By James E. McFeely, MD

Medical Director, Critical Care Units, Alta Bates Summit Medical Center, Berkeley, CA

Dr. McFeely reports no financial relationships relevant to this field of study.

There are more than 275,000 hospitalizations for acute pancreatitis per year, with more than $2.6 billion spent on care worldwide. Many of these cases require ICU admission. Mortality rates vary between 2% and 17% depending on illness severity. Despite this burden of illness, questions remain regarding the most basic elements of care. There are some recommended treatment guidelines for the initial management of acute pancreatitis. Many of these recommendations come from a recent guideline issued by the American Gastroenterological Association.1,2

There are two categories of pancreatitis: interstitial edematous pancreatitis (acute inflammation without necrosis) and necrotizing pancreatitis with pancreatic or peripancreatic tissue necrosis. Pancreatitis severity is classified as mild (no organ failure), moderate (transient organ failure for less than 48 hours), or severe (organ failure for longer than 48 hours). Many severity scoring systems have been assessed for their utility for pancreatitis, but none are superior to the systemic inflammatory response syndrome (SIRS) criteria or Acute Physiology and Chronic Health Evaluation (APACHE) II score.

Initial patient evaluation should include assessment of organ failure. Laboratory analysis should include chemistries, complete blood count (CBC), triglycerides, calcium, and lactic acid levels. Measurement of lipase and amylase can be useful for initial diagnosis, but they are not useful markers to follow and do not predict severity or prognosis. ICU admission is appropriate for patients with severe acute pancreatitis with significant underlying disease, cardiopulmonary organ failure, coma, or significant electrolyte or acid-base abnormalities. Initial management is supportive with fluids, pain management, and nutritional support. Unfortunately, the best practice for some of these elements of care remains unclear. (See Table 1.)

IV Fluids

There is evidence that aggressive fluid replacement in the initial stages (first 12 to 24 hours) is associated with a reduction in mortality.3 A small study suggested Ringer’s lactate may reduce the incidence of SIRS compared to normal saline.4 Haydock et al conducted a systematic review to analyze fluid management in pancreatitis. They identified 15 studies that met inclusion critieria. Nine of these compared aggressive vs. nonaggressive resuscitation and were split five to four on the best approach. In two of these studies, researchers tried to use goal-directed therapy (using different goals): one revealed benefit, and one did not.

There is no consensus on which crystalloid to use. Both saline and Ringer’s lactate have been used, but have not been compared head to head in a large randomized trial. The exception is in cases of hypercalcemia-induced pancreatitis, where Ringer’s lactate is not recommended because it contains 3 mEq/L calcium.5 Hydroxyethyl starch-containing fluids also are not recommended.

Despite this lack of guidance, many practitioners initially try aggressive fluid resuscitation with a goal of maintaining urine output at least 0.5 mL/kg/hour while watching for signs of volume depletion or overload. Frequent monitoring of vitals, urine output, and labs, including blood urea nitrogen and hemoglobin, can help with adjustments in the rate of administration. Glucose levels should be monitored frequently and treated, as hyperglycemia is associated with an increased frequency of secondary pancreatic infection. If the patient remains oliguric despite aggressive fluid resuscitation, the possibility of abdominal compartment syndrome should be considered and bladder pressures should be transduced.

Nutrition

Traditionally, bowel rest was recommended to avoid stimulation of pancreatic exocrine function. This is no longer the case. Early (within 24 hours) enteral nutrition is recommended and is thought to help maintain the gut mucosa and decrease bacterial translocation. In a systematic review, Vaughn et al identified nine trials that compared early vs. late feeding.6 The investigators found no difference in mortality with early feeding, but noted trends toward worsening pancreatic necrosis and multiple organ failure with delayed feeding.

In a meta-analysis of randomized, controlled trials comparing enteral feeding with total parenteral nutrition, Yi et al found clear evidence that enteral feeding is superior, with less mortality, multiple organ failure, infections, and peripancreatic necrosis.7 For patients who cannot take oral nutrition, nasogastric or nasojejunal feeding should be initiated with a high protein, low-fat, semi-elemental formula that will minimize pancreatic enzyme stimulation.

Prophylactic Antibiotics

Up to 20% of patients with pancreatitis develop an extrapancreatic infection. In randomized trials of the use of prophylactic antibiotics for severe necrotizing pancreatitis, no difference was observed in mortality nor in pancreatic or peripancreatic rates of infection. There was no difference in development of single or multiple organ failures or hospital length of stay. Based on these studies, prophylactic antibiotics should not be used routinely for pancreatitis.8

Timing of Invasive Procedures/surgeries

In a systematic review comparing urgent endoscopic retrograde cholangiopancreatography (ERCP) to conservative management in acute gallstone pancreatitis. No difference was observed in mortality, organ failures, infection, or total rates of necrotizing pancreatitis. As a result, urgent ERCP is not recommended routinely for acute pancreatitis. The exception to this is in cases of acute cholangitis, when it is indicated regardless of the presence of pancreatitis, and in cases in which a visible common bile duct obstruction is seen on imaging.

There has been debate regarding timing of cholecystectomy in acute gallstone pancreatitis. van Baal et al conducted a systematic review and found that advocates for early intervention point to fewer late complications from gallstones, while advocates for delayed surgery believe that a delayed approach is safer and perhaps associated with better outcomes because of decreased inflammation in the surgical bed.9

A single, good-quality randomized trial included in the review revealed substantial evidence that cholecystectomy performed during initial admission is associated with significant reductions in a composite outcome of mortality and gallstone-related complications, with no increase in surgical difficulty or conversion from a laparoscopic to an open procedure. Based on these findings, early cholecystectomy is recommended.9

Alcohol Avoidance Intervention

There are few studies evaluating the role of alcohol counseling in patients with alcohol-induced pancreatitis. The results of one randomized trial showed a trend toward lower overall readmission rates, but no change in the rate of recurrent pancreatitis. A Cochrane Review of a brief alcohol intervention in a primary care setting showed a significant reduction in consumption, a finding that persisted in a follow-up meta-analysis. Thus, a brief alcohol intervention is recommended in cases of alcohol-induced acute pancreatitis.10

Summary

Acute pancreatitis continues to be a disease in need of more research to define the best management practices. Current recommendations include avoiding prophylactic antibiotics, and TPN. Early enteral feedings, performing a cholecystectomy if indicated during the index hospitalization, and providing alcohol avoidance counseling are recommended. Less certain is how to provide initial fluid resuscitation (including which fluid to use), what rate to administer, and what goal to aim for. Hopefully, these questions will be answered by good quality trials in the near future.

REFERENCES

  1. Crockett SD, Wani S, Gardner TB, et al. American Gastroenterological Association Institute guideline on initial management of acute pancreatitis. Gastroenterology 2018;154:1096-1101.
  2. Vege SS, DiMagno MJ, Forsmark CE, et al. Initial medical treatment of acute pancreatitis: American Gastroenterological Association Institute technical review. Gastroenterology 2018;154:1103-1139.
  3. Gardner TB, Vege SS, Chari ST, et al. Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality. Pancreatology 2009;9:770-776.
  4. Wu BU, Hwang JQ, Gardner TH, et al. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011;9:710-717.
  5. Haydock MD, Mittal A, Wilms HR, et al. Fluid therapy in acute pancreatitis: Anybody’s guess. Ann Surg 2013;257:182-188.
  6. Vaughn VM, Shuster D, Rogers MAM, et al. Early versus delayed feeding in patients with acute pancreatitis: A systematic review. Ann Intern Med 2017;166:883-892.
  7. Yi F, Ge L, Zhao J, et al. Meta-analysis: Total parenteral nutrition versus total enteral nutrition in predicted severe acute pancreatitis. Intern Med 2012;51:523-530.
  8. Lim CL, Lee W, Liew YX, et al. Role of antibiotic prophylaxis in necrotizing pancreatitis: A meta-analysis. J Gastrointest Surg 2015;19:480-491.
  9. van Baal MC, Besselink MG, Bakker OJ, et al. Timing of cholecystectomy after mild biliary pancreatitis: A systematic review. Ann Surg 2012;255:860-866.
  10. Kaner EF, Beyer F, Dickinson HO, et al. Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database Syst Rev 2007;(2):CD004148.

Table 1. Quality of Evidence for Interventions in Acute Pancreatitis

Intervention

Recommendation

Quality of Evidence

Intravenous fluids (rate, type, goal)

None

Very low

Early vs. delayed feeding

Early

Low

Total parenteral nutrition vs. enteral feeding

Enteral

Moderate

Early vs delayed cholecystectomy

Early

Moderate

Alcohol avoidance intervention

Yes

Moderate