Fluid resuscitation represents a pivotal early therapeutic intervention in the management of acute pancreatitis (AP), yet a consensus on the optimal fluid type remains elusive. The present study endeavors to elucidate the differential effects of lactated Ringer's solution (LR) and normal saline (NS) in the initial treatment of AP.

A comprehensive literature search was conducted through the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, spanning from inception until July 2024. The primary outcome of interest was the likelihood of developing moderate-to-severe AP.

This meta-analysis synthesized evidence from six randomized controlled trials (RCTs) and four observational studies, involving a total of 1500 AP patients. Patients were stratified into two groups based on the administered fluid: LR (n = 689) and NS (n = 811). Our findings revealed that, compared to the NS group, patients in the LR group demonstrated a significantly lower risk of moderate-to-severe AP (OR 0.48; 95%Cl 0.34 to 0.67; P < 0.001; I2  = 0%), a shorter hospital stay (MD = -0.74, 95% confidence interval [CI] -1.20 to -0.28, P = 0.001; I2  = 0%), and a reduced intensive care unit (ICU) admission rate [relative risk (RR) = 0.42, 95% CI 0.20-0.89, P = 0.02; I2  = 0%]. Moreover, the LR group also showed a lower incidence of local complications (RR = 0.58, 95% CI 0.34-0.98, P = 0.04). Conversely, no statistically significant differences were observed between the two groups in terms of mortality, organ failure rates, Fluid administered 24 h, systemic inflammatory response syndrome (SIRS).

Our analysis underscores the superior efficacy of LR solution in comparison to NS. It provides compelling evidence of LR's ability to significantly mitigate the onset of moderate to severe pancreatitis. Additionally, our findings reveal that LR is associated with a reduced need for ICU admissions, a lower incidence of local complications, and a shorter overall hospital stay, thereby offering a more favorable clinical outcome. However, no notable differences were discerned in other complications. Subgroup analyses further suggest LR's potential to curb pancreatic necrosis and other indices, albeit these findings necessitate corroboration through extensive experimentation.

Isotonic crystalloids are recommended as the first choice for fluid therapy in acute pancreatitis (AP), with normal saline (NS) and lactate Ringer's (LR) used most often. Evidence based recommendations on the type of fluid are conflicting and generally come from small single-center randomized controlled trials (RCTs). We therefore conducted a systematic review and meta-analysis to compare the effect of balanced solutions (BS) versus NS on patient-centered clinical outcomes in AP.

From four databases searched up to October 2024, we included only RCTs of adult patients with AP that compared the use of BS (including LR, acetate Ringer's, etc.) with NS. The primary outcome was the disease advances from AP to moderately severe and severe AP (MSAP/SAP). Trial sequential analyses (TSA) were conducted to control for type-I and type-II errors and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence.

Six RCTs were identified and included, involving 260 patients treated with BS and 298 patients with NS. Patients who received the BS had less MSAP/SAP [odds ratio (OR) = 0.50, 95 % confidence interval (CI): 0.29 to 0.85, P = 0.01, I2 = 0 %; 5 studies, 299 patients], reduced need of ICU admission (OR = 0.60, 95 % CI: 0.39 to 0.93, P = 0.02, I2 = 0 %; 5 studies, 507 patients) and shorter length of hospital stay [mean difference (MD) = -0.88, 95 % CI:1.48 to -0.28, P = 0.004, I2 = 0 %; 6 studies, 558 patients; confirmed by TSA with high certainty] compared with those who received NS. The evidence for most of the clinical outcomes was rated as moderate to low due to the risk of bias, imprecision and inconsistency.

BS, compared with NS, was associated with improved clinical outcomes in patients with AP. However, given the moderate to low quality of evidence for most of the outcomes assessed, further trials are warranted.

Acute pancreatitis (AP) is a heterogeneous inflammation of the pancreas, most frequently attributable to gallstones or alcohol. AP accounts for an estimated 300 000 patients admitted each year in the USA, and an estimated US$2.6 billion/year in hospitalization costs. Disease severity is classified as mild, moderate, or severe, dependent on the presence or degree of concomitant organ failure. Locally, pancreatitis may be complicated by fluid collections, necrosis, infection, and hemorrhage. Infection of necrotizing pancreatitis (NP) is associated with a doubling of mortality risk. The modern management of AP is evolving. Recent data suggest a shift from normal saline to lactated Ringer's solution, and from aggressive to more judicious volume resuscitation. Similarly, while historical wisdom advocated keeping patients nothing by mouth to 'rest the pancreas', recent data convincingly show fewer complications and reduced mortality with early enteral nutrition, when tolerated by the patient. The use of antibiotics in NP is controversial. Current recommendations suggest reserving antibiotics for cases with highly suspected or confirmed infected necrosis, as well as in patients with biliary pancreatitis complicated by acute cholecystitis or cholangitis. Regarding the management of local complications, control of acute hemorrhage can be attained either endovascularly or via laparotomy. Abdominal compartment syndrome is associated with a mortality risk of 50%-75%. Routine monitoring of intra-abdominal pressure is recommended in patients at high risk. Pancreatic pseudocysts require intervention in symptomatic patients or those with infection or other complications. Endoscopic transmural drainage may be considered as the first step when technically feasible. Necrotizing pancreatitis without suspicion of infection is often managed medically, while the delay, drain, debride approach remains the standard of care for the vast majority of infected pancreatic necrosis. Robotic surgery, in appropriately selected patients, allows for a one-step approach, and merits further study to explore its initially promising results.

Acute pancreatitis (AP) is an inflammatory disease that can represent a challenge for clinicians, in fact, the early determination of its severity in the first 72 h is crucial for prognosis, recognizing the etiology and carrying out risk stratification to determine a more specific therapy. No accurate early prognostic scores for disease severity have been published, so the severity of AP often cannot be properly defined in the first few hours of the disease. This initial phase represents a "no man's land", in which there is no certainty in the stratification of the damage, prognosis is difficult to establish, therapy must be started promptly, although there is still no effective medical therapy against pancreatic enzymatic activation. Therefore, it is very difficult at this stage to make the correct decisions to achieve the best outcome for the patient with AP. Literature search was carried out using the PubMed database by entering early management of acute pancreatitis [title] or therapy of acute pancreatitis [title] and selecting the most relevant articles for the diagnosis and therapy of acute pancreatitis in clinical practice. This document provides suggestions on managing the key clinical decisions for patients suffering from AP before disease severity is defined, to achieve the best outcomes for patients with AP.

Severe acute pancreatitis often presents as a complex critical illness associated with a high rate of infectious morbidity, multiple organ failure, and in-hospital mortality. Breakdown of gut barrier defenses, dysbiosis of intestinal microbiota, and exaggerated immune responses dictate that early enteral nutrition (EN) is preferred over parenteral nutrition (PN) as the primary route of nutrition therapy. EN, however, is not feasible in all cases because of intolerance, risk of complications, or a direct contraindication to enteral feeding. For these patients, PN can be provided in a manner that is safe, is metabolically appropriate, and follows the principles of modern critical care nutrition. Adherence to goal-directed fluid resuscitation, provision of trophic doses of PN to meet 20%-25% of protein and/or calorie requirements through the acute phases of illness, use of less-inflammatory intravenous lipid emulsions, and close monitoring of electrolytes, triglyceride levels, and signs of refeeding syndrome all serve to optimize the response to this route of nutrition support. For these reasons, prescribing PN remains an important strategy in the management of this difficult population of patients.

Acute pancreatitis is a commonly encountered pathology in the emergency department. We presented a clinical review summarizing the contemporary emergency medicine approach to managing acute pancreatitis. Although the diagnostic criteria for acute pancreatitis are straightforward, it has many possible causes, several treatment options, and both short- and long-term sequelae. We discussed diagnostic, intervention, and disposition considerations relevant to emergency clinicians and considered risk assessment using available clinical decision tools. We also discussed changes to traditional treatments and ongoing investigational therapies, including steroids, monoclonal antibodies, and calcium release-activated calcium channel inhibitors.

Background/Objectives: Acute pancreatitis (AP) is an inflammatory condition with diverse origins, often resulting in significant morbidity and mortality due to systemic inflammatory response syndrome (SIRS) and multiorgan failure. Fluid resuscitation is pivotal in early management, and it is aimed at preventing hypovolemia-induced ischemia and necrosis. This review evaluates fluid therapy strategies in AP, including fluid types, resuscitation rates, and clinical outcomes. Methods: This systematic review was conducted in January 2025 using databases such as PubMed, Medline, and Google Scholar, focusing on studies published between 2010 and 2024. Search terms included "acute pancreatitis", "fluid resuscitation", and related keywords. Studies involving adults with AP were analyzed to compare the outcomes of crystalloid and colloid use, aggressive vs. moderate fluid resuscitation, and administration timings. The primary outcomes were mortality and severe complications, while secondary outcomes included organ failure, SIRS, and length of hospital stay. Results: Crystalloids, particularly Ringer's lactate (RL), are superior to normal saline in reducing SIRS, organ failure, and intensive care unit stays without significantly affecting mortality rates. Colloids were associated with adverse events such as renal impairment and coagulopathy, limiting their use. Aggressive fluid resuscitation increased the risk of fluid overload, respiratory failure, and acute kidney injury, particularly in severe AP, while moderate hydration protocols achieved comparable clinical outcomes with fewer complications. Conclusions: Moderate fluid resuscitation using RL is recommended for managing AP, balancing efficacy with safety. Further research is needed to establish optimal endpoints and protocols for fluid therapy, ensuring improved patient outcomes while minimizing complications.

Activation of inflammasomes is the activation of inflammation‑related caspase mediated by the assembly signal of multi‑protein complex and the maturity of inflammatory factors, such as IL‑1β and IL‑18. Among them, the Nod‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most thoroughly studied type of inflammatory corpuscle at present, which is involved in the occurrence and development of numerous human diseases. Therefore, targeting the NLRP3 inflammasome has become the focus of drug development for related diseases. In this paper, the research progress of the NLRP3 inflammasome in recent years is summarized, including the activation and regulation of NLRP3 and its association with diseases. A deep understanding of the regulatory mechanism of NLRP3 will be helpful to the discovery of new drug targets and the development of therapeutic drugs.

Organ failure (OF) is a sinister development in the clinical course of acute pancreatitis, and its prediction is crucial for triaging the patient. Persistent systemic inflammatory response syndrome and raised interleukin-6 levels have a good predictive accuracy. Pathophysiology involves the release of damage-associated molecular patterns as a consequence of pancreatic injury, recruitment of inflammatory cells, and the release of proinflammatory cytokines and chemokines causing cytokine storm. Respiratory system is the most common and earliest to fail. Although a few therapeutic options are in the pipeline, renewed efforts are required to develop targeted therapies to mitigate systemic inflammation and OF.

Although endoscopic retrograde cholangiopancreatography (ERCP) has been shown to be a safe and effective approach in treating these diseases while carrying lower morbidity than traditional surgical treatments, ERCP has associated risks, with post-ERCP pancreatitis (PEP) being the most common serious adverse event and carries significant morbidity and health care cost. PEP results from multifactorial factors involving trauma to the pancreatic duct and papilla, leading to subsequent obstruction and impairment of pancreatic drainage. Important risk factors for PEP include history of prior PEP, suspected sphincter of Oddi dysfunction, difficult cannulation, pancreatic duct contrast injections, and pancreatic sphincterotomy.

Acute pancreatitis is an inflammatory condition of the exocrine pancreas that is a common indication for hospital admission and has had an increasing incidence in the last few decades. The diagnosis of acute pancreatitis requires the satisfaction of two out of three criteria: (1) abdominal pain radiating to the back, (2) serum lipase or amylase levels three or more times the upper limit of the normal level, and (3) findings indicating pancreatitis obtained via a computed tomography (CT) scan or magnetic resonance imaging (MRI). The different etiologies include gallstones, autoimmune disorders, alcohol abuse, smoking, hypertriglyceridemia, obesity, drugs, and post-endoscope retrograde cholangiopancreatography (ERCP). The initial investigation includes serum amylase and lipase analysis, a lipid panel including triglycerides, analysis of immunoglobulins, a full blood count, electrolyte analysis, a hemoglobin A1c test, a complete metabolic panel, and transabdominal ultrasound. The initial therapy includes oxygen supplementation, the provision of intravenous fluids, pain control, and a nutrition regime. Early oral feeding is encouraged if tolerated; if not, liquid supplement provision or enteral tube feeding within 48 h of admission has shown better outcomes. Some complications of acute pancreatitis are necrosis, infection, insulin resistance leading to diabetes mellitus, and pancreatic exocrine insufficiency requiring enzyme supplementation. Patients need to attend regular follow-ups and abstain from alcohol and smoking (if warranted) to prevent the recurrence of acute pancreatitis. The mortality rate of acute pancreatitis has decreased in the past few decades because of better management skills, but the recent rise in acute pancreatitis episodes is concerning. Sustained endeavors through clinical trials are required to establish a broad variety of drugs that can be used for acute pancreatitis episodes.

To compare the effect of balanced multielectrolyte solutions (BMESs) versus normal saline (NS) for intravenous fluid on chloride levels and clinical outcomes in patients with predicted severe acute pancreatitis (pSAP).

Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown.

In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (acute physiology and chronic health evaluation II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for a one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase (sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day 3. Secondary endpoints included a composite of clinical and laboratory measures.

Overall, 259 patients were enrolled from 11 sites to receive NS (n = 147) or BMES (n = 112). On trial day 3, the mean chloride level was significantly lower in patients who received BMES [101.8 mmol/L (SD: 4.8) vs 105.8 mmol/L (SD: 5.9), difference -4.3 mmol/L (95% CI: -5.6 to -3.0 mmol/L) ; P < 0.001]. For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome (19/112, 17.0% vs 43/147, 29.3%, P = 0.024) and increased organ failure-free days [3.9 days (SD: 2.7) vs 3.5 days (SD: 2.7), P < 0.001] by trial day 7. They also spent more time alive and out of the intensive care unit [26.4 days (SD: 5.2) vs 25.0 days (SD: 6.4), P = 0.009] and hospital [19.8 days (SD: 6.1) vs 16.3 days (SD: 7.2), P < 0.001] by trial day 30.

Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits (Trial registration number: ChiCTR2100044432).

Adverse events after endoscopic retrograde cholangiopancreatography (ERCP) are rare, and post-ERCP pancreatitis is a serious adverse event. This study aimed to determine the role of aggressive intravenous hydration with lactated Ringer's solution at a specific volume with 20% human albumin before ERCP in reducing the incidence of post-ERCP pancreatitis.

This study was a single-centre randomized clinical trial. The participants were randomly assigned to two groups: those who received aggressive intravenous hydration with 20% human albumin and lactated Ringer's solution (intervention group), and those who received standard-volume intravenous hydration with lactated Ringer's solution (control group). The primary endpoint was post-ERCP pancreatitis. Participants and outcome assessors were blinded to treatment allocation. Comparison was performed using the chi-square, the Fisher's exact, the Student's t, or the Mann-Whitney U tests, where appropriate.

Of 300 randomized participants, 149 and 144 participants from the intervention and control group were included in the analysis. There was no significant difference in the post-ERCP pancreatitis rate (n = 10; 6.7% versus n = 9; 6.3%, P = 0.873) between the intervention and control groups. High-risk procedures (that is pancreatic duct wiring, pancreatic duct injection, precut sphincterotomy, and balloon dilation of the ampulla) were significantly associated with post-ERCP pancreatitis compared with low-risk procedures (n = 15; 15% versus n = 4; 2.1%, P < 0.001). In the high-risk procedures population, the intervention and control groups had increased post-ERCP pancreatitis rates (P = 0.716). Two participants in each group developed pulmonary congestion.

Aggressive peri-ERCP intravenous hydration with lactated Ringer's solution combined with 50 ml of 20% human albumin did not prevent post-ERCP pancreatitis. None of the subgroups presented with prophylactic effects.

Thai Clinical Trials Registry (TCTR20240405003).

Delayed graft function after kidney transplantation is linked to poor graft survival and increased chronic allograft injury. Recent guidelines suggest using balanced crystalloids over 0.9% saline owing to better metabolic profiles, but their impact on DGF remains unclear.

We searched PubMed, Embase, and Cochrane Central Registry of Clinical Trials from inception until February 29, 2024, and included RCTs that randomised adult participants to receive either intravenous balanced fluids or 0.9% saline intraoperatively. We pooled data using a random-effects model and present risk ratios (RRs) or mean differences, with 95% confidence intervals (CIs). We assessed individual study risk of bias using the modified Cochrane tool and certainty of evidence using GRADE. Outcomes analysed were delayed graft function incidence, vasopressor requirements, length of hospital stay, and postoperative metabolic profiles.

Of 106 publications identified, we included 11 RCTs (n=1717). Pooled analysis showed that the use of balanced fluids was associated with a lower incidence of delayed graft function compared with 0.9% saline (RR 0.82, 95% CI: 0.69 to 0.98, P=0.01, moderate certainty). Balanced crystalloids were associated with higher postoperative serum pH, higher serum bicarbonate, and lower serum chloride concentration, but effects on vasopressor requirements, length of hospital stay, and serum creatinine were uncertain.

Balanced crystalloid intravenous fluid therapy reduced delayed graft function incidence and maintained more favourable serum chemistry profiles compared with 0.9% saline in patients undergoing kidney transplantation. However, crystalloid type did not significantly influence vasopressor requirements and length of hospital stay.

Some evidence suggests that fluid resuscitation with lactated Ringer's solution (LR) may have an anti-inflammatory effect on acute pancreatitis (AP) when compared to normal saline (NS) and may be associated with a decrease in severity, but existing single-center randomized controlled trials showed conflicting results. The WATERLAND trial aims to investigate the efficacy and safety of fluid resuscitation using LR compared to NS in patients with AP.

The WATERLAND trial is an international multicenter, open-label, parallel-group, randomized, controlled, superiority trial. Patients will be randomly assigned in a 1:1 ratio to receive LR versus NS-based fluid resuscitation for at least 48 h. The primary outcome will be moderately severe or severe AP, according to the revision of the Atlanta classification. The secondary objectives of the WATERLAND trial are to determine the effect of LR versus NS fluid resuscitation on several efficacy and safety outcomes in patients with AP. A total sample of 720 patients, 360 in the LR group and 360 in the NS group, will achieve 90% power to detect a difference between the group proportions of 10%, assuming that the frequency of moderately severe or severe AP in the LR group will be 17%. A loss to follow-up of 10% of patients is expected, so the total sample size will be 396 patients in each treatment arm (792 patients overall). The test statistic used is the two-sided Z test with pooled variance set at a 0.05 significance level.

The WATERLAND study aims to improve the early management of AP. Fluid resuscitation is an inexpensive treatment available in any hospital center worldwide. If a better evolution of pancreatitis is demonstrated in one of the treatment arms, it would have important repercussions in the management of this frequent disease.

ClinicalTrials.gov, NCT05781243. Registration date on January 4, 2023. EudraCT number 2023-000010-18, first posted March 23, 2023.

Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer's solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke.

Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins.

Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived.

NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.

Fluid resuscitation is an important way in the treatment of acute pancreatitis (AP). This meta-analysis aimed to compare the safety and efficacy of Lactate Ringer's solution (LR) and Normal Saline (NS) in the treatment of patients with acute pancreatitis. Searched in PubMed, Web of Science Core Collection (Clarivate), Embase, Cochrane Library, CNKI, China Wanfang, and China VIP database. All randomized controlled clinical trials (RCTs) were identified. Six studies with 431 patients were included. Compared with NS, LR can significantly reduce the incidence of SIRS at 24h, reduce the length of hospitalization, moderate-severe AP, ICU admission and local complications, especially pancreatic necrosis. It is safe and effective to choose LR for fluid resuscitation in AP, but due to the small number of included studies, multi-center and large-sample RCTs are still needed for further verification. PROSPERO registration number: CRD42022322788.

We aimed to evaluate comparative outcomes of aggressive versus non-aggressive intravenous fluid (IVF) therapy in patients with acute pancreatitis.

A systematic search of electronic data sources and bibliographic reference lists were conducted. All randomized controlled trials (RCTs) reporting outcomes of aggressive versus non-aggressive IVF therapy in acute pancreatitis were included and their risk of bias were assessed. Effect sizes were determined for overall mortality, systemic inflammatory response syndrome (SIRS), sepsis, respiratory failure, pancreatic necrosis, severe pancreatitis, clinical improvement, AKI, and length of stay using random-effects modeling. Trial sequential analysis was conducted to determine risk of types 1 or 2 errors.

We included 10 RCTs reporting 993 patients with acute pancreatitis who received aggressive (n = 475) or non-aggressive (n = 518) IVF therapy. Aggressive IVF therapy was associated with significantly higher rate of sepsis (OR: 2.68, P = 0.0005) and longer length of stay (MD: 0.94, P < 0.00001) compared with the non-aggressive approach. There was no statistically significant difference in mortality (RD: 0.02, P = 0.31), SIRS (OR: 0.93, P = 0.89), respiratory failure (OR: 2.81, P = 0.07), pancreatic necrosis (OR: 1.98, P = 0.06), severe pancreatitis (OR: 1.31, P = 0.38), clinical improvement (OR: 1.12, P = 0.83) or AKI (OR: 1.06, P = 0.91) between the two groups. Sub-group analysis demonstrated higher morbidity and mortality associated with the aggressive approach in more severe disease. Trial sequential analysis detected risk of type 2 error.

Aggressive IVF therapy may be associated with higher morbidity in patients with acute pancreatitis compared with the non-aggressive approach, particularly in patients with more severe disease. It may also prolong length of hospital stay. The available evidence is subject to type 2 error indicating the need for adequately powered RCTs.

Fluid resuscitation reduces mortality and morbidity in acute pancreatitis (AP); however, whether glucose-containing fluids negatively impact AP remains uncertain. We aimed to examine the association between glucose-containing fluids and AP outcomes.

This multicenter retrospective cohort study included patients diagnosed with AP between January 2015 and December 2018. Glucose density was defined as total glucose content divided by total fluid volume (g/dl) on day 1, and was considered high if the level exceeded the median. Endpoints were early organ failure (OF), including cardiovascular, renal, or respiratory system failure within 7 days; 30-day OF; ICU admission; and AP-related 90-day mortality. Logistic regression models, restricted cubic spline curves, and Cox proportional hazards models were used for statistical analysis.

From the database, 1,146 patients with AP were included. Early OF occurred in 8.8% of patients within 7 days. The high glucose-density group (>5 g/dl) had increased risk of early OF (9.7% vs. 8.2%; adjusted odds ratio [aOR], 1.69; 95% confidence interval [CI], 1.03-2.80; P = 0.039), respiratory failure (8.0% vs. 6.2%; aOR, 1.88; 95% CI, 1.09-3.24; P = 0.024), cardiovascular failure (3.4% vs. 2.4%; aOR, 3.59; 95% CI, 1.28-10.0; P = 0.015), and ICU admission (6.8% vs. 5.8%; aOR, 2.06; 95% CI, 1.08-3.94; P = 0.029), with a dose-response effect observed for cardiovascular failure and ICU admission. A significant increase 30-day OF risk (adjusted hazard ratio [aHR], 1.70; 95% CI, 1.19-2.45) was also noted.

Excess glucose-containing fluid was associated with increased risks of overall, respiratory, and cardiovascular OF and ICU admission in AP.

Patients with Cystic Fibrosis (CF) are at increased risk of acute (AP) and chronic (CP) pancreatitis, and their complications. The extent of remaining healthy pancreatic parenchyma determines the risk of developing future episodes of pancreatitis, as well as pancreatic exocrine or endocrine insufficiency. Pancreatitis may be the presenting symptom of CF, and genetic testing is especially important in pediatrics. AP and recurrent AP are managed with intravenous fluid hydration and pain control, in addition to early refeeding and treatment of complications. With the use of modulator therapy in CF, pancreatic function may be restored to some extent. CP related pain is managed with analgesics and neuromodulators, with surgery if indicated in specific situations including TPIAT as a possible type of surgical intervention. Long-term sequelae of CP in patients with CF include exocrine pancreatic insufficiency treated with pancreatic enzyme replacement therapy, fat-soluble vitamin deficiencies and associated metabolic complications such as bone disease/osteoporosis, pancreatogenic diabetes, and less commonly, pancreatic cancer. We review the presentation and etiologies of pancreatitis in CF patients as well as the management of AP and CP primarily in children.

Acute pancreatitis (AP) is increasing in incidence across the world, and in all age groups. Major changes in management have occurred in the last decade. Avoiding total parenteral nutrition and prophylactic antibiotics, avoiding overly aggressive fluid resuscitation, initiating early feeding, avoiding endoscopic retrograde cholangiopancreatography in the absence of concomitant cholangitis, same-admission cholecystectomy, and minimally invasive approaches to infected necrosis should now be standard of care. Increasing recognition of the risk of recurrence of AP, and progression to chronic pancreatitis, along with the unexpectedly high risk of diabetes and exocrine insufficiency after AP is the subject of large ongoing studies. In this review, we provide an update on important changes in management for this increasingly common disease.

Maintenance intravenous fluids are the most frequently ordered medications for hospitalized children. Since the American Association of Pediatrics published national guidelines, there has been an increased reflexive use of isotonic solutions, especially 0.9% saline, as a prophylaxis against hyponatremia. In this educational review, we discuss the potential deleterious effects of using 0.9% saline, including the development of hyperchloremia, metabolic acidosis, acute kidney injury, hyperkalemia, and a proinflammatory state. Balanced solutions with anion buffers cause relatively minimal harm when used in most children. While the literature supporting one fluid choice over the other is variable, we highlight the benefits of balanced solutions over saline and the importance of prescribing fluid therapy that is individualized for each patient.

Fluid resuscitation is fundamental in acute pancreatitis (AP) treatment. However, the optimal choice between normal saline (NS) and Ringer's solution (RS), and its impact on mortality in critically ill patients, remains controversial. This retrospective cohort study, utilizing a national Japanese inpatient database, investigates this question.

Using the Japanese Diagnosis Procedure Combination database between July 2010 and March 2021, we identified adult patients hospitalized in intensive care units (ICU) or high-dependency care units (HDU) for AP who survived at least three days and received sufficient fluid resuscitation (≥ [10 ml/kg/hr*1 h + 1 ml/kg/hr*71 h] ml) within three days of admission including emergency room infusions. Patients were classified into groups based on the predominant fluid type received: the NS group (> 80% normal saline) and the RS group (> 80% Ringer's solution). Propensity score matching was employed to reduce potential confounding factors and facilitate a balanced comparison of in-hospital mortality between the two groups.

Our analysis included 8710 patients with AP. Of these, 657 (7.5%) received predominantly NS, and 8053 (92.5%) received predominantly RS. Propensity score matching yielded 578 well-balanced pairs for comparison. The NS group demonstrated significantly higher in-hospital mortality than the RS group (12.8% [474/578] vs. 8.5% [49/578]; risk difference, 4.3%; 95% confidence interval, 0.3% to 8.3%).

In patients admitted to ICU or HDU with AP receiving adequate fluid resuscitation, RS can be a preferred infusion treatment compared to NS.

Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis (PEP). Despite advances in the prevention strategies, prevention of PEP remains imperfect, necessitating more refined hydration methods. This study investigates the effectiveness of lactated Ringer's solution versus plasma solution in preventing PEP.

This multicentre, double-blind, randomised controlled trial, will be initiated by the investigator-sponsor, and conducted in three tertiary centres in South Korea. The aim of this study is to assess the effectiveness of hydration in preventing PEP in patients with naïve papillae. It will target patients with naïve papillae, focusing on those at medium to high risk of PEP. Patients aged ≤18 years and those with serious comorbidities, acute/chronic pancreatitis and various other medical conditions will be excluded. Eligible participants will be randomly assigned into two arms in equal numbers: (1) PEP prevention using lactated Ringer's solution and (2) PEP prevention using plasma solution. The primary outcome of this study will be the occurrence of PEP, and secondary outcomes will be additional risk factors and potential adverse events related to ERCP. With a total enrolment of 844 patients, the study will be able to detect significant differences between the intervention arms.

Ethical approval is obtained from each institution (Asan Medical Centre, 2023-0382; Seoul National University Hospital, H-2302-05-1404; Samsung Medical Centre, SMC 2023-02-001-009). All participants provided informed consent following clear explanation of the study procedures. The results of the study will be disseminated in peer-reviewed journals and research conferences.

NCT05832047.

Ver 4.1 (2023).

Acute pancreatitis (AP) is an inflammatory disease characterized by localized pancreatic injury and a systemic inflammatory response. Fatty acids (FAs), produced during the breakdown of triglycerides (TGs) in blood and peripancreatic fat, escalate local pancreatic inflammation to a systemic level by damaging pancreatic acinar cells (PACs) and triggering M1 macrophage polarization. This paper provides a comprehensive analysis of lipases' roles in the onset and progression of AP, as well as the effects of long-chain fatty acids (LCFAs) on the function of pancreatic acinar cells (PACs). Abnormalities in the function of PACs include Ca2+ overload, premature trypsinogen activation, protein kinase C (PKC) expression, endoplasmic reticulum (ER) stress, and mitochondrial and autophagic dysfunction. The study highlights the contribution of long-chain saturated fatty acids (LC-SFAs), especially palmitic acid (PA), to M1 macrophage polarization through the activation of the NLRP3 inflammasome and the NF-κB pathway. Furthermore, we investigated lipid lowering therapy for AP. This review establishes a theoretical foundation for pro-inflammatory mechanisms associated with FAs in AP and facilitating drug development.

Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-α, IFN-γ, IL-1β, TNF-α, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.

Acute Pancreatitis (AP) is associated with high mortality and current treatment options are limited to supportive care. We found that blockade of activin A (activin) in mice improves outcomes in two murine models of AP. To test the hypothesis that activin is produced early in response to pancreatitis and is maintained throughout disease progression to stimulate immune cells, we first performed digital spatial profiling (DSP) of human chronic pancreatitis (CP) patient tissue. Then, transwell migration assays using RAW264.7 mouse macrophages and qPCR analysis of "neutrophil-like" HL-60 cells were used for functional correlation. Immunofluorescence and western blots on cerulein-induced pancreatitis samples from pancreatic acinar cell-specific Kras knock-in (Ptf1aCreER™; LSL-KrasG12D) and functional WT Ptf1aCreER™ mouse lines mimicking AP and CP to allow for in vivo confirmation. Our data suggest activin promotes neutrophil and macrophage activation both in situ and in vitro, while pancreatic activin production is increased as early as 1 h in response to pancreatitis and is maintained throughout CP in vivo. Taken together, activin is produced early in response to pancreatitis and is maintained throughout disease progression to promote neutrophil and macrophage activation.

Serum creatinine (Cr) and albumin (Alb) are important predictors of mortality in individuals with various diseases, including acute pancreatitis (AP). However, most previous studies have only examined the relationship between single Cr or Alb levels and the prognosis of patients with AP. To our knowledge, the association between short- and long-term all-cause mortality in patients with AP and the blood creatinine to albumin ratio (CAR) has not been investigated. Therefore, this study aimed to evaluate the short- and long-term relationships between CAR and all-cause mortality in patients with AP.

We conducted a retrospective study utilizing data from the Medical Information Market for Intensive Care (MIMIC-IV) database. The study involved analyzing various mortality variables and obtaining CAR values at the time of admission. The X-tile software was used to determine the optimal threshold for the CAR. Kaplan-Meier (K-M) survival curves and multivariate Cox proportional hazards regression models were used to assess the relationship between CAR and both short- and long-term all-cause mortality. The predictive power, sensitivity, specificity, and area under the curve (AUC) of CAR for short- and long-term mortality in patients with AP after hospital admission were investigated using Receiver Operating Characteristic analysis. Additionally, subgroup analyses were conducted.

A total of 520 participants were included in this study. The CAR ideal threshold, determined by X-tile software, was 0.446. The Cox proportional hazards model revealed an independent association between CAR≥0.446 and all-cause mortality at 7-day (d), 14-d, 21-d, 28-d, 90-d, and 1-year (y) before and after adjustment for confounders. K-M survival curves showed that patients with CAR≥0.446 had lower survival rates at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y. Additionally, CAR demonstrated superior performance, with higher AUC values than Cr, Alb, serum total calcium, Glasgow Coma Scale, Systemic Inflammatory Response Syndrome score, and Sepsis-related Organ Failure Assessment score at 7-d, 14-d, 21-d, 28-d, 90-d, and 1-y intervals. Subgroup analyses showed that CAR did not interact with a majority of subgroups.

The CAR can serve as an independent predictor for short- and long-term all-cause mortality in patients with AP. This study enhances our understanding of the association between serum-based biomarkers and the prognosis of patients with AP.

During pregnancy and in the post-partum period, several diseases may arise or become exacerbated. Acute pancreatitis is an inflammatory disease with an increasing incidence in Western countries. The incidence of acute pancreatitis during pregnancy is not different with respect to the general population, but this incidence increases in the first 2 years after delivery. Biliary sludge and stones are the most frequent aetiologies, followed by hypertriglyceridemia. Taking care of the mother and foetus through a potentially severe disease requires a team consisting of an obstetrician, a gastroenterologist, an anaesthesiologist, and a surgeon. It is necessary to monitor the health of the foetus/child and the mother during pregnancy, childbirth, and puerperium. The management of this care depends on the systemic and local complications, the severity of the acute pancreatitis, and the trimester of pregnancy. Some diagnostic tools and many drugs are not safe for foetuses, while interventional endoscopy and surgery have limitations and can only be used after an accurate evaluation of benefit/risk ratios. Despite these limitations, maternal mortality due to acute pancreatitis is low during pregnancy, mainly thanks to multidisciplinary approaches for these patients. A careful diet to prevent obesity, alcohol abstinence, routine serum triglyceride control, and breastfeeding for at least three months may prevent acute pancreatitis during and after pregnancy.

Acute pancreatitis poses a significant health risk due to the potential for pancreatic necrosis and multi-organ failure. Fluid resuscitation has demonstrated positive effects; however, consensus on the ideal intravenous fluid type and infusion rate for optimal patient outcomes remains elusive.

A comprehensive literature search was conducted using PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between 2005 and January 2023. Reference lists of potential studies were manually searched to identify additional relevant articles. Randomized controlled trials and retrospective studies comparing high (≥ 20 ml/kg/h), moderate (≥ 10 to < 20 ml/kg/h), and low (5 to < 10 ml/kg/h) fluid therapy in acute pancreatitis were considered.

Twelve studies met our inclusion criteria. Results indicated improved clinical outcomes with low versus moderate fluid therapy (OR = 0.73; 95% CI [0.13, 4.03]; p = 0.71) but higher mortality rates with low compared to moderate (OR = 0.80; 95% CI [0.37, 1.70]; p = 0.55), moderate compared to high (OR = 0.58; 95% CI [0.41, 0.81], p = 0.001), and low compared to high fluids (OR = 0.42; 95% CI [0.16, 1.10]; P = 0.08). Systematic complications improved with moderate versus low fluid therapy (OR = 1.22; 95% CI [0.84, 1.78]; p = 0.29), but no difference was found between moderate and high fluid therapy (OR = 0.59; 95% CI [0.41, 0.86]; p = 0.006).

This meta-analysis revealed differences in the clinical outcomes of patients with AP receiving low, moderate, and high fluid resuscitation. Low fluid infusion demonstrated better clinical outcomes but higher mortality, systemic complications, and SIRS persistence than moderate or high fluid therapy. Early fluid administration yielded better results than rapid fluid resuscitation.

Acute pancreatitis (AP) is a leading cause of gastrointestinal-related hospitalizations in the United States, resulting in 300000 admissions per year with an estimated cost of over $2.6 billion annually. The severity of AP is determined by the presence of pancreatic complications and end-organ damage. While moderate/severe pancreatitis can be associated with significant morbidity and mortality, the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%. Despite favorable outcomes, the majority of mild AP patients are admitted, contributing to healthcare cost and burden. In this Editorial we review the performance of an emergency department (ED) pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations, resource utilization, and costs after several years of implementation of the pathway. We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital, and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway. We conclude that by implementing innovative clinical pathways which are established and reproducible, selected AP patients can be safely discharged from the ED, reducing hospitalizations and healthcare costs, without compromising clinical outcomes. We also identify a subset of patients most likely to succeed in this pathway.

To estimate the difference in serum chloride levels between children receiving 5% Dextrose in Ringer's Lactate (RLD5) vs. 5% Dextrose Normal Saline (DNS) and to estimate the incidence of dyselectrolytemia, hyperchloremic metabolic acidosis (HCMA), acute kidney injury (AKI) and all-cause mortality in both groups.

A randomised controlled trial was conducted in non-critically ill children aged 6 mo to 14 y, admitted between August 2021 and July 2022, requiring intravenous fluids. A sample size of 140 was estimated and randomised, with controls receiving 5% DNS and the intervention group receiving RLD5. Kidney function tests and blood gas analysis were done at admission, 24 h and 48 h after starting the maintenance IV fluid, and outcomes were analysed at 24 h and 48 h. Data was collected using a pre-designed data collection form that included demographic and clinical profile details, and outcomes were analysed using SPSS Version 20 software.

Seventy-one children per group were enrolled. The mean chloride difference between the two groups at 24 and 48 h were 1.67 (p-value 0.03) and 2.78 (p-value 0.01), respectively. The incidence of AKI at 24 h and 48 h was 1.4% and 2.8% in the RLD5 group and 0% and 1.4% in the DNS group, respectively. At 24 h and 48 h, 2.8% and 2.8% of children had HCMA in the RLD5 group, and 14% and 4.2% had HCMA in the DNS group, respectively. There was no mortality in either group.

Though clinically insignificant, there was a statistically significant difference in the serum chloride levels between the groups.

Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will provide an evidence-based practical approach to the management of patients with AP.

Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and viral infections. Recent studies have illuminated the emergence of vaccine-induced acute pancreatitis, notably associated with COVID-19 vaccinations, presenting diverse mechanisms ranging from direct viral-mediated injury to autoimmune reactions. Understanding this link is pivotal for public health, yet challenges persist in identifying and managing cases post-vaccination. Comprehensive literature reviews employing the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement outline the potential pathways and mechanisms leading to vaccine-induced pancreatitis, emphasizing the need for deeper investigations into underlying health conditions and modifications to vaccine components. Notably, the rare occurrences of vaccine-induced pancreatitis extend beyond COVID-19 vaccines, with reports also documenting associations with measles, mumps, and rubella (MMR), human papillomavirus (HPV), and other viral vaccinations. Mechanistically, hypotheses such as molecular mimicry and immunologic injury have been proposed, necessitating ongoing vigilance and exploration. Regulatory agencies play a crucial role in monitoring and communicating vaccine safety concerns, emphasizing transparency to address potential risks and maintain public trust. Understanding and communicating these rare adverse events with transparency remain integral for informed vaccination policies and to allay concerns surrounding vaccine safety.

Acute pancreatitis (AP) is a leading gastrointestinal disease that causes hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including assessment of disease severity, fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer's solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. The routine use of prophylactic antibiotics is generally limited, and the procalcitonin-based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. The management approach for patients with local complications of AP, particularly those with infected necrotizing pancreatitis, is discussed in detail, including indications, timing, anatomical considerations, and selection of intervention methods. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis, lipid-lowering medications in hypertriglyceridemia-induced AP, and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and preventing recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP.

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.

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).

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).

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.