Study on the Level of Neuromuscular Blockade

Effect to Gastrointestinal Barrier Function During Laparoscopic Gastrectomy With Deep vs Moderate Neuromuscular Blockade.

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03782233

Enrollment

Registered

2018-12-20

Start date

2019-01-01

Completion date

2019-12-31

Last updated

2020-09-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neuromuscular Blockade

Keywords

Neuromuscular Blockade, Gastrointestinal Barrier Function

Brief summary

On the basis of moderate pneumoperitoneum pressure(10 mmHg), this study evaluates the effect of different level of neuromuscular blockade to gastrointestinal barrier function during laparoscopic gastrectomy. 83 patients are randomized to 2 arms ,The patients in deep neuromuscular blockade group（group D, PTC=1-2）will receive high dose rocuronium (0.5-0.6 mg/kg/h) ;While the patients in moderate neuromuscular blockade group（group M, TOF=1-2）will receive moderate dose rocuronium (0.2-0.3 mg/kg/h)

Interventions

DRUGA continuous intravenous infusion of 0.5-0.6 mg/kg/h Rocuronium Bromide Intravenous Solution (50 Mg/5 mL) to keep the target neuromuscular blockade (PTC = 1-2).

50 patients undergoing laparoscopic gastrectomy surgery will be allocated to group D. A continuous intravenous infusion of 0.5-0.6 mg/kg/h rocuronium to keep the target neuromuscular blockade (PTC = 1-2).

DRUGA continuous intravenous infusion of 0.2-0.3 mg/kg/h Rocuronium Bromide Intravenous Solution (50 Mg/5 mL) to keep the target neuromuscular blockade (TOF = 1-2).

33 patients undergoing laparoscopic gastrectomy surgery will be allocated to group M. A continuous intravenous infusion of 0.2-0.3 mg/kg/h rocuronium to keep the target neuromuscular blockade (TOF = 1-2).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

Inclusion criteria

1. Age:40-80; 2. BMI \< 30kg/m2； 3. ASA classification:Ⅰ-Ⅲ； 4. Undergoing elective laparoscopic gastrectomy.

Exclusion criteria

1. Preoperative history of inflammatory intestinal diseases, intestinal flora disorders, obstructive jaundice, intestinal obstruction, irritable bowel syndrome and other digestive diseases; 2. Severe heart, lung, liver, kidney, brain and other diseases; 3. Serious infection, pancreatitis, burns, trauma, need a large dose, long-term use of antibiotics before the operation; 4. A history of abdominal surgery; 5. Combined with gravis myasthenia, serious electrolyte disorders or neuromuscular diseases.

Design outcomes

Primary

Measure	Time frame	Description
Plasma Concentration of D-lactic Acid Before the Surgery	1 day before the surgery	The level of D-lactic acid can indicate the damage to the gastrointestinal barrier .
Plasma Concentration of Diamine Oxidase (DAO) Before the Surgery	1 day Before the Surgery	The level of DAO can indicate the damage to the gastrointestinal barrier .
Total Number of Operational Taxonomic Units (OUTs) of Intestinal Microbiota	the first time of defecation after operation	Intestinal microbiota was analyzed by 16S rRNA sequencing. To be specific, first, DNA was extracted and quantified. Bacterial 16S rRNA genes of the V3-V4 region were amplified from extracted DNA using the barcoded primers (5'- CCTACGGRRBGCASCAGKVRVGAAT-3') and (5'- GGACTACNVGGGTWTCTAATCC-3'). PCR reactions were performed and the PCR mixture applied to the PCR amplifier. Then, the PCR products were checked for size and specificity by agarose gel electrophoresis and purified. Finally, high-throughput sequencing was performed using the Illumina MiSeq platform. The raw reads were filtered to remove low quality sequences and the filtered data were further merged into tags by FLASH(Version 1.2.7). Then the Uchime algorithm in Usearch software was applied to remove chimeric tags. Resulting tags for each sample were clustered into operational taxonomic units(OTUs) at the level of 97% similarity. Higher values represent a more abundant amount of bacteria in gut.
Postoperative Exhaust Time	It is calculated from the end of the operation to the time of exhaust.	It's a regular measurement to evaluate the function of gastrointestinal tract . It is calculated from the end of the operation to the time of exhaust.
Plasma Concentration of D-lactic Acid 24 h After the Surgery	24 h after the surgery	The level of D-lactic acid can indicate the damage to the gastrointestinal barrier .
Plasma Concentration of Diamine Oxidase (DAO) 24 h After the Surgery	24 h after the Surgery	The level of DAO can indicate the damage to the gastrointestinal barrier .
Relative Abundance of Intestinal Microbiota	the first time of defecation after operation	Intestinal microbiota is one of the factors related to the recovery of intestinal function. It can be analyzed by 16S rRNA sequencing of the postoperative feces.
16s rRNA Sequencing of Postoperative Feces	the first time of defecation after operation	Alpha and Beta diversity; relative abundance of gut microbiota. Alpha diversity includes Chao 1 index, Shannon index, and Simpson index. A higher value of Chao 1 index corresponds to more abundant number of microbiota. A higher value of Shannon index corresponds to more abundance. And A higher value of Simpson index corresponds to less diversity. Bata diversity was assessed by PCoA analysis. A three dimensional scatter plot was presented to visualize the similarities and differences between the two groups.

Secondary

Measure	Time frame	Description
Postoperative VAS (48 h After Surgery, Rest State)	48 h after surgery	VAS pain score: 0 - completely painless, 10 - unbearable pain.
Duration of Surgery	From the first dose of anesthetic to the end of the surgery	Time from the first dose of anesthetic to the end of the surgery
Surgical Condition Scores Rated by Surgeons (Average Scores)	during surgery	evaluation of the surgical condition by 5 point scale: 5 points: optimal; 4 points: good; 3 points: acceptable; 2 points: poor; 1 point: extremely poor.
Postoperative VAS (48 h After Surgery, Active State)	48 h after surgery	VAS pain score: 0 - completely painless, 10 - unbearable pain.
Surgical Condition Scores Rated by Surgeons	During operation, within 2 hours	evaluation of the surgical condition by 5 point scale: 5 points: optimal; 4 points: good; 3 points: acceptable; 2 points: poor; 1 point: extremely poor.
Duration of CO2 Pneumoperitoneum	from the beginning to the end of CO2 pneumoperitoneum	Time from the beginning to the end of CO2 pneumoperitoneum
Duration of Postoperative Hospital Stay	from the end of surgery to the time of being discharged from hospital	Duration from the day of surgery to the day the patient discharged from the hospital
Postoperative VAS (12 h After Surgery, Rest State)	12 h after surgery	VAS pain score: 0 - completely painless, 10 - unbearable pain.
Postoperative VAS (12 h After Surgery, Active State)	12 h after surgery	VAS pain score: 0 - completely painless, 10 - unbearable pain.
Postoperative VAS (24 h After Surgery, Rest State)	24 h after surgery	VAS pain score: 0 - completely painless, 10 - unbearable pain.
Postoperative VAS (24 h After Surgery, Active State)	24 h after surgery	VAS pain score: 0 - completely painless, 10 - unbearable pain.

Countries

China

Participant flow

Participants by arm

Arm	Count
Deep Neuromuscular Blockade（Group D） 50 patients undergoing laparoscopic gastrectomy surgery will be allocated to group D. A continuous intravenous infusion of 0.6 mg/kg/h rocuronium to keep the target neuromuscular blockade (PTC = 1-2).	46
Moderate Neuromuscular Blockade (Group M) 33 patients undergoing laparoscopic gastrectomy surgery will be allocated to group M. A continuous intravenous infusion of 0.2 mg/kg/h rocuronium to keep the target neuromuscular blockade (TOF = 1-2).	31
Total	77

Baseline characteristics

Characteristic	Deep Neuromuscular Blockade（Group D）	Moderate Neuromuscular Blockade (Group M)	Total
Age, Continuous	60.6 years STANDARD_DEVIATION 10.8	60.0 years STANDARD_DEVIATION 8.1	60.4 years STANDARD_DEVIATION 9.8
Body mass index (BMI)	23.6 kg/m^2 STANDARD_DEVIATION 2.8	24.3 kg/m^2 STANDARD_DEVIATION 2.7	23.92 kg/m^2 STANDARD_DEVIATION 2.76
Race and Ethnicity Not Collected	—	—	0 Participants
Region of Enrollment China	46 participants	31 participants	77 participants
Sex: Female, Male Female	17 Participants	9 Participants	26 Participants
Sex: Female, Male Male	29 Participants	22 Participants	51 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 77	0 / 77
other Total, other adverse events	0 / 77	0 / 77
serious Total, serious adverse events	0 / 77	0 / 77

Outcome results

Primary

16s rRNA Sequencing of Postoperative Feces

Alpha and Beta diversity; relative abundance of gut microbiota. Alpha diversity includes Chao 1 index, Shannon index, and Simpson index. A higher value of Chao 1 index corresponds to more abundant number of microbiota. A higher value of Shannon index corresponds to more abundance. And A higher value of Simpson index corresponds to less diversity. Bata diversity was assessed by PCoA analysis. A three dimensional scatter plot was presented to visualize the similarities and differences between the two groups.

Time frame: the first time of defecation after operation

Population: There were 8 patients group D and 5 patients in group M defecating before being discharged from the hospital. There are so much basic data about the 16s rRNA sequencing that we can not upload them. The amount of work was formidable. You may contact with me if necessary for all the sequencing data.

Arm	Measure	Group	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	16s rRNA Sequencing of Postoperative Feces	alpha diversity - Chao1	763.7 score on a scale	Standard Deviation 183.7
Deep Neuromuscular Blockade（Group D）	16s rRNA Sequencing of Postoperative Feces	alpha diversity - Shannon index	4.93 score on a scale	Standard Deviation 1
Deep Neuromuscular Blockade（Group D）	16s rRNA Sequencing of Postoperative Feces	alpha diversity - Simpson index	0.9 score on a scale	Standard Deviation 0.07
Moderate Neuromuscular Blockade (Group M)	16s rRNA Sequencing of Postoperative Feces	alpha diversity - Chao1	599.3 score on a scale	Standard Deviation 164
Moderate Neuromuscular Blockade (Group M)	16s rRNA Sequencing of Postoperative Feces	alpha diversity - Shannon index	4.15 score on a scale	Standard Deviation 0.9
Moderate Neuromuscular Blockade (Group M)	16s rRNA Sequencing of Postoperative Feces	alpha diversity - Simpson index	0.83 score on a scale	Standard Deviation 0.1

Primary

Plasma Concentration of Diamine Oxidase (DAO) 24 h After the Surgery

The level of DAO can indicate the damage to the gastrointestinal barrier .

Time frame: 24 h after the Surgery

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Plasma Concentration of Diamine Oxidase (DAO) 24 h After the Surgery	18.1 U/L	Standard Deviation 3.3
Moderate Neuromuscular Blockade (Group M)	Plasma Concentration of Diamine Oxidase (DAO) 24 h After the Surgery	26.5 U/L	Standard Deviation 4.7

Primary

Plasma Concentration of Diamine Oxidase (DAO) Before the Surgery

The level of DAO can indicate the damage to the gastrointestinal barrier .

Time frame: 1 day Before the Surgery

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Plasma Concentration of Diamine Oxidase (DAO) Before the Surgery	15.5 U/L	Standard Deviation 3
Moderate Neuromuscular Blockade (Group M)	Plasma Concentration of Diamine Oxidase (DAO) Before the Surgery	16.4 U/L	Standard Deviation 3.6

Primary

Plasma Concentration of D-lactic Acid 24 h After the Surgery

The level of D-lactic acid can indicate the damage to the gastrointestinal barrier .

Time frame: 24 h after the surgery

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Plasma Concentration of D-lactic Acid 24 h After the Surgery	1230.7 ng/ml	Standard Deviation 138.4
Moderate Neuromuscular Blockade (Group M)	Plasma Concentration of D-lactic Acid 24 h After the Surgery	1297.5 ng/ml	Standard Deviation 147.8

Primary

Plasma Concentration of D-lactic Acid Before the Surgery

The level of D-lactic acid can indicate the damage to the gastrointestinal barrier .

Time frame: 1 day before the surgery

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Plasma Concentration of D-lactic Acid Before the Surgery	1100.4 ng/ml	Standard Deviation 156.6
Moderate Neuromuscular Blockade (Group M)	Plasma Concentration of D-lactic Acid Before the Surgery	1087.8 ng/ml	Standard Deviation 146

Primary

Postoperative Exhaust Time

It's a regular measurement to evaluate the function of gastrointestinal tract . It is calculated from the end of the operation to the time of exhaust.

Time frame: It is calculated from the end of the operation to the time of exhaust.

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Postoperative Exhaust Time	58.9 hour	Standard Deviation 15.9
Moderate Neuromuscular Blockade (Group M)	Postoperative Exhaust Time	70.5 hour	Standard Deviation 26.6

Primary

Relative Abundance of Intestinal Microbiota

Intestinal microbiota is one of the factors related to the recovery of intestinal function. It can be analyzed by 16S rRNA sequencing of the postoperative feces.

Time frame: the first time of defecation after operation

Population: There were 8 patients group D and 5 patients in group M defecating before being discharged from the hospital.

Arm	Measure	Group	Value (MEDIAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Roseburia	0.000019780046 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Class-Flavobacteriia	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Order-Desulfovibrionales	0.0081493789065 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Order-Flavobacteriales	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Family-Fusobacteriaceae	0.0005340612390 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Family-Desulfovibrionaceae	0.0081493789065 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Family-[Weeksellaceae]	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Blautia	0.0097021125088 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Dialister	0.0002175805047 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Collinsella	0.0024329456444 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Fusobacterium	0.0005340612390 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Bilophila	0.0050636917477 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Aggregatibacter	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Megasphaera	0.000059340138 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Neisseria	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-TG5	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Family-[Tissierellaceae]	0.0021362449560 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Genus-Selenomonas	0 percentage of all intestinal microbiota	Standard Deviation 0
Deep Neuromuscular Blockade（Group D）	Relative Abundance of Intestinal Microbiota	Class-Deltaproteobacteria	0.0010483424321 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Roseburia	0 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Class-Deltaproteobacteria	0.0010483424321 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Fusobacterium	0.0196020254767 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Class-Flavobacteriia	0.000019780046 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Family-[Tissierellaceae]	0.0001186802753 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Order-Desulfovibrionales	0.0010483424321 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Bilophila	0.0010087823403 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-TG5	0.000019780045 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Family-Fusobacteriaceae	0.0196020254767 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Aggregatibacter	0.0007120816520 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Family-Desulfovibrionaceae	0.0010285623862 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Order-Flavobacteriales	0.00003956 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Family-[Weeksellaceae]	0.000019780046 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Megasphaera	0.0019780045889 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Blautia	0.0024725057362 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Selenomonas	0.000039560092 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Dialister	0.0042724899121 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Neisseria	0.000019780046 percentage of all intestinal microbiota	Standard Deviation 0
Moderate Neuromuscular Blockade (Group M)	Relative Abundance of Intestinal Microbiota	Genus-Collinsella	0 percentage of all intestinal microbiota	Standard Deviation 0

Primary

Total Number of Operational Taxonomic Units (OUTs) of Intestinal Microbiota

Intestinal microbiota was analyzed by 16S rRNA sequencing. To be specific, first, DNA was extracted and quantified. Bacterial 16S rRNA genes of the V3-V4 region were amplified from extracted DNA using the barcoded primers (5'- CCTACGGRRBGCASCAGKVRVGAAT-3') and (5'- GGACTACNVGGGTWTCTAATCC-3'). PCR reactions were performed and the PCR mixture applied to the PCR amplifier. Then, the PCR products were checked for size and specificity by agarose gel electrophoresis and purified. Finally, high-throughput sequencing was performed using the Illumina MiSeq platform. The raw reads were filtered to remove low quality sequences and the filtered data were further merged into tags by FLASH(Version 1.2.7). Then the Uchime algorithm in Usearch software was applied to remove chimeric tags. Resulting tags for each sample were clustered into operational taxonomic units(OTUs) at the level of 97% similarity. Higher values represent a more abundant amount of bacteria in gut.

Time frame: the first time of defecation after operation

Population: There were only 8 patients in group D and 5 patients in group M defecating before discharged from hospital.

Arm	Measure	Value (NUMBER)
Deep Neuromuscular Blockade（Group D）	Total Number of Operational Taxonomic Units (OUTs) of Intestinal Microbiota	1695 units
Moderate Neuromuscular Blockade (Group M)	Total Number of Operational Taxonomic Units (OUTs) of Intestinal Microbiota	1287 units

Secondary

Duration of CO2 Pneumoperitoneum

Time from the beginning to the end of CO2 pneumoperitoneum

Time frame: from the beginning to the end of CO2 pneumoperitoneum

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Duration of CO2 Pneumoperitoneum	132.3 minute	Standard Deviation 31.2
Moderate Neuromuscular Blockade (Group M)	Duration of CO2 Pneumoperitoneum	147.0 minute	Standard Deviation 34.8

Secondary

Duration of Postoperative Hospital Stay

Duration from the day of surgery to the day the patient discharged from the hospital

Time frame: from the end of surgery to the time of being discharged from hospital

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Duration of Postoperative Hospital Stay	9.2 days	Standard Deviation 4
Moderate Neuromuscular Blockade (Group M)	Duration of Postoperative Hospital Stay	9.1 days	Standard Deviation 5.1

Secondary

Duration of Surgery

Time from the first dose of anesthetic to the end of the surgery

Time frame: From the first dose of anesthetic to the end of the surgery

Arm	Measure	Value (MEAN)	Dispersion
Deep Neuromuscular Blockade（Group D）	Duration of Surgery	155.0 minutes	Standard Deviation 34.2
Moderate Neuromuscular Blockade (Group M)	Duration of Surgery	174.6 minutes	Standard Deviation 34.9

Secondary