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Peritoneal InflammationNCT02975947

Effect of Warmed Humidified CO2 on Peritoneum During Laparotomy

A study testing Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand) and Standard heating in people with Peritoneal Inflammation and Peritoneum; Injury, run by Concord Repatriation General Hospital at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Peritoneal Inflammation, Peritoneum; Injury
What is being tested?
Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand) and Standard heating
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteAustralia
Study dates
Aug 2013to Jun 2016
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults above age 18.
  • Elective patients.
  • Pathologies: colorectal carcinoma, polyposis syndromes, diverticular diseases, prolapses, and patients with inflammatory bowel disease undergoing elective resection.
  • For colorectal carcinoma, all patients whether they are having curative or palliative surgery will be included.
  • Patients undergoing open elective colectomy, with or without stoma formation/ bowel anastomosis.

Who cannot join

  • Patients undergoing acute surgery (emergency surgery).
  • Patients undergoing Laparoscopic colectomy (multiport, single incision and also hand assisted) as all these patients receive heated humidified CO2.
  • For COPD patients, the exclusion criteria would be patients: (1) On home oxygen, (2) Type 2 respiratory failure (CO2 retainers) (3) FEV1<1L, or FEV1/FVC <50% of predicted

Trial locations and contacts

1 site in 1 country.

Australia1 site
  • Concord Repatriation General Hospital

    Sydney, New South Wales, 2138

Other trials in Australia

About this study

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:

Read more
  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.

Read the detailed description

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.
Being tested
Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand), Standard heating
Medical subject headings
Peritonitis, Wounds and Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand)Device

    The study group will receive warmed (37°C), humidified (98% RH) carbon dioxide into the open peritoneal cavity using the Fisher \& Paykel's HUMIGARD system (Fisher \& Paykel Healthcare Ltd, Auckland, New Zealand). This will create a local atmosphere of 100% carbon dioxide (warmed, humidified) in the open peritoneal cavity.

  • Standard heatingDevice

    Standard intraoperative warming measures including heated blankets, heating with forced warmed air, warming of fluids, and insulation of limbs and head

Study groups in NCT02975947
Study groupRoleWhat they receive
Control GroupActive comparatorStandard intraoperative warming measures including heated blankets, heating with forced warmed air, warming of fluids, and insulation of limbs and head.
Receives: Device: Standard heating
Study GroupExperimentalThe study group will receive warmed (37°C), humidified (98% RH) carbon dioxide delivered into the open peritoneal cavity.
Receives: Device: Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Inflammatory cytokine level in the peritoneal biopsy samples

    Peritoneal samples will be taken when the peritoneal cavity is being opened (at beginning of operation), and also when the peritoneal cavity is being closed (at end of the operation). The change in the level of inflammatory cytokines in between these two time points will be measured

    Measured: At the moment of time when: (1) peritoneal cavity is being opened, (2) when peritoneal cavity is being closed (expected average of 2 hours after peritoneal cavity is first opened)

  2. Intraoperative temperature at 30 minutes from start of operation

    Temperature readings during the operation will be taken. Both core body temperature (esophageal) and intraperitoneal temperature will be measured.

    Measured: 30 minutes from start of operation

  3. Intraoperative temperature at 60 minutes from start of operation

    Temperature readings during the operation will be taken. Both core body temperature (esophageal) and intraperitoneal temperature will be measured.

    Measured: 60 minutes from start of operation

Secondary outcomes (3)
  1. Postoperative Analgesia requirement for pain

    Postoperative pain as measured by MEDD (Morphine Equivalent Daily Dose)

    Measured: Time from when the patient is moved out of operating theater to when the patient is no longer an inpatient in the hospital ward (discharged), with an expected average of 1 week

  2. Length of in-patient hospital stay

    number of days patient stayed postoperatively in hospital

    Measured: duration of hospital stay, an expected average of 1 week

  3. Anastomotic leaks

    The occurrence of anastomotic leak in the 6 months after the surgery

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Nov 2016 (estimated)
  2. Study startAug 2013
  3. Primary completionJun 2016
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02975947
Sponsor's protocol ID
HREC/12/CRGH/196
Status last verified
Nov 2016
First submitted
2 Nov 2016
Last updated
29 Nov 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Persson M, van der Linden J. Intraoperative CO2 insufflation can decrease the risk of surgical site infection. Med Hypotheses. 2008;71(1):8-13. doi: 10.1016/j.mehy.2007.12.016. Epub 2008 Mar 4.

    PubMed 18304752
  • Persson M, van der Linden J. Can wound desiccation be averted during cardiac surgery? An experimental study. Anesth Analg. 2005 Feb;100(2):315-320. doi: 10.1213/01.ANE.0000140243.97570.DE.

    PubMed 15673849
  • Persson M, Elmqvist H, van der Linden J. Topical humidified carbon dioxide to keep the open surgical wound warm: the greenhouse effect revisited. Anesthesiology. 2004 Oct;101(4):945-9. doi: 10.1097/00000542-200410000-00020.

    PubMed 15448528
  • Persson M, Svenarud P, Flock JI, van der Linden J. Carbon dioxide inhibits the growth rate of Staphylococcus aureus at body temperature. Surg Endosc. 2005 Jan;19(1):91-4. doi: 10.1007/s00464-003-9334-z. Epub 2004 Nov 11.

    PubMed 15529188
  • Persson M, van der Linden J. Wound ventilation with ultraclean air for prevention of direct airborne contamination during surgery. Infect Control Hosp Epidemiol. 2004 Apr;25(4):297-301. doi: 10.1086/502395.

    PubMed 15108726
  • Svenarud P, Persson M, Van Der Linden J. Efficiency of a gas diffuser and influence of suction in carbon dioxide deairing of a cardiothoracic wound cavity model. J Thorac Cardiovasc Surg. 2003 May;125(5):1043-9. doi: 10.1067/mtc.2003.50.

    PubMed 12771877
  • Svenarud P, Persson M, van der Linden J. Intermittent or continuous carbon dioxide insufflation for de-airing of the cardiothoracic wound cavity? An experimental study with a new gas-diffuser. Anesth Analg. 2003 Feb;96(2):321-7, table of contents. doi: 10.1097/00000539-200302000-00005.

    PubMed 12538172
  • Hannenberg AA, Sessler DI. Improving perioperative temperature management. Anesth Analg. 2008 Nov;107(5):1454-7. doi: 10.1213/ane.0b013e318181f6f2. No abstract available.

    PubMed 18931198
  • Sessler DI. Temperature monitoring and perioperative thermoregulation. Anesthesiology. 2008 Aug;109(2):318-38. doi: 10.1097/ALN.0b013e31817f6d76.

    PubMed 18648241
  • Insler SR, Sessler DI. Perioperative thermoregulation and temperature monitoring. Anesthesiol Clin. 2006 Dec;24(4):823-37. doi: 10.1016/j.atc.2006.09.001.

    PubMed 17342966
  • Sessler DI. Non-pharmacologic prevention of surgical wound infection. Anesthesiol Clin. 2006 Jun;24(2):279-97. doi: 10.1016/j.atc.2006.01.005.

    PubMed 16927930
  • Binda MM, Koninckx PR. Prevention of adhesion formation in a laparoscopic mouse model should combine local treatment with peritoneal cavity conditioning. Hum Reprod. 2009 Jun;24(6):1473-9. doi: 10.1093/humrep/dep053. Epub 2009 Mar 3.

    PubMed 19258346
  • Tsuchiya M, Sato EF, Inoue M, Asada A. Open abdominal surgery increases intraoperative oxidative stress: can it be prevented? Anesth Analg. 2008 Dec;107(6):1946-52. doi: 10.1213/ane.0b013e318187c96b.

    PubMed 19020142
  • Peng Y, Zheng M, Ye Q, Chen X, Yu B, Liu B. Heated and humidified CO2 prevents hypothermia, peritoneal injury, and intra-abdominal adhesions during prolonged laparoscopic insufflations. J Surg Res. 2009 Jan;151(1):40-7. doi: 10.1016/j.jss.2008.03.039. Epub 2008 Apr 23.

    PubMed 18639246
  • Brokelman WJ, Holmdahl L, Bergstrom M, Falk P, Klinkenbijl JH, Reijnen MM. Heating of carbon dioxide during insufflation alters the peritoneal fibrinolytic response to laparoscopic surgery : A clinical trial. Surg Endosc. 2008 May;22(5):1232-6. doi: 10.1007/s00464-007-9597-x. Epub 2007 Oct 18.

    PubMed 17943363

Questions about this trial

What is this clinical trial studying?

A study testing Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand) and Standard heating in people with Peritoneal Inflammation and Peritoneum; Injury, run by Concord Repatriation General Hospital at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Inflammatory cytokine level in the peritoneal biopsy samples (time frame: At the moment of time when: (1) peritoneal cavity is being opened, (2) when peritoneal cavity is being closed (expected average of 2 hours after peritoneal cavity is first opened)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02975947, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2016.

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