Management of severe acute pancreatitisBMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l6227 (Published 02 December 2019) Cite this as: BMJ 2019;367:l6227
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We were pleased to see the recent publication by Hines and Pandol which has given us a detailed contemporary review of severe pancreatitis and its management. However, given the recent developments in therapies for other pathologies like burn, trauma, and sepsis which share common pathophysiologic mechanisms with pancreatitis, we are concerned with the authors’ continued support of large-volume fluid resuscitation as a primary treatment modality for pancreatitis.
This support is not surprising given the current guidelines. The International Association of Pancreatology/American Pancreatic Association (IAP/APA) 2013 guidelines on fluid management in acute pancreatitis strongly recommend 5-10mL/kg/h of IV fluid early in resuscitation with moderate quality evidence and with weak agreement among expert opinion.1 The more recently updated American Gastroenterological Association (AGA) 2018 guidelines conditionally recommend goal directed fluid resuscitation with a very low quality of evidence.2 We believe these guidelines, and much of the current clinical practice, can potentially cause harm to the patient through the dangers of over-resuscitation. The IAP/APA guidelines recommending 5-10mL/kg/hr fluid therapy are at least more consistent with the idea of a controlled fluid resuscitation, which has corollaries to the burn standards of care,3.but even within these controlled fluid replacement rates it is easy to over-resuscitate a patient over a short period of time, as the average sized male would still be receiving up to 700mL/hr of IV fluid. This is especially relevant since patients presenting with severe pancreatitis and hypotension often exhibit significant diastolic dysfunction thus making them less able to tolerate large fluid loads and potentially contributing to acute respiratory distress syndrome (ARDS) from elevated filling pressures.4 Additionally, it has been shown that patients with severe pancreatitis receiving greater than 4 liters of fluid in the first 24 hours were at a significantly greater risk for developing an acute kidney injury as well as requiring continuous renal replacement therapy.5 Furthermore, over resuscitation in patients with acute pancreatitis is well known to cause abdominal compartment syndrome, respiratory failure, and contributes to overall poor clinical outcomes.6,7
The trend toward a more conservative fluid resuscitation that utilizes endpoint for resuscitation, or at least a more pronounced cultural acknowledgement of the harms of over-resuscitation, has already been recognized and adopted in other fields where early aggressive IV fluid was once believed to be essential, such as severe burn, trauma, and sepsis. These are all complex medical processes that share a similar pathophysiology with pancreatitis. Generally speaking, in each there is inflammation causing capillary leak, decreased perfusion of organs, coagulation abnormalities and microcirculatory dysfunction. The nidus for the multi-system organ failure is a deranged and inappropriate inflammatory response to the burn, trauma, infection, or pancreatic process. It is now increasingly recognized in each of these fields that although fluid resuscitation is essential, it must be intentional, patient-specific, and goal-directed. Run-away fluid resuscitation, where fluids beget more fluids owing to interstitial leak from a vicious propagation of inflammation and accelerated glycocalyx degradation, ends in the detrimental consequences of over-resuscitation, including abdominal compartment syndrome, renal dysfunction, ARDS, and coagulopathy, all ultimately leading to increased mortality.3,7,8,9,10,11 Unfortunately, the research and clinical practice in the area of fluid resuscitation for severe pancreatitis has lagged behind the significant and mortality-improving advances already made for burn, trauma and sepsis. We believe that when treating acute pancreatitis, an individualized, controlled, goal-directed, and sometimes even restrictive approach in resuscitation is paramount based on reflections from other pathologies, and should be an area of more robust research going forward.
1. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Panceatology 2013;13(Suppl 2):e1-15. doi:10.1016/j.pan.2013.07.063
2. Vege SS, DiMagna MJ, Forsmark CE, Martel M, Barkun AN. Initial Medical Treatment of Acute Pancreatitis: American Gastroenterological Association Institute Technical Review. Gastroenterology 2018;154:1103-39. doi:10.1053/j.gastro.2018.01.031
3. Chung KK, Blackbourne LH, Wolf SE. Evolution of burn resuscitation in operation Iraqi freedom. Journal of Burn Care & Research 2006;27:606-611
4. Thandassery RB, Choudhary N, Bahl A, Kochhar R. Characterization of cardiac dysfunction by echocardiography in early severe acute pancreatitis. Pancreas 2017
5. Chen Y, Ke L, Gu P, et al. Aggressive resuscitation is associated with the development of acute kidney injury in acute pancreatitis. Pancreatology 2016;16:S24-S25
6. De Waele JJ, Leppäniemi AK. Intra-abdominal hypertension in acute pancreatitis. World J Surg 2009;33:1128-1133
7. de-Madaria E, Soler-Sala G, Sánchez-Payá J, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastoenerol 2011;106:1843-1850
8. Haut ER, Kalish BT, Cotton BA, et al. Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: A national trauma data bank analysis. Annals of Surgery 2011; 253:371-377
9. Hippensteel JA, Uchimido R, Tyler PD, et al. Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation. Critical Care 2019;23: 1-10. https://doi.org/10.1186/s13054-019-2534-2
10. Marik PE, Linde-Zwirble WT, Bittner EA, et al. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med. 2017 May;43:625-32.
11. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011;364(26):2483-95
Competing interests: No competing interests
Thank-you for an interesting review on the topic. There is one area that is not mentioned of interest to the reader.
Colonic complications appear to be an all too common occurrence in acute necrotising pancreatitis and may pay an important influence in the final pathway to death. Colonic perforation is cited as a rare complication of acute pancreatitis. This follows a single study of 100 patients with acute pancreatitis in 1967(1). Data from a number of sources suggests that colonic complications are in fact common in patients with necrotising pancreatitis(2). This is a difficult diagnosis to make clinically and is often only made incidentally on CT or at laparotomy. The bottom line here is that the interaction between the colon and necrotic material is complex, and of vital importance to a patient’s outcomes. Through a combination of local vascular dysfunction, from the SIRS response and direct inflammation from necrotic material the microvasculature of the large bowel is particularly compromised. This may result in a number of sequela including colonic necrosis, perforation, bleeding, delayed colonic stenosis and strictures, and increased translocation of bacteria leading to subsequent infected necrosis (1,2,3,4,5). This usually occurs as late complications and is associated with severe disease.
The best available data suggests that these are common complications from necrotising pancreatitis occurring in 15% of patients with severe disease but could be as high as 40% in patients with necrotising pancreatitis(2). This topic requires further investigation and research to establish both the current frequency of complications and methods of reducing or attenuating harm from the complications. In the meantime, clinicians should remain vigilant to the possibility of these colonic complications. Further research may be warranted to examine the potential for interventions to reduce the microvascular changes leading to necrosis (such as early minimally invasive necrosectomy(5) and antioxidants).
Aside from this minor addition, thank-you for a providing an excellent article on the current state of play in research and care of patients suffering from this most terrible disease.
1) Lukash WM. Complications of acute pancreatitis. Unusual sequelae in 100 cases. Arch Surg 1967; 94: 848-52.
2) Mohamed S & Siriwardena A. Understanding the colonic complications of pancreatitis. Pancreatology. 2008;8:153–158.
3) Van Minnen et al. Colonic involvement in acute pancreatitis. A retrospective study of 16 patients. Dig Surg. 2004;21(1):33-38.
4) Aldridge MC, Francis ND, Glazer G, Dudley HAF: Colonic complications of severe acute pancreatitis. Br J Surg 1989;76:362–367.
5) Puri Y et al, Successful Management of Gastrointestinal Haemorrhage Associated with Ischaemic Colonic Ulceration in Acute Pancreatitis with Video Assisted Retroperitoneal Debridement. JOP. J Pancreas (Online) 2011 May 6; 12(3):271-273.Hospital, Paris, France
Competing interests: No competing interests