Acute Pancreatitis: A Clinical Perspective PDF

Acute Pancreatitis: A clinical perspective Carlos Daniel Orozco Sierra 1, *, Reiner León Cifuentes 1, Daniela Rodríguez Sierra 2, Mayra Manrique 1, Víctor Jaimes 1 and David Fernando Farah Borrero 1 1 Department of Internal Medicine, Faculty of Health Sciences, Libre University, Barranquilla, Colo...

Acute Pancreatitis: A clinical perspective Carlos Daniel Orozco Sierra 1, *, Reiner León Cifuentes 1, Daniela Rodríguez Sierra 2, Mayra Manrique 1, Víctor Jaimes 1 and David Fernando Farah Borrero 1 1 Department of Internal Medicine, Faculty of Health Sciences, Libre University, Barranquilla, Colombia. 2 Medicine Program, Faculty of Health Sciences, Del Norte University, Barranquilla, Colombia. World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 Publication history: Received on 08 August 2023; revised on 17 September 2023; accepted on 19 September 2023 Article DOI: https://doi.org/10.30574/wjarr.2023.19.3.1901 Abstract Acute pancreatitis is one of the main gastrointestinal disorders that is characterized by an acute inflammatory process of the pancreatic tissue with variability in severity, usually with a mild and self-limiting presentation, and presenting a low mortality. Biliary etiology is the leading cause of acute pancreatitis worldwide, with greater involvement in the female gender. Within the diagnostic approach, acute abdominal pain and intense onset in the epigastrium radiating to the back is usually the most representative symptom that leads to suspicion of this entity, accompanied by elevation of pancreatic enzymes and the presence of typical image findings of inflammation of the pancreas. The objection to identifying which patients are at risk of developing local or systemic complications has led to the creation of different scales predicting the severity of pancreatitis with performances that are still debatable. Therapeutic management has two fundamental pillars, fluid resuscitation to maintain or restore tissue perfusion and adequate nutritional support to counteract the catabolic state and reduce the rate of infectious complications. In the context in which the cause is a biliary origin, its resolution is important to avoid progression to chronic pancreatitis. Keywords: Pancreatitis; Acute; Amylase; Abdominal Pain; BISAP. 1. Introduction Acute pancreatitis (AP) is one of the principal gastrointestinal disorders that cause abdominal pain and is a reason for consultation in the emergency room potentially lethal, associated with a substantial mortality and morbidity rate (1). It's a complex entity with a variable progression that represents a grand cost to the health system worldwide. In the US, it represents 2.6 billion dollars to the health system annually (2). 2. Epidemiology In the past decades, the incidence of acute pancreatitis has considerably increased, close to 20% worldwide and it has a general mortality rate that fluctuates between 1% and 5% and up to 30% in severe cases. Besides, around 20% of patients with AP will develop moderate to severe pancreatitis with peripancreatic necrosis and or target organ damage (3) (Figure 1). A possible theory that could explain the rise of its incidence around the world is the high prevalence of obesity, sedentarism, and alcoholic beverage consumption, besides the frequent realization of laboratory tests that contribute to the rise of statistics in the detection and diagnosis of acute pancreatitis. Moreover, the etiology of acute pancreatitis may vary geographically. For example, gallstones represent 26% of cases of AP in the US and increase up to 66% in Latin America (4). In Latin America in 2006 it was reported an incidence of 15.9 cases for every 100,000 habitants in Brazil, a prevalence of 3% in Mexico in 2001, and in Peru the Ministry of Health  Corresponding author: Carlos Daniel Orozco Sierra; ORCID ID:https://orcid.org/0000-0002-5877-5760. Copyright © 2023 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0.  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 statistics by the year 2009 stated an incidence of 28 cases for every 100,000 habitants. Gallstone etiology is the principal cause of almost 70% of registered pancreatitis cases in the emergency room (5)(6). Figure 1 Mortality rate in acute pancreatitis. (Modified from Van Dijk SM et al. Acute pancreatitis: recent advances through randomized trials. Gut. 2017;66(11):2024-32. In Colombia, it is unknown the real incidence of acute pancreatitis (7). In an observational descriptive study accomplished by Universidad Nacional de Colombia, the characterization of acute pancreatitis patients in the time span between April 2016 and September 2017; they found a higher incidence of AP in the female genre, with an average age of 53 years old where the principal etiology was gallstone of about 70% (8). Another analytic retrospective descriptive study of patients with acute pancreatitis diagnosis that were admitted to a third-level hospital in the time spent between January 1 of 2015 and July 31 of 2017 found that the total studied population had a higher predilection for the female genre among the 4th and 6th decade of life, and yet it was found that ages older than 60 had statistical significance (p = 0,04) as a risk factor of severity (9). 3. Definition and classification Acute Pancreatitis is defined as a disorder characterized by acute necroinflammatory changes in the pancreas, with consequent destruction of acinar cells (10). Physiologically, it can be defined as an acute inflammatory process of the pancreas with variable effects on other regional tissues or distant organ systems (11). Besides, based on the definitions revised by the 2012 Atlanta classification system, it can be classified according to its severity: mild, moderately severe, and severe (table 1). Being moderately severe and severe, characterized by the involvement of different organs (respiratory, renal, cardiac) or decompensation of a chronic illness previously diagnosed. Likewise, AP is morphologically classified into 2 subtypes: interstitial edematous pancreatitis and necrotizing pancreatitis (12). 814  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 Table 1 Definition of severity in acute pancreatitis. (Revised Atlanta Classification 2012). Mild acute pancreatitis Without organ failure Without local or systemic complications Moderately severe acute pancreatitis Organ failure < 48 hours and/or Systemic or local complications without persistent organ failure Severe acute pancreatitis Persistent organ failure (> 48 hours) Adapted from: Mederos MA, Reber HA, Girgis MD. Acute Pancreatitis: A Review. JAMA. January 2021;325(4):382. 3.1. Etiology and risk factors The etiology of acute pancreatitis may be variable. It can even be multicausal depending on the risk factors and the patient's comorbidities (table 2). That being said, the principal causes of AP still are gallstones, followed by excessive alcohol consumption (13). Table 2 Causes of acute pancreatitis. (Modified from Forsmark CE, et al. Acute Pancreatitis. N Engl J Med. 2016;375(20):1972-81) Cause Approximate Observation frequency Gallstones 40% Alteration of liver enzymes, Hepatobiliary ultrasound. Alcohol 30% History of chronic pancreatitis, CAGE* test.. Hypertriglyceridemia 2-5% Fasting triglycerides > 1000 mg/dl (11.3 mmol/L). Genetic cause Unknown Acute, chronic and recurrent pancreatitis. Drugs 20 mg/dL as an independent mortality predictor (2B). Procalcitonin is the most sensitive laboratory test for the detection of pancreatic infection and low serum values appear to be strong negative predictors of infected necrosis (2A). Sérum triglyceride levels higher than 11.3 mmol/l (1000 mg/dl) indicate the etiology of acute pancreatitis associated with hypertriglyceridemia (2C). 5.1. Stratification of risks and severity There is no severity score established as the gold standard to predict complications of acute pancreatitis (19). Due to the variability of the clinical progress and the high mortality rate of cases with severe AP, there have been developed multiple predictive and prognosis scales to guide medical conduct. Besides, there is no evidence of Head-to-Head clinical trials that determine the superiority of a clinical scale over others. The modified Marshall score collects the assessment of three systems: renal, respiratory, and cardiovascular, where a two-point or higher score for each defines the presence of organ failure. Due to its simplicity, this score has an easy application in order to estimate in an objective manner the severity of the disease on its onset (20). However, in an observational study performed recently in Colombia by Rodríguez A. et al. where they wanted to establish the concordance between the Marshall, Ranson, and APACHE II scores, found that there is a poor correlation between the different scores of risk classification, so they shouldn't be interpreted equivalently. In addition, this study suggests that between the mentioned scores, the Marshall score could overestimate the risk in cities above 2,000 meters above sea level (21). 817  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 Probably the BISAP scale (Bedside index of severity of acute pancreatitis), provides the most reliable score and it is applied in clinical practice every day because its simplicity and capacity to predict the severity, mortality, and organ damage in the same way the APACHE II score and other scales (19). In some cases, it is considered a loss of valuable time (in a critically ill patient) if it is necessary to establish therapeutic conduct with tools or scores where the prediction is obtained 24 or 72 hours later. In table 3, it is shown the characteristics and differences of the main principal scales for AP. Likewise, based on the available evidence and recommendations in Figure 2 is proposed a diagnosis algorithm for patients with acute pancreatitis (5)(19)(22). Figure 2 Proposed algorithm for the diagnosis of patients with acute pancreatitis. Abbreviations: MRI: Nuclear magnetic resonance; AP: Acute pancreatitis. NUL: normal upper limit; BISAP: Bedside Index of Severe Acute Pancreatitis Other methods used as tools to predict prognoses are the use of computed tomography, and novel predictors based on artificial intelligence. Computed tomography with contrast, with Balthazar scale by degrees of severity, is increasingly falling into disuse due to its limitations, the greater prevalence of mild forms of AP, the requirement of contrast and not having adequate performance in the first 48 hours. On the other hand, there are studies that compared the use of computerized machine learning models compared to APACHE II, RANSON or GLASGOW score, which have concluded greater accuracy in predicting severity in AP (AUC between 0.84 and 0.92). However, their results are lack of validation in clinical trials and do not have standardized algorithms (23). 818  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 Table 3 Comparison of risk factors scales: APACHE II, BISAP, Ranson based on the severity definitions of the revised Atlanta classification. (Modified from Mederos MA, et al. Acute Pancreatitis: A Review. JAMA. 2021;325(4):382.) APACHE II BISAP (2008, Gut) Ranson Variables Age BUN > 25 mg/dl (>8.9 Admission: Temperature mmol/L) Age > 55 years Mean arterial pressure Alteration of the state of Leukocyte count > 16,000/μL consciousness pH LDH > 350 U/L > 2 Criteria SIRS Heart rate AST >250 U/L Age > 60 years Respiratory rate Glucose > 200 mg/dl. Existing pleural effusion Sodium Within 48 hours: Potassium Decrease in hematocrit > 10% Creatinine Increase in BUN > 5mg/dl Acute kidney injury Pao2 < 60 mmhg Hematocrit Base deficit > 4 meq/L White blood cell count Fluid loss > 6 L Glasgow Scale FIO2 Original purpose Disease severity and Predictor of mortality in Predictor of mortality in patients mortality in ICU patients with AP with AP. patients. Severity prediction, 0.82 (0.03) Score: ≥3 0.08) AUC (SE) 0.87 (0.16) Severity prediction Score: ≥8 Score: ≥3 Score: ≥3 Sensitivity (95% CI) 0.83 (0.77-0.88) 0.51 (0.43-0.60) 0.66 (0.59-0.72) Specificity (95% CI) 0.59 (0.56-0,63) 0.91 (0.89-0.92) 0.78 (0.76-0.81) Mortality prediction, 0.83 (0.16) Score: ≥3 0.92 (0.05) AUC (SE) 0.87 (0.03) Mortality prediction Score: ≥8 Score: ≥3 Score: ≥3 Sensitivity (95% CI) 0.95 (0.77- 1.00) 0.56 (4.23-0.7.55) 0.93 (0.78-0.99) Specificity (95% CI) 0.68 (0.63-0.73) 0.91 (0.90-0.91) 0.69 (0.65-0.79) Advantages It can be calculated in 5 variables Understandable the first 24 hours Easy to calculate (1 Specific for PA point/variable) Can be calculated in < 24 hours Specific for PA Limitations Designed for patients Lower sensitivity and It is calculated after 48 hours admitted to the ICU specificity than APACHE II Variables not routinely taken in Large number of patients - not admitted to the variables ICU It is not specific for AP Abbreviations: AP: acute pancreatitis; APACHE II: Acute Physiology and ChronicHealth Evaluation II; AST: aspartate aminotransferase; AUC: area under the curve; BISAP: Bedside Index of Severe Acute Pancreatitis; BUN: blood urea nitrogen; FIO2: inspired fraction of oxygen; ICU: intensive care unit; PAO2: arterial partial pressure of oxygen; SIRS: systemic inflammatory response syndrome 819  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 6. Treatment The use of score tools are useful to guide the therapy, but they should never overrule the clinical judgment, so the recommendation aims to perform a medical therapy guided by the severity of the disease and concomitant complications. There are 2 fundamental pillars approaching the treatment: 1. Fluid resuscitation to maintain or restore tissue perfusion and 2. Adequate nutritional support to counter the catabolic state and reduce the infectious complication rates. There are not unified criteria that could determine which patient requires intensive or intermediate care unit management. It can be guided by clinical criteria in conjunction with the complication risk stratification established as moderately severe and severe, in addition to persistent organ failure despite the establishment of an adequate fluid resuscitation (19). 6.1. Fluid resuscitation The decrease in intravascular volume is not due to a single cause. The interstitial fluid sequestration, reduction of oral consumption, emesis, and peripancreatic inflammation, all contribute to this deficit (24). Consequently, the hydric intake should be initiated early on, preferably with isotonic solutions. According to the AGA, and IPA/APA society recommend goal-guided therapy for fluid management, however, this is with a conditional recommendation that has very low quality (24) (25). Even in some scenarios such as sepsis, goal-guided resuscitation has demonstrated clinical benefit (26). Randomized clinical trials regarding the type of fluid to use between saline solution at 0.9% and ringer lactate have not demonstrated important outcomes. However, there was a decrease in systemic inflammatory response (SIR) and CRP with the use of ringer lactate but without effect in mortality rate, therefore AGA society has not realized any recommendations (conditional recommendation, very low quality of evidence). Furthermore, retrospective analysis has shown better evidence of the results of using ringer lactate over saline solution aggressively (during the first 24 hours) meaning 20 ml/kg/ bolus and continuing with 3 ml/k/h (5)(22). In addition, it must be considered the possible co- morbidities (heart failure, chronic kidney disease) due to the risk of fluid overload. Subsequently in a recent clinical trial it has been shown early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes (27). Therapy should be guided by clinical monitoring of vital signs such as heart rate, mean arterial pressure, and urine output to determine the individualization of the crystalloid input rate. The goals proposed by IAP/APA (International Association of Pancreatology/American Pancreatic Association) are MAP: 65-85 mmHg, heart rate less than 120 Bpm, urine output 0.5-1 ml/k/h and hematocrit between 34-44%. 6.2. Nutrition Current guidelines recommend that in acute pancreatitis, feeding should be started within the first 24 hours of diagnosis to reduce complications (28). Based on the high catabolic demand and the risk of infection, the complete resolution of pain is not necessary, nor is the decrease of pancreatic enzymes to their normal level to start enteral nutrition in patients with mild AP. It has been associated with a lower hospital stay (24). In the moderately severe/ severe AP cases with no pain resolution at the fifth (5th) day is recommended to start a low-fat solid or semi-solid enteral nutrition, by nasogastric tube or nasoduodenal tube, because it has been described a beneficial effect by minimizing the exocrine pancreatic secretion. Parenteral nutrition should be reserved for cases of no tolerance to enteral nutrition or cases without achieving nutritional goals with enteral formulas (22). 6.3. Antibiotics (AB) In the past few years, the principal gastroenterology societies have recommended with evidence-based knowledge that is not indicated antibiotic use as a prophylactic therapy in patients with AP (19)(22). The recommendation is antimicrobial coverage against Gram-positive, Gram-negative, aerobic, and anaerobic bacteria in evidence of infection (infected pancreatic and necrosis). Enterobacteriaceae are the principal microorganisms found followed by Staphylococcus aureus, Streptococcus faecalis, Enterococcus and candidas spp (19). 820  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 Occasionally it can be difficult to clinically differentiate the inflammatory process from the pancreas and the infection itself, so it is recommended the use of procalcitonin level to discriminate patients that really benefit from antimicrobial medicine. Primarily the scheme should have as first-line medication piperacillin-tazobactam due to its adequate penetration to pancreatic tissue, but other options could be quinolones and carbapenems. The ideal test to guide the anti-microbial therapy is culture and Gram stain in samples taken by tomography-guided fine needle aspiration, but it is not routinely recommended (19). Clinical suspicion of infection is based on infection signs (temperature above 38.5° and an increase in the serum inflammatory markers), when there is a new or persistent organ insufficiency that usually is more reliable after the initial phase of IRS or when it is identified CT scan findings of infection such as collections or gas inside the pancreatic collection (4). Besides antibiotics should be administered for extrapancreatic infections such as cholangitis, catheter infections, bacteremia, urinary tract infections, or pneumonia (strong recommendation high-quality evidence) (25)(29). 6.4. Endoscopic retrograde cholangiopancreatography (ERCP) Generally, ERCP should not be routinely performed. It is recommended during the first 48 hours in cases of severe gallstone AP with concomitant cholangitis and/or persistent gallbladder obstruction. Besides, its use is controversial in cases of severe gallstone pancreatitis in early acute phase (22). 6.5. Other recommendations Analgesia: Such as the pain is the main presenting symptom, it should be treated as fast as possible and efficiently. Today's evidence about opioid use is limited, and there is not general recommendation so the patient should be individualized, and evaluate the availability of medicine, drug interaction, and local pain control protocols of each Institution. It has been demonstrated a grade of benefit by using epidural analgesia (Bupivacaine) in critically ill patients with a low evidence level to be recommended at the moment (22)(24). Cholecystectomy: It should be performed prior to the discharge of patients with acute mild gallstone pancreatitis if there are no surgical contraindications (5) (25). Alcohol: Intervention strategies for alcohol consumption should be performed as early as the moment of diagnosis of alcohol consumption-related AP during hospitalization and alcohol abstinence must be repeatedly reinforced, especially in cases associated with hypertriglyceridemia (30) (31). All of this with educational sessions in order to change the habit of consuming, every 6 weeks after medical discharge for at least 2 years (5). Table 4 Recommended indications for percutaneous and surgical intervention of pancreatic necrotic collections. (Modified from Leppäniemi A, et al. 2019 WSES guidelines for the management of severe acute pancreatitis. World J Emerg Surg. 2019;14(1):27.) Indications for percutaneous/endoscopic drainage Indications for surgical intervention. of pancreatic collection. Clinical deterioration with signs or strong suspicion of As a continuous step in a stepped approach after a infected necrotizing pancreatitis (recommendation 1C). percutaneous/endoscopic procedure with established > 4 weeks after onset of illness: indications. Ongoing organ failure without signs of infected necrosis. Abdominal compartment syndrome. Continuous obstruction of the gastric, biliary or intestinal Acute continuous bleeding when the endovascular outlet due to a large walled necrotic collection. approach is unsuccessful. Disconnected duct syndrome. Intestinal ischemia or acute necrotizing cholecystitis during AP. Symptomatic or growing pseudocyst. Intestinal fistula extending into the peripancreatic > 8 weeks after onset of illness: collection. Continuous pain and/or discomfort Abbreviations: AP: acute pancreatitis. Collection and necrosis treatment: surgical interventions for control of local infected tissue are a debatable point and include invasive and minimally invasive techniques. Pancreatic pseudocysts do not routinely require surgical 821  World Journal of Advanced Research and Reviews, 2023, 19(03), 813–823 interventions if they don't present with clinical signs (persistent abdominal pain, pancreatic secretion obstruction, fluid drain due to the pancreatic duct disconnection, and infection) (11). In daily practice, there is an effort to delay any invasive intervention for at least 4 weeks to allow the isolation of the necrotic collection (14). The table 4 presents indications for surgical and percutaneous drainage (19). 7. Conclusions Acute pancreatitis is an inflammatory disorder of the pancreas that potentially threatens life. The clinician's perspective about this pathology should be centered on the diagnosis and recognizing that there is not always needed to perform initial image studies to establish a diagnosis and stratify its severity. It is required a good analysis of the associated risk factors, medical record, possible etiology, and risk stratification of each patient as quickly as possible to adequately guide the management stay, the studies to perform, early treatment to avoid complications, inappropriate use of antibiotic schemes and negative outcomes of the disease. In the same way, the pillars of the initial treatment are adequate fluid resuscitation and enteral nutrition once there is no abdominal pain, individualizing the patient's scenario. The medical follow-up should include programs that support alcohol abstinence as required and monitoring pancreas endocrine function due to the risk of secondary pancreatic insufficiency. 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