Article in PDF format - JOP Home page

JOP. J Pancreas (Online) 2011 Mar 9; 12(2):205-208.

Fluid Therapy in Acute Pancreatitis. A Systematic Review of Literature

Nicholas S Solanki, Savio George Barreto

Department of Surgery, Royal Adelaide Hospital. Adelaide, South Australia, Australia

Dear Sir,

Acute pancreatitis is an acute inflammation of the pancreas associated with a high morbidity and even the risk of mortality [1, 2]. To date, there exists no specific treatment for this disease [3, 4, 5] and fluid therapy forms the cornerstone of management of these patients who present acutely to emergency departments around the world. There is a need to review the data on fluid resuscitation in acute pancreatitis to aid the development of evidence-based guidelines.

A systematic search of the scientific literature was carried out using EMBASE, PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for the years 1965-2011 to obtain access to all publications, especially randomized controlled trials, systematic reviews, and meta-analyses involving the various factors related to the use of fluid resuscitation in acute pancreatitis.

The search strategy was that described by Dickersin et al. [6] with the appropriate specific search terms, namely, "acute pancreatitis", "fluid resuscitation", "haemoconcentration", "hemoconcentration", "fluids", "pancreatitis", "systematic", and "randomized controlled trials". All available major publications from the past 45 years were considered.

Using the above search strategy, a total of 12 studies were identified describing regimens for fluid therapy. These included two randomized controlled trials, one retrospective cohort study, and 9 reviews.

Rationale for Fluids in Acute Pancreatitis

The impact of retroperitoneal fluid losses and dehydration on the development of hypovolemia seen in patients with severe acute pancreatitis resulting in high mortality was recognized in the 1950s [7, 8]. Although, this fluid loss was largely shown to respond to intravenous fluid therapy [9, 10, 11], the initial understanding was that the shock was mainly due to a loss of red blood cells [12]. Thereafter, despite the link between hemoconcentration at admission and mortality in acute pancreatitis being suggested by Davis et al. [13] and Gray et al. [14], a reduction in hematocrit in the first 48 hours was considered a poor risk factor in acute pancreatitis [15, 16] as evidence by the scoring system proposed by Ranson et al. [11]. Ranson et al. [11] attributed the low hematocrit to pre-existing anemia encountered in alcoholics while Trapnell [16] founds the fall in hematocrit to correlate with internal hemorrhage. The early use of fluid therapy has certainly reduced early mortality in acute pancreatitis associated with hypovolemia. In the 1990s, the importance of hemoconcentration was re-visited by the group from the Brigham and Womenís Hospital in Boston [17, 18]. Since then, hemoconcentration based on a serum hematocrit level at admission has been consistently demonstrated to be linked to the development of pancreatic necrosis [19, 20, 21, 22]. Pancreatic microcirculation depends on circulating volume and responds poorly to other influences.

Available Evidence on Regimens for Fluid Therapy in Acute Pancreatitis

Human Studies

Table 1 lists the articles/studies involving fluids in acute pancreatitis [23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34], their conclusions, as well as, the level of evidence [35].

Table 1. Summary of the available studies to date on fluid therapy in acute pancreatitis.



Type of study (sample size)


Level of evidence

Mao et al. [31]



Rapid hemodilution increases incidence of sepsis within 28 days and in-hospital mortality

HCT should be maintained between 30% and 40% in acute response stage


Mao et al. [32]



Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within
72 h of severe acute pancreatitis onset


Gardner et al. [25]


Retrospective cohort (n=45)

Patients with severe acute pancreatitis should receive 1/3 or more of initial 72 h cumulative i.v. fluid volume during first 24 h


Pezzilli et al. [28]


Review a

Prompt adequate i.v. fluid administration to correct volume deficit and maintain basal fluid requirements


Forsmark et al. [24]


Review a

Target: urine output 0.5 mL/kg body weight/h or more

Crystalloids: preferred

Indications for colloids:
Packed red blood cells, when HCT falls less than 25%

Albumin: serum albumin level drops to 2 g/dL

Precautions: evidence of cardiovascular system dysfunction or pulmonary capillary leak syndrome

Central venous pressure or pulmonary artery catheter indicated in severe acute pancreatitis


Otsuki et al. [26]


Review a

Ringerís lactate: 60-160 mL/kg body weight/day

About 1/3-1/2 of amount required for first 24 h, within the first 6 h

Hourly: pulse, blood pressure, urine output, c.Central venous pressure monitoring


Pandol et al. [27]



Severe volume depletion: 500-1,000 mL/h for several hours with amount of fluid reduced once signs of severe volume depletion have subsided non pancreatic fluid loss: 300-500 mL/h

No clinical volume depletion: 250-300 mL/h

Fluid rates reassessed 1-2 hourly for severely depleted patients or at least 4 hourly for other patients


Banks et al. [23]



Aggressive i.v. fluid replacement


Whitcomb et al. [33]



Aggressive hydration (e.g. a bolus of fluids to achieve hemodynamic stability, followed by
250-500 mL/h crystalloids in an average sized patient without substantial kidney or heart disease


Tenner et al. [29]



Intravenous hydration 250-300 mL/h or more for 48 h


Vege et al. [30]



Aggressive i.v. fluid replacement


Wilmer et al. [34]



After initial rapid resuscitation, fluid replacement should aim at 35 mL/kg body weight/day

Crystalloids: preferred


HCT: hematocrit; RCT: randomized controlled trial
a Guidelines/recommendations (American Gastroenterology Association, Italian, Japanese)

The only two randomized controlled trials till date have been based on studies conducted by Mao et al. [31, 32]

In their first randomized controlled trial published in 2009, Mao et al. [32] randomized 76 patients within 72 hours of onset of severe acute pancreatitis to undergo either rapid fluid expansion (Group I; n=36) or controlled fluid expansion (Group II; n=40). They found that the patients in Group I had poorer outcomes based on measures such as higher APACHE II scores on days 1, 2, and 3 (P<0.05), greater need for mechanical ventilation (94.4% versus 65%; P<0.05), higher incidence of abdominal compartment syndrome and sepsis (P<0.05), and an overall lower survival rate (69.4% versus 90%; P<0.05).

In the second randomized controlled trial [31], Mao et al. randomized 115 patients within 24 hours of onset of severe acute pancreatitis to either undergo rapid hemodilution (hematocrit less than 35%; n=56) or slow hemodilution (hematocrit equal to 35% or more; n=59) over the next 48 hours. They found a higher incidence of sepsis in the rapid hemodilution group compared to the slow hemodilution group (P<0.01) with significant differences in the time interval to development of sepsis (7.4Ī1.9 days versus 10.2Ī2.3 days; P<0.01) in the first 28 days. The survival rate of the slow hemodilution group was also better (84.7% versus 66.1%; P<0.05).

The type of fluids used in the two studies included a combination of crystalloids (normal saline and/or lactated Ringerís solutions) and colloids (plasma and 6% hydroxyl ethyl starch).

A retrospective cohort study by Gardner et al. [25] examined primary clinical outcomes including mortality, development of organ failure and duration of hospitalization in patients who received more than 33% (early resuscitation; n=17) or less than 33% (late resuscitation; n=28) of their cumulative 72-hour intravenous fluid volume within the first 24 h of presentation. They found that patients in the "late resuscitation" group experienced greater mortality than those in the "early resuscitation" group (18% versus 0%; P< 0.04) and demonstrated a trend toward greater rates of persistent organ failure (43% versus 35%; P=0.31).

Animal Studies

Animal studies conducted over the last four decades [36, 37, 38, 39, 40, 41] have aided our understanding of fluid resuscitation in overcoming microcirculatory disturbances in acute pancreatitis and attenuating end-organ injury. However, in the context of aiding the decision on the choice of fluid in the clinical setting, the results have not been particularly helpful.


Based on the review of literature we can conclude that hemoconcentration in a patient with acute pancreatitis (based on serial measurements of hematocrit) within the first 48 hours of admission is a marker of poor prognosis and indicates the need for fluid resuscitation. The ideal cut-off level for serum hematocrit (44% or 47%) remains to be determined. What can also be concluded from the available literature is that fluid therapy remains the cornerstone in the early management of acute pancreatitis and especially in the prevention of severe acute pancreatitis. In patients who go on to develop severe acute pancreatitis either due to a late presentation or despite resuscitation, fluid therapy has the potential to reduce the progression of pancreatic necrosis and its associated risk of mortality.

In 2008, Gardner et al. [42] reviewed the available evidence on fluid resuscitation in acute pancreatitis and found that there was a paucity of evidence to support clinical recommendations at that time. To date, there continues to be a lack of high-level evidence to guide the ideal "initial" fluid strategy for all patients presenting with acute pancreatitis in terms of choice of fluid, namely crystalloids and/or colloids, and if crystalloids, Ringerís lactate or normal saline, as well as in terms of rate of administration. While crystalloids appear to be the ideal choice based on expert opinion and the guidelines/recommendations from America, Italy and Japan [23, 24, 26, 27, 28, 29, 30, 33, 34], these recommendations are not based on high-level evidence in patients with acute pancreatitis. In patients with severe acute pancreatitis, the two randomized trials available [31, 32] used a combination of crystalloids and colloids, and favored controlled resuscitation over rapid infusion within the first 72 hours. Considering that both these trials were performed by the same group, these results need to be validated by other groups.

There has been no further impetus even in animal studies since the last major review by Gardner et al. [42]

In conclusion, fluid therapy remains the mainstay of early management of patients with acute pancreatitis and severe acute pancreatitis. High-level evidence is lacking to guide protocols for fluid resuscitation in patients presenting with acute pancreatitis. In those patients with severe acute pancreatitis, the available evidence indicates that controlled fluid resuscitation with crystalloids and colloids offers the best outcome. Hematocrit remains a useful marker to guide fluid resuscitation in acute pancreatitis. However, the timing and ideal "cut-off" level needs to be determined.


  1. Barreto S, Rodrigues J. Acute pancreatitis in Goa. A hospital-based study. J Indian Med Assoc 2008; 106:575-6, 578. [More details]

  2. Barreto S, Rodrigues J. Comparison of Apache II and Imrie scoring systems in predicting the severity of acute pancreatitis. World J Emerg Surg 2007; 2:33. [More details]

  3. Barreto S, Carati C, Schloithe A, Mathison R, Davison J, Toouli J, et al. The efficacy of combining feg and galantide in mild caerulein-induced acute pancreatitis in mice. Peptides 2010; 31:1076-82. [More details]

  4. Barreto S, Carati C, Schloithe A, Toouli J, Saccone GT. The combination of neurokinin-1 and galanin receptor antagonists ameliorates caerulein-induced acute pancreatitis in mice. Peptides 2010; 31:315-21. [More details]

  5. Barreto SG, Bazargan M, Zotti M, Hussey DJ, Sukocheva OA, Peiris H, et al. Galanin receptor 3. A potential target for acute pancreatitis therapy. Neurogastroenterol Motil 2011; 23:e141-51. [More details]

  6. Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994; 309:1286-91. [More details]

  7. Keith LM Jr., Watman RN. Blood volume deficits in pancreatitis. Surg Forum 1955; 5:380-4. [More details]

  8. Siler VE, Wulsin JH. Consideration of the lethal factors in acute pancreatitis. AMA Arch Surg 1951; 63:496-504. [More details]

  9. Elliott DW. The mechanism of benefit derived from concentrated human serum albumin in experimental acute pancreatitis. Surg Forum 1955; 5:384-90. [More details]

  10. Elliott DW, Zollinger RM, Moore R, Ellison EH. The use of human serum albumin in the management of acute pancreatitis; experimental and clinical observations. Gastroenterology 1955; 28:563-87. [More details]

  11. Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974; 139:69-81. [More details]

  12. Zollinger RM, Keith LM Jr., Ellison EH. Pancreatitis. N Engl J Med 1954; 251:497-502. [More details]

  13. Davis CE Jr., Amir-Jahed AK, Chalkley MR Jr, Richardson GS. Fatal acute pancreatitis. A survey. Va Med Mon (1918) 1962; 89:578-83. [More details]

  14. Gray SH, Rosenman LD. Acute pancreatitis. The significance of hemoconcentration at admission to the hospital. Arch Surg 1965; 91:485-9. [More details]

  15. Jacobs ML, Daggett WM, Civette JM, Vasu MA, Lawson DW, Warshaw AL, et al. Acute pancreatitis: Analysis of factors influencing survival. Ann Surg 1977; 185:43-51. [More details]

  16. Trapnell JE. The natural history and prognosis of acute pancreatitis. Ann R Coll Surg Engl 1966; 38:265-87. [More details]

  17. Baillargeon JD, Orav J, Ramagopal V, Tenner SM, Banks PA. Hemoconcentration as an early risk factor for necrotizing pancreatitis. Am J Gastroenterol 1998; 93:2130-4. [More details]

  18. Brown A, Orav J, Banks P. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas 2000; 20:367-72. [More details]

  19. Lankisch PG, Mahlke R, Blum T, Bruns A, Bruns D, Maisonneuve P, Lowenfels AB. Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A critical appraisal. Am J Gastroenterol 2001; 96:2081-5. [More details]

  20. Muddana V, Whitcomb DC, Khalid A, Slivka A, Papachristou GI. Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis. Am J Gastroenterol 2009; 104:164-70. [More details]

  21. Remes-Troche JM, Duarte-Rojo A, Morales G, Robles-Diaz G. Hemoconcentration is a poor predictor of severity in acute pancreatitis. World J Gastroenterol 2005; 11:7018-23. [More details]

  22. Wu BU, Conwell DL, Singh VK, Repas K, Maurer R, Bollen TL, et al. Early hemoconcentration is associated with pancreatic necrosis only among transferred patients. Pancreas 2010; 39:572-6. [More details]

  23. Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006; 101:2379-400. [More details]

  24. Forsmark CE, Baillie J. AGA institute technical review on acute pancreatitis. Gastroenterology 2007; 132:2022-44. [More details]

  25. Gardner TB, Vege SS, Chari ST, Petersen BT, Topazian MD, Clain JE, et al. Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality. Pancreatology 2009; 9:770-6. [More details]

  26. Otsuki M, Hirota M, Arata S, Koizumi M, Kawa S, Kamisawa T, et al. Consensus of primary care in acute pancreatitis in Japan. World J Gastroenterol 2006; 12:3314-23. [More details]

  27. Pandol SJ, Saluja AK, Imrie CW, Banks PA. Acute pancreatitis: bench to the bedside. Gastroenterology 2007; 132:1127-51. [More details]

  28. Pezzilli R, Zerbi A, Di Carlo V, Bassi C, Delle Fave GF, et al. Practical guidelines for acute pancreatitis. Pancreatology 2010; 10:523-35. [More details]

  29. Tenner S. Initial management of acute pancreatitis: Critical issues during the first 72 hours. Am J Gastroenterol 2004; 99:2489-94. [More details]

  30. Swaroop VS, Chari ST, Clain JE. Severe acute pancreatitis. JAMA 2004; 291:2865-8. [More details]

  31. Mao EQ, Fei J, Peng YB, Huang J, Tang YQ, Zhang SD. Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis. Chin Med J (Engl) 2010; 123:1639-44. [More details]

  32. Mao EQ, Tang YQ, Fei J, Qin S, Wu J, Li L, et al. Fluid therapy for severe acute pancreatitis in acute response stage. Chin Med J (Engl) 2009; 122:169-73. [More details]

  33. Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med 2006; 354:2142-50. [More details]

  34. Wilmer A. ICU management of severe acute pancreatitis. Eur J Intern Med 2004; 15:274-80. [More details]

  35. Wright JG, Swiontkowski MF, Heckman JD. Introducing levels of evidence to the journal. J Bone Joint Surg Am 2003; 85:1-3. [More details]

  36. Horton JW, Dunn CW, Burnweit CA, Walker PB. Hypertonic saline-dextran resuscitation of acute canine bile-induced pancreatitis. Am J Surg 1989; 158:48-56. [More details]

  37. Kerner T, Vollmar B, Menger MD, Waldner H, Messmer K. Determinants of pancreatic microcirculation in acute pancreatitis in rats. J Surg Res 1996; 62:165-71. [More details]

  38. Knol JA, Inman MG, Strodel WE, Eckhauser FE. Pancreatic response to crystalloid resuscitation in experimental pancreatitis. J Surg Res 1987; 43:387-92. [More details]

  39. Schmidt J, Fernandez-del Castillo C, Rattner DW, Lewandrowski KB, Messmer K, Warshaw AL. Hyperoncotic ultrahigh molecular weight dextran solutions reduce trypsinogen activation, prevent acinar necrosis, and lower mortality in rodent pancreatitis. Am J Surg 1993; 165:40-4. [More details]

  40. Shields CJ, Sookhai S, Winter DC, Dowdall JF, Kingston G, Parfrey N, et al. Attenuation of pancreatitis-induced pulmonary injury by aerosolized hypertonic saline. Surg Infect (Larchmt) 2001; 2:215-23. [More details]

  41. Shields CJ, Winter DC, Sookhai S, Ryan L, Kirwan WO, Redmond HP. Hypertonic saline attenuates end-organ damage in an experimental model of acute pancreatitis. Br J Surg 2000; 87:1336-40. [More details]

  42. Gardner TB, Vege SS, Pearson RK, Chari ST. Fluid resuscitation in acute pancreatitis. Clin Gastroenterol Hepatol 2008; 6:1070-76. [More details]

Article in PDF format

Received February 14th, 2011 - Accepted February 15th, 2011

Key words Dehydration; Evidence-Based Medicine; Resuscitation; Therapeutics

Conflicts of interest: None declared

Savio G Barreto
Department of Surgery
Royal Adelaide Hospital
North Terrace
Adelaide 5000
South Australia
Phone: +61-8.8222.4000
E-mail: georgebarreto@yahoo.com; barr0264@flinders.edu.au

JOP Home page