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

Severe acute pancreatitis (SAP) includes persistent systemic inflammation (SIRS) and multiorgan 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. The model includes vascular, interstitial and "third-space" compartments with variable permeability of plasma proteins at the capillaries. Consented patients from University of Pittsburgh Medical Center Presbyterian Hospital were studied. Preadmission and daily hematocrit (HCT), blood urea nitrogen (BUN), creatine (Cr), albumin (Alb), and total protein (TP) were collected, and nonalbumin plasma protein (NAPP = TP minus the Alb) was calculated. Subjects served as their own controls for trajectory analysis. Of 57 SAP subjects, 18 developed MOF (5 died), and 39 were non-MOF (0 died). Compared with preadmission levels, admission HCT increased in MOF +5.00 [25%-75% interquartile range, IQR] versus non-MOF -0.10 [-1.55, 1.40] (P < 0.002) with HCT > +3 distinguishing MOF from non-MOF (odds ratio 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-to-Cr ratios remained constant. Pancreatic necrosis was more common in MOF (56%) than non-MOF (23%). Changing capillary permeability to allow loss of NAPP in this model predicts loss of plasma oncotic pressure and reduced vascular volume, hypotension with prerenal 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. This study is registered on https://clinicaltrials.gov at NCT03075605.NEW & NOTEWORTHY Acute pancreatitis is a sudden inflammatory response to pancreatic injury that may spread to systemic inflammation, multiorgan failure, and death in some patients. With the use of the predictions of a new mechanistic model, we compared patients with severe acute pancreatitis with or without multiorgan failure. All biomarkers of capillary leak and clinical features of multiorgan failure were accurately predicted. This provides a new paradigm for understanding and developing new treatments for patients with severe acute pancreatitis.

Assessment of Weight Loss and Gastrointestinal Symptoms Suggestive of Exocrine Pancreatic Dysfunction After Acute Pancreatitis.

INTRODUCTION: Studies evaluating the natural history of exocrine pancreatic dysfunction (EPD) after acute pancreatitis (AP) are sparse. This study aims to assess incidence and predictors of weight loss and gastrointestinal (GI) symptoms suggestive of EPD 12 months after an AP episode. METHODS: Patients enrolled in the Pancreatitis-associated Risk of Organ Failure Study at the time of an AP episode were included. Weight and GI symptom data were prospectively collected by self-report at enrollment and at 3- and 12-month (windows 2-7 and 8-20) telephone follow-ups. Multivariable logistic regression was used to assess factors associated with ≥10% total body weight loss (EPD surrogate) at 12 months. A generalized estimating equation was used to measure each factor's population effect (in pounds) over 12 months after AP. RESULTS: Follow-up at 12 months in 186 patients (median age = 54 years, 46% men, 45% biliary, 65% first AP attack) revealed weight loss ≥10% from baseline, occurring in 44 patients (24%). Risk of weight loss increased with higher baseline body mass index, previous diagnosis of diabetes mellitus, and worsening AP severity (all P < 0.010). GI symptoms were reported in 13/31 (42%) patients at 12 months. AP severity was independently associated with ≥10% weight loss at 12 months. Over 12 months, men lost more weight than women (average 9.5 lbs); patients with severe AP lost, on average, 14 lbs. DISCUSSION: Weight loss after AP occurs in one-quarter of patients and is associated with AP severity. EPD incidence after AP is likely underappreciated. Further work is needed to assess EPD and potential for pancreatic enzyme supplementation.