Clinical trial NCT03782233
Conditions: Neuromuscular Blockade
Keywords: Neuromuscular Blockade Gastrointestinal Barrier Function
Sponsor: The First Affiliated Hospital with Nanjing Medical University
Start date: 2019-01-01; Completion date: 2019-12-31
Enrollment: 83 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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)

Detailed description:

Arms: arm 1: Patients undergoing elective laparoscopic surgery for gastrectomy will be randomized to receive deep neuromuscular blockade (post-tetanic count = 1-2) using high dose rocuronium. arm 2: 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.
Interventions: intervention 1: 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). intervention 2: 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).
Intervention descriptions: intervention 1: 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). intervention 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).

Protocol documents:
Prot_SAP_000.pdf: 
Title: Effect to Gastrointestinal Barrier Function During Laparoscopic 
Gastrectomy with Deep vs Moderate Neuromuscular Blockade  
NCT number: NCT03782233  
Date: 2018-11-05 


Study Protocol and Statistical Analysis Plan 
Study Protocol 
1. Perioperative vital signs and surgical conditions 
Arterial blood pressure, heart rate, pulse oxygen saturation and other perioperative vital 
signs in moderate neuromuscular blockade group (group M) and deep neuromuscular 
blockade group (group D) will be recorded. Volume of perioperative blood loss and 
infusion volume (including crystalloid solution, colloidal solution and blood products) 
will be recorded either. Surgical condition scores, intraoperative pressure of CO2 
pneumoperitoneum and duration of pneumoperitoneum will be recorded. Blood gas 
analysis will be performed hourly during the operation. 
2. Extubation 
After the operation, the extubation time of patients in the two groups and the modified 
Aldrete score at 1min, 5min and 15min after the extubation will be recorded. 
3. Postoperative pain scores 
Assessment and record of Visual analogue scale (VAS) at rest and activity 6 h, 12 h, 24 
h, 48 h after extubation. (VAS pain score: 0 - completely painless, 10 - unbearable pain.) 
4. Evaluations of intestinal barrier function 
4.1 The concentrations of d-lactic acid and diamine oxidase 
5ml peripheral venous blood will be extracted from the patients of the two groups on 
the first day before surgery and the first day after surgery for plasma d-lactic acid level 
and diamine oxidase activity detection. 
4.2 Parameters of intestinal mucosal  
(1) After the removal of gastric tumor, jejunum tissues of the two groups of patients 
will be collected. The height, width and number of villi in the intestinal mucosa will be 
observed and determined by microscopy. The density of mitochondria, length and width 
of villi, and clearance of intestinal epithelial cells will be analyzed by scanning electron 
microscopy to detect the damage of intestinal mucosal mechanical barrier.  
(2) The expression level of sIgA+ in the submucosal lamina propria will be detected by 
immunohistochemistry to reflect the damage of intestinal mucosal immune barrier. 
5. Intestinal microecology 
The change of intestinal mucosal biological barrier function was reflected mainly 
through selective bacterial culture of feces. The first, second, third and one-month 
postoperative defecation of the patients in two groups before and after surgery will be 


collected and analyzed with the following methods:  
(1) Routine examination of feces;  
(2) Selective culture of aerobic bacteria (such as Enterococcus, Enterobacter spp.) and 
anaerobic bacteria (such as Bifidobacteria, Lactobacillus), calculate the ratio of 
Bifidobacteria to Escherichia Coli. (B/E value), which is an important indicator to 
evaluate the status of intestinal flora, in the health condition, B/E value should be at 
least >10, otherwise it is regarded as flora imbalance;  
(3) 16S rRNA sequencing of the feces to analyzed the microbiota; 
(3) Determine the pH of feces;  
(4) Determination of fecal ammonia. 
6. The postoperative recovery of intestinal function  
The postoperative recovery of intestinal function in the two groups will be evaluated, 
including the first postoperative exhaust time, defecation time and feeding time, time 
of removal of abdominal drainage tube, postoperative hospital stays the incidence of 
diarrhea and abdominal distension within one month after operation. 
 
Statistical Analysis Plan 
SPSS 20.0 software will be used for statistical analysis. The measurement data will be 
tested by t test or Mann-Whitney U test. The data will be expressed as mean ± standard 
deviation. Nominal variables are summarized as number of subjects (proportion, %) 
and will be compared with the Chi-square test or Fisher's exact probability. P < 0.05 
will be considered statistically significant. On the basis of the primary parameters, we 
estimated that 83 patients will be needed with an α error of 0.05, a β error of 0.2 and a 
drop-out rate of about 10%. 
 

ICF_001.pdf: 
Title: Effect to Gastrointestinal Barrier Function During Laparoscopic 
Gastrectomy with Deep vs Moderate Neuromuscular Blockade 
NCT number: NCT03782233 
Date: 2018-11-04 


 
 
 
Dear 
Sir/Madam: 
Informed consent 
 
We are glad to invite you to participate in the research project ‘Effect of different depth 
of neuromuscular block on intestinal barrier function after laparoscopic gastrectomy’ 
approved by Wu Jieping Medical Foundation. The study will be conducted at the First 
Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), with an 
estimated 83 participants. This study has been supervised and approved by the ethics 
committee of the First Affiliated Hospital of Nanjing Medical University (Jiangsu 
Province Hospital). 
Why do we carry out this study? At present, the main surgical management for gastric 
tumors includes traditional open surgery and laparoscopic surgery. In recent years, 
clinical studies have found that laparoscopic gastrectomy can promote the 
postoperative recovery process of patients, but the potential impact of laparoscopic 
surgery on the physiology of patients must be paid attention to by anesthesiologists. 
The aim of this study is to observe the changes of intestinal barrier function, intestinal 
microecology and postoperative recovery of intestinal function in patients with 
different depth of neuromuscular blockade (NMB) during laparoscopic gastrectomy. 
If you participate in the study, what do you need to do? Inclusion criteria: (1)40-80 
years old; (2) Body mass index < 30kg/m2; (3) ASA classification I-Ⅲ; (4) undergoing 
elective laparoscopic gastrectomy. General anesthesia and the non-depolarizing muscle 
relaxant rocuronium were given for tracheal intubation and muscle relaxant 
maintenance. If selected, there is a 50% chance that you will receive a moderate or deep 
NMB with the non-depolarizing muscle relaxant rocuronium during the operation. We 
will collect 5 ml venous blood samples and fecal samples before and after the operation. 
During the operation, 2cm jejunum tissue will be collected. On the first and second day 
after the operation, 5ml venous blood samples and the first postoperative feces will be 
collected. We will follow you up within 2 weeks after the operation to record the time 
of your first exhaust, defecation, feeding and water intake. All the examinations 
mentioned above, including the detection of intestinal barrier and intestinal 
microecology through tissue samples, blood and feces, is a research examination (that 
is, if you do not participate in this study, you do not need to accept this examination), 
which will not harm your body. 
Who should not participate in the study? 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. If you have any situation mentioned above, you will 
not be included in this study. 
What are the risks of participating in a study? All anesthetic drugs have the potential 
to produce side effects, including neuromuscular relaxation drugs which can cause 
allergies, injection pain, etc. Since the drugs used in this study, such as rocuronium, are 
common anesthetics in clinical anesthesia, these side effects may occur as long as you 
accept this treatment, even if you do not participate in this clinical study. 
What are the benefits of participating in the study? Your condition may be improved 
if you participate this study. And it may help determine which treatment is a safer and 
more effective management for other patients with similar conditions. 
Do I have to pay for the study? In order to compensate you for any inconvenience that 
may be caused by your participation in this study. The study will cover the cost of tissue, 
blood and stool tests and registration fees during follow-up. However, the anesthesia- 
related drugs are not free. We will strengthen the examination to observe the possible 
side effects and adverse events caused by muscle relaxants, such as allergy and 
respiratory depression, and take measures to prevent and cure them. However, if there 
are any advert events, the cost of other treatments will not be covered. If there is any 
harm related to the test, the treatment and compensation will be provided according to 
the relevant provisions of the state. 
Is personal information confidential? Your medical records will be kept in the hospital, 
and researchers, research authorities, and ethics committees will be allowed access to 
your medical records. Any public report of the results of this study will not disclose 
your personal identity. To the extent permitted by law, we will make every effort to 
protect the privacy of your personal medical data. 
Do I have to take part in the study? Participation in the study is completely voluntary. 
You may refuse to participate in the study or withdraw from the study at any time during 
the study, which will not affect your doctor's treatment. If you do not participate in the 
study or you drop out of the study, there are many alternative drugs, such as cis- 
atracurium, neostigmine, etc. If you decide to withdraw from this study, please contact 


your doctor. You may be required to have an examination that will protect your health. 
Subject statement: I have read the description of this study above and fully understand 
the risks and benefits of participating in this study. I volunteered for this study. 
I agree □ or reject □ the use of my medical records and pathological specimens 
for other studies other than this study. 
Participant’s signature: date: _ _ _ _ _ year _ _ _ _ day _ _ _ _ _ 
Participant’s contact number: 
Doctor statement: I confirm that I have explained to the patient the details of this study, 
in particular the risks and benefits associated with participating in this study. 
Doctor's signature: date: _ _ _ _ _ _ year _ _ _ _ day _ _ _ _ _ 
Doctor's work phone: 
Ethics  committee  of  the  First Affiliated  Hospital  of  Nanjing  Medical  University 
(Jiangsu Province Hospital). Ethics committee tel: 025-68306360