Effect of Low-pressure Pneumoperitoneum on Pain and Inflammation in Laparoscopic Cholecystectomy: A Prospective Randomized Clinical Trial
Phase: NA
Conditions: Pneumoperitoneum, Pain, Inflammatory Response
Sponsor: University of Jordan

 
 
 
 
 
 
 
 
Effect of Low-pressure Pneumoperitoneum on Pain and Inflammation 
Post Laparoscopic Cholecystectomy: A Randomized, Double-blinded, 
Controlled, Clinical Trial. 
 
ClinicalTrials.gov Identifier: not yet assigned  
 
Date protocol accepted by IRB at the University of Jordan: 15th January 2020 
 
 

Study Summary: 
In the era of laparoscopic abdominal surgeries, pneumoperitoneum pressure is set to a point of 
12-15 mmHg. The new generation of surgeon has been questioning if we could do laparoscopic 
surgeries with no compromise at a lower pneumoperitoneum pressure in the aim of improving 
the quality of patients’ lives postoperatively and efficacy of health care system. In reviewing the 
literature, such intervention has showed benefit in terms of decreasing postoperative pain (1) 
and rise of inflammatory markers (2). This study is designed as a randomized double- blinded 
controlled clinical trial to challenge such hypothesis. The study shall be conducted on patients 
at The University of Jordan hospital booked electively for laparoscopic cholecystectomy then 
randomized into two groups operated at either standard or low pneumoperitoneum pressure 
then assessed post operatively for pain and rise of inflammatory markers. 
 
Research design: 
It is a clinical trial, designed to look for a statistical difference in pain and rise of inflammatory 
markers post operatively between interventional group which is operated at a low-pressure 
pneumoperitoneum of 8-10 mmHg compared to the standard of care of pneumoperitoneum 
set at a pressure of 12-14 mmHg. 
further to increase validity of results and strengthen the study design, the study participants are 
randomized, the groups are masked, and the data is blinded to investigators, analyst, and 
participants. 
 
 

Research subjects: 
All patients admitted to surgery ward through clinic with the diagnosis of multiple gallbladder 
stones undergoing laparoscopic cholecystectomy are to be considered for enrollment in this 
study. 
Inclusion criteria: 
 
Elective admission for laparoscopic cholecystectomy 
 
Minimum age of 12 years  
 
American Society of Anesthesiologists (ASA) score 1 or 2 
 
Exclusion criteria: 
 
Current or previous diagnosis of acute cholecystitis confirmed by ultrasound. 
 
previous GI surgeries, except bariatric and anti-reflux surgeries 
 
Currently on immunosuppressant agents 
 
Pregnancy 
 
Breastfeeding 
 
Currently diagnosed with drug addiction 
 
American Society of Anesthesiologists (ASA) score 3, 4, 5, or emergency surgery 
 
Allocation to groups: 
participants are to be given numbers in study and be labeled with it. A preset computer-
generated list is to be used to divide patients between two study arms into either of masked 
groups. Allocation to groups is random according to the computer-generated randomized list. 
Masking (blinding) method: 
The two study arms are to be color coded. The codes are to be used for randomization, data 
entry and analysis. None of the participants, investigators and analyst are to be informed of 
color code reference. the principal investigator, operating surgeon and circulating nurse during 
operation are to be informed of the color code meaning. After closure of the study, the color 
codes can be disclosed to the public. 
Criteria to discontinuation: 
Any participant withdrawing consent during any time of the study. 
Patients found to have intra operative adhesions and evidence of previous inflammation are 
not to be discontinued from the study. 

Sample size: 
A convenient sample of 100 participants is decided, divided into 50 for each study group. 
 
Intervention: 
Interventional group is to be operated at low-pressure pneumoperitoneum which is set at 8-10. 
Control group is to be operated at standard-pressure pneumoperitoneum which is set at 12-14. 
The pressure set point is to be determined at the beginning of surgery, any change to pressure 
after initial insufflation is not to change the participants study arm grouping. 
Observations: 
Pre-operative demographics are to be collected for each patient, including patient name, 
medical record number (MRM), age, gender, weight, height, ASA score, medical history, surgical 
history, current medications, marital status, smoking status, operation date. 
During operation, the following are to be observed and recorded: time of surgery start, time of 
surgery end, total time of insufflation, method of insufflation (open, closed), operator level of 
experience, intraoperative findings (adhesions, inflammation, perforation, bile leak), difficulty 
of surgery subjectively assessed by operator (easy, moderate, difficult), estimated blood loss, 
change of pneumoperitoneum pressure set point, intraoperative mortality, intraoperative 
complications. 
Post-operative during hospital-stay the following are to be collected: pain score out of 10 
according to patient perception recorded at 6hr, 12hr and 24hr post-op, hospital stay length in 
days, total analgesia given post-op (number of dosage and type). 
Post-operative after hospital discharge the following are to be collected: pain score out of 10 
according to patient perception recorded on 7th day post-op and to be collected via phone call, 
post-operative complications up to day 30 (readmission, CBD stone, pancreatitis, cholangitis,  
..etc.), and histopathology result. 
The following inflammatory markers are to be investigated: white blood cell count, platelet 
count, erythrocyte sedimentation rate, C reactive protein level, albumin level, free serum 
cortisol level, interlukein-6 level, interlukein-17 level, interlukein-1 beta level, tumor necrosis 
factor alpha level. 
Flow of study work:  
After ensuring patients eligibility for study and obtaining informed consent, they are to be 
allocated to one of study arms randomly. Observations are to be taken and entered to on-line 
excel. After discharge patients are to be followed on day 7 post-op to collect pain score via 
phone call, complications are to be followed up to day 30 post-op from electronic records. 

Regarding inflammatory markers, the tests are to be performed at Jordan University Hospital 
laboratories, the blood samples are to be collected safely by study assistants and delivered to 
the lab labeled with patient name, MRM, date, and time of collection. The runoff tests are done 
as standardizes by hospital laboratory policies. 
 
 
 
 
Specifications to operation: 
Patients enrolled in the study are to undergo laparoscopic cholecystectomy as per the following 
protocol: 
 
Regarding general anesthesia, the use of dexamethasone during induction is to be 
avoided 
 
Regarding creation of pneumoperitoneum, the choice is given to operating surgeon 
to choose either open, closed, or optical technique 
 
Regarding number and site of trocars, the choice is given to operating surgeon to 
perform as per trained  
 
Cholecystectomy is to be performed as standardized, after establishment of critical 
view of safety, the operating surgeon is to carry on steps to establish hemostasis, 
clipping of cystic duct, and dissection of gallbladder from its liver bed 
 
Retrieval of specimen is to be done through umbilical port 
 
The use of endoclose device for closure of fascia is to be avoided 
 
The infiltration of local anesthesia at site of trocars is to be avoided 
 
Regarding skin closure, the choice is given to operating surgeon to perform as per 
trained  
Data management and analysis: 
The principal investigator is to ensure adherence to protocol and data validity. To ensure this, 
data will be reviewed each end of month, and a progress summary is to be written and 
provided to study regulatory every six months.  
Analysis is to be conducted using SPSS version 1.0.0.1406. analysis plan is attached in separate 
file. 
Ethical considerations: 
No data to be collected without obtaining patient informed consent, the signed paper is to be 
kept for a minimum of two years 

Funding: 
The study is funded by a grant through the University of Jordan scientific research deanship. 
References: 
1- Gurusamy KS, Vaughan J, Davidson BR. Low pressure versus standard pressure 
pneumoperitoneum in laparoscopic cholecystectomy. Cochrane Database of 
Systematic Reviews 2014, Issue 3. Art. No.: CD006930. DOI: 
10.1002/14651858.CD006930.pub3. 
2- Agarwal BB, Nanavati JD, Agarwal N, et al. Biomolecular inflammatory response to 
surgical energy usage in laparoscopic surgery: results of a randomized study. Surg 
Endosc Other Interv Tech. 2016;30(5). doi:10.1007/s00464-015-4408-2.