Closed or Open Abdomen for the Management of Abdominal Sepsis
Closed or Open Abdomen for the Management of Abdominal Sepsis
This is a prospective randomized clinical study. The study will comprise the randomized
 decision to either A) primarily close the fascia after laparotomy for intra-abdominal
 infection (CLOSED); or B) leave the fascia open after laparotomy and apply a temporary
 abdominal closure (TAC) device (OPEN) with a vacuum drain.

 Although debatable, both procedures (CLOSED or OPEN abdomen) are acceptable based on current
 suggested standard of care. Thus, high quality data to direct clinical decision making in
 this highly lethal condition is urgently required.
Severe complicated intra-abdominal sepsis (SCIAS) is a World-Wide challenge, with high
 mortality rates, and ever increasing incidence. Most cases are subjected to secondary
 peritonitis in which there is a physical disruption of the integrity of the gastrointestinal
 (GI) tract leading to contamination of the peritoneal cavity. Ultimately, the resultant organ
 damage results in auto-amplifying biomediator generation and systemic inflammation. Mortality
 rates range from 10% to over 40% when shock is present. The key principles of treating SIAS
 are early antibiotic administration and the earliest possible operative intervention to
 provide source control of GI perforations/disruptions. A further potential therapeutic option
 may be to utilize open abdomen (OA) management with active negative peritoneal pressure
 therapy (ANPPT) to remove intra-peritoneal inflammatory ascites and to ameliorate the
 systemic damage from SCIAS. Recent data from a randomized controlled trial including either
 severe peritonitis or trauma patients, showed the 30-days mortality differed between
 commercial open abdomen systems and non-commercial technique, which favored the more
 effective commercial device. Although there is a biologic rationale for such an intervention
 from animal models as well as non-standardized clinical utilization currently, the open
 abdomen management with ANPPT remains a novel therapy with much clinical equipoise. Thus, the
 Closed Or Open after Laparotomy (COOL) study will constitute a prospective randomized
 controlled trial to address this issue.

 There is a complex relationship between pressure, ischemia, and inflammation within the
 peritoneal cavity. Independently the damaged gut seems to act as a continued source of
 inflammation propagating systemic inflammatory response syndrome (SIRS) and potentiating
 multi-organ dysfunction syndrome (MODS). Although extremely complicated, visceral ischemia
 further generates multiple immunological mediators with the pro-inflammatory cytokines tumor
 necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), as well as inhibitive cytokines such
 as interleukin 10 (IL-10). Post-operative complications associate with increasing levels of
 systemic IL-6, and peritoneal TNF-α. Jansson and colleagues believe that peritoneal cytokines
 in humans respond more extensively compared to systemic cytokines, and that a normal
 postoperative course is characterized by decreasing levels of peritoneal cytokines based on
 studies of both elective and emergency surgery. Overall, the peritoneal cytokine response is
 much higher than the systemic response in peritonitis.

 ANPPT therapy may be a more direct and focused solution to this complicated problem, and that
 will be complementary to the other benefits of open abdomen management in the sickest
 patients. Whether improved post-operative courses can be obtained through this relatively
 simple approach of actively removing peritoneal cytokines in humans is therefore a secondary
 objective of this trial.

 Another potential benefit of ANPPT after severe infection may be the attendant decompression
 of the abdominal compartment and prevention of even modest degrees of intra-abdominal
 hypertension (IAH). Patients with intra-abdominal infections are at risk of elevated
 intra-abdominal pressure (IAP) both as a result of the primary intra-peritoneal disease, and
 as large fluid resuscitation often required maintaining organ perfusion. Recent studies have
 demonstrated a high prevalence of IAH following aggressive resuscitation of septic patients.
 Intra-abdominal hypertension is present in as many as 80% of septic medical and surgical ICU
 patients. Reintam also reported that septic patients with IAH had a 50% rate of mortality
 compared to 19% without IAH, making IAH a significant marker for an increased risk of death.
 Within our own institution, rates of IAH were over 87% of septic ICU patients and further 61%
 of these patients had severe IAH at levels commensurate with abdominal compartment syndrome
 (ACS). Although direct translation to humans is uncertain, even modest degrees of IAH (often
 clinically ignored) have been found to have profound effects on propagating multiple organ
 failure in animals with ischemia/intra-peritoneal infections.

 The study intervention will comprise the randomized decision to either A) primarily close the
 fascia after laparotomy for SCIAS (CLOSED); or B) leave the fascia open after laparotomy for
 SCIAS and apply an ANPPT temporary abdominal closure (TAC) device (OPEN).

 Patients will be randomized intra-operatively once it is determined that COMPLICATED and
 SEVERE Intra-Abdominal Infection (SCIAS) is present. SEVERE will be defined and denoted by
 the presence of any organ dysfunction exemplified by septic shock OR a
 Predisposition-Infection-Response-Organ Dysfunction Score > 3 or a
 World-Society-of-Emergency-Surgery-Sepsis-Severity-Score > 8, and COMPLICATED with the
 presence of purulent, feculent, or enteric spillage over at least 2 intra-peritoneal
 quadrants.
Inclusion Criteria:

 -  Presence of purulent, feculent, or enteric spillage over at least 2 intra-peritoneal
 quadrants intra-operatively;

 -  Septic shock, or

 -  Predisposition-Infection-Response-Organ Dysfunction Score > 3, or

 -  World-Society-of-Emergency-Surgery-Sepsis-Severity-Score > 8

 Exclusion Criteria:

 -  Pregnant;

 -  Confirmed or strongly suspected severe IAH (IAP>20 mmHg);

 -  No intentional of providing ongoing care;

 -  pancreatitis as the source of peritonitis;

 -  uncontrolled bleeding