Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery

• Sponsor: Stony Brook University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02812186
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 79
• Location: 1
• Arms: 2
• Actual Duration (Months): 25.3
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This is a two period cross-over study randomizing patients undergoing laparoscopic surgery into 2 different groups: group 1 in which patients receive "deep neuromuscular blockade" in the beginning portion of their laparoscopic surgery followed by a period of "moderate blockade" and, group 2 in which patients receive "moderate neuromuscular blockade" in the beginning portion of their laparoscopic surgery followed by a period of "deep blockade". The deep neuromuscular block is defined as post tetanic count of 1 to 2 and the moderate neuromuscular block is defined as 1-2 twitches. In all patients, sugammadex is used to reverse the block at the end of surgery in order to obtain optimal extubating conditions.

Condition or Disease	Intervention/Treatment	Phase
Cholecystitis; Endometriosis; Bowel Obstruction; Fibroids; Prostate Cancer; Chronic Kidney Disease; Uterine Prolapse	Procedure: Deep to Moderate NMB; Procedure: Moderate to Deep NMB; Drug: Rocuronium	Phase 4

Detailed Description

Neuromuscular blockade (NMB) is frequently utilized in laparoscopic procedures to improve surgical conditions by relaxing the abdominal muscles and thus facilitating insufflation with carbon dioxide to optimize surgical view. Increased airway pressures can lead to an increase in alveolar and perivascular edema, a decline in dynamic lung compliance and hypoxemia.

Several studies have investigated surgical view under deep vs. moderate neuromuscular blockade. Literature supports deep neuromuscular blockade providing better operating conditions/view by a surgeon and low airway pressures but, potentially, longer duration to extubation and worse respiratory mechanics at the end of anesthesia versus moderate neuromuscular blockade which shows worse operating conditions/view by a surgeon and worse airway pressures but possibly shorter duration to extubation and better respiratory mechanics at the end of anesthesia.

Thus, there is clearly equipoise with regard to the comparative effectiveness of deep vs medium NMB. Therefore, this study is designed to ascertain if a deep neuromuscular block will decrease the airway pressures in patients undergoing laparoscopic procedures compared to those under a moderate block. A reduction in airway pressures may lead to a decrease in the complications associated with elevated airway pressures including hypoxemia, total static lung compliance, alveolar edema, and long term morbidity. Additionally, the study aims to determine if time from administration of sugammadex to reversal is different between patients that have a moderate NMB as compared to a deep NMB.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Effect of Deep Versus Moderate Neuromuscular Blockade on Peak Airway Pressures During Elective Laparoscopic Surgery
• Actual Study Start Date: Dec 27, 2016
• Actual Primary Completion Date: Jan 17, 2019
• Actual Study Completion Date: Feb 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Deep to Moderate NMB This group will undergo deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion of the surgery followed by a period of moderate blockade.	Procedure: Deep to Moderate NMB; Rocuronium infusion will be paused and the Train of Four (TOF) monitor will be set to every 1-2 min. Once the patient has achieved a "moderate" NMB state (one to two twitches), the infusion of the muscle relaxant will be resumed at a low dose to maintain the patient at this level of blockade.; Drug: Rocuronium
Other: Moderate to Deep NMB This group will undergo moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery followed by a period of deep blockade.	Procedure: Moderate to Deep NMB; Rocuronium infusion will be increased in increments of 0.1-0.2 mg/kg/hr. and the TOF monitor will be set to every 1-2 min. Once the patient has no twitches and a PTC of 0-1 ("deep" NMB) the infusion will be adjusted to maintain the patient at this level of NMB.; Drug: Rocuronium

Outcome Measures

Primary Outcome Measures

1. Peak Airway Pressures [Intra-operative, from intubation time to extubation time]

   To determine if a deep NMB can lead to lower peak airway pressures in patients undergoing laparoscopic procedures when compared to a moderate NMB

Secondary Outcome Measures

1. Abdominal Insufflation Pressure [Intra-operative, from intubation time to extubation time]

   To compare surgical operating condition by Abdominal Insufflation Pressure in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB

2. Surgical Rating Scale [Intra-operative, from intubation time to extubation time]

   To compare surgical operating condition by Surgical Rating Scale (SRS) in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB Surgical Rating Score scores are on a 1-5 scale with 1 = extremely poor conditions, 2 = poor conditions, 3 = adequate conditions, 4 = good conditions, 5= excellent conditions. Higher scores mean a better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Each participant must be willing and able to provide written informed consent for the study.

• Each participant must be American Society of Anesthesiologists (ASA) class I, II or III.

• Each participant must be scheduled for elective laparoscopic surgery (this includes robotic laparoscopic surgery).

• Expected surgical duration of 60 min or longer

Exclusion Criteria:

• Inability to give informed oral or written consent

• Known or suspected neuromuscular disorders impairing neuromuscular function;

• True allergies as defined as hypotension, bronchospasm, or anaphylaxis to muscle relaxants, anesthetics or opioids

• A history (patient or family) of malignant hyperthermia

• A contraindication for neostigmine administration

• Renal insufficiency, as defined by serum creatinine levels at 2.5 fold the normal level

• Body mass index >40 kg/m^2

• Significant respiratory disease.

• Planned postoperative mechanical ventilation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stony Brook University Hospital	Stony Brook	New York	United States	11794

Sponsors and Collaborators

• Stony Brook University
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Ruchir Gupta, MD, Stony Brook Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 5, 2018

More Information

Publications

None provided.

• Responsible Party: Ruchir Gupta, Clinical Assistant Professor, Stony Brook University
• ClinicalTrials.gov Identifier: NCT02812186
• Other Study ID Numbers: 823925
• First Posted: Jun 24, 2016
• Last Update Posted: Apr 8, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ruchir Gupta, Clinical Assistant Professor, Stony Brook University: Neuromuscular blockade
• Additional relevant MeSH terms: Cholecystitis; Intestinal Obstruction; Kidney Diseases; Renal Insufficiency, Chronic; Endometriosis; Uterine Prolapse; Prolapse; Rocuronium

Study Results

Participant Flow

Arm/Group Title	Deep to Moderate Neuromuscular Block (NMB)	Moderate to Deep NMB
Arm/Group Description	This group will undergo deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion of the surgery followed by a period of moderate blockade. Rocuronium	This group will undergo moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery followed by a period of deep blockade. Rocuronium
Period Title: Period 1
STARTED	40	39
COMPLETED	29	24
NOT COMPLETED	11	15
Period Title: Period 1
STARTED	29	24
COMPLETED	29	24
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Deep to Moderate NMB	Moderate to Deep NMB	Total
Arm/Group Description	This group will undergo deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion of the surgery followed by a period of moderate blockade.	This group will undergo moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery followed by a period of deep blockade.	Total of all reporting groups
Overall Participants	29	24	53
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.8 (14.9)	50.8 (15.4)	51.8 (15.15)
Sex: Female, Male (Count of Participants)
Female	17 58.6%	14 58.3%	31 58.5%
Male	12 41.4%	10 41.7%	22 41.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	29 100%	24 100%	53 100%
Procedure (Count of Participants)
General	26 89.7%	15 62.5%	41 77.4%
General/Gynecology	1 3.4%	2 8.3%	3 5.7%
Gynecology	2 6.9%	5 20.8%	7 13.2%
Urology	0 0%	2 8.3%	2 3.8%

Outcome Measures

1. Primary Outcome

Title	Peak Airway Pressures
Description	To determine if a deep NMB can lead to lower peak airway pressures in patients undergoing laparoscopic procedures when compared to a moderate NMB
Time Frame	Intra-operative, from intubation time to extubation time

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deep NMB	Moderate NMB
Arm/Group Description	This group underwent deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion of the surgery or during the second portion of the surgery	This group underwent moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery or during the second period of the surgery
Measure Participants	53	53
Mean	25.5	28.3
Maximum	28	30

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep NMB, Moderate NMB
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Abdominal Insufflation Pressure
Description	To compare surgical operating condition by Abdominal Insufflation Pressure in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB
Time Frame	Intra-operative, from intubation time to extubation time

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deep NMB	Moderate NMB
Arm/Group Description	This group underwent deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion or during the second portion of the surgery	This group underwent moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery or during the second portion of the surgery
Measure Participants	53	53
Median (Inter-Quartile Range) [mmHg]	15	15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep NMB, Moderate NMB
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Surgical Rating Scale
Description	To compare surgical operating condition by Surgical Rating Scale (SRS) in patients undergoing laparoscopic procedures using deep NMB versus moderate NMB Surgical Rating Score scores are on a 1-5 scale with 1 = extremely poor conditions, 2 = poor conditions, 3 = adequate conditions, 4 = good conditions, 5= excellent conditions. Higher scores mean a better outcome.
Time Frame	Intra-operative, from intubation time to extubation time

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deep NMB	ModerateNMB
Arm/Group Description	This group underwent deep neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion of the surgery or during the second portion of the surgery	This group underwent moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery or during the second portion of the surgery
Measure Participants	53	53
Median (Inter-Quartile Range) [units on a scale]	5	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deep NMB, Moderate NMB
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Intraoperative (intubation time to extubation time)
Arm/Group Title	Deep NMB		Moderate NMB
Arm/Group Description	This group will underwent neuromuscular blockade, defined as post tetanic count (PTC) of 1 to 2, in the beginning portion or during the second portion of the surgery		This group underwent moderate neuromuscular blockade, defined as 1-2 twitches, in the beginning portion of the surgery or during the second portion of the surgery
All Cause Mortality
	Deep NMB		Moderate NMB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)
Serious Adverse Events
	Deep NMB		Moderate NMB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)
Other (Not Including Serious) Adverse Events
	Deep NMB		Moderate NMB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/53 (0%)		0/53 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.