Peter R. Farrell

Objectives: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS.Study Design: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C‐reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP).Results: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02).Conclusion: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.

Background: Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and health system cost. Matrix metalloproteinases (MMPs) are endopeptidases which degrade extracellular matrix proteins and increase activity of pro-inflammatory cytokines. Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity. Prior limited studies of MMPs and TIMPs have found some to be associated with development of SAP. The aim of this study was to further investigate the role of MMPs and TIMPs in detecting pediatric patients at risk for developing moderately severe AP or SAP. Methods: Plasma samples were prospectively collected for patients <21 years of age presenting with AP between November 2015 and October 2019, along with healthy controls. Bead-based multiplex assays were utilized to test levels of 12 MMPs and TIMPs. Results: Samples were collected from 7 subjects who developed SAP, 7 with moderately severe AP, 45 with mild AP and 44 healthy controls. MMP-9 (p = 0.04) and TIMP-1 (p = 0.01) levels were significantly higher in SAP patients. A multivariable logistic regression model using MMP-9 and TIMP-1 predicted SAP (AUROC 0.87, 95% CI 0.76–0.98). Conclusion: We have demonstrated that MMP9 and TIMP1 levels are increased at AP presentation in pediatric patients who developed SAP during the course of illness. Further studies are needed to validate the use of MMPs and TIMPs as predictive tools for development of SAP in pediatric pancreatitis.

Objectives: The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor.Study Design: Patients from 2 hospitals were included for the validation model (Children's Hospital of the King's Daughters and Children's National Hospital). Children's Hospital of the King's Daughters and Cincinnati Children's Hospital Medical Center data were used for analysis of BUN at 24 to 48 hours.Results: The validation cohort included 73 patients; 22 (30%) with either severe or moderately severe AP, combined into the all severe AP (SAP) group. Patients with SAP had higher BUN (P = 0.002) and lower albumin (P = 0.005). Admission BUN was confirmed as a significant predictor (P = 0.005) of SAP (area under the receiver operating characteristic [AUROC] 0.73, 95% confidence interval [CI] 0.60–0.86). Combining BUN (P = 0.005) and albumin (P = 0.004) resulted in better prediction for SAP (AUROC 0.83, 95% CI 0.72–0.94). A total of 176 AP patients were analyzed at 24–48 hours; 39 (22%) met criteria for SAP. Patients who developed SAP had a significantly higher BUN (P < 0.001) after 24 hours. Elevated BUN levels within 24 to 48 hours were independently predictive of developing SAP (AUROC: 0.76, 95% CI: 0.66–0.85). Patients who developed SAP had a significantly smaller percentage decrease in BUN from admission to 24 to 48 hours (P = 0.002).Conclusion: We externally validated the prior model with admission BUN levels and further optimized it by incorporating albumin. We also found that persistent elevation of BUN is associated with development of SAP. Our model can be used to risk stratify patients with AP on admission and again at 24 to 48 hours.

Objective: The aim of the study was to evaluate lactated ringers (LR) versus normal saline (NS) in pediatric acute pancreatitis (AP). Methods: This retrospective study used Pediatric Health Information System database of primary AP patients, 2013 to 2017. Results: The study included 1581 first time AP patients with exclusive use of a single fluid (111 LR, 1470 NS) for the first 48 hours. The LR cohort had a significantly shorter length of stay (P < 0.001) compared with NS. A multivariable logistic regression analysis suggests use of NS in the first 48 hours (after controlling for total parenteral nutrition, operation, and infection during the admission) had a significantly increased likelihood of requiring a hospitalization for 4 days or more compared with the LR group (odds ratio, 3.31; 95% confidence interval, 1.95–5.62). The overall cost was significantly less in the LR group. There was no statistical difference observed in risk factors for AP, intensive care transfer, organ dysfunction, or mortality. Conclusions: This represents the first large data set analysis of LR versus NS in pediatric AP. The use of LR was associated with a shorter length of stay and reduced cost compared with NS. Future randomized trials will help determine the ideal fluid choice for pediatric AP.

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