Key points

Introduction

Acute pancreatitis is a frequently devastating pancreatic inflammation that has been associated with significant morbidity, mortality, and hospitalization costs. The incidence of acute pancreatitis has been increasing and features an overall mortality rate of 5% that may be as high as 30% in the most severe cases. It was the most common inpatient gastrointestinal diagnosis in 2009, totaling more than 270,000 United States hospitalizations and incurring costs of more than 2.6 billion dollars. The updated Atlanta classification divides acute pancreatitis into mild and severe types. Mild, characterized by pancreatic inflammation without necrosis or organ failure, is known as interstitial edematous pancreatitis, which is usually self-limiting and resolves in about 1 week. Severe pancreatitis, occurring in about 20% of cases, predisposes to local complications such as pancreatic necrosis, abscess formation, and pseudocysts. Severe pancreatitis is subdivided further into moderate and severe depending on the presence and duration (>48 hours) of organ failure. This article details treatment of acute pancreatitis, including highlighting new insights into prognostication and focusing on intravenous fluid resuscitation and the current evidence behind the use of antibiotics and pharmacologic therapies.

Introduction

Acute pancreatitis is a frequently devastating pancreatic inflammation that has been associated with significant morbidity, mortality, and hospitalization costs. The incidence of acute pancreatitis has been increasing and features an overall mortality rate of 5% that may be as high as 30% in the most severe cases. It was the most common inpatient gastrointestinal diagnosis in 2009, totaling more than 270,000 United States hospitalizations and incurring costs of more than 2.6 billion dollars. The updated Atlanta classification divides acute pancreatitis into mild and severe types. Mild, characterized by pancreatic inflammation without necrosis or organ failure, is known as interstitial edematous pancreatitis, which is usually self-limiting and resolves in about 1 week. Severe pancreatitis, occurring in about 20% of cases, predisposes to local complications such as pancreatic necrosis, abscess formation, and pseudocysts. Severe pancreatitis is subdivided further into moderate and severe depending on the presence and duration (>48 hours) of organ failure. This article details treatment of acute pancreatitis, including highlighting new insights into prognostication and focusing on intravenous fluid resuscitation and the current evidence behind the use of antibiotics and pharmacologic therapies.

Predicting severity

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  Simple, universally obtainable markers such as the change in blood urea nitrogen (BUN) level are equally predictive of severity when compared with more complicated systems.

Predicting the severity of acute pancreatitis can be challenging. Since 1974, when the Ranson’s criteria were first proposed, multiple scoring systems (ie, APACHE-II, Bedside Index for Severity in Acute Pancreatitis [BiSAP], Marshall Score) were developed as a means of improving the ability to predict severity in acute pancreatitis. However, despite the use of these often complex systems, laboratory abnormalities in hematocrit, creatinine, and BUN can be used as effective prognostic indicators with equivalent accuracy. For example, an increased risk of pancreatic necrosis has been linked with an elevated hematocrit level at admission or within the first 24 hours as well as an elevated creatinine level within the first 48 hours. With regard to BUN, A 2011 meta-analysis of 1043 acute pancreatitis cases found that a BUN ≥20 mg/dL (odds ratio, 4.6 and 4.3, respectively) at admission, or an increase in levels within the first 24 hours, was associated with an increased risk of mortality and death. Thus, it is recommended that a simple marker, such as BUN, be used as means of assessing severity and potential progression to organ failure.

Fluid resuscitation

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  The goal is to decrease hematocrit and BUN levels within the first 24 hours of hospitalization .

  
  
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  The goal is early aggressive fluid resuscitation with 250 to 500 mL/h of isotonic crystalloid in the first 12 to 24 hours or urine output of at least 0.5 mL/kg/h .

  
  
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  Lactated Ringer’s solution should be used as the resuscitation fluid of choice .

Now commonly recognized as the primary form of initial management, the importance of adequate fluid resuscitation cannot be understated. In severe cases, acute pancreatitis can lead to pancreatic necrosis and ongoing pancreatic enzyme release. One of the triggers of necrosis is thought to be inadequate glandular perfusion. The pancreatic microcirculation encompasses the celiac and superior mesenteric arteries that branch off to supply the pancreatic acinus. Acute pancreatitis invokes a state of hypovolemia, causing a combination of microangiopathic effects and pancreatic edema that decreases blood flow. This disruption in perfusion may be an important factor responsible for the transition from mild, interstitial edematous disease to severe, necrotizing pancreatitis. Current proposed mechanisms of this pathophysiology include hypercoagulability with microthrombi, endothelial damage from free radicals, increased capillary permeability, and hypovolemia. The resultant ischemia produces a flush of cytokines and inflammatory mediators, which can progress into the development of the systemic inflammatory response syndrome (SIRS) and pancreatic necrosis and eventually lead to persistent (>48 hour) organ failure.

As the above data suggest, inadequate fluid resuscitation leading to poor pancreatic microcirculatory perfusion has been associated with acute necrotizing pancreatitis. Specifically, we now know that early fluid resuscitation has more of a therapeutic effect than delayed fluid resuscitation. In one study evaluating specifically the time course of intravenous hydration, early was defined as receiving greater than one-third of the total 72 hours fluid volume within the first 24 hours of hospitalization, whereas late was defined as receiving less than one-third of the total volume. Although the investigation did not focus on the total infused fluid volume, it concluded that the group receiving early fluid resuscitation experienced less mortality than those receiving later resuscitation. Other studies have since supported this claim, including a retrospective analysis of 436 acute pancreatitis patients, which found an association between early fluid resuscitation and decreased SIRS, organ failure at 72 hours, length of hospital stay, and a lower rate of intensive care unit admission.

Although early fluid resuscitation is generally agreed to be an intervention of paramount importance, currently no standard guidelines exist on the optimal fluid type, volume, rate, or duration of treatment. Although human studies regarding the rate of hydration consistently show decreased morbidity and mortality with aggressive hydration in the first 24 hours, the total volume of hydration at the 48-hour mark seems to have a limited effect on patient outcomes. The current American College of Gastroenterology guidelines recommend 250 to 500 mL/h of isotonic crystalloid solution in the first 12 to 24 hours with frequent re-evaluation every 6 hours, with an ultimate goal of decreasing the BUN levels. Some experts recommend that in addition to the 1- to 2-L fluid bolus given in the emergency department, the starting infusion should be at a rate of 250 to 300 mL/h or enough to produce a urine output of at least 0.5 mL/kg/h. The goal within the first 24 hours is a total infusion volume of 2.5 to 4 L, with adjustments to be made based on the patient’s age, weight, physical examination, and comorbid conditions.

The type of resuscitation fluid has not been satisfactorily studied. However, in the most widely cited prospective study of fluid resuscitation in acute pancreatitis, Wu and colleagues found that the use of Lactated Ringer’s solution, as opposed to normal saline, resulted in less SIRS and a decreased C-reactive protein level at 48 hours. No other prospective fluid studies have evaluated different types of resuscitative fluid, and thus it is generally recommended, in the absence of better evidence, that Lactated Ringer’s solution be used as the resuscitative fluid of choice.

It is also important to recognize the consequences of overresuscitation—most notably the development of intra-abdominal compartment syndrome. In a study of patients with predicted severe pancreatitis whose hematocrit level was aggressively lowered at the time of admission, those with aggressive lowering of their hematocrit level had greater morbidity and mortality.

Pharmacologic strategies