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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02975947

Registration number

NCT02975947

Ethics application status

Date submitted

2/11/2016

Date registered

29/11/2016

Titles & IDs

Public title

Effect of Warmed Humidified CO2 on Peritoneum During Laparotomy

Scientific title

Effect of Intraoperative Humidified CO2 Insufflation in Open Laparotomy Colorectal Surgery Patients: a Randomized Controlled Trial

Secondary ID [1]

HREC/12/CRGH/196

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Peritoneal Inflammation

Peritoneum; Injury

Condition category

Condition code

Inflammatory and Immune System

Other inflammatory or immune system disorders

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Devices - Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand)
Treatment: Devices - Standard heating

Active comparator: Control Group - Standard intraoperative warming measures including heated blankets, heating with forced warmed air, warming of fluids, and insulation of limbs and head.

Experimental: Study Group - The study group will receive warmed (37°C), humidified (98% RH) carbon dioxide delivered into the open peritoneal cavity.

Treatment: Devices: Humidified, warmed CO2 insufflation of open peritoneum using Fisher & Paykel's HUMIGARD (Fisher & Paykel Healthcare Ltd, Auckland, New Zealand)
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.

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

Intervention code [1]

Treatment: Devices

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Change in Inflammatory cytokine level in the peritoneal biopsy samples

Timepoint [1]

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)

Primary outcome [2]

Intraoperative temperature at 30 minutes from start of operation

Timepoint [2]

30 minutes from start of operation

Primary outcome [3]

Intraoperative temperature at 60 minutes from start of operation

Timepoint [3]

60 minutes from start of operation

Secondary outcome [1]

Postoperative Analgesia requirement for pain

Timepoint [1]

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

Secondary outcome [2]

Length of in-patient hospital stay

Timepoint [2]

duration of hospital stay, an expected average of 1 week

Secondary outcome [3]

Anastomotic leaks

Timepoint [3]

6 months

Eligibility

Key inclusion criteria

* 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.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

* 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

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Parallel

Other design features

Phase

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

1/08/2013

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

1/06/2016

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Concord Repatriation General Hospital - Sydney

Recruitment postcode(s) [1]

2138 - Sydney

Funding & Sponsors

Primary sponsor type

Other

Name

Concord Repatriation General Hospital

Address

Country

Ethics approval

Ethics application status

Summary

Brief 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. 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.

Trial website

https://clinicaltrials.gov/study/NCT02975947

Trial related presentations / 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.
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.
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.
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.
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.
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.
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.
Hannenberg AA, Sessler DI. Improving perioperative temperature management. Anesth Analg. 2008 Nov;107(5):1454-7. doi: 10.1213/ane.0b013e318181f6f2. No abstract available.
Sessler DI. Temperature monitoring and perioperative thermoregulation. Anesthesiology. 2008 Aug;109(2):318-38. doi: 10.1097/ALN.0b013e31817f6d76.
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.
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.
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.
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.
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.
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.
Ivarsson ML, Bergstrom M, Eriksson E, Risberg B, Holmdahl L. Tissue markers as predictors of postoperative adhesions. Br J Surg. 1998 Nov;85(11):1549-54. doi: 10.1046/j.1365-2168.1998.00859.x.
Moehrlen U, Ziegler U, Boneberg E, Reichmann E, Gitzelmann CA, Meuli M, Hamacher J. Impact of carbon dioxide versus air pneumoperitoneum on peritoneal cell migration and cell fate. Surg Endosc. 2006 Oct;20(10):1607-13. doi: 10.1007/s00464-005-0775-4. Epub 2006 Jul 3.
Erikoglu M, Yol S, Avunduk MC, Erdemli E, Can A. Electron-microscopic alterations of the peritoneum after both cold and heated carbon dioxide pneumoperitoneum. J Surg Res. 2005 May 1;125(1):73-7. doi: 10.1016/j.jss.2004.11.029.
Enfors SO, Molin G. The influence of high concentrations of carbon dioxide on the germination of bacterial spores. J Appl Bacteriol. 1978 Oct;45(2):279-85. doi: 10.1111/j.1365-2672.1978.tb04223.x. No abstract available.
Ott DE. Correction of laparoscopic insufflation hypothermia. J Laparoendosc Surg. 1991 Aug;1(4):183-6. doi: 10.1089/lps.1991.1.183.
Frank SM, Beattie C, Christopherson R, Norris EJ, Perler BA, Williams GM, Gottlieb SO. Unintentional hypothermia is associated with postoperative myocardial ischemia. The Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology. 1993 Mar;78(3):468-76. doi: 10.1097/00000542-199303000-00010.
Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A. Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. Lancet. 1996 Feb 3;347(8997):289-92. doi: 10.1016/s0140-6736(96)90466-3.
Hazebroek EJ, Schreve MA, Visser P, De Bruin RW, Marquet RL, Bonjer HJ. Impact of temperature and humidity of carbon dioxide pneumoperitoneum on body temperature and peritoneal morphology. J Laparoendosc Adv Surg Tech A. 2002 Oct;12(5):355-64. doi: 10.1089/109264202320884108.
Cheong JY, Chami B, Fong GM, Wang XS, Keshava A, Young CJ, Witting P. Randomized clinical trial of the effect of intraoperative humidified carbon dioxide insufflation in open laparotomy for colorectal resection. BJS Open. 2020 Feb;4(1):45-58. doi: 10.1002/bjs5.50227. Epub 2019 Nov 17.

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Type	Citations or Other Details
Journal	Persson M, van der Linden J. Intraoperative CO2 in... [More Details]
Journal	Persson M, van der Linden J. Can wound desiccation... [More Details]
Journal	Persson M, Elmqvist H, van der Linden J. Topical h... [More Details]
Journal	Persson M, Svenarud P, Flock JI, van der Linden J.... [More Details]
Journal	Persson M, van der Linden J. Wound ventilation wit... [More Details]
Journal	Svenarud P, Persson M, Van Der Linden J. Efficienc... [More Details]
Journal	Svenarud P, Persson M, van der Linden J. Intermitt... [More Details]
Journal	Hannenberg AA, Sessler DI. Improving perioperative... [More Details]
Journal	Sessler DI. Temperature monitoring and perioperati... [More Details]
Journal	Insler SR, Sessler DI. Perioperative thermoregulat... [More Details]
Journal	Sessler DI. Non-pharmacologic prevention of surgic... [More Details]
Journal	Binda MM, Koninckx PR. Prevention of adhesion form... [More Details]
Journal	Tsuchiya M, Sato EF, Inoue M, Asada A. Open abdomi... [More Details]
Journal	Peng Y, Zheng M, Ye Q, Chen X, Yu B, Liu B. Heated... [More Details]
Journal	Brokelman WJ, Holmdahl L, Bergstrom M, Falk P, Kli... [More Details]
Journal	Ivarsson ML, Bergstrom M, Eriksson E, Risberg B, H... [More Details]
Journal	Moehrlen U, Ziegler U, Boneberg E, Reichmann E, Gi... [More Details]
Journal	Erikoglu M, Yol S, Avunduk MC, Erdemli E, Can A. E... [More Details]
Journal	Enfors SO, Molin G. The influence of high concentr... [More Details]
Journal	Ott DE. Correction of laparoscopic insufflation hy... [More Details]
Journal	Frank SM, Beattie C, Christopherson R, Norris EJ, ... [More Details]
Journal	Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A. ... [More Details]
Journal	Hazebroek EJ, Schreve MA, Visser P, De Bruin RW, M... [More Details]

Results not provided in https://clinicaltrials.gov/study/NCT02975947

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For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02975947