Peritoneal Damage
Conditions
Keywords
low pressure pneumoperitoneum, standard pressure pneumoperitoneum, laparoscopy cholecystectomy
Brief summary
The investigators hypothesized that applying a low intraperitoneal pressure pneumoperitoneum (≤ 8mmHg) during laparoscopic cholecystectomy, the adverse impact on the surgical peritoneal environment (measured as gene expression of extracellular matrix, adhesion and inflammatory cytokine as well as oxidative stress response and apoptotic index), can be minimized and probably clinical outcomes might be better.
Detailed description
Cholelithiasis is one of the most frequent abdominal diseases requiring surgical treatment. Laparoscopic cholecystectomy is currently the procedure of choice to remove the gallbladder. There is growing evidence that increased intra-abdominal pressure pneumoperitoneum, even for short periods of time, is associated with both transient and sometimes persistent adverse effects that might negatively affect the surgical peritoneal environment .There are some studies that have demonstrated that using low intraperitoneal pressure pneumoperitoneum, undesired effects like adverse impact on peritoneal tissue and negative clinical outcomes could be reduced.Therefore intraperitoneal pressure target during laparoscopy should be the lowest to allow surgery be securely performed. Many strategies have been tested in order to improve the volume of gas can be insufflated inside the abdominal cavity while maintaining low pneumoperitoneum pressure during laparoscopy.So far the most studied strategy has been deep neuromuscular blockade.However the effect of the depth of neuromuscular blockade in the intraabdominal volume is still controversial as sometimes in humans its benefits are marginal.There is scarce information in the medical literature regarding the adverse impact on peritoneal tissue of high pneumoperitoneum pressure during laparoscopy in humans. In addition available data are provided by non-prospective, non-randomized and small sample studies, so randomized controlled trials are required to ascertain this issues.To our knowledge our study is the first prospective and randomized controlled trial in humans aiming to study the adverse impact of high pressure pneumoperitoneum on peritoneal tissue as well as to associate it with clinical outcomes.
Interventions
PROCEDURELow pressure pneumoperitoneum
Low pressure pneumoperitoneum
PROCEDUREstandard pneumoperitoneum pressure
standard pneumoperitoneum pressure
Sponsors
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients older than 18 years, signed informed consent, undergoing laparoscopic cholecystectomy for symptomatic cholelithiasis or gallbladder polyps.
Exclusion criteria
* Emergency surgery. * Previous surgery at supramesocolic compartment. * Previous peritoneal inflammatory process. * Pregnancy or breastfeeding. * Patient refusal to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Peritoneal Markers | he values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1). | logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum |
| Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | The values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1). | f. CTGF connective tissue growth factor. g. MMP-9 matrix metalloproteinase-9. h. PAI-I plasminogen activator inhibitor-I. i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer. |
| Oxidative Stress Response Marker:MDA (Malondialdehyde) | The values of the main variables will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1) | MDA (malondialdehyde) determination will be done with ELISA |
| Apoptotic Index | The values of the main variables will be obtained from the study of peritoneal tissue samples, one hour after the creation of the pneumoperitoneum compared to basal peritoneal tissue samples. | This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final |
Countries
Spain
Participant flow
Recruitment details
Data were collected from January 2017 to May 2019
Participants by arm
| Arm | Count |
|---|---|
| Experimental Low pneumoperitoneum pressure (8 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage | 47 |
| Control Standard pneumoperitoneum pressure (12 mmHg or lower) during laparoscopic cholecystectomy to evaluate the peritoneal tissue damage | 48 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Converted to open surgery | 2 | 1 |
| Overall Study | for surgery not performed | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Experimental | Control | Total |
|---|---|---|---|
| Age, Continuous | 54.47 years STANDARD_DEVIATION 16.88 | 51.71 years STANDARD_DEVIATION 15.72 | 53.04 years STANDARD_DEVIATION 16.26 |
| ASA I | 16 Participants | 12 Participants | 28 Participants |
| ASA II | 23 Participants | 32 Participants | 55 Participants |
| ASA III | 7 Participants | 4 Participants | 11 Participants |
| ASA IV | 0 Participants | 0 Participants | 0 Participants |
| ASA Unknow | 1 Participants | 0 Participants | 1 Participants |
| BMI | 26.63 kg/m^2 STANDARD_DEVIATION 4.07 | 27.51 kg/m^2 STANDARD_DEVIATION 4.6 | 27.07 kg/m^2 STANDARD_DEVIATION 4.3 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 32 Participants | 37 Participants | 69 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Apoptotic Index
This measure is reported as the mean of the difference of the percentage of apoptotic cells at baseline minus the final
Time frame: The values of the main variables will be obtained from the study of peritoneal tissue samples, one hour after the creation of the pneumoperitoneum compared to basal peritoneal tissue samples.
Population: 13 samples excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Apoptotic Index | -1.92 difference of the percentage | Standard Deviation 24.3 |
| Experimental | Apoptotic Index | -0.56 difference of the percentage | Standard Deviation 12.3 |
p-value: 0.86295% CI: [-7.49, 10.21]t-test, 2 sided
Primary
Inflammatory Peritoneal Markers
logaritmic levels of mRNA of the different markers at time 1 hour after creation of the pneumoperitoneum
Time frame: he values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).
Population: 23 excluded samples
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Inflammatory Peritoneal Markers | Interleukin 1 | 0.80 log (pg/ml) | Standard Deviation 1 |
| Control | Inflammatory Peritoneal Markers | Interlerukin 6 | 4.26 log (pg/ml) | Standard Deviation 1.34 |
| Control | Inflammatory Peritoneal Markers | Interleukin 10 | 0.76 log (pg/ml) | Standard Deviation 1.01 |
| Control | Inflammatory Peritoneal Markers | vascular endotelial growth factor A | 0.09 log (pg/ml) | Standard Deviation 0.99 |
| Control | Inflammatory Peritoneal Markers | Tumor necrosis factor α | -0.71 log (pg/ml) | Standard Deviation 0.99 |
| Control | Inflammatory Peritoneal Markers | CXC lingand 2 | 2.18 log (pg/ml) | Standard Deviation 0.99 |
| Experimental | Inflammatory Peritoneal Markers | Tumor necrosis factor α | -0.74 log (pg/ml) | Standard Deviation 0.71 |
| Experimental | Inflammatory Peritoneal Markers | Interleukin 1 | 1.14 log (pg/ml) | Standard Deviation 1.06 |
| Experimental | Inflammatory Peritoneal Markers | vascular endotelial growth factor A | -0.05 log (pg/ml) | Standard Deviation 0.5 |
| Experimental | Inflammatory Peritoneal Markers | Interlerukin 6 | 3.24 log (pg/ml) | Standard Deviation 1.21 |
| Experimental | Inflammatory Peritoneal Markers | CXC lingand 2 | 2.22 log (pg/ml) | Standard Deviation 0.72 |
| Experimental | Inflammatory Peritoneal Markers | Interleukin 10 | 1.10 log (pg/ml) | Standard Deviation 0.84 |
Comparison: Interleukin 1 (IL1)p-value: 0.058t-test, 2 sided
p-value: 0.00195% CI: [-1.6, -0.44]t-test, 2 sided
Comparison: Interleukin 10p-value: 0.05295% CI: [-0.76, 0.81]t-test, 2 sided
Comparison: Vascular Endotelial Grow Factor Ap-value: 0.81595% CI: [-0.5, 0.22]t-test, 2 sided
Comparison: TNF alfap-value: 0.74295% CI: [-0.42, 0.36]t-test, 2 sided
Comparison: Chemokine CXC ligand 2p-value: 0.60395% CI: [-0.36, 0.44]t-test, 2 sided
Primary
Oxidative Stress Response Marker:MDA (Malondialdehyde)
MDA (malondialdehyde) determination will be done with ELISA
Time frame: The values of the main variables will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1)
Population: It was impossible to measure MDA due to laboratory problems.
Primary
Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of)
f. CTGF connective tissue growth factor. g. MMP-9 matrix metalloproteinase-9. h. PAI-I plasminogen activator inhibitor-I. i. E-selectin. Samples will be processed to obtain total RNA with TRI Reagent™ (Sigma) and will be quantified with NanoDrop spectrophotometer.
Time frame: The values will be obtained from the study of peritoneal tissue samples one hour after the creation of the pneumoperitoneum (T1).
Population: 13 samples excluded
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | Connective tissue growth factor | 0.89 log (pg/ml) | Standard Error 0.61 |
| Control | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | Matrix metalloproteinasa-9 | 0.56 log (pg/ml) | Standard Error 1.15 |
| Control | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | Plasminogenin activator inhibitor | 0.74 log (pg/ml) | Standard Error 0.89 |
| Control | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | E- selectin | 0.66 log (pg/ml) | Standard Error 139 |
| Experimental | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | E- selectin | 0.57 log (pg/ml) | Standard Error 1.77 |
| Experimental | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | Connective tissue growth factor | 0.61 log (pg/ml) | Standard Error 0.84 |
| Experimental | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | Plasminogenin activator inhibitor | 0.24 log (pg/ml) | Standard Error 1.15 |
| Experimental | Remodeling Peritoneal Markers :( Gene Expression (mRNA) Levels of) | Matrix metalloproteinasa-9 | 0.47 log (pg/ml) | Standard Error 1.31 |
Comparison: Matrix metalloproteinase-9p-value: 0.695% CI: [-0.47, 0.65]t-test, 2 sided
Comparison: Plasminogen activator inhibitor-1p-value: 0.02895% CI: [0.03, 0.97]t-test, 2 sided
Comparison: E-selectinp-value: 0.80795% CI: [-0.64, 0.82]t-test, 2 sided