

Sponsors and Collaborators

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

More Information

Publications:

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.

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.

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:CD010683. Review.

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.

Blobner M, Frick CG, Stäuble 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.

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). pii: E498. doi: 10.3390/jcm8040498.

• Responsible Party: Giovanni Landoni, MD, Associate Professor, Università Vita-Salute San Raffaele
• ClinicalTrials.gov Identifier: NCT04609410
• Other Study ID Numbers: MODELS/22/OSR
• First Posted: October 30, 2020
• Last Update Posted: December 22, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Giovanni Landoni, Università Vita-Salute San Raffaele:

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

Additional relevant MeSH terms:

Liver Neoplasms; Hemorrhage; Blood Loss, Surgical; Pathologic Processes; Intraoperative Complications; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases