It is the festive season and with it, comes the patient that has more than their usual few drinks. They present to the emergency department soon after, with abdominal pain and nausea and when their lipase comes back; a diagnosis of pancreatitis. This disease carries an overall risk of mortality of 2%, but it may be as high as 30% (1).

Fluid resuscitation in pancreatitis, has long been called the cornerstone of treatment in these patient. In a recent case we diagnosed pancreatitis in a patient who was haemodynamically stable, with almost normal blood parameters and a mildly raised blood glucose. IV fluids then need to be given. However, we don’t know how much fluid we need to give. Although there are consensus guidelines, the evidence is retrospective and not very good for the most. If you give too little, you might cause harm secondary to hypoperfusion. If the patient gets too much fluid and develops heart failure and needs to be dried out in ICU, is that good for the patient? Some studies are saying definitely not. Can too little or too much cause harm? What is the right amount of fluid to give in pancreatitis?

What is the definition of Pancreatitis?

Two of the following three findings need to be present(2):

  1. Abdominal Pain
  2. Serum lipase or amylase that are > 3 times the upper limit of normal
  3. Evidence of pancreatitis on CT or MRI

The Most Common Causes of Pancreatitis

Gallstones (40%)
Alcohol(30%)- 4-5 drinks per day for about 5 years
The rest- drugs, hypertriglyredemia, trauma, surgery (3,4)

How do we predict severity?

It isn’t as straight forward as we think. Some important factors include(5):

age >60
co-morbidities
obesity
long term alcohol use
elevated urea and creatinine
elevated haematocrit
The level of lipase or amylase elevation, is not predictive.
There are several scoring systems in place that attempt to predict, who will develop severe pancreatitis. They include(6):
APACHE II
The Glascow System
HAPS
BISAP
There are others also. They are complex and not easy to calculate and they do have a high false positive rate.
In a recent review article(7) the authors discuss the presence of systemic inflammatory response syndrome (SIRS). If this persists for 48 hours or more after symptom onset, it is indicative of a poor prognosis.
SIRS can be diagnosed by having two or more of four clinical findings:
Temperature, <36°C or > 38°C
Pulse > 90 beats per minute
Respiratory rate > 20 breaths per minute
White-cell count <4000 or >12,000 per cubic mm

Fluid Requirements: How much do we need?

Fluid Sequestration

One of the great concerns with pancreatitis, is the intravascular fluid depletion that results from third space loss. This sequestration of fluid, is what aggressive fluid resuscitation regiments are based on. Mostly, this is expert opinion, not based on any hard data. There are however some studies that have looked at this very topic. Ranson(8) in a retrospective study calculated a mean fluid sequestration at 48h of 3.7 L in mild pancreatitis and 5.6 L in severe pancreatitis. In a prospective study de-Madaria(9) calculated the median fluid sequestration in the first 48 h after hospitalization to be 3.2 L (1.4-5 L), in those without necrosis and 6.4 L (3.6-9.5 L) in those with necrosis, and 7.5 L (4.4-12 L) in those with organ failure.

Resuscitation requirements

The recommendations of fluid resuscitation in pancreatitis are based on expert opinion. This opinion recommends ‘aggressive’ fluid resuscitation in the first 24 hours and is largely based on retrospective studies that are 7-8 years old (10,11). Other work is suggesting that being overly aggressive with fluid can lead to sepsis, respiratory failure and an increased mortality(12,13). Let’s look at some of these studies.

Gardner’s study of 2009(10), one of the two pivotal retrospective studies on which guidelines are based, looked at the effects of fluid resuscitation rates in the first 24 hours, on outcomes of mortality, persistent organ failure and duration of hospital stay. This paper effectively defined aggressive resuscitation as receiving > 33% of total fluid given in 72 hours, in the first 24 hours. How much is that? It certainly must differ from patient to patient.

There were only 45 patients in this study and it was retrospective, however the results are difficult to ignore. 17 patients received aggressive resuscitation and 28 did not. In terms of mortality, the ‘late resuscitation’ group experienced greater mortality (18 vs. 0%,p<0.04). There was also a trend towards greater rates of persistent organ failure (43 vs. 35%, p = 0.31).

Wall(14) in a further retrospective study looked at patients resuscitated in 1998 and compared them with those resuscitated(more aggressively) in 2008, ie., 234 mL/h in first 6 h vs 194 mL/h in first 6 h and 188 mL/h during first 12 h and found a corresponding decrease in mortality and necrosis.

Can aggressive resuscitation result in worst outcomes?

More recent, prospective studies, do indicate this. de-Madaria (9) prospectively divided patients into three groups depending on the amount of fluid given in the first 24 h. Administration of > 4.1 L during the initial 24 h was found to be associated with persistent organ failure and acute collections. Less fluid had better outcomes. Eckerwall(15) looked at patients receiving > 4L or < 4L in the first 24 hours, and found that patients who received > 4.0 L had more respiratory complications (66% vs 53%, P < 0.001). Other studies have also found that more fluid in the first 24-48 hours results in a higher rate respiratory complications and higher mortality(16).

More recent studies(17,18) have found that rates greater than 15mL/kg/hr Mao resulted in increased sepsis and mortality and a more controlled rate of fluid expansion i.e. 5-10mL/kg/hr was associated with better outcomes. These studies indicate that a potential total of 2.5-4L over the first 24 hours is an appropriate fluid volume to give.

So we see that there is no one right answer here. There are two schools of thought. One states that pancreatic necrosis is an irreversible condition, that has already occurred by the time we intervene and fluids do not improve it. The side believing in aggressive fluid resuscitation will argue that increased fluid delivery results in improved organ perfusion(19).

How do we know we are giving enough fluid?

The ability to diagnose from the end of the bed that a patient is ‘dry’ may be difficult. Research(18) suggests that a heart rate of <120 bpm, a MAP of 65-85 mmHg and urine output of 0.5-1 ml/kg/h can be used estimates of fluid requirements. We need to remember that those patients with co-morbidities such as heart failure, will tolerate less fluid. We also need to be aware that in some cases surrogate markers such as urine output will be falsely low, due to acute tubular necrosis, so we need to use other parameters as well.

The use of BUN to monitor fluid needs may not be as effective as initially thought(20) and even central venous pressure monitoring, in the sickest patients, has been brought under question(21). The use of haematocrit has been shown be a potential marker, with rapid haemodilution being associated with increased mortality(18).

The Current Guidelines(22)

What Fluid to give?

“Ringer’s lactate is recommended for initial fluid resuscitation in acute pancreatitis.”

How much fluid to give?

“..goal directed intravenous fluid therapy with 5-10 ml/kg/h should be used initially until resuscitation goals…..in most patients, a total infusion of 2500-4000 ml will suffice to reach the resuscitation goals within the first 24 h.

What are the Resuscitation Goals?

“(1) non-invasive clinical targets of heart rate <120/min, mean arterial pressure between 65 and 85 mmHg and urinary output >0.5-1 ml/kg/h,

(2) invasive clinical targets of stroke volume variation, and intrathoracic blood volume determination, and

(3) biochemical targets of hematocrit 35-44%.

What are the indications for ICU admission?

(1) pulse <40 or >150 beats/min;
(2) systolic arterial pressure <80 mmHg or mean arterial pressure <60 mmHg or diastolic arterial pressure >120 mmHg;
(3) respiratory rate >35 breaths/min;
(4) serum so- dium <110 mmol/l or >170 mmol/l;
(5) serum potassium <2.0 mmol/l or >7.0 mmol/l;
(6) paO2 <50 mmHg (<6.7 kPa);
(7) pH < 7.1 or >7.7; 8) serum glucose >800 mg/dl (>44.4 mmol/L);
(9) serum calcium > 15 mg/dl (>3.75 mmol/L);
(10) anuria, or
(11) coma

References

  1. Dellinger EP, Forsmark CE, Layer P, et al. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg2012;256:875-880
  2. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis — 2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102-111
  3. Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas2006;33:323-330
  4. Coté GA, Yadav D, Slivka A, et al. Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2011;9:266-273
  5. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013;144:1252-1261
  6. Mounzer R, Langmead CJ, Wu BU, et al. Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis. Gastroenterology2012;142:1476-1482
  7. Chris E. Forsmark, M.D., Santhi Swaroop Vege, M.D., and C. Mel Wilcox, M.D. Acute Pancreatitis. N Engl J Med 2016; 375:1972-1981
  8. 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.
  9. de-Madaria E, Soler-Sala G, Sánchez-Payá J, Lopez-Font I, Martínez J, Gómez-Escolar L, Sempere L, Sánchez-Fortún C, Pérez-Mateo M. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol. 2011;106:1843–1850.
  10. Gardner TB, Vege SS, Chari ST, et al. Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality. Pancreatology 2009;9:770-776
  11. Gardner TB, Vege SS, Pearson RK, Chari ST. Fluid resuscitation in acute pancreatitis. Clin Gastroenterol Hepatol 2008;6:1070-1076
  12. Mole DJ, Hall A, McKeown D, Garden OJ, Parks RW. Detailed fluid resuscitation profiles in patients with severe acute pancreatitis. HPB (Oxford) 2011;13:51-58
  13. Mao EQ, Tang YQ, Fei J, et al. Fluid therapy for severe acute pancreatitis in acute response stage. Chin Med J (Engl) 2009;122:169-173
  14. Wall I, Badalov N, Baradarian R, Iswara K, Li JJ, Tenner S. Decreased mortality in acute pancreatitis related to early aggressive hydration. Pancreas. 2011;40:547–550.
  15. Eckerwall G, Olin H, Andersson B, Andersson R. Fluid resuscitation and nutritional support during severe acute pancreatitis in the past: what have we learned and how can we do better? Clin Nutr. 2006;25:497–504.
  16. Kuwabara K, Matsuda S, Fushimi K, Ishikawa KB, Horiguchi H, Fujimori K. Early crystalloid fluid volume management in acute pancreatitis: association with mortality and organ failure. Pancreatology. 2011;11:351–361.
  17. Mao EQ, Tang YQ, Fei J, Qin S, Wu J, Li L, Min D, Zhang SD. Fluid therapy for severe acute pancreatitis in acute response stage. Chin Med J (Engl) 2009;122:169–173.
  18. 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;123:1639–1644.
  19. Sarr MG. Early fluid “resuscitation/therapy” in acute pancreatitis: which fluid? What rate? What parameters to gauge effectiveness? Ann Surg. 2013;257:189–190
  20. Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, et al. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 9: 710–717.e1, 2011
  21. Mole DJ, Hall A, McKeown D, Garden OJ, Parks RW. Detailed fluid resuscitation profiles in patients with severe acute pancreatitis. HPB 13: 51–58, 2011.
  22. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 13: e1–15, 2013