Study on the Level of Neuromuscular Blockade

Study Overview
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Brief Summary
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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)

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

Conditions
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Neuromuscular Blockade

Intervention / Treatment
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* 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).


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age:40-80; BMI < 30kg/m2； ASA classification:Ⅰ-Ⅲ； Undergoing elective laparoscopic gastrectomy. Exclusion Criteria: Preoperative history of inflammatory intestinal diseases, intestinal flora disorders, obstructive jaundice, intestinal obstruction, irritable bowel syndrome and other digestive diseases; Severe heart, lung, liver, kidney, brain and other diseases; Serious infection, pancreatitis, burns, trauma, need a large dose, long-term use of antibiotics before the operation; A history of abdominal surgery; Combined with gravis myasthenia, serious electrolyte disorders or neuromuscular diseases.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: deep neuromuscular blockade group (Group D)<br>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).<br>* 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).<br>|
| Other: moderate neuromuscular blockade group (Group M)<br>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).<br>* 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).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuromuscular Blockade, Gastrointestinal Barrier Function