MODELS: Bleeding in Laparoscopic Liver Surgery

Sponsor

Università Vita-Salute San Raffaele (Other)

Overall Status

Recruiting

CT.gov ID

NCT04609410

Collaborator

(none)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

5.4

Patients Per Site Per Month

Study Details

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	N/A

Study Design

Study Type:

Interventional

Anticipated 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 :

Oct 30, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 1, 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

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

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

Secondary Outcome Measures

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

Other Outcome Measures

30-day mortality [day 30]
mortality
Pulmonary complications at day 30 [day 30]
rate of pulmonary complications
90-day quality of life [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Ospedale San Raffaele	Milano		Italy	20132

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