Effect of Deep Versus Moderate Neuromuscular Block During Sevoflurane Anesthesia on Intraoperative Surgical Conditions. (BLISS4)

Effect of Deep Versus Moderate Neuromuscular Block During Sevoflurane Anesthesia on Intraoperative Surgical Conditions in Patients Undergoing Laparoscopic Renal Surgery

A deep neuromuscular block (NMB) is often associated with improved surgical conditions especially in laparoscopic surgery. We previously showed that deep NMB is superior to a moderate NMB under propofol anesthesia. However, this may not apply to sevoflurane anesthesia and sevoflurane by itself produces some degree of muscle relaxation. We therefore plan to investigate the effect of deep NMB on surgical conditions under sevoflurane anesthesia maintenance.

Study Overview

• Status: Completed
• Conditions: Surgical Conditions
• Intervention / Treatment: Drug: Deep neuromuscular block

Detailed Description

Neuromuscular blocking agents (NMBAs) are routinely administered during general anaesthesia to facilitate endotracheal intubation and to optimize surgical conditions. Increasing data suggest superiority of a deep neuromuscular block (defined by a post-tetanic count of 1-2 twitches) in creating optimal working conditions for the surgical team. However, it is unknown whether other aspects of the anaesthetic technique, most notably the choice of anaesthetic (for example, total intravenous versus inhalational anaesthesia), influence the relationship between the depth of the neuromuscular block and surgical conditions, particularly in laparoscopic surgery. Volatile anaesthetics are known for their ability to potentiate neuromuscular blocking agents an effect that is less existent with propofol. We previously showed that surgical working conditions in laparoscopic surgery during propofol anaesthesia are highly reliant on the depth of the neuromuscular block. Whether such a relationship also exists for inhalational anaesthetics, is unknown. To investigate this, we conducted a prospective, randomized, double blind study in which patients scheduled for laparoscopic renal surgery were randomized to receive either a moderate or a deep neuromuscular block during sevoflurane anaesthesia. The primary outcome was the intraoperative surgical condition assessed by a surgeon using the validated Leiden-Surgical Rating Scale. We hypothesized that the use of an inhalational anaesthetic would obviate the need for a deep NMB due to its intrinsic muscle relaxant potentiating properties to produce optimal working conditions.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with renal or prostatic disease who are will undergo an elective laparoscopic renal surgical procedure or laparoscopic prostatectomy;
• American Society of Anesthesiologists (ASA) class I-III
• > 18 years of age;
• Ability to give oral and written informed consent.

Exclusion Criteria:

• Known or suspected neuromuscular disorders impairing neuromuscular function;
• Allergies to muscle relaxants, anesthetics or narcotics;
• A (family) history of malignant hyperthermia;
• Women who are or may be pregnant or are currently breast feeding;
• Renal insufficiency, as defined by glomerular filtration rate < 30 ml/h creatinine.
• Previous retroperitoneal surgery at the site of the current surgery.
• Body mass index > 35 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Moderate neuromuscular block; Subjects will receive moderate neuromuscular block, aimed at 1-2 twitches train of four
EXPERIMENTAL: Deep neuromuscular block; Subjects will receive deep neuromuscular block, aimed at 1-2 twitches post tetanic count	Drug: Deep neuromuscular block; Deep neuromuscular block will be achieved with high dose rocuronium to achieve a depth of 1-2 twitches post tetanic count; Other Names: high dose rocuronium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leiden Surgical Rating Scale	During the on average 3 hour procedure, the surgical condition will be scored by the surgeon using a 5-point surgical rating scale at 15 minute intervals(1: poor ; 5: optimal) Mean and standard deviation of the average of all leiden surgical rating scale will be reported.	during surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Measurements and Outcomes; Pain Scores	Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -mean pain scores (numeric rating scale; 0 no pain - 10 worst pain imaginable)	During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals
Intraoperative Hemodynamic Conditions	Perioperative average blood pressure will be reported, mean blood pressure ranging from 65 tot 110 millimeters mercury is considered normal	Perioperative measurements at 15 minute interval (on average during 3 hours)
Postoperative Measurements and Outcomes; Sedation Levels	Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -ramsay sedation levels (0 = normal alertness, eyes open, responds normal to command 1 = drowsy with open eyes, closed and opened on command 2 = drowsy with closed eyes, opened in response to light auditory stimulus 3 = eyes closed, opened in response to rubbing the shoulder or a loud auditory stimulus 4 = eyes closed and opened only briefly in response to touching the subject 5 = eyes closed, unarousable by touch, aroused by painful 6 = unarousable by pain)	During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals
Postoperative Measurements and Outcomes; Saturation	Postoperative measurements and outcomes of during PACU stay, all scores are reported as means and standard deviation of the average over the follow up period -blood oxygen saturation in percent levels between 95-100 are considered normal	During post-anesthetic care unit stay (average stay 2 hours) at 15 minute intervals
Intraoperative Nociception Level	The median and full range of the average nociception level index will be reported. The nociception level index consist of Ta multiparameter nonlinear combination of heart rate, heart rate variability, amplitude of the finger photoplethysmogram, skin conductance level, fluctuations in skin conductance, and their time derivatives, derived from random forest regression. Random forest is an algorithmic modeling approach that enables combining multiple parameters of different origin and discovering their complex nonlinear interactions. Normal range is between 10-20; 0 indicates no nociceptive events (in example, pain stimuli), 100 indicates severe painful stimuli.	Perioperative measurements at 15 minute interval (on average during 3 hours)

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 14, 2017
• Primary Completion (ACTUAL): April 1, 2020
• Study Completion (ACTUAL): June 1, 2020

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (ACTUAL): May 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 13, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Rocuronium
• Other Study ID Numbers: p17.049

Drug and device information, study documents

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