Severe acute pancreatitis: Capillary permeability model linking systemic inflammation to multiorgan failure.

BACKGROUND AND AIMS Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multi-organ failure (MOF). The mechanism of transition from SIRS to MOF is unclear. We developed a fluid compartment model and used clinical data to test predictions. METHODS The model includes vascular, interstitial and "third space" compartments with variable permeability of plasma proteins at the capillaries. Consented patients from UPMC Presbyterian Hospital were studied. Pre-admission and daily hematocrit (HCT), blood urea nitrogen (BUN), creatine (Cr), albumin (Alb) and total protein (TP) were collected, and non-albumin plasma protein (NAPP=TP-Alb) was calculated. Subjects served as their own controls for trajectory analysis. RESULTS Of 57 SAP subjects 18 developing MOF (5 died) and 39 non-MOF (0 died). Compared to pre-admission levels, admission HCT increased in MOF +5.00 [3.70, 8.70] versus non-MOF -0.10 [-1.55, 1.40] (p +3 distinguishing MOF from non-MOF (OR 17.7, p=0.014). Preadmission Alb fell faster in MOF than non-MOF (p<0.01). By day 2 TP and NAPP dropped in MOF but not non-MOF (p<0.001). BUN and Cr levels increased in MOF (p=0.001) but BUN/Cr ratios remained constant. Pancreatic necrosis was more common in MOF (56%) than non-MOF (23%). CONCLUSIONS Changing capillary permeability to allow loss of NAPP in this model predicts loss of plasma oncotic pressure and reduced vascular volume, hypotension with pre-renal azotemia and acute kidney dysfunction, pancreas necrosis, and pulmonary edema from capillary leak in the lung with acute respiratory distress syndrome. Sequential biomarker analysis in humans with or without MOF is consistent with this model.