Question 16

With respect to the management of patients presenting with acute pancreatitis, briefly discuss the following issues:


a) The optimal timing and method of delivery of nutrition.(40% marks)

b) The role of antimicrobials.(40% marks)

c) The role of endoscopic retrograde cholangio-pancreatography (ERCP).(20% marks) 
 

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College answer

(a) Method of delivery of nutrition                                                                                                  

  • Mild pancreatitis – oral diet if tolerated. Commence at admission or within 24 hours.
    • No superiority of enteral over oral in this group (NEJM 2014)
  • If unable to tolerate oral intake
    • Enteral preferred to TPN
    • Cochrane 2010 – reduced mortality and other end-points (including infective, MOF)
  • Jejunal not shown to be superior to gastric feeding. Limited evidence (2 small metaanalyses). 
    • No evidence of benefit in delaying feeding awaiting jejunal tube placement – especially in light of apparent benefit of early feeding.
    • Gastric feeding succeeds in delivering nutritional targets in 90%
  • Commence enteral feeds within 48 hours of admission, TPN >5 days

        (b) Use of antimicrobials                                                                                                            

  • Prophylactic antibiotics not recommended o Not indicated for peripancreatic fluid collections or necrosis without clinical (or radiological) evidence of sepsis
    •  Number of meta-analyses – no improvement in mortality, rates of infected necrosis
  • If clinical suspicion of infected necrosis or peripancreatic collection – FNA with culture (high sensitivity)
  • Antibiotics if positive FNA result OR unstable and sepsis suspected while awaiting further investigation
  • If used – choose appropriate antibiotic(s) with GP and Gn cover. Consider antifungal agents.
  • Treatment of other infective complications – e.g. hospital-acquired pneumonia, line-related, urinary tract.

        (c) Role of ERCP                                                                                                                        

  • Not routinely indicated
  • May be cause
  • Should be performed early (24-48 hrs.) in acute gallstone pancreatitis associated with persistent biliary obstruction or cholangitis
    • May not be tolerated / safe in critically unwell patient – consider percutaneous drainage as alternative

Discussion

Nutrition in acute pancreatitis:

  • For mild or moderate pancreatitis:
    • Fast for the first 3-4 days? Oh's Manual suggests that these patients need no feeding whatsoever until the disease settles (i.e. for 5-7 days), but the 2017 college answer recommends immediate feeding. The college quote a study ("NEJM 2014") to support their answer, which presumably is the PYTHON trial by Bakker et al (2014). This was an RCT which compared immediate enteral feeding with oral diet initiated 72 hours after presentation, which is not exactly "commence at admission or within 24 hours" ​​​​​.​
    • Advance to normal oral diet before 72 hours. Bakker et al (2014) found that enteral nutrition is no better than oral.
    • No need to rush enteral nutrition. Only progress to enteral nutrition of the patient is not tolerating oral diet after 5-7 days
    • Avoid TPN. Only progress to TPN if enteral nutrition has been trialled and is clearly not tolerated. The college mention another study ("Cochrane 2010") to support their aversion to TPN,  presumably referring to the meta-analysis by Al-Omran et al (2010). After pruning the evidence tree the authors found only two trials to analyse, with a total of 70 patients. They were forced to conclude that the data were insufficient for any firm recommendation, but that the trend was in the direction of better outcomes with enteral nutrition. This vaguely reflects "reduced mortality and other end-points (including infective, MOF)" which is what the college examiners said about it.
  • For severe pancreatitis:
    • EN is preferable to PN (ASPEN and ESPEN agree on this)
    • EN should be started early.
    • Tube position does not matter (gastric vs jejunal). The college refer to "2 small metaanalyses" in support of their assertion, presumably referring to Chang et al (2013)  with 157 patients and Petrov et al (2008) with 92 patients. A mor recent addition is Zhu et al (2016) who brought the numbers up to 237.  None of these ever found any benefit in jejunal feeding unless you've got clearly demonstrated impaired gastric emptying, i.e. a gastric outlet obstruction. 
    • Elemental feeds are preferred (ASPEN)
    • Nutritional requirements should be:
      • 25-35 kcal/kg of total body weight per day
      • 1.2 to 1.5g/kg of protein
      • 3-6g/kg of carbohydrate
      • go easy on the lipids (up to 2g/kg)
    • When to use parentral nutrition? These guidelines are much less prescriptive than previous statements. "when EN is contraindicated or not well tolerated", they say.

Antibiotics in pancreatitis:

  • There is no role for prophylactic antibiotics in severe acute pancreatitis.
  • Up to 20% of these patients go on to develop extrapancreatic infections which require antibiotics.
  • Half of bacterial cultures of pancreatic necrosis are of non-enteric origin.
  • Of course clinically significant extrapancreatic infections should still be treated with antibiotics

The role of ERCP in pancreatitis:

"May be cause", the college say economically, as if to type a "the" into their answer would incur an intolerable time cost. 

  • ERCP specifically:
    • Diagnostic use:
      • To establish that there are gall stones in the common bile duct
      • To determine that the sphincter of Oddi is dysfunctional
      • To investigate pancreatic duct stenosis
      • To get biopsy samples of a neoplasm
      • To investigate any sort of anastomosis
      • To perform intra-ductal ultrasound
    • Therapeutic use:
      • Sphincterotomy, for stenosis or sphincter dysfunction
      • Stone extraction or fragmentation
      • Placement of a pancreatic duct or common bile duct stent
  • Endoscopy more generally adds a few strategies:
    • Placement of nasojejunal tubes
    • Transgastric drainage of pancreatic pseudocysts

References

ASPEN guidelines

Specifically, section L of the 2016 statement

ESPEN guidelines :
specifically,
MACFIE, J., and ESPEN CONSENSUS GROUP. "ESPEN guidelines on nutrition in acute pancreatitis." Clinical Nutrition 21.2 (2002): 173-183.

Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR, Imrie CW. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005 Feb;100(2):432-9.

Windsor AC, Kanwar S, Li AG, et al. Compared with parenteral  nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 1998;42: 431-435.

Ragins H, Levenson SM, Signer R, Stamford W, Seifter E Intrajejunal administration of an elemental diet at neutral pH avoids pancreatic stimulation. Studies in dog and man. .Am J Surg. 1973 Nov;126(5):606-14.

B. W. M. Spanier,1, M. J. Bruno, E. M. H. Mathus-Vliegen Enteral Nutrition and Acute Pancreatitis: A Review Gastroenterol Res Pract. 2011; 2011: 857949. Published online 2010 August 3.

Casaer, Michael P., et al. "Early versus late parenteral nutrition in critically ill adults." N Engl J Med 365.6 (2011): 506-517.

Abou-Assi, Souheil, Kimberly Craig, and Stephen JD O’Keefe. "Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study." The American journal of gastroenterology 97.9 (2002): 2255-2262.

Petrillo-Albarano, Toni, et al. "Use of a feeding protocol to improve nutritional support through early, aggressive, enteral nutrition in the pediatric intensive care unit*." Pediatric Critical Care Medicine 7.4 (2006): 340-344.

Mirtallo, Jay M., et al. "International consensus guidelines for nutrition therapy in pancreatitis." Journal of Parenteral and Enteral Nutrition (2012): 0148607112440823.

Al-Omran, Mohammed, Ala Groof, and Derek Wilke. "Enteral versus parenteral nutrition for acute pancreatitis." Cochrane Database Syst Rev 1.1 (2003).

Ho, Kwok M., Geoffrey J. Dobb, and Steven AR Webb. "A comparison of early gastric and post-pyloric feeding in critically ill patients: a meta-analysis." Intensive care medicine32.5 (2006): 639-649.

Chang, Yu-sui, et al. "Nasogastric or nasojejunal feeding in predicted severe acute pancreatitis: a meta-analysis." Critical Care 17.3 (2013): R118.

Petrov, Maxim S., M. Isabel TD Correia, and John A. Windsor. "Nasogastric tube feeding in predicted severe acute pancreatitis. A systematic review of the literature to determine safety and tolerance." JOP. Journal of the Pancreas (2008).

Vaughn, Valerie M., et al. "Early versus delayed feeding in patients with acute pancreatitis: a systematic review." Annals of Internal Medicine 166.12 (2017): 883-892.

Oh's Intensive Care manual: Chapter   43  (pp. 495)  Severe  acute  pancreatitis by Duncan  LA  Wyncoll

Heinrich, Stefan, et al. "Evidence-based treatment of acute pancreatitis: a look at established paradigms." Annals of surgery 243.2 (2006): 154-168.

Pederzoli, Paolo, et al. "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem." Surgery, gynecology & obstetrics 176.5 (1993): 480-483.

Wilmer, Alexander. "ICU management of severe acute pancreatitis." European journal of internal medicine 15.5 (2004): 274-280.

Villatoro, Eduardo, Mubashir Mulla, and Mike Larvin. "Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis."Cochrane Database Syst Rev 5.5 (2010).

Mirtallo, Jay M., et al. "International consensus guidelines for nutrition therapy in pancreatitis." Journal of Parenteral and Enteral Nutrition 36.3 (2012): 284-291.

Baltatzis, Minas, et al. "Antibiotic use in acute pancreatitis: Global overview of compliance with international guidelines." Pancreatology (2016).

Tenner, Scott, et al. "American College of Gastroenterology guideline: management of acute pancreatitis." The American journal of gastroenterology 108.9 (2013): 1400-1415.

Gabbrielli, Armando, et al. "ERCP in acute pancreatitis: What takes place in routine clinical practice?." World journal of gastrointestinal endoscopy 2.9 (2010): 308.

Wu, Bechien U., and Peter A. Banks. "Clinical management of patients with acute pancreatitis." Gastroenterology 144.6 (2013): 1272-1281.

Cherian, Jijo V., et al. "ERCP in acute pancreatitis.Hepatobiliary Pancreat Dis Int 6.3 (2007): 233-240.

Zhu, Youfeng, et al. "Nasogastric nutrition versus nasojejunal nutrition in patients with severe acute pancreatitis: a meta-analysis of randomized controlled trials." Gastroenterology research and practice 2016 (2016).