Managing severe acute pancreatitis

Severe acute pancreatitis has been known since the time of Rembrandt, with Nicolaes Tulp—the physician credited as first describing it—immortalized in the famous painting, The Anatomy Lesson. However, progress in managing this disease has been disappointing. Treatment is mainly supportive, and we lack any true disease-modifying therapy. But we are learning to recognize the disease and treat it supportively better than in the past.

The early hours of severe acute pancreatitis are critical for instituting appropriate intervention. Prompt fluid resuscitation is key to preventing immediate and later morbidity and death. This article focuses on identifying and managing the most severe form of acute pancreatitis—necrotizing disease—and its complications.

NECROTIZING DISEASE ACCOUNTS FOR MOST PANCREATITIS DEATHS

The classification and definitions of acute pancreatitis were recently revised from the 1992 Atlanta system and published early in 2013.¹ In addition, the American Pancreatic Association and the International Association of Pancreatology met in 2012 to develop evidence-based guidelines on managing severe pancreatitis.

An estimated 210,000 new cases of acute pancreatitis occur each year in the United States. About 20% of cases of severe acute pancreatitis are necrotizing disease, which accounts for nearly all the morbidity and death associated with acute pancreatitis.

The clinical spectrum of acute pancreatitis ranges from mild to life-threatening, reflecting interstitial (death rate < 1%) to necrotizing histology (the latter associated with a 25% risk of death if the pancreatitis becomes infected and a 10% risk if it is sterile). When death occurs early in the disease course, it tends to be from multiorgan failure; when death occurs later in the course, it tends to be from infection. Appropriate early treatment may prevent death in both categories.

DIAGNOSING ACUTE PANCREATITIS AND PREDICTING ITS SEVERITY

The diagnosis of acute pancreatitis requires two of the following three criteria:

• Clinical presentation—epigastric pain, nausea, vomiting
• Biochemical—amylase level more than three times the upper limit of normal, or lipase more than three times the upper limit of normal
• Evidence from computed tomography (CT), ultrasonography, or magnetic resonance imaging.

Although the biochemical criteria are variably sensitive for detecting acute pancreatitis (55%–100%), the specificity is very high (93% to 99%).

Recently, urinary trypsinogen-2, measured by dipstick, has also been used to aid diagnosis. It has a reasonable sensitivity (53%–96%) and specificity (85%) if positive (> 50 ng/mL).

Speed is critical

Over the years, many clinical prediction rules have been used for predicting the severity of acute pancreatitis. The Ranson criteria,² from 1974, and the Acute Physiology and Chronic Health Evaluation (APACHE) II system³ are cumbersome and require waiting up to 48 hours after the onset of acute pancreatitis to obtain a complete score. The Imrie-Glasgow score is another predictor.

The systemic inflammatory response syndrome (SIRS) is currently the most important indicator of prognosis.⁴ Originally adopted for predicting the development of organ failure with sepsis, it requires at least two of the following criteria:

• Heart rate > 90 beats/min
• Core temperature < 36°C or > 38°C
• White blood cells < 4,000 or > 12,000/mm³
• Respirations > 20/min.

The advantages of this system are that it identifies risk very early in the course of the disease and can be assessed quickly in the emergency department.

The Bedside Index for Severity of Acute Pancreatitis (BISAP) score is another simple, easy-to-perform prognostic index,^5,6 calculated by assigning 1 point for each of the following if present within the first 24 hours of presentation:

• Blood urea nitrogen > 25 mg/dL
• Abnormal mental status (Glasgow coma score < 15)
• Evidence of systemic inflammatory response syndrome
• Age > 60 years
• Pleural effusion seen on imaging study.

A score of 3 points is associated with a 5.3% rate of hospital death, 4 points with 12.7%, and 5 points with 22.5%.

At its most basic, severe acute pancreatitis is defined by organ failure (at least one organ from the respiratory, renal, or cardiovascular system) lasting for more than 48 hours. Failure for each organ is defined by the Marshall scoring system.¹

EARLY MANAGEMENT IS KEY TO OUTCOME

The window of opportunity to make a significant difference in outcome is within the first 12 to 24 hours of presentation. Volume resuscitation is the cornerstone of early management. By the time of presentation for severe acute pancreatitis, the pancreas is already necrotic, so the aim is to minimize the systemic inflammatory response syndrome with the goals of reducing rates of organ failure, morbidity, and death. Necrotizing pancreatitis is essentially an ischemic event, and the goal of volume resuscitation is to maintain pancreatic and intestinal microcirculation to prevent intestinal ischemia and subsequent bacterial translocation.⁷

Early resuscitation with lactated Ringer’s solution recommended

The evidence supporting a specific protocol for fluid resuscitation in severe acute pancreatitis is not strong, but a few studies provide guidance.

Wu et al⁸ randomized 40 patients with acute pancreatitis to one of four arms: “goal-directed fluid resuscitation” with either lactated Ringer’s solution or normal saline, or standard therapy (by physician discretion) with either lactated Ringer’s solution or normal saline. Goal-directed therapy involved a bolus of 20 mL/kg given over 30 to 45 minutes at presentation followed by infusion with rates dependent on an algorithm based on change in blood urea nitrogen level at set times. Patients receiving either goal-directed or standard therapy had significantly lower rates of systemic inflammatory response syndrome at 24 hours than at admission. Most striking was that treatment with lactated Ringer’s solution was associated with dramatically improved rates, whereas normal saline showed no improvement.

In a retrospective study of patients with acute pancreatitis, Warndorf et al⁹ identified 340 patients who received early resuscitation (more than one-third of the total 72-hour fluid volume within 24 hours of presentation) and 90 patients who received late resuscitation (less than one-third of the total 72-hour fluid volume within 24 hours of presentation). Patients who received early resuscitation developed less systemic inflammatory response syndrome and organ failure, and required fewer interventions.

Monitoring for optimum fluid resuscitation

Fluid resuscitation should be carefully managed to avoid administering either inadequate or excessive amounts of fluid. Inadequate fluid resuscitation can result in renal failure, progression of necrosis, and possibly infectious complications. Excessive resuscitation—defined as more than 4 L in the first 24 hours—is associated with respiratory failure, pancreatic fluid collections, and abdominal compartment syndrome.

Optimum resuscitation is controlled fluid expansion averaging 5 to 10 mL/kg per hour, with 2,500 to 4,000 mL given in the first 24 hours.

Adequate volume resuscitation can be evaluated clinically with the following goals:

• Heart rate < 120 beats per minute
• Mean arterial pressure 65–85 mm Hg
• Urinary output > 1 mL/kg per hour
• Hematocrit 35%–44%.