Complicated Intra-abdominal Sepsis Research Articles

The unrestricted global effort to complete the COOL trial

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. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) (https://clinicaltrials.gov/ct2/show/NCT03163095). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study.MethodsThe COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer.DiscussionOA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of “damage control”; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention.Trial registration: National Institutes of Health (https://clinicaltrials.gov/ct2/show/NCT03163095).

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

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

TNM: a simple classification system for complicated intra-abdominal sepsis after acute appendicitis

Delayed diagnosis in case of acute appendicitis (AA) could lead to complicated intra-abdominal sepsis (IAS). Grading systems are not commonly employed in the clinical practice, because they are too complicated or too specific. Therefore, we suggest grading the severity of complicated IAS after AA with a simple system: TNM, an acronym borrowed by cancer staging where T indicates temperature, N neutrophils, and M multiple organ failure (MOF). This prospective observational study evaluates the predictive value of the TNM score on mortality of patients with complicated IAS after AA. Sixty-eight patients with complicated IAS after AA were treated. Three classes of attributes were chosen: temperature (T), neutrophils count (N), and MOF (M). After defining the categories T (T0-T4), N (N0-N3) and M (M0-M2), these were grouped in stages (0-IV). Variables analyzed for their possible relation to death were age, sex, temperature, neutrophils count, preoperative organ failure, immunocompromised status, stage (0-IV). Odds ratios were calculated in a univariate and multivariate analysis. TNM staging was: one patient stage 0; 16 patients at stage I; 26 patients at stage II; 16 patients at stage III; nine patients at stage IV. Death occurred in 15 patients (22%). Neutrophil count, preoperative organ failure, immunocompromised status, stages III-IV were potential predictors of postoperative death in univariate analysis; only stage IV was significant independent predictor of postoperative mortality in multivariate analysis. TNM classification is very easy to use; it helps to define the mortality risk and is useful to objectively compare patients with sepsis.

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

BackgroundThe risk of death in severe complicated intra-abdominal sepsis (SCIAS) remains high despite decades of surgical and antimicrobial research. New management strategies are required to improve outcomes. The Closed Or Open after Laparotomy (COOL) trial investigates an open-abdomen (OA) approach with active negative pressure peritoneal therapy. This therapy is hypothesized to better manage peritoneal bacterial contamination, drain inflammatory ascites, and reduce the risk of intra-abdominal hypertension leading to improved survival and decreased complications. The total costs and cost-effectiveness of this therapy (as compared with standard fascial closure) are unknown.MethodsWe propose a parallel cost-utility analysis of this intervention to be conducted alongside the 1-year trial, extrapolating beyond that using decision analysis. Using resource use metrics (e.g., length of stay, re-admissions) from patients at all study sites and microcosting data from patients enrolled in Calgary, Alberta, the mean cost difference between treatment arms will be established from a publicly-funded health care payer perspective. Quality of life will be measured at 6 months and 1 year postoperatively with the Euroqol EQ-5D-5 L and SF-36 surveys. A within-trial analysis will establish cost and utility at 1 year, using a bootstrapping approach to provide confidence intervals around an estimated incremental cost-effectiveness ratio. If neither operative strategy is economically dominant, Markov modeling will be used to extrapolate the cost per quality-adjusted life years gained to 2-, 5-, 10-year, and lifetime horizons. Future costs and benefits will be discounted at 1.5% per annum. A cost-effectiveness acceptability curve will be generated using Monte Carlo simulation. If all trial outcomes are similar, the primary analysis will default to a cost-minimization approach. Subgroup analysis will be carried out for patients with and without septic shock at presentation, and for patients whose initial APACHE II scores are > 20 versus ≤ 20.DiscussionIn addition to an estimate of the clinical effectiveness of an OA approach for SCIAS, an understanding of its cost effectiveness will be required prior to its adoption in any resource-constrained environment. We will estimate this key parameter for use by clinicians and policymakers.Trial RegistrationClinicalTrials.gov, NCT03163095, registered May 22, 2017.

Could Soluble Cluster of Differentiation 163 Be Useful as Prognostic Biomarker in Patients With Complicated Intra-abdominal Infections?

Introduction Early prognostic evaluation and timely treatment are crucial for the final outcome in patients with complicated intra-abdominal infections (cIAIs). Over the years, different biomarkers for early prognosis were explored, and yet none has shown ideal characteristics. This review aimed to assess the potential application of soluble cluster of differentiation 163 (sCD163) as outcome predictor in patients with cIAIs. Methods We have searched in PubMed database the literature relating the prognostic performance of sCD163 in patients with cIAIs and/or sepsis. Our search terms were soluble CD163, sCD163, intra-abdominal infections, complicated intra-abdominal infections, IAIs, cIAIs, sepsis, prognostic, outcome, and mortality. Results A total of 8 studies with 2308 patients met our inclusion criteria. Six studies showed significant prognostic value of sCD163 levels, and 2 showed no association between sCD163 and mortality. Conclusions This review found association between sCD163 levels and mortality. We concluded that sCD163 could be a reliable and meaningful mortality predictor in septic patients with cIAIs. Nevertheless, more large prospective studies with surgical patients only are needed before the final evaluation of this biomarker.

Temperature-Neutrophils-Multiple Organ Failure Grading for Complicated Intra-Abdominal Infections.

Background: The grading systems for intra-abdominal sepsis (IAS) are not employed commonly in clinical practice because they are too complicated or too specific. We propose to grade IAS with a simple grading system: the TNM system, which is an acronym borrowed from cancer staging, where T indicates Temperature, N indicates Neutrophils, and M indicates Multiple organ failure (MOF). The aim of this prospective observational study is to assess the predictive value of the TNM score on deaths of patients with complicated IAS. Patients and Methods: We considered 147 patients with complicated IAS. Three classes of attribute were chosen: Temperature (T), Neutrophil count (N), and MOF (M). After defining the categories T (T0-T4), N (N0-N3), and M (M0-M2), they were grouped in stages (0-IV). We analyzed specific variables for their possible relation to death: Age, gender, blood transfusion, causes of IAS, T, N, pre-operative organ failure, immunocompromised status, stage 0, I, II, III, and IV. Odds ratios were calculated in a uni-variable and multi-variable analysis. Results: This was the distribution in classes, based on TNM stages: One patient was in stage 0; 15 patients in stage I; 47 patients in stage II; 56 patients in stage III; 28 patients in stage IV. Death occurred in 45 (30.6%) patients. The N, pre-operative organ failure, immunocompromised status, stage III-IV were potential predictors of post-operative death in uni-variable analysis. Only pre-operative organ failure and stage IV were significant independent predictors of post-operative death in multi-variable analysis. Conclusions: The TNM classification is an easy system that could be considered to define the death risk of patients with IAS and to compare patients with sepsis.

The role of the intra-abdominal view in complicated intra-abdominal infections

BackgroundThe prognostic role of what a surgeon observes in the abdomen of patients with complicated intra-abdominal infection (cIAI) is largely unknown. The aim of this prospective study was to systemically analyze components of the intra-abdominal view (IAV) and their association to severe complicated intra-abdominal sepsis (SCIAS) or mortality.MethodsThe study cohort consisted of adult patients with cIAI. The operating surgeon filled a paper form describing the intra-abdominal view. Demographics, operative details, and preoperative physiological status were collected. Descriptive, univariate, and multivariate statistical analyses were performed, and a new score was developed based on regression coefficients. The primary outcome was a composite outcome of SCIAS or 30-day mortality, in which SCIAS was defined as organ dysfunctions requiring intensive care unit admission.ResultsA total of 283 patients were analyzed. The primary outcome was encountered in 71 (25%) patients. In the IAV, independent risk factors for the primary outcome were fecal or bile as exudate (odds ratio (OR) 1.98, 95% confidence interval 1.05–3.73), diffuse peritonitis (OR 2.15, 1.02–4.55), diffuse substantial redness of the peritoneum (OR 5.73, 2.12–15.44), and a non-appendiceal source of cIAI (OR 11.20, 4.11–30.54). Based on these factors, an IAV score was developed and its performance analyzed. The area under the receiver operating characteristic for the IAV score was 0.81. The IAV score also correlated significantly with several outcomes and organ dysfunctions.ConclusionsThe extent of peritonitis, diffuse substantial redness of the peritoneum, type of exudate, and source of infection associate independently with SCIAS or mortality. A high IAV score associates with mortality and organ dysfunctions, yet it needs further external validation. Combining components of IAV into comprehensive scoring systems for cIAI patients may provide additional value compared to the current scoring systems.Trial registrationThe study protocol was retrospectively registered on April 4, 2016, right after the first enrolled patient at Clinicaltrials.gov database (NCT02726932).

Utility of sequential organ failure assessment score in predicting outcome for patients with peritoneal sepsis

Background: Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. The sequential organ failure assessment (SOFA) score numerically quantifies the number and severity of failed organs. We examined the utility of the SOFA score for assessing outcome of patients with severe peritoneal sepsis.Methods: This is a prospective observational study. A total of 100 patients who presented to emergency department of Victoria hospital with features suggestive of peritoneal sepsis from January 2018 to August 2018 were included in the study. The presence of organ dysfunction was assessed using a sequential organ failure assessment (SOFA). Clinical, microbiologic, and laboratory factors were considered for assessing the outcome.Results: Forty-two patients had two or more sites of infection on admission. Bacteraemia was confirmed in 20 patients. 88 patients were surgical. The median age of patients was 69 years. Males being more commonly affected than females. Twenty-eight days survival rate was 41%. The incidence of organ dysfunction on day 1 was noted more frequently for renal, cardiovascular, and neurological systems. SOFA score on day 1 and day 3 were significantly higher in non-survivors than those in survivors. Patients with three and higher number of organ systems with dysfunction had a lower survival rate than the subgroups of patients with one or two organ systems with dysfunction.Conclusions: The SOFA score provides potentially valuable prognostic information on in hospital survival when applied to patients with severe peritoneal sepsis.

Research progress of the open abdomen in the treatment of gastrointestinal fistula with complicated intra-abdominal infection

Gastrointestinal fistula patients may suffer from complicated intra-abdominal infection and sepsis with improper treatment, which is characterized by high mortality ranging from 20% to 60%, as well as high medical costs. Gastrointestinal fistula patients with complicated intra-abdominal infections are not often diagnosed early, and proper treatment remains an unsolved problem. Therefore it is a great challenge for surgeons to repair broken intestines under complicated intra-abdominal infection conditions and to repair ruptured intestines under conditions of severe abdominal adhesions and swelling of the intestinal wall and mesentery. After the open abdominal approach was first adopted to treat complicated intra-abdominal infection patients by Duff and Moffat in 1981, it gradually began to be used more widely. However, some investigators have reported that the open abdomen approach has not been effective in controlling controlled mortality, instead, it may even increase mortality. For this reason, the approach has only been used in large medical centers rather than having been widely popularized. In this review, the effect, timing, indications of open abdomen approach and the principles for the open abdominal wound management are summarized, and the reason for the various efficacy among different centers is also analyzed. We provide a new perspective for clinicians to manage the gastrointestinal fistula patients with complicated intra-abdominal infection.

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

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.

Getting the invite list right: a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria

BackgroundSevere complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent. An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database.MethodsAll consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality.ResultsPredictive systems with an area under-the-receiving-operating characteristic (AUC) curve > 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score ≥ 2 (78.4%), followed by the WSESSSS score ≥ 8 (73.1%), SOFA ≥ 3 (75.2%), and APACHE II ≥ 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS ≥ 8 increased detection to 80%. Including CPIRO score ≥ 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA ≥ 4 and WSESSSS ≥ 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality).ConclusionsNo one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest “inclusion-criteria” to recognize patients with a high chance of mortality and ICU admission.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03163095; Registered on May 22, 2017.

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Tigecycline

Damage control surgery/laparostomy in nontrauma emergency abdominal surgery: A new concept of care

Introduction: The established success of damage control surgery (DCS) in trauma of torso motivates surgeon to apply similar concept in managing complicated intra-abdominal sepsis. The main objective of this study is to audit our new practice of such in nontrauma emergency abdominal surgery. Materials and Methods: We retrospectively reviewed all emergency abdominal surgeries (nontrauma) done from February 2013 to February 2014. All patients who had damage control procedures done for complicated intra-abdominal sepsis were analyzed. Results: A total of 60 patients were operated within that period. Six patients (10%) had undergone DCS with or without laparostomy. All were male with mean age of 48.5-year-old (26-61-years-old). Most were in ASA 3 (83%, 5 patients) with only one in ASA 4. Primary indications were ischemic bowel with mesenteric vein thrombosis (3 patients, 50%), abdominal compartment syndrome (ACS), bleeding post near total splenectomy for splenic abscess and gangrenous proctitis with purulent peritonitis. Nearly, all patients (5 patients, 83.3%) were severely acidotic with pH <7.2 intra-operatively, which triggered the DCS. Nevertheless, only 3 patients (50%) benefited from laparostomy and all of them achieved complete fascial closure within 2.6 days (mean). Their mean total Intensive Care Unit (ICU) stay was 15 days (9-32 days). Overall predicted mean Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity mortality rate was 51%. However, the observed (actual) mortality rate was only 33% (2 patients). Conclusion: The result of the practice of DCS in the septic abdomen is very encouraging. It appears able to reduce the mortality by 35%. A comparative analysis with larger series is therefore warranted to further confirm the findings.

Postoperative enterococcal infection after treatment of complicated intra-abdominal sepsis.

The prevalence of enterococcal isolation and factors associated with postoperative enterococcal infection remain ill defined. A prospective longitudinal observational study was conducted of consecutive patients with a first episode of intra-abdominal infection and a positive microbiological culture who did or did not develop a postoperative septic complication involving enterococci. The prevalence of initial enterococcal isolation was determined for each focus of infection. Postoperative enterococcal infections were related to whether appropriate (piperacillin--tazobactam), suboptimal (carbapenems) or inappropriate (cefotaxime plus metronidazole) antienterococcal therapy had been administered empirically. Enterococci were isolated in 42 (21 per cent) of the 200 patients investigated. The isolation rates were 11 per cent for community-acquired peritonitis, 50 per cent for postoperative peritonitis and 23 per cent for intra-abdominal abscesses of both origins. No enterococci were isolated from 49 patients with perforated appendicitis. Independent factors for postoperative enterococcal infection were type of intra-abdominal infection (P = 0.006), Acute Physiology And Chronic Health Evaluation (APACHE) II score greater than 12 (P = 0.04) and inappropriate empirical antibiotic cover (P = 0.05). Postoperative enterococcal infections were associated with a high mortality rate (21 versus 4 per cent; P < 0.0007). Enterococci are frequently isolated from intra-abdominal infections of non-appendiceal origin and are often involved in postoperative infectious complications, particularly peritonitis. Empirical antibiotic therapy covering Enterococcus faecalis should be contemplated in some circumstances.