Kathryn Repas

Lactated Ringer's Solution Reduces Systemic Inflammation Compared With Saline in Patients With Acute Pancreatitis

BACKGROUND & AIMS Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis. We performed a randomized controlled trial to evaluate the impact of a goal-directed fluid resuscitation protocol on systemic inflammation in patients with acute pancreatitis. We then determined the impact of resuscitation with lactated Ringers solution, compared with normal saline. METHODS We performed a randomized controlled trial of 40 patients with acute pancreatitis at 3 New England hospitals from May 2009-February 2010. Patients received goal-directed fluid resuscitation with lactated Ringers solution, goal-directed fluid resuscitation with normal saline, standard fluid resuscitation with lactated Ringers solution, or standard fluid resuscitation with normal saline. Systemic inflammation was measured on the basis of levels of systemic inflammatory response syndrome (SIRS) and C-reactive protein (CRP) level after 24 hours. RESULTS The volumes of fluid administered during a 24-hour period were similar among patients given goal-directed or standard fluid resuscitation (mean, 4300 vs 4600 mL, respectively; P = .87). Goal-directed resuscitation did not significantly reduce incidence of SIRS, compared with standard resuscitation (11.8% vs 13.0%, respectively; P = .85) or levels of CRP after 24 hours (87.1 vs 69.2 mg/dL, respectively; P = .75). By contrast, there was a significant reduction in SIRS after 24 hours among subjects resuscitated with lactated Ringers solution, compared with normal saline (84% reduction vs 0%, respectively; P = .035); administration of lactated Ringers solution also reduced levels of CRP, compared with normal saline (51.5 vs 104 mg/dL, respectively; P = .02). CONCLUSIONS Patients with acute pancreatitis who were resuscitated with lactated Ringers solution had reduced systemic inflammation compared with those who received saline.

A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis.

OBJECTIVES:Our aim was to prospectively evaluate the ability of the bedside index for severity in acute pancreatitis (BISAP) score to predict mortality as well as intermediate markers of severity in a tertiary center.METHODS:The BISAP score was evaluated among 397 consecutive cases of acute pancreatitis admitted to our institution between June 2005 and December 2007. BISAP scores were calculated on all cases using data within 24 h of presentation. The ability of the BISAP score to predict mortality was evaluated using trend and discrimination analysis. The optimal cutoff score for mortality from the receiver operating curve was used to evaluate the development of organ failure, persistent organ failure, and pancreatic necrosis.RESULTS:Among 397 cases, there were 14 (3.5%) deaths. There was a statistically significant trend for increasing mortality (P < 0.0001) with increasing BISAP score. The area under the receiver operating curve for mortality by BISAP score in the prospective cohort was 0.82 (95% confidence interval: 0.70, 0.95), which was similar to that of the previously published validation cohort. A BISAP score ≥3 was associated with an increased risk of developing organ failure (odds ratio=7.4, 95% confidence interval: 2.8, 19.5), persistent organ failure (odds ratio=12.7, 95% confidence interval: 4.7, 33.9), and pancreatic necrosis (odds ratio=3.8, 95% confidence interval: 1.8, 8.5).CONCLUSIONS:The BISAP score represents a simple way to identify patients at risk of increased mortality and the development of intermediate markers of severity within 24 h of presentation. This risk stratification capability can be utilized to improve clinical care and facilitate enrollment in clinical trials.

A comparative evaluation of radiologic and clinical scoring systems in the early prediction of severity in acute pancreatitis.

OBJECTIVES:The early identification of clinically severe acute pancreatitis (AP) is critical for the triage and treatment of patients. The aim of this study was to compare the accuracy of computed tomography (CT) and clinical scoring systems for predicting the severity of AP on admission.METHODS:Demographic, clinical, and laboratory data of all consecutive patients with a primary diagnosis of AP during a two-and-half-year period was prospectively collected for this study. A retrospective analysis of the abdominal CT data was performed. Seven CT scoring systems (CT severity index (CTSI), modified CT severity index (MCTSI), pancreatic size index (PSI), extrapancreatic score (EP), ‘‘extrapancreatic inflammation on CT’’ score (EPIC), ‘‘mesenteric oedema and peritoneal fluid’’ score (MOP), and Balthazar grade) as well as two clinical scoring systems: Acute Physiology, Age, and Chronic Health Evaluation (APACHE)-II and Bedside Index for Severity in AP (BISAP) were comparatively evaluated with regard to their ability to predict the severity of AP on admission (first 24 h of hospitalization). Clinically severe AP was defined as one or more of the following: mortality, persistent organ failure and/or the presence of local pancreatic complications that require intervention. All CT scans were reviewed in consensus by two radiologists, each blinded to patient outcome. The accuracy of each imaging and clinical scoring system for predicting the severity of AP was assessed using receiver operating curve analysis.RESULTS:Of 346 consecutive episodes of AP, there were 159 (46%) episodes in 150 patients (84 men, 66 women; mean age, 54 years; age range, 21–91 years) who were evaluated with a contrast-enhanced CT scan (n=131 episodes) or an unenhanced CT scan (n=28 episodes) on the first day of admission. Clinically severe AP was diagnosed in 29/159 (18%) episodes; 9 (6%) patients died. Overall, the Balthazar grading system (any CT technique) and CTSI (contrast-enhanced CT only) demonstrated the highest accuracy among the CT scoring systems for predicting severity, but this was not statistically significant. There were no statistically significant differences between the predictive accuracies of CT and clinical scoring systems.CONCLUSIONS:The predictive accuracy of CT scoring systems for severity of AP is similar to clinical scoring systems. Hence, a CT on admission solely for severity assessment in AP is not recommended.

Early systemic inflammatory response syndrome is associated with severe acute pancreatitis.

BACKGROUND & AIMS There have been few clinical studies of systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis. The aim of this study was to evaluate the role of SIRS in assessing severity of acute pancreatitis. METHODS We prospectively enrolled 252 consecutive patients with acute pancreatitis who were admitted directly to our institution between 2005-2007. The incidence and duration of SIRS (transient <or=48 hours vs persistent >48 hours) during the first 7 days of hospitalization, and the number of SIRS criteria (0-4) on the first day of hospitalization (day 1) were evaluated with individual markers of severity, including persistent organ failure, pancreatic necrosis, need for intensive care unit, and mortality. RESULTS SIRS occurred in 155/252 patients (62%) on day 1. SIRS on day 1 predicted severe disease with high sensitivity (85%-100%). The absence of SIRS on day 1 was associated with a high negative predictive value (98%-100%). Patients with a higher number of systemic inflammatory response (SIR) criteria on day 1 and persistent SIRS had an increased risk for severe disease (P < .01). CONCLUSIONS The majority of patients hospitalized with acute pancreatitis have SIRS on day 1. The severity of acute pancreatitis is greater among patients with SIRS on day 1 and, in particular, among those with 3 or 4 SIRS criteria, compared with those without SIRS on day 1.

Blood urea nitrogen in the early assessment of acute pancreatitis: an international validation study.

BACKGROUND Objective assessment of acute pancreatitis (AP) is critical to help guide resuscitation efforts. Herein we (1) validate serial blood urea nitrogen (BUN) measurement for early prediction of mortality and (2) develop an objective BUN-based approach to early assessment in AP. METHODS We performed a secondary analysis of 3 prospective AP cohort studies: Brigham and Womens Hospital (BWH), June 2005 through May 2009; the Dutch Pancreatitis Study Group (DPSG), March 2004 through March 2007; and the University of Pittsburgh Medical Center (UPMC), June 2003 through September 2007. Meta-analysis and stratified multivariate logistic regression adjusted for age, sex, and creatinine levels were calculated to determine risk of mortality associated with elevated BUN level at admission and rise in BUN level at 24 hours. The accuracy of the BUN measurements was determined by area under the receiver operating characteristic curve (AUC) analysis compared with serum creatinine measurement and APACHE II score. A BUN-based assessment algorithm was derived on BWH data and validated on the DPSG and UPMC cohorts. RESULTS A total of 1043 AP cases were included in analysis. In pooled analysis, a BUN level of 20 mg/dL or higher was associated with an odds ratio (OR) of 4.6 (95% confidence interval [CI], 2.5-8.3) for mortality. Any rise in BUN level at 24 hours was associated with an OR of 4.3 (95% CI, 2.3-7.9) for death. Accuracy of serial BUN measurement (AUC, 0.82-0.91) was comparable to that of the APACHE II score (AUC, 0.72-0.92) in each of the cohorts. A BUN-based assessment algorithm identified patients at increased risk for mortality during the initial 24 hours of hospitalization. CONCLUSIONS We have confirmed the accuracy of BUN measurement for early prediction of mortality in AP and developed an algorithm that may assist physicians in their early resuscitation efforts.

An Assessment of the Severity of Interstitial Pancreatitis

BACKGROUND & AIMS There is limited information on the incidence of and factors associated with severe disease among patients with interstitial pancreatitis (IP). We evaluated a large cohort of patients with IP and compared data with those from patients with extrapancreatic necrosis (EXPN). METHODS We evaluated 149 consecutive patients with IP admitted over a 2.5-year period. Transferred patients were excluded. We collected data on age, Charlson comorbidity score (CCI), measures of severity on admission or within 24 hours (Acute Physiology and Chronic Health Evaluation II, bedside index for severity of acute pancreatitis scores), persistent (>48 h) systemic inflammatory response syndrome, persistent organ failure, need for intensive care unit, length of hospital stay (in days), and mortality. We also analyzed levels of severity among those with IP and EXPN. Statistical analysis was performed using SAS version 9.1 (Cary, NC). RESULTS Among the patients with IP, the median CCI score was 1, the median Acute Physiology and Chronic Health Evaluation II score was 7, and the median bedside index for severity of acute pancreatitis score was 1. In addition, the median length of hospital stay was only 4 days; only 1% had persistent organ failure and only 1% to 2% required intervention. The mortality rate of IP was 3%; it was associated significantly with comorbidity (the median CCI scores of nonsurvivors and survivors was 4 and 1, respectively, P = .003). Patients with EXPN had greater levels of disease severity, compared with patients with IP. CONCLUSIONS IP is severe in only 1% to 3% of patients; mortality of IP is associated strongly with comorbidity. EXPN is more frequently severe than IP; EXPN must be distinguished from IP in clinical studies.

High prevalence of low-trauma fracture in chronic pancreatitis.

OBJECTIVES:Chronic pancreatitis (CP) is associated with risk factors that may negatively impact bone and mineral metabolism. The important clinical end point of osteoporosis is “low-trauma” fracture. The purpose of this study was to examine the prevalence of “low-trauma” fracture in patients with CP, compared with fracture rates in “high-risk” gastrointestinal (GI) illnesses, for which metabolic bone disease screening guidelines are in place.METHODS:This is a retrospective cohort database study examining patients with CP and “high-risk” GI illnesses seen at a single tertiary care center. Time points ranged between 31 July 1998 and 31 July 2008. The main outcome measure was “low-trauma” fracture prevalence using specific International Classification of Diseases, Ninth Revision, Clinical Modification fracture codes.RESULTS:A total of 3,192 CP patients and 1,461,207 non-CP patients were included in the study. The fracture prevalence (patients with fracture per total patients) was as follows: controls, 1.1% (16,208/1,436,699); Crohns disease, 3.0% (182/6057); CP, 4.8% (154/3192); cirrhosis, 4.8% (805/16,658); celiac disease, 5.0% (74/1480); and postgastrectomy, 5.4% (17/313). Prevalence for each group was statistically greater than controls (P<0.001). CP fracture prevalence was greater than controls (P<0.001) and Crohns disease (P<0.001), and comparable with the remaining “high-risk” GI illness groups (P>0.05). The odds of fracture (odds ratio (OR), 95% confidence interval (CI)) compared with controls, adjusted for age, gender, and race was: CP 2.4 (2.1, 2.9); Crohns disease 1.7 (1.5, 2.0); gastrectomy 2.5 (1.5, 4.1); cirrhosis 2.6 (2.4, 2.7); and celiac disease 2.7 (2.1, 3.4). The odds of fracture for each disease group were statistically greater than controls (P<0.0001).CONCLUSIONS:The prevalence of low-trauma fracture in CP patients is comparable with or higher than that of “high-risk” GI illnesses, for which osteoporosis screening guidelines exist.

Comparative Evaluation of the Modified CT Severity Index and CT Severity Index in Assessing Severity of Acute Pancreatitis

OBJECTIVE The purpose of this study was to compare the modified CT severity index (MCTSI) with the CT severity index (CTSI) regarding assessment of severity parameters in acute pancreatitis (AP). Both CT indexes were also compared with the Acute Physiology, Age, and Chronic Health Evaluation (APACHE II) index. MATERIALS AND METHODS Of 397 consecutive cases of AP, 196 (49%) patients underwent contrast-enhanced CT (n = 175) or MRI (n = 21) within 1 week of onset of symptoms. Two radiologists independently scored both CT indexes. Severity parameters included mortality, organ failure, pancreatic infection, admission to and length of ICU stay, length of hospital stay, need for intervention, and clinical severity of pancreatitis. Discrimination analysis and kappa statistics were performed. RESULTS Although for both CT indexes a significant relationship was observed between the score and each severity parameter (p < 0.0001), no significant differences were seen between the CT indexes. Compared with the APACHE II index, both CT indexes more accurately correlated with the need for intervention (CTSI, p = 0.006; MCTSI, p = 0.01) and pancreatic infection (CTSI, p = 0.04; MCTSI, p = 0.06) and more accurately diagnosed clinically severe disease (area under the curve, 0.87; 95% CI, 0.82-0.92). Interobserver agreement was excellent for both indexes: for CTSI, 0.85 (95% CI, 0.80-0.90) and for MCTSI, 0.90 (95% CI, 0.85-0.95). CONCLUSION No significant differences were noted between the CTSI and the MCTSI in evaluating the severity of AP. Compared with APACHE II, both CT indexes more accurately diagnose clinically severe disease and better correlate with the need for intervention and pancreatic infection.

Early readmission in acute pancreatitis: Incidence and risk factors

OBJECTIVES:Early unplanned readmission is a potential target for quality improvement and cost reduction. The aims of this study were to (i) determine the frequency of early readmission following hospitalization for acute pancreatitis (AP) and (ii) identify risk factors for early readmission in patients hospitalized for AP.METHODS:A retrospective, observational cohort study was performed including all inpatients with AP at a tertiary-care hospital between June 2005 and December 2007. Early readmission was defined as admission to the hospital or reevaluation in the emergency department within 30 days of discharge. We analyzed demographics, etiology, markers of severity (according to Atlanta symposium), comorbidities, complications, therapeutic interventions, and discharge symptoms as potential risk factors for readmission.RESULTS:There were a total of 248 patients discharged with AP during the study period, of whom 19% (47/248) had an early readmission. Median time to readmission was 9 days (interquartile range, 5–15). Median rehospitalization length of stay was 4 days (2.5–8). In multivariate analysis, the strongest risk factors for early readmission included (i) gastrointestinal symptoms (nausea, vomiting, or diarrhea) at discharge (odds ratio (OR) 44.2; 95% confidence interval (CI) 4.1–472.1); (ii) discharge on less than a solid diet (OR 23.8; 95% CI 4.8–118.2); and (iii) moderate to heavy alcohol use (OR 10.1; 95% CI 1.2–82.6).CONCLUSIONS:(i) Early readmission is a common occurrence in AP. (ii) Risk factors for early readmission included moderate to heavy alcohol use, persistent symptoms, and diet at the time of discharge.

Optimized sample preparation of endoscopic collected pancreatic fluid for SDS-PAGE analysis

The standardization of methods for human body fluid protein isolation is a critical initial step for proteomic analyses aimed to discover clinically relevant biomarkers. Several caveats have hindered pancreatic fluid proteomics, including the heterogeneity of samples and protein degradation. We aim to optimize sample handling of pancreatic fluid that has been collected using a safe and effective endoscopic collection method (endoscopic pancreatic function test). Using SDS‐PAGE protein profiling, we investigate (i) precipitation techniques to maximize protein extraction, (ii) auto‐digestion of pancreatic fluid following prolonged exposure to a range of temperatures, (iii) effects of multiple freeze–thaw cycles on protein stability, and (iv) the utility of protease inhibitors. Our experiments revealed that TCA precipitation resulted in the most efficient extraction of protein from pancreatic fluid of the eight methods we investigated. In addition, our data reveal that although auto‐digestion of proteins is prevalent at 23 and 37°C, incubation on ice significantly slows such degradation. Similarly, when the sample is maintained on ice, proteolysis is minimal during multiple freeze–thaw cycles. We have also determined the addition of protease inhibitors to be assay‐dependent. Our optimized sample preparation strategy can be applied to future proteomic analyses of pancreatic fluid.