In Focus

 

Historical perspective

The term “pancreas” derives its name from the Greek words pan (all) and kreas (flesh). Understanding pancreas physiology was first attempted in the 17th century by Regnier de Graaf^1. Giovanni Morgagni is credited with the first description of the syndrome of acute pancreatitis (AP) in 1761². Reginald Huber Fitz proposed the first classification of AP into hemorrhagic, gangrenous, and suppurative types in 1889³. The distinction of acute from chronic pancreatitis was not well described until the middle of the 20th century when Mandred W. Comfort gave a detailed account of chronic relapsing pancreatitis in 1946⁴.

AP is the one of the most common gastrointestinal disorders requiring hospitalization, accounting for roughly 270,000 admissions annually in the U.S., which translates into a $2.6 billion annual health care expenditure.
 

Diagnosis and classification of severity

The diagnosis of AP is based on the presence of two of the three following criteria: typical abdominal pain (severe, upper abdominal pain frequently radiating to the back), serum amylase and/or lipase levels greater than 3 times the upper limit of normal, and/or characteristic imaging findings.

The original 1992 Atlanta classification provided the first blueprint to standardize how severity of AP was defined⁵. Over the years, better understanding of AP pathophysiology and its complications led to a greater focus on local and systemic determinants of severity⁶ and eventually the Revised Atlanta Classification (RAC) in 2013 (Table 1).
 

Management of acute pancreatitis

Prevention

As with any disorder, management starts with prevention. Primary prevention of AP has only been well studied in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Post-ERCP pancreatitis (PEP) is the most common and arguably the most dreaded complication of ERCP with reported incidence of approximately 10%⁷. Several medications and endoscopic interventions have been assessed for the prevention of PEP. Of these, placement of prophylactic pancreatic duct stents^8,9 and administration of rectal nonsteroidal anti-inflammatory drugs, especially indomethacin, have shown significant benefit in reducing risk for PEP^10,11. It is unclear at this point whether rectal indomethacin alone (without pancreatic duct stenting) is sufficient in patients at high risk for PEP. The SVI (Stent Vs. Indomethacin) trial¹², an ongoing multicenter randomized controlled trial, aims to answer this specific question.

Determination of etiology

The most common causes of AP are gallstones and alcohol, accounting for more than two-thirds of all cases¹³. Other etiologies include hypertriglyceridemia, ERCP, drugs induced, familial/hereditary, and post-traumatic. Initial work up includes a thorough history to quantify alcohol consumption and assess for recently started medications, measurement of liver injury tests¹⁴ and triglyceride levels, and performance of a transabdominal ultrasound to evaluate for biliary dilation, chole- and choledocholithiasis¹⁵.

Assessment of disease severity

There is a plethora of scoring systems developed to predict AP severity and outcomes at presentation and/or within the first 24 hours. These include the Ranson’s criteria described in 1974, the APACHE-II (Acute Physiology and Chronic Health Evaluation II), BISAP (Bedside Index of Severity in Acute Pancreatitis) scores, and others. They all have similar, but only modest, accuracy^16,17. Experts recommend¹⁸ that the Systemic Inflammatory Response Syndrome (SIRS) may be the most useful score in daily clinical practice, given that all of its four parameters are readily available (temperature, heart rate, respiratory rate, and white blood cell count) and the score is easy to calculate. Recent studies suggest that admission hematocrit and rise in blood urea nitrogen (BUN) at 24 hours are as accurate as more complex scoring systems in predicting severe disease¹⁹.

 

Fluid resuscitation

Despite extensive research and trials using medications such as ulinastatin, octreotide, pentoxifylline, gabexate, N-acetyl cysteine, steroids, IL-10, and antibiotics²⁰, no pharmacologic agent has been shown to significantly alter the clinical course/outcomes of AP.

Adequate intravenous hydration remains the cornerstone of early management in AP²¹. Studies have demonstrated that increased intestinal permeability, secondary to reduced intestinal capillary microcirculation, leads to bacterial translocation and development of SIRS²². Intestinal microcirculation does not become as readily impaired, and there is a certain “latency” to its onset, from the insult that triggers pancreatitis. This gives rise to the concept of a “golden window” of 12-24 hours from the insult to potentially reverse such changes and prevent organ dysfunction. It has been shown that patients who are adequately resuscitated with intravenous fluids have lower risk for local and systemic complications²³.

What remains debatable is the amount and type of fluid administered. Lactated Ringers (LR) is likely the optimal solution, based on a small prospective randomized-controlled study showing that administration of LR reduced SIRS compared with saline²⁴. Endpoints to guide adequacy of fluid resuscitation in the first 24-48 hours include measurement of urine output (at least 0.5 mL/kg per hour)²⁵, decrease in hematocrit²⁶ and BUN levels²⁷.

 

 

Selecting level of care and ICU management

Patients with predicted severe AP or those with persistent SIRS despite initial fluid resuscitation should be managed in a closely monitored unit, ideally an ICU. Patients with impending respiratory failure require mechanical ventilation, renal failure complicated by metabolic acidosis and/or hyperkalemia requires hemodialysis, and cardiovascular shock requires the initiation of vasopressors and continuous monitoring of blood pressure via an arterial line. A special entity that requires ICU level care is hypertriglyceridemia (HTG)-induced severe AP. HTG should be considered as the etiology of AP in certain clinical scenarios²⁸: previous history of HTG, poorly controlled diabetes mellitus, history of significant alcohol use, third trimester of pregnancy, and use of certain medications associated with HTG such as oral estrogens, tamoxifen, and propofol. Levels of triglyceride greater than 1000 mg/dL strongly point toward HTG being the etiology.

Plasmapheresis, which filters and removes triglycerides from plasma, has been reported as an efficient treatment in such patients based on case series^29,30. At this time its use may only be justified in patients with predicted severe AP from HTG, preferably within the first 24 hours of presentation.


Urgent ERCP

Urgent ERCP (within 24-48 hours of admission) in patients with biliary AP is indicated³¹ when there is strong clinical suspicion for concomitant cholangitis and/or evidence of ongoing biliary obstruction (secondary to choledocholithiasis) on imaging. Currently, predicted severe AP of biliary etiology does not constitute an indication of urgent ERCP in the absence of the above parameters³².

 

Nutrition

Recovery of the gut function is often delayed for several days or weeks in patients with severe AP. Studies have shown that prolonged fasting in such circumstances leads to malnutrition and worse prognosis^33,34. Enteral nutrition via a nasogastric (NG) or nasojejunal (NJ) tube is the preferred route of nutritional support, as it is associated with lower risk of infection, multi-organ failure, and mortality when compared to total parenteral nutrition³³.

The question of whether NJ feeding offers any additional advantages over NG feeding has not been clearly answered with a recent randomized trial showing NG feeds not to be inferior to NJ feeds³⁵. In regards to the timing of initiation of enteral nutrition, early nasoenteric feeding within 24 hours from presentation was found not to be superior compared to on-demand feeding in patients with predicted severe AP³⁶.


Strategies to decrease risk of recurrent attacks

The etiology of AP can be determined in the majority of patients. In many instances, recurrence can be prevented, i.e., in biliary or alcoholic etiologies. In patients with mild biliary AP, evidence supports³⁷ the performance of cholecystectomy during the index admission. In cases of severe biliary AP complicated by pancreatic necrosis and/or peripancreatic fluid collections, cholecystectomy should be delayed for a few weeks until the collections regress or mature³⁸. In poor surgical candidates, ERCP with biliary sphincterotomy offers an alternative, but less effective, means of reducing the risk of recurrent attacks in patients with biliary AP³⁹. In subjects with first AP attack of alcoholic etiology, counseling focusing on alcohol cessation has shown to reduce risk of recurrences⁴⁰. Similarly, appropriate plans to treat and follow-up underlying metabolic etiologies (hypercalcemia and HTG) should be preferably instituted prior to the patients’ discharge.

 

 

Management of peripancreatic fluid collections

Patients with AP frequently develop peripancreatic fluid collections (PFCs). Based on the revised Atlanta classification, those are categorized into four types (Table 2, Figures 1-4).

The majority of acute PFCs in patients without evidence of pancreatic necrosis regress within a few weeks and thus intervention is not indicated early in the disease course. Current literature supports delaying the drainage/debridement of such collections for several weeks. The mortality from interventions decreases as the time to intervention from onset of symptoms increases⁴¹. Delaying intervention gives more time for recovery from systemic complications and allows the encapsulating wall and contents to organize further.

It is only the mature PFCs, which are symptomatic resulting in abdominal pain, nausea, early satiety, gastric outlet obstruction, failure to thrive, and/or biliary obstruction, that need to be drained/debrided⁴². Minimally invasive approaches have shown to result in better outcomes when compared to open laparotomy. Minimally invasive approaches include placement of percutaneous drainage catheters by interventional radiology (retroperitoneal approach preferred when feasible), endoscopic drainage/debridement, laparoscopy, and retroperitoneal necrosectomy following a step-up approach⁴³.

 

While surgery is still an option for patients with symptomatic mature PFCs, endoscopic ultrasound-guided drainage in expert hands has been shown to be cost effective, with shorter hospital stay and even decreased risk of cyst recurrence compared with surgical cyst-gastrostomy creation⁴⁴. Ultrasound or computed tomography-guided drainage of such collections with a percutaneous catheter is an equally efficacious option when compared to the endoscopic approach. However, patients undergoing endotherapy require fewer procedures and imaging studies and shorter length of stay⁴⁵ when compared with radiological interventions.

 

Management of pancreatic necrosis

Although this topic has generated much debate, the majority of available evidence shows no clinical benefit from using prophylactic antibiotics to prevent infection in pancreatic necrosis⁴⁶.

Infectious complications are the major cause of late mortality in AP. The predominant source is bacterial translocation from the GI tract^47,48. Infected pancreatic necrosis should be suspected in patients with imaging evidence of pancreatic or extrapancreatic necrosis, who have a sudden deterioration in clinical status, typically 2-3 weeks after onset of symptoms or if gas bubbles are seen within a necrotic collection (Figure 2). When infected pancreatic necrosis is suspected or established, antibiotics such as carbapenems, fluoroquinolones, metronidazole, and cephalosporin should be started, which have better penetrance into ischemic pancreatic tissue. CT guided aspiration has lost much of its utility, since there has been a paradigm shift to delaying drainage of infected (suspected or established) pancreatic necrosis. A negative or positive CT aspirate does not dictate timing of intervention and is only recommended if a fungal or drug resistant infection is suspected¹⁵. As mentioned above, when debridement of an infected necroma is contemplated, the two guiding principles are to delay drainage and use minimally invasive approaches.

Vascular complications

Vascular complications such as splanchnic vein thrombosis can occur in up to a quarter of AP patients⁴⁹. Anticoagulation is not usually indicated unless thrombosis is extensive and causes bowel ischemia. Arterial pseudoaneurysms are rare but life threatening complications of AP. They typically require interventional radiology guided coil embolization to prevent massive bleeding⁵⁰.

Abdominal compartment syndrome

Abdominal compartment syndrome is an end result of third spacing of fluid into the abdominal cavity secondary to inflammation and fluid resuscitation in severe pancreatitis. Abdominal pressure in patients can be monitored by measuring bladder pressures. Intra-abdominal hypertension is defined as a sustained pressure greater than 12 mm Hg, while abdominal compartment syndrome is defined as sustained intra-abdominal pressure greater than 20 mm Hg with new organ failure⁵¹. Intra-abdominal hypertension (IAH) is present in up to 75% of patients with severe AP. While all conservative measures to prevent development or worsening of IAH should be implemented (adequate sedation, decompression of bowel in patients with ileus, etc.), current guidelines do not recommend aggressive interventions to treat it. On the other hand, abdominal compartment syndrome is a life-threatening complication that requires urgent intervention to decrease intra-abdominal pressure, such as percutaneous drain placement or surgical fasciotomy^52,53.

Conclusion

The key principles in the management of acute pancreatitis are aggressive hydration and preventing development of end organ failure. In the last two decades there has been a paradigm shift in the guidelines for management of peripancreatic fluid collections and pancreatic necrosis. When feasible, drainage of these collections should be delayed and be performed using minimally invasive interventions. There is still an urgent need for developing and testing disease-specific treatments targeting control of the inflammatory response in the early phase of acute pancreatitis and prevention of development of severe disease with end-organ dysfunction.

Dr. Gulati is a gastroenterology and hepatology fellow at Allegheny Health Network, Pittsburgh, and Dr. Papachristou is professor of medicine, University of Pittsburgh School of Medicine, Pittsburgh.

References

1. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Chapter 55, 923-33.

2. Morgagni G.B. [Fie Books on the Seats and Causes of Diseases as Discovered by the Anatomist]. Venice, Italy: Typographia Remondiniana;1761.

3. Fitz R.H. Boston Med Surg J. 1889;120:181-8.

4. Comfort M., Gambill E., Baggesnstoss A. Gastroenterology. 1946;6:238-76.

5. Bollen T.L., van Santvoort H.C., Besselink M.G., et al. Br J Surg. 2008;95:6–21.

6. Dellinger E.P., Forsmark C.E., Layer P., et al. Ann Surg. 2012 Dec;256[6]:875-80.

7. Kochar B., Akshintala V.S., Afghani E., et al. Gastrointest Endosc. 2015 Jan;81[1]:143-9.

8. Choudhary A., Bechtold M.L., Arif M., et al. Gastrointest Endosc. 2011 Feb;73[2]:275-82.

9. Shi Q.Q., Ning X.Y., Zhan L.L., Tang G.D., Lv X.P. World J Gastroenterol. 2014 Jun 14;20[22]:7040-8.

10. Elmunzer B.J., Waljee A.K., Elta G.H., Taylor J.R., Fehmi S.M., Higgins P.D. Gut. 2008 Sep;57[9]:1262-7.

11. Sethi S., Sethi N., Wadhwa V., Garud S., Brown A. Pancreas. 2014 Mar;43[2]:190-7. 
12. Elmunzer B.J., Serrano J., Chak A., et al. Trials. 2016 Mar 3;17[1]:120.

13. Lowenfels A.B., Maisonneuve P., Sullivan T. Curr Gastroenterol Rep. 2009;11:97-103.

14. Agarwal N., Pitchumoni C.S., Sivaprasad A.V. Am J Gastroenterol. 1990;85:356-66.

15. Tenner S., Baillie J., DeWitt J. Vege S.S. Am J Gastroenterol. 2013;108:1400-15.

16. Papachristou G.I., Muddana V., Yadav D., et al. Am J Gastroenterol. 2010;105:435-41.

17. Mounzer R., et al. Gastroenterology 2012;142:1476-82.

18. Working Group IAP/APA Acute Pancreatitis Guidelines. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

19. Koutroumpakis E., Wu B.U., Bakker O.J., et al. Am J Gastroenterol. 2015 Dec;110[12]:1707-16.

20. Bang U.C., Semb S., Nojgaard C., Bendtsen F. World J Gastroenterol. 2008 May 21;14[19]:2968-76.

21. Warndorf M.G., Kurtzman J.T., Bartel M.J., et al. Clin Gastroenterol Hepatol. 2011 Aug;9[8]:705-9.

22. Hotz H.G., Foitzik T., Rohweder J., et al. J Gastrointest Surg. 1998 Nov-Dec;2[6]:518-25.

23. Brown A., Baillargeon J.D., Hughes M.D., et al. Pancreatology 2002;2:104-7.

24. Wu B.U., Hwang J.Q., Gardner T.H., et al. Clin Gastroenterol Hepatol. 2011 Aug;9[8]:710-7.

25. Forsmark C.E., Baillie J., AGA Institute Clinical Practice and Economics Committee, AGA Institute Governing Board. Gastroenterology. 2007 May;132[5]:2022-44.

26. Lankisch P.G., Mahlke R., Blum T., et al. Am J Gastroenterol. 2001;96:2081-5.

27. Wu B.U., Johannes R.S., Sun X., et al. Gastroenterology 2009;137:129-35.

28. Scherer J., Singh V.P., Pitchumoni C.S., Yadav D. J Clin Gastroenterol. 2014 Mar;48[3]:195-203.

29. Gubensek J., Buturovic-Ponikvar J., Romozi K., Ponikvar R. PLoS One. 2014 Jul 21;9[7]:e102748.

30. Chen J.H., Yeh J.H., Lai H.W., Liao C.S. World J Gastroenterol. 2004 Aug 1;10[15]:2272-4.

31. Tse F., Yuan Y. Cochrane Database Syst Rev. 2012 May 16;[5]:CD009779.

32. Folsch U.R., Nitsche R., Ludtke R., et al. N Engl J Med. 1997;336:237-42.

33. Al-Omran M., Albalawi Z.H., Tashkandi M.F., Al-Ansary L.A. Cochrane Database Syst Rev. 2010 Jan 20;[1]:CD002837.

 

34. Li J.Y., Yu T., Chen G.C., et al. PLoS One. 2013;8[6]:e64926.

35. Singh N., Sharma B., Sharma M., et al. Pancreas. 2012 Jan;41[1]:153-9.

36. Bakker O.J., van Brunschot S., van Santvoort H.C., et al. N Engl J Med. 2014 Nov 20;371[21]:1983-93.

37. Van Baal M.C., Besselink M.G., Bakker O.J., et al. Ann Surg. 2012;255:860–6.

38. Nealon W.H., Bawduniak J., Walser E.M. Ann Surg. 2004 Jun;239[6]:741-9.

39. Sanjay P., Yeeting S., Whigham C., Judson H., Polignano F.M., Tait I.S. Surg Endosc. 2008 Aug;22[8]:1832-7.

40. Nordback I., Pelli H., Lappalainen-Lehto R., Järvinen S., Räty S., Sand J. Gastroenterology. 2009 Mar;136[3]:848-55.

41. Besselink M.G., Verwer T.J., Schoenmaeckers E.J., et al. Arch Surg. 2007;142:1194-201.

42. Besselink M., van Santvoort H., Freeman M. et al. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

43. Hjalmar C., van Santvoort, H., Besselink M.G., et al. N Engl J Med. 2010;362:1491-502.

44. Varadarajulu S., Bang J.Y., Sutton B.S., et al. Gastroenterology. 2013;145:583-90.e1.

45. Akshintala V.S., Saxena P., Zaheer A., et al. Gastrointest Endosc. 2014 Jun;79[6]:921-8.

46. Jiang K, Huang W, Yang XN., et al. World J Gastroenterol. 2012;18:279–84.

47. Dervenis C., Smailis D., Hatzitheoklitos E. J Hepatobiliary Pancreat Surg. 2003;10[6]:415Y418.

48. Gloor B., Muller C.A., Worni M., et al. Arch Surg. 2001;136[5]:592Y596.

49. Nadkarni N.A., Khanna S., Vege S.S. Pancreas. 2013 Aug;42[6]:924-31.

50. Marshall G.T., Howell D.A., Hansen B.L., Amberson S.M., Abourjaily G.S., Bredenberg C.E. Arch Surg. 1996 Mar;131[3]:278-83.

51. Malbrain M.L., Cheatham M.L., Kirkpatrick A., et al. Intensive Care Med. 2006 Nov;32[11]:1722-32.

52. De Waele J.J. Leppaniemi A.K. World J Surg. 2009;33:1128-33.

53. Kirkpatrick A.W., Roberts D.J., De W.J., et al. Intensive Care Med. 2013 Jul;39[7]1190-206.
 

 

Historical perspective

The term “pancreas” derives its name from the Greek words pan (all) and kreas (flesh). Understanding pancreas physiology was first attempted in the 17th century by Regnier de Graaf^1. Giovanni Morgagni is credited with the first description of the syndrome of acute pancreatitis (AP) in 1761². Reginald Huber Fitz proposed the first classification of AP into hemorrhagic, gangrenous, and suppurative types in 1889³. The distinction of acute from chronic pancreatitis was not well described until the middle of the 20th century when Mandred W. Comfort gave a detailed account of chronic relapsing pancreatitis in 1946⁴.

AP is the one of the most common gastrointestinal disorders requiring hospitalization, accounting for roughly 270,000 admissions annually in the U.S., which translates into a $2.6 billion annual health care expenditure.
 

Diagnosis and classification of severity

The diagnosis of AP is based on the presence of two of the three following criteria: typical abdominal pain (severe, upper abdominal pain frequently radiating to the back), serum amylase and/or lipase levels greater than 3 times the upper limit of normal, and/or characteristic imaging findings.

The original 1992 Atlanta classification provided the first blueprint to standardize how severity of AP was defined⁵. Over the years, better understanding of AP pathophysiology and its complications led to a greater focus on local and systemic determinants of severity⁶ and eventually the Revised Atlanta Classification (RAC) in 2013 (Table 1).
 

Management of acute pancreatitis

Prevention

As with any disorder, management starts with prevention. Primary prevention of AP has only been well studied in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Post-ERCP pancreatitis (PEP) is the most common and arguably the most dreaded complication of ERCP with reported incidence of approximately 10%⁷. Several medications and endoscopic interventions have been assessed for the prevention of PEP. Of these, placement of prophylactic pancreatic duct stents^8,9 and administration of rectal nonsteroidal anti-inflammatory drugs, especially indomethacin, have shown significant benefit in reducing risk for PEP^10,11. It is unclear at this point whether rectal indomethacin alone (without pancreatic duct stenting) is sufficient in patients at high risk for PEP. The SVI (Stent Vs. Indomethacin) trial¹², an ongoing multicenter randomized controlled trial, aims to answer this specific question.

Determination of etiology

The most common causes of AP are gallstones and alcohol, accounting for more than two-thirds of all cases¹³. Other etiologies include hypertriglyceridemia, ERCP, drugs induced, familial/hereditary, and post-traumatic. Initial work up includes a thorough history to quantify alcohol consumption and assess for recently started medications, measurement of liver injury tests¹⁴ and triglyceride levels, and performance of a transabdominal ultrasound to evaluate for biliary dilation, chole- and choledocholithiasis¹⁵.

Assessment of disease severity

There is a plethora of scoring systems developed to predict AP severity and outcomes at presentation and/or within the first 24 hours. These include the Ranson’s criteria described in 1974, the APACHE-II (Acute Physiology and Chronic Health Evaluation II), BISAP (Bedside Index of Severity in Acute Pancreatitis) scores, and others. They all have similar, but only modest, accuracy^16,17. Experts recommend¹⁸ that the Systemic Inflammatory Response Syndrome (SIRS) may be the most useful score in daily clinical practice, given that all of its four parameters are readily available (temperature, heart rate, respiratory rate, and white blood cell count) and the score is easy to calculate. Recent studies suggest that admission hematocrit and rise in blood urea nitrogen (BUN) at 24 hours are as accurate as more complex scoring systems in predicting severe disease¹⁹.

 

Fluid resuscitation

Despite extensive research and trials using medications such as ulinastatin, octreotide, pentoxifylline, gabexate, N-acetyl cysteine, steroids, IL-10, and antibiotics²⁰, no pharmacologic agent has been shown to significantly alter the clinical course/outcomes of AP.

Adequate intravenous hydration remains the cornerstone of early management in AP²¹. Studies have demonstrated that increased intestinal permeability, secondary to reduced intestinal capillary microcirculation, leads to bacterial translocation and development of SIRS²². Intestinal microcirculation does not become as readily impaired, and there is a certain “latency” to its onset, from the insult that triggers pancreatitis. This gives rise to the concept of a “golden window” of 12-24 hours from the insult to potentially reverse such changes and prevent organ dysfunction. It has been shown that patients who are adequately resuscitated with intravenous fluids have lower risk for local and systemic complications²³.

What remains debatable is the amount and type of fluid administered. Lactated Ringers (LR) is likely the optimal solution, based on a small prospective randomized-controlled study showing that administration of LR reduced SIRS compared with saline²⁴. Endpoints to guide adequacy of fluid resuscitation in the first 24-48 hours include measurement of urine output (at least 0.5 mL/kg per hour)²⁵, decrease in hematocrit²⁶ and BUN levels²⁷.

 

 

Selecting level of care and ICU management

Patients with predicted severe AP or those with persistent SIRS despite initial fluid resuscitation should be managed in a closely monitored unit, ideally an ICU. Patients with impending respiratory failure require mechanical ventilation, renal failure complicated by metabolic acidosis and/or hyperkalemia requires hemodialysis, and cardiovascular shock requires the initiation of vasopressors and continuous monitoring of blood pressure via an arterial line. A special entity that requires ICU level care is hypertriglyceridemia (HTG)-induced severe AP. HTG should be considered as the etiology of AP in certain clinical scenarios²⁸: previous history of HTG, poorly controlled diabetes mellitus, history of significant alcohol use, third trimester of pregnancy, and use of certain medications associated with HTG such as oral estrogens, tamoxifen, and propofol. Levels of triglyceride greater than 1000 mg/dL strongly point toward HTG being the etiology.

Plasmapheresis, which filters and removes triglycerides from plasma, has been reported as an efficient treatment in such patients based on case series^29,30. At this time its use may only be justified in patients with predicted severe AP from HTG, preferably within the first 24 hours of presentation.


Urgent ERCP

Urgent ERCP (within 24-48 hours of admission) in patients with biliary AP is indicated³¹ when there is strong clinical suspicion for concomitant cholangitis and/or evidence of ongoing biliary obstruction (secondary to choledocholithiasis) on imaging. Currently, predicted severe AP of biliary etiology does not constitute an indication of urgent ERCP in the absence of the above parameters³².

 

Nutrition

Recovery of the gut function is often delayed for several days or weeks in patients with severe AP. Studies have shown that prolonged fasting in such circumstances leads to malnutrition and worse prognosis^33,34. Enteral nutrition via a nasogastric (NG) or nasojejunal (NJ) tube is the preferred route of nutritional support, as it is associated with lower risk of infection, multi-organ failure, and mortality when compared to total parenteral nutrition³³.

The question of whether NJ feeding offers any additional advantages over NG feeding has not been clearly answered with a recent randomized trial showing NG feeds not to be inferior to NJ feeds³⁵. In regards to the timing of initiation of enteral nutrition, early nasoenteric feeding within 24 hours from presentation was found not to be superior compared to on-demand feeding in patients with predicted severe AP³⁶.


Strategies to decrease risk of recurrent attacks

The etiology of AP can be determined in the majority of patients. In many instances, recurrence can be prevented, i.e., in biliary or alcoholic etiologies. In patients with mild biliary AP, evidence supports³⁷ the performance of cholecystectomy during the index admission. In cases of severe biliary AP complicated by pancreatic necrosis and/or peripancreatic fluid collections, cholecystectomy should be delayed for a few weeks until the collections regress or mature³⁸. In poor surgical candidates, ERCP with biliary sphincterotomy offers an alternative, but less effective, means of reducing the risk of recurrent attacks in patients with biliary AP³⁹. In subjects with first AP attack of alcoholic etiology, counseling focusing on alcohol cessation has shown to reduce risk of recurrences⁴⁰. Similarly, appropriate plans to treat and follow-up underlying metabolic etiologies (hypercalcemia and HTG) should be preferably instituted prior to the patients’ discharge.

 

 

Management of peripancreatic fluid collections

Patients with AP frequently develop peripancreatic fluid collections (PFCs). Based on the revised Atlanta classification, those are categorized into four types (Table 2, Figures 1-4).

The majority of acute PFCs in patients without evidence of pancreatic necrosis regress within a few weeks and thus intervention is not indicated early in the disease course. Current literature supports delaying the drainage/debridement of such collections for several weeks. The mortality from interventions decreases as the time to intervention from onset of symptoms increases⁴¹. Delaying intervention gives more time for recovery from systemic complications and allows the encapsulating wall and contents to organize further.

It is only the mature PFCs, which are symptomatic resulting in abdominal pain, nausea, early satiety, gastric outlet obstruction, failure to thrive, and/or biliary obstruction, that need to be drained/debrided⁴². Minimally invasive approaches have shown to result in better outcomes when compared to open laparotomy. Minimally invasive approaches include placement of percutaneous drainage catheters by interventional radiology (retroperitoneal approach preferred when feasible), endoscopic drainage/debridement, laparoscopy, and retroperitoneal necrosectomy following a step-up approach⁴³.

 

While surgery is still an option for patients with symptomatic mature PFCs, endoscopic ultrasound-guided drainage in expert hands has been shown to be cost effective, with shorter hospital stay and even decreased risk of cyst recurrence compared with surgical cyst-gastrostomy creation⁴⁴. Ultrasound or computed tomography-guided drainage of such collections with a percutaneous catheter is an equally efficacious option when compared to the endoscopic approach. However, patients undergoing endotherapy require fewer procedures and imaging studies and shorter length of stay⁴⁵ when compared with radiological interventions.

 

Management of pancreatic necrosis

Although this topic has generated much debate, the majority of available evidence shows no clinical benefit from using prophylactic antibiotics to prevent infection in pancreatic necrosis⁴⁶.

Infectious complications are the major cause of late mortality in AP. The predominant source is bacterial translocation from the GI tract^47,48. Infected pancreatic necrosis should be suspected in patients with imaging evidence of pancreatic or extrapancreatic necrosis, who have a sudden deterioration in clinical status, typically 2-3 weeks after onset of symptoms or if gas bubbles are seen within a necrotic collection (Figure 2). When infected pancreatic necrosis is suspected or established, antibiotics such as carbapenems, fluoroquinolones, metronidazole, and cephalosporin should be started, which have better penetrance into ischemic pancreatic tissue. CT guided aspiration has lost much of its utility, since there has been a paradigm shift to delaying drainage of infected (suspected or established) pancreatic necrosis. A negative or positive CT aspirate does not dictate timing of intervention and is only recommended if a fungal or drug resistant infection is suspected¹⁵. As mentioned above, when debridement of an infected necroma is contemplated, the two guiding principles are to delay drainage and use minimally invasive approaches.

Vascular complications

Vascular complications such as splanchnic vein thrombosis can occur in up to a quarter of AP patients⁴⁹. Anticoagulation is not usually indicated unless thrombosis is extensive and causes bowel ischemia. Arterial pseudoaneurysms are rare but life threatening complications of AP. They typically require interventional radiology guided coil embolization to prevent massive bleeding⁵⁰.

Abdominal compartment syndrome

Abdominal compartment syndrome is an end result of third spacing of fluid into the abdominal cavity secondary to inflammation and fluid resuscitation in severe pancreatitis. Abdominal pressure in patients can be monitored by measuring bladder pressures. Intra-abdominal hypertension is defined as a sustained pressure greater than 12 mm Hg, while abdominal compartment syndrome is defined as sustained intra-abdominal pressure greater than 20 mm Hg with new organ failure⁵¹. Intra-abdominal hypertension (IAH) is present in up to 75% of patients with severe AP. While all conservative measures to prevent development or worsening of IAH should be implemented (adequate sedation, decompression of bowel in patients with ileus, etc.), current guidelines do not recommend aggressive interventions to treat it. On the other hand, abdominal compartment syndrome is a life-threatening complication that requires urgent intervention to decrease intra-abdominal pressure, such as percutaneous drain placement or surgical fasciotomy^52,53.

Conclusion

The key principles in the management of acute pancreatitis are aggressive hydration and preventing development of end organ failure. In the last two decades there has been a paradigm shift in the guidelines for management of peripancreatic fluid collections and pancreatic necrosis. When feasible, drainage of these collections should be delayed and be performed using minimally invasive interventions. There is still an urgent need for developing and testing disease-specific treatments targeting control of the inflammatory response in the early phase of acute pancreatitis and prevention of development of severe disease with end-organ dysfunction.

Dr. Gulati is a gastroenterology and hepatology fellow at Allegheny Health Network, Pittsburgh, and Dr. Papachristou is professor of medicine, University of Pittsburgh School of Medicine, Pittsburgh.

References

1. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Chapter 55, 923-33.

2. Morgagni G.B. [Fie Books on the Seats and Causes of Diseases as Discovered by the Anatomist]. Venice, Italy: Typographia Remondiniana;1761.

3. Fitz R.H. Boston Med Surg J. 1889;120:181-8.

4. Comfort M., Gambill E., Baggesnstoss A. Gastroenterology. 1946;6:238-76.

5. Bollen T.L., van Santvoort H.C., Besselink M.G., et al. Br J Surg. 2008;95:6–21.

6. Dellinger E.P., Forsmark C.E., Layer P., et al. Ann Surg. 2012 Dec;256[6]:875-80.

7. Kochar B., Akshintala V.S., Afghani E., et al. Gastrointest Endosc. 2015 Jan;81[1]:143-9.

8. Choudhary A., Bechtold M.L., Arif M., et al. Gastrointest Endosc. 2011 Feb;73[2]:275-82.

9. Shi Q.Q., Ning X.Y., Zhan L.L., Tang G.D., Lv X.P. World J Gastroenterol. 2014 Jun 14;20[22]:7040-8.

10. Elmunzer B.J., Waljee A.K., Elta G.H., Taylor J.R., Fehmi S.M., Higgins P.D. Gut. 2008 Sep;57[9]:1262-7.

11. Sethi S., Sethi N., Wadhwa V., Garud S., Brown A. Pancreas. 2014 Mar;43[2]:190-7. 
12. Elmunzer B.J., Serrano J., Chak A., et al. Trials. 2016 Mar 3;17[1]:120.

13. Lowenfels A.B., Maisonneuve P., Sullivan T. Curr Gastroenterol Rep. 2009;11:97-103.

14. Agarwal N., Pitchumoni C.S., Sivaprasad A.V. Am J Gastroenterol. 1990;85:356-66.

15. Tenner S., Baillie J., DeWitt J. Vege S.S. Am J Gastroenterol. 2013;108:1400-15.

16. Papachristou G.I., Muddana V., Yadav D., et al. Am J Gastroenterol. 2010;105:435-41.

17. Mounzer R., et al. Gastroenterology 2012;142:1476-82.

18. Working Group IAP/APA Acute Pancreatitis Guidelines. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

19. Koutroumpakis E., Wu B.U., Bakker O.J., et al. Am J Gastroenterol. 2015 Dec;110[12]:1707-16.

20. Bang U.C., Semb S., Nojgaard C., Bendtsen F. World J Gastroenterol. 2008 May 21;14[19]:2968-76.

21. Warndorf M.G., Kurtzman J.T., Bartel M.J., et al. Clin Gastroenterol Hepatol. 2011 Aug;9[8]:705-9.

22. Hotz H.G., Foitzik T., Rohweder J., et al. J Gastrointest Surg. 1998 Nov-Dec;2[6]:518-25.

23. Brown A., Baillargeon J.D., Hughes M.D., et al. Pancreatology 2002;2:104-7.

24. Wu B.U., Hwang J.Q., Gardner T.H., et al. Clin Gastroenterol Hepatol. 2011 Aug;9[8]:710-7.

25. Forsmark C.E., Baillie J., AGA Institute Clinical Practice and Economics Committee, AGA Institute Governing Board. Gastroenterology. 2007 May;132[5]:2022-44.

26. Lankisch P.G., Mahlke R., Blum T., et al. Am J Gastroenterol. 2001;96:2081-5.

27. Wu B.U., Johannes R.S., Sun X., et al. Gastroenterology 2009;137:129-35.

28. Scherer J., Singh V.P., Pitchumoni C.S., Yadav D. J Clin Gastroenterol. 2014 Mar;48[3]:195-203.

29. Gubensek J., Buturovic-Ponikvar J., Romozi K., Ponikvar R. PLoS One. 2014 Jul 21;9[7]:e102748.

30. Chen J.H., Yeh J.H., Lai H.W., Liao C.S. World J Gastroenterol. 2004 Aug 1;10[15]:2272-4.

31. Tse F., Yuan Y. Cochrane Database Syst Rev. 2012 May 16;[5]:CD009779.

32. Folsch U.R., Nitsche R., Ludtke R., et al. N Engl J Med. 1997;336:237-42.

33. Al-Omran M., Albalawi Z.H., Tashkandi M.F., Al-Ansary L.A. Cochrane Database Syst Rev. 2010 Jan 20;[1]:CD002837.

 

34. Li J.Y., Yu T., Chen G.C., et al. PLoS One. 2013;8[6]:e64926.

35. Singh N., Sharma B., Sharma M., et al. Pancreas. 2012 Jan;41[1]:153-9.

36. Bakker O.J., van Brunschot S., van Santvoort H.C., et al. N Engl J Med. 2014 Nov 20;371[21]:1983-93.

37. Van Baal M.C., Besselink M.G., Bakker O.J., et al. Ann Surg. 2012;255:860–6.

38. Nealon W.H., Bawduniak J., Walser E.M. Ann Surg. 2004 Jun;239[6]:741-9.

39. Sanjay P., Yeeting S., Whigham C., Judson H., Polignano F.M., Tait I.S. Surg Endosc. 2008 Aug;22[8]:1832-7.

40. Nordback I., Pelli H., Lappalainen-Lehto R., Järvinen S., Räty S., Sand J. Gastroenterology. 2009 Mar;136[3]:848-55.

41. Besselink M.G., Verwer T.J., Schoenmaeckers E.J., et al. Arch Surg. 2007;142:1194-201.

42. Besselink M., van Santvoort H., Freeman M. et al. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

43. Hjalmar C., van Santvoort, H., Besselink M.G., et al. N Engl J Med. 2010;362:1491-502.

44. Varadarajulu S., Bang J.Y., Sutton B.S., et al. Gastroenterology. 2013;145:583-90.e1.

45. Akshintala V.S., Saxena P., Zaheer A., et al. Gastrointest Endosc. 2014 Jun;79[6]:921-8.

46. Jiang K, Huang W, Yang XN., et al. World J Gastroenterol. 2012;18:279–84.

47. Dervenis C., Smailis D., Hatzitheoklitos E. J Hepatobiliary Pancreat Surg. 2003;10[6]:415Y418.

48. Gloor B., Muller C.A., Worni M., et al. Arch Surg. 2001;136[5]:592Y596.

49. Nadkarni N.A., Khanna S., Vege S.S. Pancreas. 2013 Aug;42[6]:924-31.

50. Marshall G.T., Howell D.A., Hansen B.L., Amberson S.M., Abourjaily G.S., Bredenberg C.E. Arch Surg. 1996 Mar;131[3]:278-83.

51. Malbrain M.L., Cheatham M.L., Kirkpatrick A., et al. Intensive Care Med. 2006 Nov;32[11]:1722-32.

52. De Waele J.J. Leppaniemi A.K. World J Surg. 2009;33:1128-33.

53. Kirkpatrick A.W., Roberts D.J., De W.J., et al. Intensive Care Med. 2013 Jul;39[7]1190-206.
 

 

Historical perspective

The term “pancreas” derives its name from the Greek words pan (all) and kreas (flesh). Understanding pancreas physiology was first attempted in the 17th century by Regnier de Graaf^1. Giovanni Morgagni is credited with the first description of the syndrome of acute pancreatitis (AP) in 1761². Reginald Huber Fitz proposed the first classification of AP into hemorrhagic, gangrenous, and suppurative types in 1889³. The distinction of acute from chronic pancreatitis was not well described until the middle of the 20th century when Mandred W. Comfort gave a detailed account of chronic relapsing pancreatitis in 1946⁴.

AP is the one of the most common gastrointestinal disorders requiring hospitalization, accounting for roughly 270,000 admissions annually in the U.S., which translates into a $2.6 billion annual health care expenditure.
 

Diagnosis and classification of severity

The diagnosis of AP is based on the presence of two of the three following criteria: typical abdominal pain (severe, upper abdominal pain frequently radiating to the back), serum amylase and/or lipase levels greater than 3 times the upper limit of normal, and/or characteristic imaging findings.

The original 1992 Atlanta classification provided the first blueprint to standardize how severity of AP was defined⁵. Over the years, better understanding of AP pathophysiology and its complications led to a greater focus on local and systemic determinants of severity⁶ and eventually the Revised Atlanta Classification (RAC) in 2013 (Table 1).
 

Management of acute pancreatitis

Prevention

As with any disorder, management starts with prevention. Primary prevention of AP has only been well studied in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Post-ERCP pancreatitis (PEP) is the most common and arguably the most dreaded complication of ERCP with reported incidence of approximately 10%⁷. Several medications and endoscopic interventions have been assessed for the prevention of PEP. Of these, placement of prophylactic pancreatic duct stents^8,9 and administration of rectal nonsteroidal anti-inflammatory drugs, especially indomethacin, have shown significant benefit in reducing risk for PEP^10,11. It is unclear at this point whether rectal indomethacin alone (without pancreatic duct stenting) is sufficient in patients at high risk for PEP. The SVI (Stent Vs. Indomethacin) trial¹², an ongoing multicenter randomized controlled trial, aims to answer this specific question.

Determination of etiology

The most common causes of AP are gallstones and alcohol, accounting for more than two-thirds of all cases¹³. Other etiologies include hypertriglyceridemia, ERCP, drugs induced, familial/hereditary, and post-traumatic. Initial work up includes a thorough history to quantify alcohol consumption and assess for recently started medications, measurement of liver injury tests¹⁴ and triglyceride levels, and performance of a transabdominal ultrasound to evaluate for biliary dilation, chole- and choledocholithiasis¹⁵.

Assessment of disease severity

There is a plethora of scoring systems developed to predict AP severity and outcomes at presentation and/or within the first 24 hours. These include the Ranson’s criteria described in 1974, the APACHE-II (Acute Physiology and Chronic Health Evaluation II), BISAP (Bedside Index of Severity in Acute Pancreatitis) scores, and others. They all have similar, but only modest, accuracy^16,17. Experts recommend¹⁸ that the Systemic Inflammatory Response Syndrome (SIRS) may be the most useful score in daily clinical practice, given that all of its four parameters are readily available (temperature, heart rate, respiratory rate, and white blood cell count) and the score is easy to calculate. Recent studies suggest that admission hematocrit and rise in blood urea nitrogen (BUN) at 24 hours are as accurate as more complex scoring systems in predicting severe disease¹⁹.

 

Fluid resuscitation

Despite extensive research and trials using medications such as ulinastatin, octreotide, pentoxifylline, gabexate, N-acetyl cysteine, steroids, IL-10, and antibiotics²⁰, no pharmacologic agent has been shown to significantly alter the clinical course/outcomes of AP.

Adequate intravenous hydration remains the cornerstone of early management in AP²¹. Studies have demonstrated that increased intestinal permeability, secondary to reduced intestinal capillary microcirculation, leads to bacterial translocation and development of SIRS²². Intestinal microcirculation does not become as readily impaired, and there is a certain “latency” to its onset, from the insult that triggers pancreatitis. This gives rise to the concept of a “golden window” of 12-24 hours from the insult to potentially reverse such changes and prevent organ dysfunction. It has been shown that patients who are adequately resuscitated with intravenous fluids have lower risk for local and systemic complications²³.

What remains debatable is the amount and type of fluid administered. Lactated Ringers (LR) is likely the optimal solution, based on a small prospective randomized-controlled study showing that administration of LR reduced SIRS compared with saline²⁴. Endpoints to guide adequacy of fluid resuscitation in the first 24-48 hours include measurement of urine output (at least 0.5 mL/kg per hour)²⁵, decrease in hematocrit²⁶ and BUN levels²⁷.

 

 

Selecting level of care and ICU management

Patients with predicted severe AP or those with persistent SIRS despite initial fluid resuscitation should be managed in a closely monitored unit, ideally an ICU. Patients with impending respiratory failure require mechanical ventilation, renal failure complicated by metabolic acidosis and/or hyperkalemia requires hemodialysis, and cardiovascular shock requires the initiation of vasopressors and continuous monitoring of blood pressure via an arterial line. A special entity that requires ICU level care is hypertriglyceridemia (HTG)-induced severe AP. HTG should be considered as the etiology of AP in certain clinical scenarios²⁸: previous history of HTG, poorly controlled diabetes mellitus, history of significant alcohol use, third trimester of pregnancy, and use of certain medications associated with HTG such as oral estrogens, tamoxifen, and propofol. Levels of triglyceride greater than 1000 mg/dL strongly point toward HTG being the etiology.

Plasmapheresis, which filters and removes triglycerides from plasma, has been reported as an efficient treatment in such patients based on case series^29,30. At this time its use may only be justified in patients with predicted severe AP from HTG, preferably within the first 24 hours of presentation.


Urgent ERCP

Urgent ERCP (within 24-48 hours of admission) in patients with biliary AP is indicated³¹ when there is strong clinical suspicion for concomitant cholangitis and/or evidence of ongoing biliary obstruction (secondary to choledocholithiasis) on imaging. Currently, predicted severe AP of biliary etiology does not constitute an indication of urgent ERCP in the absence of the above parameters³².

 

Nutrition

Recovery of the gut function is often delayed for several days or weeks in patients with severe AP. Studies have shown that prolonged fasting in such circumstances leads to malnutrition and worse prognosis^33,34. Enteral nutrition via a nasogastric (NG) or nasojejunal (NJ) tube is the preferred route of nutritional support, as it is associated with lower risk of infection, multi-organ failure, and mortality when compared to total parenteral nutrition³³.

The question of whether NJ feeding offers any additional advantages over NG feeding has not been clearly answered with a recent randomized trial showing NG feeds not to be inferior to NJ feeds³⁵. In regards to the timing of initiation of enteral nutrition, early nasoenteric feeding within 24 hours from presentation was found not to be superior compared to on-demand feeding in patients with predicted severe AP³⁶.


Strategies to decrease risk of recurrent attacks

The etiology of AP can be determined in the majority of patients. In many instances, recurrence can be prevented, i.e., in biliary or alcoholic etiologies. In patients with mild biliary AP, evidence supports³⁷ the performance of cholecystectomy during the index admission. In cases of severe biliary AP complicated by pancreatic necrosis and/or peripancreatic fluid collections, cholecystectomy should be delayed for a few weeks until the collections regress or mature³⁸. In poor surgical candidates, ERCP with biliary sphincterotomy offers an alternative, but less effective, means of reducing the risk of recurrent attacks in patients with biliary AP³⁹. In subjects with first AP attack of alcoholic etiology, counseling focusing on alcohol cessation has shown to reduce risk of recurrences⁴⁰. Similarly, appropriate plans to treat and follow-up underlying metabolic etiologies (hypercalcemia and HTG) should be preferably instituted prior to the patients’ discharge.

 

 

Management of peripancreatic fluid collections

Patients with AP frequently develop peripancreatic fluid collections (PFCs). Based on the revised Atlanta classification, those are categorized into four types (Table 2, Figures 1-4).

The majority of acute PFCs in patients without evidence of pancreatic necrosis regress within a few weeks and thus intervention is not indicated early in the disease course. Current literature supports delaying the drainage/debridement of such collections for several weeks. The mortality from interventions decreases as the time to intervention from onset of symptoms increases⁴¹. Delaying intervention gives more time for recovery from systemic complications and allows the encapsulating wall and contents to organize further.

It is only the mature PFCs, which are symptomatic resulting in abdominal pain, nausea, early satiety, gastric outlet obstruction, failure to thrive, and/or biliary obstruction, that need to be drained/debrided⁴². Minimally invasive approaches have shown to result in better outcomes when compared to open laparotomy. Minimally invasive approaches include placement of percutaneous drainage catheters by interventional radiology (retroperitoneal approach preferred when feasible), endoscopic drainage/debridement, laparoscopy, and retroperitoneal necrosectomy following a step-up approach⁴³.

 

While surgery is still an option for patients with symptomatic mature PFCs, endoscopic ultrasound-guided drainage in expert hands has been shown to be cost effective, with shorter hospital stay and even decreased risk of cyst recurrence compared with surgical cyst-gastrostomy creation⁴⁴. Ultrasound or computed tomography-guided drainage of such collections with a percutaneous catheter is an equally efficacious option when compared to the endoscopic approach. However, patients undergoing endotherapy require fewer procedures and imaging studies and shorter length of stay⁴⁵ when compared with radiological interventions.

 

Management of pancreatic necrosis

Although this topic has generated much debate, the majority of available evidence shows no clinical benefit from using prophylactic antibiotics to prevent infection in pancreatic necrosis⁴⁶.

Infectious complications are the major cause of late mortality in AP. The predominant source is bacterial translocation from the GI tract^47,48. Infected pancreatic necrosis should be suspected in patients with imaging evidence of pancreatic or extrapancreatic necrosis, who have a sudden deterioration in clinical status, typically 2-3 weeks after onset of symptoms or if gas bubbles are seen within a necrotic collection (Figure 2). When infected pancreatic necrosis is suspected or established, antibiotics such as carbapenems, fluoroquinolones, metronidazole, and cephalosporin should be started, which have better penetrance into ischemic pancreatic tissue. CT guided aspiration has lost much of its utility, since there has been a paradigm shift to delaying drainage of infected (suspected or established) pancreatic necrosis. A negative or positive CT aspirate does not dictate timing of intervention and is only recommended if a fungal or drug resistant infection is suspected¹⁵. As mentioned above, when debridement of an infected necroma is contemplated, the two guiding principles are to delay drainage and use minimally invasive approaches.

Vascular complications

Vascular complications such as splanchnic vein thrombosis can occur in up to a quarter of AP patients⁴⁹. Anticoagulation is not usually indicated unless thrombosis is extensive and causes bowel ischemia. Arterial pseudoaneurysms are rare but life threatening complications of AP. They typically require interventional radiology guided coil embolization to prevent massive bleeding⁵⁰.

Abdominal compartment syndrome

Abdominal compartment syndrome is an end result of third spacing of fluid into the abdominal cavity secondary to inflammation and fluid resuscitation in severe pancreatitis. Abdominal pressure in patients can be monitored by measuring bladder pressures. Intra-abdominal hypertension is defined as a sustained pressure greater than 12 mm Hg, while abdominal compartment syndrome is defined as sustained intra-abdominal pressure greater than 20 mm Hg with new organ failure⁵¹. Intra-abdominal hypertension (IAH) is present in up to 75% of patients with severe AP. While all conservative measures to prevent development or worsening of IAH should be implemented (adequate sedation, decompression of bowel in patients with ileus, etc.), current guidelines do not recommend aggressive interventions to treat it. On the other hand, abdominal compartment syndrome is a life-threatening complication that requires urgent intervention to decrease intra-abdominal pressure, such as percutaneous drain placement or surgical fasciotomy^52,53.

Conclusion

The key principles in the management of acute pancreatitis are aggressive hydration and preventing development of end organ failure. In the last two decades there has been a paradigm shift in the guidelines for management of peripancreatic fluid collections and pancreatic necrosis. When feasible, drainage of these collections should be delayed and be performed using minimally invasive interventions. There is still an urgent need for developing and testing disease-specific treatments targeting control of the inflammatory response in the early phase of acute pancreatitis and prevention of development of severe disease with end-organ dysfunction.

Dr. Gulati is a gastroenterology and hepatology fellow at Allegheny Health Network, Pittsburgh, and Dr. Papachristou is professor of medicine, University of Pittsburgh School of Medicine, Pittsburgh.

References

1. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, Chapter 55, 923-33.

2. Morgagni G.B. [Fie Books on the Seats and Causes of Diseases as Discovered by the Anatomist]. Venice, Italy: Typographia Remondiniana;1761.

3. Fitz R.H. Boston Med Surg J. 1889;120:181-8.

4. Comfort M., Gambill E., Baggesnstoss A. Gastroenterology. 1946;6:238-76.

5. Bollen T.L., van Santvoort H.C., Besselink M.G., et al. Br J Surg. 2008;95:6–21.

6. Dellinger E.P., Forsmark C.E., Layer P., et al. Ann Surg. 2012 Dec;256[6]:875-80.

7. Kochar B., Akshintala V.S., Afghani E., et al. Gastrointest Endosc. 2015 Jan;81[1]:143-9.

8. Choudhary A., Bechtold M.L., Arif M., et al. Gastrointest Endosc. 2011 Feb;73[2]:275-82.

9. Shi Q.Q., Ning X.Y., Zhan L.L., Tang G.D., Lv X.P. World J Gastroenterol. 2014 Jun 14;20[22]:7040-8.

10. Elmunzer B.J., Waljee A.K., Elta G.H., Taylor J.R., Fehmi S.M., Higgins P.D. Gut. 2008 Sep;57[9]:1262-7.

11. Sethi S., Sethi N., Wadhwa V., Garud S., Brown A. Pancreas. 2014 Mar;43[2]:190-7. 
12. Elmunzer B.J., Serrano J., Chak A., et al. Trials. 2016 Mar 3;17[1]:120.

13. Lowenfels A.B., Maisonneuve P., Sullivan T. Curr Gastroenterol Rep. 2009;11:97-103.

14. Agarwal N., Pitchumoni C.S., Sivaprasad A.V. Am J Gastroenterol. 1990;85:356-66.

15. Tenner S., Baillie J., DeWitt J. Vege S.S. Am J Gastroenterol. 2013;108:1400-15.

16. Papachristou G.I., Muddana V., Yadav D., et al. Am J Gastroenterol. 2010;105:435-41.

17. Mounzer R., et al. Gastroenterology 2012;142:1476-82.

18. Working Group IAP/APA Acute Pancreatitis Guidelines. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

19. Koutroumpakis E., Wu B.U., Bakker O.J., et al. Am J Gastroenterol. 2015 Dec;110[12]:1707-16.

20. Bang U.C., Semb S., Nojgaard C., Bendtsen F. World J Gastroenterol. 2008 May 21;14[19]:2968-76.

21. Warndorf M.G., Kurtzman J.T., Bartel M.J., et al. Clin Gastroenterol Hepatol. 2011 Aug;9[8]:705-9.

22. Hotz H.G., Foitzik T., Rohweder J., et al. J Gastrointest Surg. 1998 Nov-Dec;2[6]:518-25.

23. Brown A., Baillargeon J.D., Hughes M.D., et al. Pancreatology 2002;2:104-7.

24. Wu B.U., Hwang J.Q., Gardner T.H., et al. Clin Gastroenterol Hepatol. 2011 Aug;9[8]:710-7.

25. Forsmark C.E., Baillie J., AGA Institute Clinical Practice and Economics Committee, AGA Institute Governing Board. Gastroenterology. 2007 May;132[5]:2022-44.

26. Lankisch P.G., Mahlke R., Blum T., et al. Am J Gastroenterol. 2001;96:2081-5.

27. Wu B.U., Johannes R.S., Sun X., et al. Gastroenterology 2009;137:129-35.

28. Scherer J., Singh V.P., Pitchumoni C.S., Yadav D. J Clin Gastroenterol. 2014 Mar;48[3]:195-203.

29. Gubensek J., Buturovic-Ponikvar J., Romozi K., Ponikvar R. PLoS One. 2014 Jul 21;9[7]:e102748.

30. Chen J.H., Yeh J.H., Lai H.W., Liao C.S. World J Gastroenterol. 2004 Aug 1;10[15]:2272-4.

31. Tse F., Yuan Y. Cochrane Database Syst Rev. 2012 May 16;[5]:CD009779.

32. Folsch U.R., Nitsche R., Ludtke R., et al. N Engl J Med. 1997;336:237-42.

33. Al-Omran M., Albalawi Z.H., Tashkandi M.F., Al-Ansary L.A. Cochrane Database Syst Rev. 2010 Jan 20;[1]:CD002837.

 

34. Li J.Y., Yu T., Chen G.C., et al. PLoS One. 2013;8[6]:e64926.

35. Singh N., Sharma B., Sharma M., et al. Pancreas. 2012 Jan;41[1]:153-9.

36. Bakker O.J., van Brunschot S., van Santvoort H.C., et al. N Engl J Med. 2014 Nov 20;371[21]:1983-93.

37. Van Baal M.C., Besselink M.G., Bakker O.J., et al. Ann Surg. 2012;255:860–6.

38. Nealon W.H., Bawduniak J., Walser E.M. Ann Surg. 2004 Jun;239[6]:741-9.

39. Sanjay P., Yeeting S., Whigham C., Judson H., Polignano F.M., Tait I.S. Surg Endosc. 2008 Aug;22[8]:1832-7.

40. Nordback I., Pelli H., Lappalainen-Lehto R., Järvinen S., Räty S., Sand J. Gastroenterology. 2009 Mar;136[3]:848-55.

41. Besselink M.G., Verwer T.J., Schoenmaeckers E.J., et al. Arch Surg. 2007;142:1194-201.

42. Besselink M., van Santvoort H., Freeman M. et al. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15.

43. Hjalmar C., van Santvoort, H., Besselink M.G., et al. N Engl J Med. 2010;362:1491-502.

44. Varadarajulu S., Bang J.Y., Sutton B.S., et al. Gastroenterology. 2013;145:583-90.e1.

45. Akshintala V.S., Saxena P., Zaheer A., et al. Gastrointest Endosc. 2014 Jun;79[6]:921-8.

46. Jiang K, Huang W, Yang XN., et al. World J Gastroenterol. 2012;18:279–84.

47. Dervenis C., Smailis D., Hatzitheoklitos E. J Hepatobiliary Pancreat Surg. 2003;10[6]:415Y418.

48. Gloor B., Muller C.A., Worni M., et al. Arch Surg. 2001;136[5]:592Y596.

49. Nadkarni N.A., Khanna S., Vege S.S. Pancreas. 2013 Aug;42[6]:924-31.

50. Marshall G.T., Howell D.A., Hansen B.L., Amberson S.M., Abourjaily G.S., Bredenberg C.E. Arch Surg. 1996 Mar;131[3]:278-83.

51. Malbrain M.L., Cheatham M.L., Kirkpatrick A., et al. Intensive Care Med. 2006 Nov;32[11]:1722-32.

52. De Waele J.J. Leppaniemi A.K. World J Surg. 2009;33:1128-33.

53. Kirkpatrick A.W., Roberts D.J., De W.J., et al. Intensive Care Med. 2013 Jul;39[7]1190-206.