Peritoneal Inflammation Clinical Trial
Official title:
Effect of Intraoperative Humidified CO2 Insufflation in Open Laparotomy Colorectal Surgery Patients: a Randomized Controlled Trial
The operating theatre is deliberately made to be cold and dry to prevent bacteria from
growing. The problem with this is that during open abdominal surgery, the intestine and the
overlying peritoneum is exposed to cold dry air. Surgeons try to stop the bowel/peritoneum
from drying by applying warmed saline packs periodically to the bowel. However, this is not
always possible. Sometimes, the surgeon has to perform an important component of the
procedure (attach bowel/blood vessels together etc) and the bowel/peritoneum visibly dries.
When bowel/peritoneum dries damage occurs, inducing inflammation. Inflamed bowel/peritoneum
causes the bowel to stick together and form adhesions. Bowel adhesions can cause bowel
obstruction. This vicious cycle is repeated when the patient undergoes repetitive open
abdominal operations.
This study aimed to be the first human study to:
1. Demonstrate that peritoneal inflammation occurs during open abdominal surgery and also
to demonstrate that pro-inflammatory cells (polymorphs, macrophages) are activated
during the progress of the operation. This study aims to show that mRNA(using Q-PCR) is
increased for pro-inflammatory cytokines. This study also aim to show that
proinflammatory cytokines (Interleukin(IL)-1,2,6,9,10, and TNF by ELISA/confirmed using
Western Blotting) are elevated during the course of the operation.
2. Demonstrate that the mechanism of bowel/peritoneal inflammation is causally related to
the bowel/peritoneum drying (dessication).
This study will attempt to prove this by using humidified, warmed carbon dioxide gas which
will warm and moisten the peritoneum/bowel. It is proposed that this will arrest the
peritoneal injury and the inflammation. The investigators will attain peritoneal samples
during open colorectal operations. The investigators will obtain samples at the beginning
and end of the operation. This study design is a randomized controlled trial, where half the
patients will receive humidified, warmed carbon dioxide gas during surgery, and the other
half will get standard open surgery without carbon dioxide. 40 patients will be recruited in
this study. Half (20) will get CO2, and other half (20) will get standard open surgery.
Forty patients undergoing open colorectal surgery will be recruited in this randomized
controlled trial.
The study group will receive warmed (37°C), humidified (98% RH) carbon dioxide. The
delivered gas will be defined by the United States Pharmacopeia and National Formulary,
which requires impurity of less than 200 parts per million, including water vapour. This
medical grade CO2 will be warmed to 37°C and humidified to 98% RH using humidification
system. The sterility of the system will be assessed regularly as per protocol.
The control group will receive no gas insufflation into the open laparotomy wound. This is
current standard practice for all patients undergoing open laparotomy for colorectal
resection.
The device that will be used for insufflation of sterile, humidified, warmed CO2 is the
Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand).
It consists of a bacterial filter and a humidification chamber filed with 180mL sterile
water, positioned on a humidifier controller that includes an integrated temperature and
flow sensor. The outlet of the humidification chamber is connected to a thermally insulated
2.5m-long heated insufflation tube that maintains temperature and humidity of the gas to its
outlet. The warm and humidified CO2 enters a gas diffuser (ST300DF VITA-diffuserTM, Cardia
Innovation AB, Stockholm, Sweden) consisting of a 25cm-long polyvinylchloride tube (inner
diameter of 2.5mm) with polyurethane foam at its end. The cylindrical polyurethane foam tip
diverts the gas jet in multiple directions via the many small paths inside the foam. The gas
is thus uniformly distributed and the large diffuser surface area greatly reduces the
velocity of the outflow. Thus the system delivers humidified CO2 at 100% relative humidity
and 37C to the surgical wound. The gas diffuser will be positioned inside the open abdominal
wound cavity (in the right cranial quadrant) at a depth of approximately 4cm from the skin
as soon as the abdominal wall retraction has been done. The insufflation of warm humidified
CO2 will then start and continue until the abdominal wall retractors are removed and
abdominal wall is commenced to be closed.
Calculation of Power: The investigators estimated sample size of 40 patients for 80% power
using the literatures' reported standard deviation of levels of 3-chlorotyrosine (which is
one of the study's primary biochemical markers of inflammation)
ANALYSIS OF BIOCHEMICAL AND MOLECULAR MARKERS: Where acquired, samples of the human tissue
obtained (above) will be homogenised and assigned to biochemistry and molecular analyses.
Total RNA will be extracted using a commercial kit, converted to cloned DNA and then probed
for various pro-inflammatory genes. Where a change in gene regulation is noted, the
investigators will assess the corresponding change in protein level using a combined
approach consisting of multiplex ELISA to quantify changes in protein levels and further
confirmation with Western blotting using corresponding specific antibodies.
STATISTICAL ANALYSIS: Statistical analysis will be performed using SPSS for Windows version
18.0 GradPack (IBM, New York, USA). Non-parametric continuous variables will be tested using
Mann-Whitney U tests and parametric continuous variable will be tested using t-test/ANOVA.
Categorical variables will be tested using Fisher exact test.
OUTCOME AND STUDY END POINT:
The study will involve both clinical and laboratory based work, and the outcomes are as
follows.
1. Laboratory based work:
From each patient, 4 samples will be taken and hence 160 samples will be analysed.
From each sample, the investigators will analyse the activation of pro-inflammatory
cells (polymorphs, macrophages), level of messenger RNA.
The investigators will analyse level of (pro)inflammatory cytokines-- IL1,2,6,9,10, and
TNF.
The investigators will assess the relationship between time (duration of operation) and
the inflammatory markers.
The study will aim to prove that prove that as duration of operation increase, the
extent of in inflammation the intestine's surface increases, and that this process can
be mitigated by using humidified warmed carbon dioxide gas.
2. Clinical based work:
The study will see whether use of humidified, warmed carbon dioxide gas results in:
- Better core body temperature control
- Less postoperative pain
- Shorter hospital stay
- Less risk of complications, including wound infection, anastomotic leaks.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT04687384 -
Systemic and Peritoneal Inflammatory Response In Robotic-assisted And Laparoscopic Surgery for Colon Cancer
|
N/A | |
| Completed |
NCT00642005 -
Humidification in Laparoscopic Colonic Surgery
|
N/A |