. 2018 Jun 22:13:26.

doi: 10.1186/s13017-018-0183-4. eCollection 2018.

Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial

Andrew W Kirkpatrick^{1

2

3}, Federico Coccolini⁴, Luca Ansaloni⁵, Derek J Roberts¹, Matti Tolonen⁶, Jessica L McKee⁷, Ari Leppaniemi⁶, Peter Faris⁸, Christopher J Doig^{2

9}, Fausto Catena¹⁰, Timothy Fabian¹¹, Craig N Jenne², Osvaldo Chiara¹², Paul Kubes^{13

14

15}, Braden Manns^{10

16

17}, Yoram Kluger¹⁸, Gustavo P Fraga¹⁹, Bruno M Pereira¹⁹, Jose J Diaz²⁰, Michael Sugrue²¹, Ernest E Moore²², Jianan Ren²³, Chad G Ball²⁴, Raul Coimbra^{25

26}, Zsolt J Balogh^{27

28}, Fikri M Abu-Zidan²⁹, Elijah Dixon^{1

10

30

31}, Walter Biffl³², Anthony MacLean¹, Ian Ball^{33

34}, John Drover^{35

36}, Paul B McBeth^{1

2

3}, Juan G Posadas-Calleja², Neil G Parry^{37

38}, Salomone Di Saverio³⁹, Carlos A Ordonez⁴⁰, Jimmy Xiao⁷, Massimo Sartelli⁴¹; Closed Or Open after Laparotomy (COOL) after Source Control for Severe Complicated Intra-Abdominal Sepsis Investigators

Affiliations

¹ 1Department of Surgery, University of Calgary, Calgary, Alberta Canada.
² 2Department of Critical Care Medicine, University of Calgary, Calgary, Alberta Canada.
³ 3The Trauma Program, University of Calgary, Calgary, Alberta Canada.
⁴ 4General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy.
⁵ 5Unit of General and Emergency Surgery, Bufalini Hospital of Cesena, Cesena, Italy.
⁶ 6Department of Abdominal Surgery, Abdominal Center, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
⁷ 7Regional Trauma Services, Foothills Medical Centre, Calgary, Alberta Canada.
⁸ 8Research Facilitation Analytics (DIMR), University of Calgary, Calgary, Alberta Canada.
⁹ 9Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁰ 10Emergency Surgery Department, Parma University Hospital, Parma, Italy.
¹¹ 11Surgery, University of Tennessee Health Sciences Center Memphis, Memphis, TN USA.
¹² General Surgery and Trauma Team Niguarda Hospital Milano, Milan, Italy.
¹³ 13Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta Canada.
¹⁴ 14Department of Physiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁵ 15Department of Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁶ 16Department of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁷ 17Libin Cardiovascular Institute and O'Brien Institute of Public Health, University of Calgary, Calgary, Alberta Canada.
¹⁸ Rambam Health Care Campus, Haifa, Israel.
¹⁹ 19Division of Trauma Surgery, University of Campinas, Campinas, SP Brazil.
²⁰ 20Department of Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School on Medicine, Baltimore, MD USA.
²¹ 21Donegal Clinical Research Academy, Letterkenny University Hospital, Donegal, Ireland.
²² 22Trauma and Critical Care Research, University of Colorado, Denver, CO USA.
²³ 23Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
²⁴ 24General, Acute Care, and Hepatobiliary Surgery, and Regional Trauma Services, University of Calgary, Calgary, Alberta Canada.
²⁵ 25Riverside University Health System Medical Center, Loma Linda, CA USA.
²⁶ 26Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA USA.
²⁷ 27John Hunter Hospital and Hunter New England Health District, Newcastle, NSW Australia.
²⁸ 28Surgery and Traumatology, University of Newcastle, Newcastle, NSW Australia.
²⁹ 29Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates.
³⁰ 30Surgical Oncology, University of Calgary, Calgary, Alberta Canada.
³¹ 31City Wide Section of General Surgery, University of Calgary, Calgary, Alberta Canada.
³² 32Scripps Memorial Hospital La Jolla, La Jolla, California USA.
³³ 33Department of Medicine, Western University, London, Ontario Canada.
³⁴ 34Department of Epidemiology and Biostatistics, Western University, London, Ontario Canada.
³⁵ 35Department of Critical Care Medicine, Queen's University, Kingston, Ontario Canada.
³⁶ 36Department of Surgery, Queen's University, Kingston, Ontario Canada.
³⁷ 37Department of Surgery, Western University, Victoria Hospital, London Health Sciences Centre, London, Ontario Canada.
³⁸ 38Department of Critical Care, Western University, Victoria Hospital, London Health Sciences Centre, London, Ontario Canada.
³⁹ 39Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁴⁰ 40Department of Surgery, Fundación Valle del Lili and Universidad Del Valle, Cali, Colombia.
⁴¹ Department of Surgery, Macerata Hospital, Macerata, Italy.

PMID: 29977328
PMCID: PMC6015449
DOI: 10.1186/s13017-018-0183-4

Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial

Andrew W Kirkpatrick et al. World J Emerg Surg. 2018.

. 2018 Jun 22:13:26.

doi: 10.1186/s13017-018-0183-4. eCollection 2018.

Authors

Affiliations

¹ 1Department of Surgery, University of Calgary, Calgary, Alberta Canada.
² 2Department of Critical Care Medicine, University of Calgary, Calgary, Alberta Canada.
³ 3The Trauma Program, University of Calgary, Calgary, Alberta Canada.
⁴ 4General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy.
⁵ 5Unit of General and Emergency Surgery, Bufalini Hospital of Cesena, Cesena, Italy.
⁶ 6Department of Abdominal Surgery, Abdominal Center, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
⁷ 7Regional Trauma Services, Foothills Medical Centre, Calgary, Alberta Canada.
⁸ 8Research Facilitation Analytics (DIMR), University of Calgary, Calgary, Alberta Canada.
⁹ 9Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁰ 10Emergency Surgery Department, Parma University Hospital, Parma, Italy.
¹¹ 11Surgery, University of Tennessee Health Sciences Center Memphis, Memphis, TN USA.
¹² General Surgery and Trauma Team Niguarda Hospital Milano, Milan, Italy.
¹³ 13Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta Canada.
¹⁴ 14Department of Physiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁵ 15Department of Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁶ 16Department of Medicine, University of Calgary, Calgary, Alberta Canada.
¹⁷ 17Libin Cardiovascular Institute and O'Brien Institute of Public Health, University of Calgary, Calgary, Alberta Canada.
¹⁸ Rambam Health Care Campus, Haifa, Israel.
¹⁹ 19Division of Trauma Surgery, University of Campinas, Campinas, SP Brazil.
²⁰ 20Department of Surgery, R Adams Cowley Shock Trauma Center, University of Maryland School on Medicine, Baltimore, MD USA.
²¹ 21Donegal Clinical Research Academy, Letterkenny University Hospital, Donegal, Ireland.
²² 22Trauma and Critical Care Research, University of Colorado, Denver, CO USA.
²³ 23Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
²⁴ 24General, Acute Care, and Hepatobiliary Surgery, and Regional Trauma Services, University of Calgary, Calgary, Alberta Canada.
²⁵ 25Riverside University Health System Medical Center, Loma Linda, CA USA.
²⁶ 26Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA USA.
²⁷ 27John Hunter Hospital and Hunter New England Health District, Newcastle, NSW Australia.
²⁸ 28Surgery and Traumatology, University of Newcastle, Newcastle, NSW Australia.
²⁹ 29Department of Surgery, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates.
³⁰ 30Surgical Oncology, University of Calgary, Calgary, Alberta Canada.
³¹ 31City Wide Section of General Surgery, University of Calgary, Calgary, Alberta Canada.
³² 32Scripps Memorial Hospital La Jolla, La Jolla, California USA.
³³ 33Department of Medicine, Western University, London, Ontario Canada.
³⁴ 34Department of Epidemiology and Biostatistics, Western University, London, Ontario Canada.
³⁵ 35Department of Critical Care Medicine, Queen's University, Kingston, Ontario Canada.
³⁶ 36Department of Surgery, Queen's University, Kingston, Ontario Canada.
³⁷ 37Department of Surgery, Western University, Victoria Hospital, London Health Sciences Centre, London, Ontario Canada.
³⁸ 38Department of Critical Care, Western University, Victoria Hospital, London Health Sciences Centre, London, Ontario Canada.
³⁹ 39Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
⁴⁰ 40Department of Surgery, Fundación Valle del Lili and Universidad Del Valle, Cali, Colombia.
⁴¹ Department of Surgery, Macerata Hospital, Macerata, Italy.

PMID: 29977328
PMCID: PMC6015449
DOI: 10.1186/s13017-018-0183-4

Abstract

Background: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. Principles of treatment include early antibiotic administration and operative source control. A further therapeutic option may be open abdomen (OA) management with active negative peritoneal pressure therapy (ANPPT) to remove inflammatory ascites and ameliorate the systemic damage from SCIAS. Although there is now a biologic rationale for such an intervention as well as non-standardized and erratic clinical utilization, this remains a novel therapy with potential side effects and clinical equipoise.

Methods: The Closed Or Open after Laparotomy (COOL) study will constitute a prospective randomized controlled trial that will randomly allocate eligible surgical patients intra-operatively to either formal closure of the fascia or use of the OA with application of an ANPTT dressing. Patients will be eligible if they have free uncontained intra-peritoneal contamination and physiologic derangements exemplified by septic shock OR a Predisposition-Infection-Response-Organ Dysfunction Score ≥ 3 or a World-Society-of-Emergency-Surgery-Sepsis-Severity-Score ≥ 8. The primary outcome will be 90-day survival. Secondary outcomes will be logistical, physiologic, safety, bio-mediators, microbiological, quality of life, and health-care costs. Secondary outcomes will include days free of ICU, ventilation, renal replacement therapy, and hospital at 30 days from the index laparotomy. Physiologic secondary outcomes will include changes in intensive care unit illness severity scores after laparotomy. Bio-mediator outcomes for participating centers will involve measurement of interleukin (IL)-6 and IL-10, procalcitonin, activated protein C (APC), high-mobility group box protein-1, complement factors, and mitochondrial DNA. Economic outcomes will comprise standard costing for utilization of health-care resources.

Discussion: Although facial closure after SCIAS is considered the current standard of care, many reports are suggesting that OA management may improve outcomes in these patients. This trial will be powered to demonstrate a mortality difference in this highly lethal and morbid condition to ensure critically ill patients are receiving the best care possible and not being harmed by inappropriate therapies based on opinion only.

Trial registration: ClinicalTrials.gov, NCT03163095.

Keywords: Bio-mediators; Intra-peritoneal sepsis; Laparotomy; Multiple organ dysfunction; Open-abdomen; Peritonitis; Randomized trial; Septic shock.

PubMed Disclaimer

Conflict of interest statement

The COOL trial has been ethically approved at the lead and pilot center by the Conjoint Health Research Ethics Board (CHREB) of the University of Calgary (REB16-1588). The study has also been registered with the National Institutes of Health (ClinicalTrials.gov, identifier: NCT03163095).Andrew W. Kirkpatrick serves in the Canadian Forces Medical Services and has consulted for the Innovative Trauma Care and Acelity Corporations. Jessica L. McKee declares that she has consulted for Innovative Trauma Care, Aceso, and the Acelity Corporations. Osvaldo Chiara reported having consulted for the Acelity Corporation. Jose J. Diaz reported having consulted for the Acelity Corporation. Michael Sugrue reported having consulted for the Smith and Nephew Corporation. Ernest E. Moore reported Research support and intellectual property related to the Haemonetics, TEM Systems, Pryor Corporations, and being a Cofounder of Thrombo Therapeutics Inc. The remaining authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 2**
Participant time line for COOL recruitment

See this image and copyright information in PMC

References

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Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial

Affiliations

Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial): study protocol for a randomized controlled trial

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Associated data

LinkOut - more resources

Full Text Sources

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Medical

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