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 Table of Contents  
Year : 2022  |  Volume : 1  |  Issue : 2  |  Page : 47-49

2023 updates on the closed or open after-source control for severe complicated intraabdominal sepsis (COOL) trial

1 Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China
2 COOL Trial Global Management, Edmonton, Alberta, Canada
3 Departments of Surgery, Critical Care Medicine, and The Trauma Program, University of Calgary, Calgary, Alberta, Canada

Date of Submission16-Jan-2023
Date of Acceptance16-Jan-2023
Date of Web Publication15-Feb-2023

Correspondence Address:
Andrew W Kirkpatrick
Department of Surgery, Critical Care Medicine, and The Trauma Program, University of Calgary, Calgary, Alberta
Jianan Ren
Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/wjsi.wjsi_1_23

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How to cite this article:
Huang J, Ren J, McKee JL, Kirkpatrick AW. 2023 updates on the closed or open after-source control for severe complicated intraabdominal sepsis (COOL) trial. World J Surg Infect 2022;1:47-9

How to cite this URL:
Huang J, Ren J, McKee JL, Kirkpatrick AW. 2023 updates on the closed or open after-source control for severe complicated intraabdominal sepsis (COOL) trial. World J Surg Infect [serial online] 2022 [cited 2023 Mar 30];1:47-9. Available from: https://www.worldsurginfect.com/text.asp?2022/1/2/47/369703

  Background of Cool Trial Top

Intra-abdominal sepsis (IAS) is the second-most common form of sepsis, and it is expected to be particularly severe because of the complex anatomic, physiologic, and microbial characteristics of the abdominal cavity and the mutual influences and communications between hollow viscera.[1],[2] Antibiotics and source control are in the tool chest of doctors to deal with IAS, but they are challenged by some cases.[3] Drug-resistant bacteria have put antibiotics in an awkward situation, in which parts of bacteria are survived and trigger persistent inflammation via pathogen-associated molecular patterns. Moreover, source control failure leads to ongoing stimulation from the residual necrotic tissues and inflammatory body fluids such as digestive fluid and aggravates inflammatory reactions through damage-associated molecular patterns.[4] As such, “inflammatory ascites” has been described as a source of inflammatory mediators that may be transported to the systemic circulation, potentially propagating multisystem organ failure through gut-mediated lymphatics.[5]

Severe complicated IAS (SCIAS) represents the most difficult situation of IAS, and the incidence is gradually increasing in recent years as populations age. SCIAS typically results from secondary peritonitis and often requires early hemodynamic support, antimicrobial therapy, and surgical abdominal exploration for source control.[6] However, even when these therapies are promptly and adequately performed, SCIAS still has a high mortality rate in both developed and developing countries. To our disappointment, novel pharmacologic therapies, even with great expectation of an anti-bio-mediator effect, have not shown benefit to improve patient outcomes.[7],[8]

Alternatively, the open abdomen (OA) is increasingly being recommended in SCIAS, for many reasons, including its potential improved control of intraperitoneal contamination and removal of inflammatory bio-mediators.[9],[10] However, patients undergoing OA treatment for IAS have been reported with a greater risk of complications compared to trauma patients, including enteroatmospheric fistula (EAF) and intra-abdominal abscess formation, and a lower rate of primary fascial closure.[11] Despite the enthusiasm of many clinicians, the use of the OA in SCIAS, it lacks a prospective randomized controlled study to determine the exact benefits that SCIAS patients might obtain from OA management; and therefore, the routine use of OA for SCIAS remains questionable.

To attempt to definitively answer this critical question, pertinent to millions around the world, the Closed or Open after Laparotomy trial (COOL trial, https://clinicaltrials.Gov/ct2/show/NCT03163095) was launched in 2018 under the partial financial support of the Acelity Corporation.[12] Currently, the ongoing COOL trial is the largest prospective randomized controlled trial to investigate the comparative benefits in intra-operative SCIAS patients, of either formal closure of the fascia, or selecting an OA with management through the use of a negative pressure wound therapy (NPWT) dressing. At the initiation of the COOL trial, OA management in SCIAS patients randomly allocated to OPEN was strictly confined to the use of the AbThera dressing, which was occasionally provided to certain centers by the Acelity Corporation.

  Why Updates and What'S New? Top

The mission statement of the COOL trial was always to benefit the most patients around the world, thus hoping for the greatest scientific generalizability. However, at the Inaugural Investigators COOL Meeting in Parma, Italy, the COOL Steering Committee placed restrictions on potential global COOL participation, by stipulating that the NPWT dressing to be used would be only the AbThera dressing based on the financial considerations. Due to financial practicalities, the AbThera dressing is not accessible in less well-resourced countries where a noncommercial and self-made NPWT dressing will be utilized instead on SCIAS patients. Therefore, this decision made by the COOL Steering Committee was very controversial, and excluded the participation of the health-care systems that cannot provide the AbThera dressing.

On August 19, 2022, the 3M Company, who had acquired the Acelity Corporation, unilaterally canceled support for the COOL trial despite an existing research contract, generating great financial stress for the COOL investigators, primarily related to large and ongoing costs globally for International Clinical Trial Insurance, despite the huge international contributions of goodwill and voluntary efforts. On the other hand, termination of the contract has broken the restrictions on the use of AbThera dressing, allowing the use of any appropriate noncommercial temporary abdominal closure (TAC) that provides visceral protection, negative peritoneal pressure, and the controlled egress of intra-abdominal fluids. This practical development may thus help to recruit more health-care systems globally to take part in the COOL trial. We treated this unexpected event as a new start point to define a really inclusive and Global COOL trial.

Due to the extended types of NPWT dressings, it is necessary to introduce this evolution to the COOL trial and explain the deep logic underlying the changes. Encouragingly, statements on the changes of COOL trial have been almost done and will be published in the very near future by Dr. Andrew W Kirkpatrick et al., which require a detailed recording of types of NPWT dressing for TAC. A sub-analysis of types of NPWT devices may be needed to explain the final outcomes.

  Call for Participation Top

Dr. Jianan Ren has led the largest and the most prestigious intestinal fistula and intra-abdominal infections center in China for decades. Many patients with IAS achieved benefits from OA management, even though some of them were complicated with EAF and had to experience a prolonged hospital stay. Having the opportunity of enlargement of the COOL trial, Dr. Ren's medical center has participated in the design of this trial since its earliest conception, and Dr. Jianan Ren et al. contributed to the trial design before the first patient was recruited. As most of the members of the World Surgical Infection Society have a formal training of OA to treat IAS and even SCIAS patients, we really appreciate and expect your participation in the COOL trial!

  References Top

Mazuski JE, Tessier JM, May AK, Sawyer RG, Nadler EP, Rosengart MR, et al. The surgical infection society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt) 2017;18:1-76.  Back to cited text no. 1
Clements TW, Tolonen M, Ball CG, Kirkpatrick AW. Secondary peritonitis and intra-abdominal sepsis: An increasingly global disease in search of better systemic therapies. Scand J Surg 2021;110:139-49.  Back to cited text no. 2
Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: Guidelines by the surgical infection society and the infectious diseases society of America. Surg Infect (Larchmt) 2010;11:79-109.  Back to cited text no. 3
Rajaee A, Barnett R, Cheadle WG. Pathogen – And danger-associated molecular patterns and the cytokine response in sepsis. Surg Infect (Larchmt) 2018;19:107-16.  Back to cited text no. 4
Kirkpatrick AW, Xiao J, Jenne CN, Roberts DJ. Inflammatory mediators in intra-abdominal sepsis. In: Sartelli M, Bassetti M, Martin-Loeches I, editors. Abdominal Sepsis: A Multidisciplinary Approach. Cham: Springer International Publishing; 2018. p. 15-28.  Back to cited text no. 5
Anaya DA, Nathens AB. Risk factors for severe sepsis in secondary peritonitis. Surg Infect (Larchmt) 2003;4:355-62.  Back to cited text no. 6
Ke L, Zhou J, Mao W, Chen T, Zhu Y, Pan X, et al. Immune enhancement in patients with predicted severe acute necrotising pancreatitis: A multicentre double-blind randomised controlled trial. Intensive Care Med 2022;48:899-909.  Back to cited text no. 7
Pickkers P, Mehta RL, Murray PT, Joannidis M, Molitoris BA, Kellum JA, et al. Effect of human recombinant alkaline phosphatase on 7-day creatinine clearance in patients with sepsis-associated acute kidney injury: A randomized clinical trial. JAMA 2018;320:1998-2009.  Back to cited text no. 8
Sartelli M, Abu-Zidan FM, Ansaloni L, Bala M, Beltrán MA, Biffl WL, et al. The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper. World J Emerg Surg 2015;10:35.  Back to cited text no. 9
Girard E, Abba J, Boussat B, Trilling B, Mancini A, Bouzat P, et al. Damage control surgery for non-traumatic abdominal emergencies. World J Surg 2018;42:965-73.  Back to cited text no. 10
Song X, Song Y, Yuan Y, Zhang P, Zhang X. Prognostic value of presepsin for outcomes and complications in enterocutaneous fistula complicated by abdominal sepsis. Int J Surg 2016;33 Pt A: 96-101.  Back to cited text no. 11
Kirkpatrick AW, Coccolini F, Ansaloni L, Roberts DJ, Tolonen M, McKee JL, et al. Closed or open after source control laparotomy for severe complicated intra-abdominal sepsis (the COOL trial): Study protocol for a randomized controlled trial. World J Emerg Surg 2018;13:26.  Back to cited text no. 12


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