Temporal Relationship Between SIRS, Organ Failure, and Death in Acute Pancreatitis: Data From a Large, Multicenter, International Study (APPRENTICE Study Group)

Abstract

Background: Although systemic inflammatory response syndrome (SIRS) has been associated with worse outcomes in acute pancreatitis (AP); its time relationship with persistent organ failure (POF) and death has been poorly described. Our aim was to investigate the dynamic relationship between SIRS, POF and death in AP. Methods: APPRENTICE is a multi-national, prospective study in AP, initiated in 2015. Twenty-two international centers participated across 4 continents. SIRS was defined as of ≥2/4 criteria. Organ failure (OF) was defined by modified Marshall score ≥2 for respiratory, renal, or cardiovascular. POF referred to OF lasting ≥ 48 hours. Death was defined as in-hospital mortality. Results: 1544 patients were prospectively enrolled (age 50, 52% male), of whom 166 (11%) developed POF and 39 (2.5%) died. SIRS on admission was found in 41%, with 22% developing POF at a median of 40 (18-85) hours. The incidence of POF peaked within 24 hours of admission, with 78%developing POF within first 96 hours of hospitalization.Among patientswith POF, 47% progressed to multi-organ failure (MOF) and renal was the first organ to fail in 45%, two concurrent organs failed in 30%, and respiratory in 23%. Among patients with POF, 20%died at a median of 9 (3-24) days after OFonset. In regards with the organ failing first in patients withMOF, renalwas associated with lower mortality (20% in renal vs. 65% in all others, P < 0.01). Conclusion: The findings of this multinational study demonstrate that SIRS is common, develops early in AP, progresses to OF within 2 days, and about a fifth of patients with POF die at a median of 10 days. The above results from APPRENTICE, will provide knowledge to clinicians in regards with the natural history of AP and also guide investigators with the design of clinical trials.