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Closed or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis: The COOL Trial

Learn about the COOL study, a randomized controlled trial investigating whether the open abdomen is indicated for intra-abdominal sepsis. Explore the benefits and potential risks of leaving the abdomen open, and discover the latest findings on mortality rates and outcomes.

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Closed or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis: The COOL Trial

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  1. Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (The COOL Trial): A Randomized Controlled Trial Protocol-ClinicalTrials.gov Identifier: NCT03163095 From the Closed Or Open after Laparotomy (COOL) for Source Control in Severe Complicated Intra-Abdominal Sepsis Investigators

  2. More information • Coolstudy.ca • World Journal of Emerg Surg • ClinicalTrials.gov Identifier: NCT03163095 • Andrew Kirkpatrick • Jessica McKee • (jlb9@ucalgary.ca) World Journal Emerg Surg 2018 COOL Study Intro Slides Nov 2018

  3. Sponsoring Societies COOL Study Intro Slides Nov 2018

  4. Disclosures • This is an Investigator Driven Protocol in which the Investigators have complete control of the data • Acelity facilitated a Protocol Development Meeting of the Steering Committee in November 2017 (but had no scientific input) • Acelity may provide modest unrestricted funding to facilitate the conduct of the trial COOL Study Intro Slides Nov 2018

  5. Simplified Question:Is the Open Abdomen Indicated for Intra-abdominal sepsis ?

  6. The OA in Trauma • Rationale and necessity increasingly being questioned • Is it over-utilized? • Equipoise to the point RCTs are being conducted in trauma Harvin; RCT on trauma TSACO COOL Study Intro Slides Nov 2018

  7. What about leaving the Abdomen Open? • An open abdomen • May allow better drainage • Allows negative pressure peritoneal therapy (NPPT) • Mitigates intra-abdominal hypertension (IAH) • Allows easier relaparotomy • Increasingly being recommended COOL Study Intro Slides Nov 2018

  8. COOL Study • Multicentre prospective randomized intra-operative randomization of patients with severe complicated intra-abdominal sepsis who can be physically closed to closure or open abdomen • N = 275 per arm • Global Investigators from countries around the world COOL Study Intro Slides Nov 2018

  9. Severe complicated intra-abdominal sepsis (SCIAS) • World-Wide challenge, with high mortality rates, and ever increasing incidence • High mortality rates • WISS study (WSES cIAIs Score Study • 41% mortality with a WISS Score > 7 Sartelli World J Emerg Surg 2015 COOL Study Intro Slides Nov 2018

  10. Death in SCIAS • 2° peritonitis • Perforation or ischemia • Multiple organ failure • Local problem that becomes systemic • Progressive organ failure • Death from extra-abdominal organ failure Sartelli, Management of intra-abdominal infections: recommendations by the WSES 2016 consensus conference. WJES 2017 COOL Study Intro Slides Nov 2018

  11. Principles of Managing SCIAS • Prompt but NOT overly aggressive resuscitation • Early antibiotic admission • Early source control of contamination or spillage • Critical • Avoid delayed or inadequate source control • 1Failure to obtain source control 1° predictor of mortality 1Tellor B, Surg Infect (Larchmt) 2015; 16(6):785-93. COOL Study Intro Slides Nov 2018

  12. Use of the OA in sepsis has been condemned • “Closing the abdomen permanently after source control and only reopening it in case of deterioration of the patient without other (percutaneous) options is the preferred strategy.” • “There is no convincing evidence that damage control surgery is beneficial in patients with abdominal sepsis.” Boldingh; Curr Opin Crit Care 2017 BUT! – while there is no strong evidence that damage control surgery is beneficial in patients with abdominal sepsis, there is none that it is detrimental and biological signals that it might be beneficial. COOL Study Intro Slides Nov 2018

  13. Fundamental benefit of an OA in IAS? • RCT in a septic porcine model of NPPT versus passive drainage • Markedly improved • organ function • reduced histologic end-organ damage • reduced serum mediator levels Kubiak Shock 2010 COOL Study Intro Slides Nov 2018

  14. With NPWT - Reduced passage of biomediators to the systemic circulation • Kubiak BD, Peritoneal negative pressure therapy, Shock 2010 • Biomediators decreased in plasma • TNF-α • IL-6 • Il-1B • IL-12 COOL Study Intro Slides Nov 2018

  15. Prospective non-randomized trial • Active NPWT associated with significantly higher 30-day PFC rates and lower 30-day all-cause mortality among patients who require an open abdomen for at least 48 h during treatment for critical illness. Cheatham, World J Surg 2013 COOL Study Intro Slides Nov 2018

  16. Mortality: Clinical Efficacy and Safety • Intention-to-treat 90-day mortality • 21.7% in the ABThera group • 50.0% in the Barker’s vacuum pack group • [HR, 0.32; 95% confidence interval (CI), 0.11–0.93; P = 0.04]. Kirkpatrick; Ann Surg 2015 COOL Study Intro Slides Nov 2018

  17. Vancouver General Experience • 211 patients with severe abdominal sepsis/septic shock (uncontrolled retrospective) • No raw mortality differences • Adjusted odds ration for mortality (APACHE-IV) • 0.41 OA with NPWT • 0.81 primary fascial closure [p = 0.01] Bleszynski; Am J Surg 2016 COOL Study Intro Slides Nov 2018

  18. Latest Retrospective Review • Retrospective review of 2015 NSQUIP data (USA) • “Propensity matched1” cohorts • Closed • Open • Odds of death (31.4% vs. 21.4%) with open RSCL was 1.78 (95% CI1.08–2.95; p = 0.02) times that of primary closure Vogler; Surg Infect 2017 age, gender, body mass index (BMI), site classification, American Society of Anesthesiologists (ASA) class, operative time, number of risk factors, and pre-operative septic state.

  19. As usual retrospective data is crap! Blesynski; Am J Surg 2016 Vogler; Surg Infect 2017 COOL Study Intro Slides Nov 2018

  20. Latest World Society Guidelines • “The open abdomen is an option for emergency surgery patients with severe peritonitis and severe sepsis/septic shock under the following circumstances: “ • 1) abbreviated laparotomy due to the severe physiological derangement, • 2) need for a deferred intestinal anastomosis, • 3) planned second look for intestinal ischemia • 4) extensive visceral oedema with the concern for development of abdominal • compartment syndrome • 5) persistent source of peritonitis (failure of source control) • (Grade 2C). Cocolinni WSES 2018 Guidelines Suggestion with weak evidence COOL Study Intro Slides Nov 2018

  21. Disclaimer to the 2018 WSES Guidelines “In all these situations, the abdomen may be left open. However, there is no definitive data regarding the use of the OA in the face of severe peritonitis and therefore, caution should be exercised when using OA in these circumstances.” Cocolinni WESE 2018 Guidelines COOL Study Intro Slides Nov 2018

  22. Hypothesis • An OA strategy with NPPT will decrease mortality in severe complicated intra-abdominal sepsis • Null hypothesis: • no difference in mortality comparing an OA Strategy with NPPT compared to a primary fascial closure strategy in patients suffering severe complicated intra-peritoneal sepsis. COOL Study Intro Slides Nov 2018

  23. Previous Experience with the Pilot Centre Foothills Medical Centre • Survival advantage to ANPPT • Feasible to do • Institutional buy-in • 66% recruitment rate • Collaboration with the Snyder Research Laboratory • http://www.snyder.ucalgary.ca/ Peritoneal VAC Ann Surg 2015 COOL Study Intro Slides Nov 2018

  24. Study Outcomes • Primary • 90-Day hospital survival after laparotomy for SCIAS

  25. The COOL Study “family” COOL-Costs (Economic outcomes) COOL Study Intro Slides Nov 2018

  26. Biomediator Measurements: Max versus Lite • Cool – Lite • Enrolling centre will just collect clinical data on clinical outcomes • Powered for a Mortality difference • Cool – Max • Biomediator data collected • COOL-Mic • Microbiology of the OA • COOL-Cells • Intra-peritoneal cellular function (Calgary only) • COOL-Costs • Economic analysis • COOL- QOL • Quality of Life 1Criticism of Peritoneal VAC too long sample collection interval given biomediator T1/2s

  27. COOL Inclusion Criteria – presence of complicated severe intra-peritoneal sepsis

  28. COOL Inclusion Criteria – presence of complicated severe intra-peritoneal sepsis

  29. Severe Intra-Abdominal Sepsis • Shock • Hypotension requiring pressors for MAP > 65 • (AND) • Serum lactate > 2 mmol/litre after resuscitation • OR • CPIRO 3 or more • OR • WSESSSS Score 8 or more

  30. Calgary Predisposition Inflammation Response and Organ Dysfunction Score Possads et al;.,Am J Crit Care 2018

  31. World Society of Emergency Surgery Sepsis Severity Score Sartelli, World J Emerg Surg 2015

  32. Quick (qSOFA) • simple qSOFA model proposed to perform more complex models like SOFA or LODS outside the ICU • Much criticism of this Shankar-Hari M, JAMA 2016; 315(8):775-87. Singer JAMA 2016; 315(8):801-10. COOL Study Intro Slides Nov 2018

  33. Exclusion Criteria • perceived inability to close without undue tension or IAH/ACS • “damage control” including packing or non-anatomic post-surgical anatomy • pregnancy, • moribund status • laparoscopic surgery (no laparotomy), • pancreatitis as the source of peritonitis, • acute SMA occlusion • peritoneal carcinomatosis • traumatic injury within 24 hours of the development of SCIAS, • age < 18 • uncontrolled bleeding.

  34. The “third” arm • Randomly allocated • Non-randomized Fascial closure Open abdomen with ANPPT • Open abdomen due to • - tension • IAH • Blind ends • packing

  35. Pragmatic Trial • Primary closure of the fascia with an intra-peritoneal drain • Any open abdomen technique utilizing any form of peritoneal vacuum drainage • Barkers • VAC • Abthera • Etc. • (mesh mediated traction acceptable) VS COOL Study Intro Slides Nov 2018

  36. Intra-operative randomization • The diagnosis of complicated intra-peritoneal sepsis can only be made at laparotomy • Deferred consent process approved in Calgary Ethics Approval; May 12 2007 COOL Study Intro Slides Nov 2018

  37. Google “coolstudy.ca” • 1st hit

  38. CPIRO Calculator COOL Study Intro Slides Nov 2018

  39. WSESSSS Calculator COOL Study Intro Slides Nov 2018

  40. If the inclusion criteria are thus met the Enrollment key becomes active COOL Study Intro Slides Nov 2018

  41. Sample Size • SCIAS with a 33% mortally rate • power 80% and an alpha of 0.05 • number needed to recruit in each arm is 275 patients. • With 40 centres, this would mean about 14 patients per year over 2 years, meaning 7 patients per year per centre. WSES multi-centre observational study of complicated intra-abdominal sepsis recruited 4533 patients from 132 institutions 1 1Sartelli; WJES 2015

  42. Further Documentation • Protocol published in the World Journal od Emergency Surgery • Hosted on the COOL website • www.coolstudy.ca • Concise Protocol Document • Comprehensive Protocol Document • Hosted on the NIH Trial Registration website • https://clinicaltrials.gov/ct2/show/NCT03163095 • Trial protocol overview COOL Study Intro Slides Nov 2018

  43. Further Information • Andrew Kirkpatrick • Andrew.Kirkpatrick@ahs.ca • Jessica McKee • ualb9@ualberta.ca • Research Committee of the World Society of Emergency Surgery COOL Study Intro Slides Nov 2018

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