This study demonstrates that patients admitted with acute pancreatitis receiving early fluid resuscitation have lower rates of SIRS and organ failure, shorter hospitalizations, and less of a need for ICU admission than do patients who are not resuscitated as aggressively. This effect is observed only in patients with interstitial disease at admission, suggesting that in patients with severe disease, early intravenous fluid resuscitation is unlikely to substantially alter the patient’s clinical course. This effect was observed despite controlling for possible confounders; Charlson comorbidity score, age, and gender.
Patients presenting with acute pancreatitis are often hypovolemic due to vomiting, reduced oral intake, third spacing of fluids, and diaphoresis. In fact, one expert has written that the minimal intravenous fluid requirements of a 70 kg person during the first 48 hours after admission is already 6 liters without considering intravascular fluid sequestration loss.13
In addition, it is believed that the release of cytokines, chemokines, neutrophils, and macrophages lead to a pro-inflammatory state causing local and systemic inflammation. Such inflammation increases vascular permeability that can lead to hypoperfusion and third spacing of fluids. Often this is profound, as described by Greer and Burchard, “inflammation begets hypoperfusion and hypoperfusion begets inflammation,” leading to a self-propagating cycle that causes vascular dysfunction in both large vessels as well as the microcirculation of the pancreas.14
Early IV fluid resuscitation is essential in correcting hypovolemia, thereby supporting the macro and microcirculation of the pancreas to prevent serious complications such as pancreatic necrosis.
Despite recognition that intravenous fluid resuscitation is an essential component to the early treatment of acute pancreatitis, very few studies have been performed to qualify the effect of this intervention. Banks and colleagues have published numerous papers recognizing the detrimental effect of hemoconcentration on outcomes in acute pancreatitis.15,16,17
In one study of 39 patients, they found that while fluid resuscitation with crystalloid solution was not shown to prevent necrosis, all patients with inadequate fluid resuscitation as evidenced by persistence of hemoconcentration at 24 hours developed necrotizing pancreatitis.17
Eckerwall described in 99 patients admitted with severe acute pancreatitis in Sweden, those receiving 4000 ml or more of fluids during the first 24 hours (n
=32) developed more respiratory complications (66% vs. 53%; P
< 0.001) as compared to patients who received less than 4000 ml of fluid.18
In a series of patients admitted with severe acute pancreatitis at the Mayo Clinic Rochester using the same definitions of early and late resuscitation, patients in the late resuscitation group experienced significantly greater mortality than those in the early group (17.9% vs. 0%, p< 0.04) and demonstrated a trend toward higher rates of organ failure (42.9% vs. 35.3%) that did not reach statistical significance.8
Recently a multicenter study evaluating the impact of targeted fluid resuscitation volume to serial blood urea nitrogen (BUN) levels vs. standard of care fluid resuscitation was completed; the results have yet to be reported.
Given the paucity of human trials, it is not surprising that current guidelines for resuscitation are mostly vague and based almost exclusively on expert opinion.10
Some of the more specific recommendations include bolusing fluids to achieve “hemodynamic stability,” followed by 250–500cc/hr of crystalloid solutions, 250–300cc/hr for 48 hours, to 250–300cc/hr in non-volume depleted patients, 300–500 cc/hr for nonpancreatic fluid loss; and 500 to 1,000 cc/hr for severe depletion.19,13,6
The value of the current study is that it demonstrates the critical importance of early fluid resuscitation in acute pancreatitis, specifically in those with interstitial disease. The results support the dogma that in patients with less severe disease, early fluid resuscitation plays a significant role in preventing the development of severe disease. Conversely, the data suggest that in patients already presenting with severe disease, aggressive fluid resuscitation is unlikely to singularly reverse the clinical course.
There are weaknesses with this study, most importantly that it was retrospective and relied on having accurate measurements of IV fluid administration. However, meticulous attention was paid to eliminating patients with missing or incomplete data, and a number were excluded. Another limitation is the relatively small number of patients admitted with severe acute pancreatitis which limited our ability to draw conclusions in regard to mortality due to probable type II error. While we attempted to control for important confounders, we could not control for advances in care (infection control, improved enteral feedings, etc) that occurred over the course of the 24 year analysis. Adjustment for year or period of admission, which may have confounded the results assuming progressive advancements in volume resuscitation concepts and overall improved ICU care, was not performed.
In addition, due to the retrospective nature of the study, a circular argument can be forwarded – did patients develop a worse outcome due to limited early fluid resuscitation within the first 24 hours or was volume restriction due to certain circumstances associated with a worse outcome such as necrosis? Although efforts were made to establish that the groups were comparable at baseline, biases may have been introduced in this regard.
While the study does not allow for definitive recommendations in regards to the amount or type of fluid resuscitation, it helps qualify the importance of early fluid resuscitation on important clinical markers in acute pancreatitis, particularly those with interstitial disease. Until an effective pharmacologic agent is developed, optimization with intravenous fluids is one of the few interventions which is associated with improved clinically important outcomes in this disease.