Work

Severe acute pancreatitis

Year: 2024

Type: article

Abstract: Severe acute pancreatitis is a potentially life-threatening condition that can cause multi-organ failure Early initiation of supportive treatment and determination of severity to identify patients in, or at risk of, organ failure to provide them with timely critical care support aimed at reversing organ failure are critical Lack of understanding about the natural course of the disease and limited treatment targets are a concern The cornerstones of management of acute pancreatitis are fluid resuscitation, adequate pain relief, and the early initiation and maintenance of nutrition The step-up approach is the preferred strategy for managing necrotizing pancreatitis, with endoscopic drainage preferred to surgical intervention The incidence of acute pancreatitis worldwide is increasing, with an over 3% increase in incidence per year in North America, Australia, the UK, and Northern Europe1. In 2019, some 2.8 million episodes of acute pancreatitis occurred globally, leading to an estimated 115 000 deaths2. Diagnosis of acute pancreatitis is usually made by clinical evaluation of signs and symptoms, blood tests (greater than 3 times upper normal cut-off value of serum amylase and/or lipase elevation), and the use of imaging when diagnostic uncertainty exists (Fig. 1). Initial diagnosis, monitoring, and management of acute pancreatitis The aetiology for an episode of acute pancreatitis must be determined, as it may have consequences for management during admission and for secondary prevention (that is, early cholecystectomy in biliary-induced pancreatitis or alcohol cessation in alcohol-induced pancreatitis). A complete workup is often not carried out, leading to the occurrence, and often overestimation, of ‘idiopathic’ acute pancreatitis3. In high-income countries, the rise in acute pancreatitis is attributed to both the increasing prevalence of metabolic syndrome (including the risk of gallstone disease) and the increase in alcohol consumption—the most common aetiological factors for the disease. Most patients (up to 70%) with an attack of acute pancreatitis will experience a mild self-limiting disease course, requiring minimal supportive care, including initial fluid resuscitation, pain management, and a short hospital stay. However, some will experience more grave symptoms, with transient (less than 48 hrs duration) or persistent (greater than 48 hrs duration) organ failure, requiring single- or multi-organ support (Fig. 2). Despite being one of the most common abdominal emergencies, lack of understanding about the natural course of the disease and limited treatment targets are a concern4. Typically, there is a large healthcare burden for those with severe acute pancreatitis, with long hospital stays, multiple interventions, prolonged intensive care stays, and long recovery times frequently necessary. Severity of acute pancreatitis (mild, moderate, and severe) Although most episodes of acute pancreatitis are mild and follow a self-limiting course, for which supportive and symptomatic therapies are needed, about one in every three patients experiences moderate or severe acute pancreatitis. In severe acute pancreatitis, the risk of death rapidly increases and may be as high as 30–40%. The two most recent classifications of acute pancreatitis subdivide the disease into severity grades (Fig. 2), with in-part overlapping categories. The ‘revised Atlanta classification’5 (RAC) proposes ‘early’ and ‘late’ phases and classifies the severity into ‘mild’, ‘moderate’, or ‘severe’. Mild acute pancreatitis, the most common form, has no organ failure, has no local or systemic complications, and usually resolves in the first week. Moderate acute pancreatitis is defined by transient organ failure, local complications, or the exacerbation of a co-morbid disease. Severe acute pancreatitis is defined by persistent organ failure (that is organ failure lasting for greater than 48 h). The ‘determinant-based classification’6 (DBC) is based on actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not and, when present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not and, when present, whether it is transient or persistent. The presence of one determinant can modify the effect of the other, such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: ‘mild’, ‘moderate’, ‘severe’, and ‘critical’. A recent cohort study found that both classification systems worked equally well with regard to predicting outcome in acute pancreatitis, with the additional ‘critical’ category of the DBC identifying a subset of critically ill patients at high risk7. Many risk scores to predict the severity of acute pancreatitis have been developed, but few have consistently shown reliability, validity, and prediction over time and hence they perform poorly as clinical decision tools8. In a systematic review and meta-analysis, a total of 94 studies evaluating 18 scores in 53 547 patients were identified9. The investigators concluded that the test characteristics and clinical utility of severity scores in acute pancreatitis remain uncertain9. For patients admitted to ICUs, a modified DBC was tested in a prospective cohort across 46 international ICUs in the Epidemiology of Acute Pancreatitis in Intensive Care Medicine study10. In this study the modified DBC performed better with regard to mortality prediction than the RAC and the DBC. The modified DBC system included four categories10: group 1 included patients with transient organ failure and without local complications; group 2 included patients with transient organ failure and local complications; group 3 included patients with persistent organ failure and without local complications; and group 4 included patients with persistent organ failure and local complications. According to the modified DBC, patients in group 1 presented low mortality (2.3%) and morbidity (5.4%), patients in group 2 presented low mortality (6.7%) and high morbidity (60.7%), patients in group 3 presented high mortality (41.5%) and low morbidity (8.3%), and patients in group 4 presented high mortality (59.1%) and morbidity (88.9%). Over the past two decades, several trials have helped inform the best decisions regarding treatment of acute pancreatitis. Most data are summarized in available guidelines11–13, yet implementation of best practice is uncertain across regions. Of concern is the unchanged mortality seen in patients with severe acute pancreatitis admitted to ICUs14, predominantly due to ‘late deaths’ (Fig. 3), despite the perceived belief that the physicians today are better able to manage organ failure and infectious complications. The absence of a specific treatment to retard or result in the cessation of progression of the inflammatory cascade set in motion by the crossing of the first critical threshold has been the underlying challenge in managing acute pancreatitis4. This has precluded the ability to intervene in a timely manner and prevent the crossing of the second critical threshold4. Early and late deaths in acute pancreatitis SIRS, systemic inflammatory response syndrome; MODS, multi-organ dysfunction syndrome. In the absence of a specific treatment, the cornerstones of management of acute pancreatitis have been fluid resuscitation, adequate pain relief, and the early initiation and maintenance of nutrition (Fig. 1). More recently, the optimal initial fluid resuscitation strategy has been investigated. The WATERFALL trial showed that a goal-directed strategy (rather than aggressive fluid strategy) was better15. The judicious and balanced use of fluid resuscitation (that incorporates Ringer’s lactate) accompanied by close monitoring of a patient’s fluid status is key to the initial management of acute pancreatitis16,17. Abdominal pain is one of the most important dimensions of the patient experience in acute pancreatitis, mediated predominantly via the splanchnic nerves18. Early and effective treatment of pain is associated with reduced patient anxiety, lower complication risk, and improved quality of life18. Non-steroidal anti-inflammatory drugs (NSAIDS) and opioids currently form the mainstay of pain management in acute pancreatitis. However, the published evidence from RCTs regarding the benefits of one medication over the other are conflicting19. Decision-making is further complicated by lack of specific pain management across guidelines19. A recent multicentre study found that there is significant reliance on opioids for pain management in acute pancreatitis worldwide and that there is a potential for worsening of severity of acute pancreatitis with opioid use20, an association previously noted in preclinical studies21. In the absence of high-quality evidence regarding how to manage pain in acute pancreatitis, a more pragmatic approach based on the WHO ladder, with pain management based on the intensity of pain and patient-reported pain scores, should be considered (Fig. 1). Considering that acute pancreatitis is a catabolic disease, which uses up the nutritional stores of the body, early initiation of nutrition is essential. Nutrition administered via the oral or enteral route is preferred, as it results in clinically relevant and statistically significant risk reduction with regard to infectious complications, pancreatic infections, length of hospital stay, need for surgical interventions, and mortality in patients with predicted severe acute pancreatitis. Failure to initiate satisfactory enteral nutrition by the fifth day from the onset of an episode should trigger the administration of parenteral nutrition. Furthermore, in patients with severe acute pancreatitis with features of exocrine insufficiency, enzyme supplementation positively effects the course of the disease, especially when administered during the early refeeding phase22. One considerable improvement in managing necrotizing pancreatitis has been the step-up approach (rather than upfront surgery) to drainage and necrosectomy of infected (peri)pancreatic necrosis23. A recent randomized, multicentre trial24 comparing surgical with endoscopic step-up strategies found no major differences, but found preferable outcomes for endoscopy (lower rate of pancreatic fistulae and shorter overall hospital stay). The results persisted in the long-term follow-up (ExTENSION trial), slightly favouring endoscopy, based on the need for fewer re-interventions and fewer pancreatic fistulae25. The step-up approach is now the preferred strategy for managing necrotizing pancreatitis, with the optimal timing usually recommended at around 4 weeks from the onset of an episode of acute pancreatitis26. This time window allows fluid collections to form and the abscess wall to mature, leading to a walled-off necrosis that can be drained using lumen-apposing metal stents (LAMS) or percutaneous drains27. Notably, one trial (DESTIN trial) proposed direct endoscopic necrosectomy over a step-up approach to reduce the number of re-interventions28. In patients with biliary acute pancreatitis and deranged liver function tests from a stone in the common bile duct the need for and timing of endoscopic retrograde cholangiopancreatography (ERCP) has been a matter of contention owing to the understanding that one of the mechanisms of acute pancreatitis was the increased pancreatic ductal pressure after its blockade by a gallstone29. However, the findings of the APEC30 and APEC-231 trials have conclusively settled this conundrum, justifying an urgent ERCP and endoscopic sphincterotomy in patients with predicted severe biliary pancreatitis only in the setting of concomitant cholangitis. Inpatient or early cholecystectomy (less than 2 weeks) after discharge should be considered in patients with mild gallstone pancreatitis. In moderate and severe pancreatitis, cholecystectomy should be considered once the post-pancreatitis complications are resolved, as an early cholecystectomy has been shown to be associated with high morbidity and mortality32. Mortality can reach 50% in patients with severe acute pancreatitis and organ failure being treated in an ICU, depending on the inclusion of the populations at risk. A nationwide Dutch cohort study of all ICUs between 2007 and 2018 found that, among 4160 patients with severe acute pancreatitis treated in 81 ICUs, the 14-day mortality was 17%, the ICU mortality was 17%, the hospital mortality was 23%, and the 1-year mortality was 33%33. The consistently low mortality over time noted in Australia and Aotearoa New Zealand14 appears to point to their early institution of critical care support for (transient) organ failure at a time when it is potentially reversible. Age and the presence of co-morbidities are also important contributors to mortality. A nationwide Swedish study found a persistently high risk of mortality at long-term follow-up after discharge for those greater than 80 years of age and with a co-morbidity34. In summary, acute pancreatitis is a common disease encountered in surgical practice globally. Early initiation of supportive treatment, determination of severity to identify patients in, or at risk of, organ failure to provide them with timely critical care support aimed at reversing organ failure, an emphasis on nutrition, a step-up approach to managing infected (peri)pancreatic necrosis, and the judicious use of ERCP in patients with concomitant cholangitis are critical for delivering optimal care to patients. Ongoing efforts to identify a specific treatment for acute pancreatitis are warranted. The authors have no funding to declare. Kjetil Søreide (Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing), S. George Barreto (Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing—review & editing), and Sanjay Pandanaboyana (Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing—review & editing) The authors declare no conflict of interest.

Source: British journal of surgery

DOI: 10.1093/bjs/znae170

Authors: Kjetil Søreide, S George Barreto, Sanjay Pandanaboyana