Study on the Level of Neuromuscular Blockade

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

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)

Study Overview

• Status: Completed
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: A 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).; Drug: A 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).

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The First Affiliated Hospital with Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: deep neuromuscular blockade group (Group D); Patients undergoing elective laparoscopic surgery for gastrectomy will be randomized to receive deep neuromuscular blockade (post-tetanic count = 1-2) using high dose rocuronium.	Drug: A 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).
Other: moderate neuromuscular blockade group (Group M); Patients undergoing elective laparoscopic surgery for gastrectomy will be randomized to receive moderate neuromuscular blockade (train-of-four count = 1-2) using moderate dose rocuronium.	Drug: A 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of D-lactic Acid Before the Surgery	The level of D-lactic acid can indicate the damage to the gastrointestinal barrier .	1 day before the surgery
Plasma Concentration of Diamine Oxidase (DAO) Before the Surgery	The level of DAO can indicate the damage to the gastrointestinal barrier .	1 day Before the Surgery
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.	the first time of defecation after operation
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.	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	The level of D-lactic acid can indicate the damage to the gastrointestinal barrier .	24 h after the surgery
Plasma Concentration of Diamine Oxidase (DAO) 24 h After the Surgery	The level of DAO can indicate the damage to the gastrointestinal barrier .	24 h after the Surgery
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.	the first time of defecation after operation
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.	the first time of defecation after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Surgery	Time from the first dose of anesthetic to the end of the surgery	From the first dose of anesthetic to the end of the surgery
Surgical Condition Scores Rated by Surgeons	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.	During operation, within 2 hours
Duration of CO2 Pneumoperitoneum	Time from the beginning to the end of CO2 pneumoperitoneum	from the beginning to the end of CO2 pneumoperitoneum
Duration of Postoperative Hospital Stay	Duration from the day of surgery to the day the patient discharged from the hospital	from the end of surgery to the time of being discharged from hospital
Postoperative VAS (12 h After Surgery, Rest State)	VAS pain score: 0 - completely painless, 10 - unbearable pain.	12 h after surgery
Postoperative VAS (12 h After Surgery, Active State)	VAS pain score: 0 - completely painless, 10 - unbearable pain.	12 h after surgery
Postoperative VAS (24 h After Surgery, Rest State)	VAS pain score: 0 - completely painless, 10 - unbearable pain.	24 h after surgery
Postoperative VAS (24 h After Surgery, Active State)	VAS pain score: 0 - completely painless, 10 - unbearable pain.	24 h after surgery
Postoperative VAS (48 h After Surgery, Rest State)	VAS pain score: 0 - completely painless, 10 - unbearable pain.	48 h after surgery
Postoperative VAS (48 h After Surgery, Active State)	VAS pain score: 0 - completely painless, 10 - unbearable pain.	48 h after surgery
Surgical Condition Scores Rated by Surgeons (Average Scores)	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.	during surgery

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: Wu Jieping Medical Foundation

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 20, 2018

Study Record Updates

• Last Update Posted (Actual): September 24, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Neuromuscular Blockade; Gastrointestinal Barrier Function
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anticonvulsants; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Pharmaceutical Solutions; Bromides; Rocuronium
• Other Study ID Numbers: He Huang

Drug and device information, study documents

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