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.