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

Abstract

BackgroundSevere 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.MethodsThe 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.DiscussionAlthough 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 registrationClinicalTrials.gov, NCT03163095.

Perforated and bleeding peptic ulcer: WSES guidelines

“…Although upper gastrointestinal perforations are often less catastrophic than lower gastrointestinal contaminations, when the patient responded with immunological activation and systemic sepsis, they are suffering from severe complicated intraabdominal sepsis. If these conditions are met, then we suggest participation and potential enrollment in the COOL Trial [68][69][70] Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/ show/NCT03163095) to help provide better guidance for clinicians in the future treating such challenging patients. In general, anastomoses should be avoided in the presence of hypotension or hemodynamic instability, especially if the patient requires vasopressors.…”

Intra-abdominal sepsis: new definitions and current clinical standards

“…Nevertheless, the openabdomen approach is indicated for patients with secondary/persisting peritonitis, who face the risk of ACS development or in whom a second-look operation is expected. The prospective COOL trial (Closed or Open after Source Control Laparotomy for Severe Complicated Intra-abdominal Sepsis) is recruiting patients with severe intra-abdominal sepsis (defined as septic shock or a Predisposition, Infection, Response, Organ Dysfunction score > 3 or a World Society of Emergency Surgeons (WSES) sepsis severity score > 8) to analyze the influence of open versus fascial closure on mortality after source control [65].…”

Protocol for a parallel economic evaluation of a trial comparing two surgical strategies in severe complicated intra-abdominal sepsis: the COOL-cost study

“…The methodology of the COOL trial has been published elsewhere [7] and is briefly summarized here. To be included in the trial, adult patients will have complicated intra-abdominal infection (purulent, feculent, or enteric contents in the peritoneal cavity at the time of operation) and present with severe disease (either septic shock, World Society of Emergency Surgery Sepsis Severity Score ≥ 8, or a Calgary Predisposition-Infection-Response-Organ dysfunction score ≥ 3).…”

“…6 Department of Community Health Sciences, University of Calgary, Calgary, Canada. 7 The Trauma Program, University of Calgary, Calgary, Canada.…”

“…An alternate strategy of leaving the fascia open ("open abdomen", OA) with active negative pressure peritoneal therapy (ANPPT) is being studied in an international, multisite-randomized controlled trial (Closed Or Open after Laparotomy, COOL); the comparator is standard fascial closure at the initial operation [7]. Investigators hypothesize that ANPPT will allow for ongoing drainage of infected, inflammatory peritoneal fluid, decreasing the systemic propagation of inflammatory mediators [8,9].…”