**2. Fluid management**

The AP treatment is currently symptomatic, and fluid management is a cornerstone of its therapy as well as being the intervention most likely to improve clinical outcomes. Patients are frequently hypovolemic due to decrease oral intake, vomiting, fever, tachypnea, and fluid sequestration associated with pancreatic and systemic inflammation. Pancreatic hypoperfusion may be attenuated by fluid resuscitation, therefore preventing pancreatic necrosis and lowering mortality [4, 7, 8].

Using experimental animal studies, it has been estimated that approximately two liters of fluid diffuse from the intravascular space to the interstitium, during the first 6 hours [7].

Fluid therapy to prevent hypovolemia and organ hypoperfusion comes from sepsis care, which has some pathophysiological similarities with AP.

After initial pancreatic acinar injury, the high amount of proteolytic enzymes produces local inflammation, proinflammatory cytokine, and vasoactive mediators release, with an increase in vascular permeability. Locally it results in interstitial fluid extravasation with edema of the gland, capillary vasoconstriction, and the production of microthrombi, which further worsen pancreatic perfusion. Cytokines such as interleukin (IL)-1, IL-6, IL-8 and systemic mediators such as tumor necrosis factor alpha (TNF-α) usually amplify this vicious circle and induce systemic inflammation, which can lead to systemic inflammatory response syndrome (SIRS).

### *The Anesthesiologist Contribution to Management of Acute Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.105821*

SIRS is an exaggerated defense response of the body to a noxious stressor, which can be represented by infection, trauma, surgery, acute inflammation, ischemia, or reperfusion. Even though the purpose is defensive, the dysregulated cytokine storm can cause a massive inflammatory cascade leading to reversible or irreversible endorgan dysfunction and even death [9]. This storm represents the link between sepsis and AP, which is initially an aseptic inflammatory disease.

Likewise, as in septic patients, a low intravascular volume results in a decreased tissue perfusion, which can cause multiorgan failure, which increases complications and mortality rate. At the same time, overly aggressive hydration, especially in patients with preexisting kidney disease or hearth failure, increases the need for mechanical ventilation, the rates of infections, and thus mortality [1, 3].

Fluid dynamics are fundamentally different in mild and severe pancreatitis. The first one is easier to manage, because it is enough to restore the fluid deficit owing to vomiting, lower intake, and insensible losses. But the second one is characterized by vascular leakage with extravasation of protein-rich fluid, liquid sequestration, and hypoperfusion [10].

At the same time, we know that a mild form can evolve into a severe one, because in a sense they represent a pathophysiological continuum. Therefore, the revaluation is crucial to direct the right hydration and the evolution of the disease itself.

### **2.1 The fluid: How much of which one?**

Unfortunately, there is still some degree of uncertainty about total amount of fluid, optimal infusion rate, and the type of solution.

Clinical data on the amount of fluid needed to prevent necrosis or to improve outcome are contradictory. In the past, an aggressive fluidic resuscitation meant a considerable and very rapid volume load, which could correspond of 2 liters bolus in the first hour and a subsequent maintenance of 20 ml/kg/h.

Even in some recent reviews, the initial volume of fluid administered varied substantially and also the strategy of maintenance—with or without initial bolus was not uniform, with infusion's rates that vary from 1 to 15 ml/kg/h. Currently, however, it has emerged that a very early volume load in the course of AP may be beneficial, while rapid volume loads in advanced stages are harmful [7]. Hence, after fluid resuscitation in the first 12–24 hours, infusion should generally be curtailed, to avoid respiratory complications or abdominal compartment syndrome.

In fact, after 20–40 minutes of infusion, only 20% of crystalloid remains in the intravascular space because most inevitably migrates to the interstitium, further worsening the oxygen diffusion. This is why too much fluid is as harmful as too little.

The value of early goal-directed therapy in these patients remains unknown. It is evident that an excessively rigid protocol of fluid management is illogical because "one size doesn't fit all," while it may be more beneficial to identify some personalized therapeutic end points [4].

Intravascular volume and an adequate perfusing pressure need to be restored, but infusion rate should be carefully tailored to individual patients, considering factors such as age and comorbidities. Fluid resuscitation should focus on improving heart rate, mean arterial pressure, central venous pressure, urine output, blood urea nitrogen concentration, and serum lactate.

It appeared that colloid administration could improve the outcome. But actually hydroxyethyl starch (HES) fluids are not recommended in AP because subsequent

studies failed to demonstrate improved mortality and instead found increasing rate of kidney injury or need for renal replacement therapy [11]. In fact, the American Gastroenterological Association (AGA) suggests against the use of HES fluids, however, with very low quality of evidence.

The use of high volumes of normal saline—0.9% sodium chloride—has also been shown to have harmful effects on plasma electrolyte balance, leading to hyperchloremic acidosis. The large chloride load results in acidosis that could promote or exacerbate inflammation and renal injury.

Now isotonic balanced crystalloids are the preferred fluid. Particularly strong evidences came from the SMART trial of 2018, which found a reduction rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction in patients given balanced crystalloid than saline [6, 12].

A recent study indeed reports a shorter hospital stay and fewer ICU admissions in the group of patients randomized to receive Ringer's lactate, which is a balanced crystalloid isotonic versus plasma and seems to have an anti-inflammatory effect.

It is worth remembering that all these fluids are artificial solutions, which differ from human plasma composition. This is true also for balanced crystalloid, which varies in its electrolyte concentration, osmolality, and pH. Clinicians must then choose the better fluid to prescribe and its adequate amount, depending on the specific patient [13].

Based on multiple studies, a continuous infusion of 3 ml/kg/h would constitute aggressive and 1.5 ml/kg/h nonaggressive fluid therapy. As a general guidance, the choice of fluid should be a balanced crystalloid and the volume infused around 3–4 liters in the first 24 hours. There also should be predefined checkpoint at 6 or 8 hours to assess volemia and the other perfusion parameters [10, 14].

### **2.2 A rational strategy**

As outlined before, initial management of AP within the first 48–72 hours of admission can modify the course of disease and length of hospital stay [5].

In the early phase, the goal is to restore circulating blood volume and improve peripheral tissue oxygenation. Easy clinical markers of adequate hemodynamic function are heart rate, blood pressure, respiratory rate, O2 saturation, and urine output [8].

Fluid resuscitation is indicated to rapidly optimize tissue perfusion targets. In **Figure 1**, a practical approach is schematized, starting from resuscitation with 500–1000 ml of balanced crystalloid that is meant to normalize macrocirculation parameters such as blood pressure and heart rate and also microcirculation features such as refill time and skin color.

Obviously, this fluidic load is commensurate to the magnitude of hypotension and volume must be adjusted to the patient's age, weight, and preexisting renal injury or heart disease.

Subsequently, it is suggested to replace the ongoing losses with a continuous infusion of about 3 ml/kg/h during the first 12 hours and can be reduced to 1.5 ml/ kg/h if physiological parameters improve or when patients resume hydration by mouth.

Caution is recommended to avoid fluid overload, and fluid administration should be guided by frequent reassessment of the hemodynamic status. However, it is particularly important to check blood pressure, heart rate, and pulse saturation every 6 or 8 hours, according to the severity of patient's disease, with the purpose of knowing if intravascular volume is adequate to ensure a good organ perfusion and oxygenation. *The Anesthesiologist Contribution to Management of Acute Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.105821*


**Figure 1.**

*Early fluid resuscitation strategy.*

Most authorities recommend titrating intravenous fluids administration to specific measurable targets of perfusion, which in a nonintensive environment, may be well represented by effective diuresis and lactate reduction. These are two indicators of adequate organ perfusion and indirectly suggest that the availability of oxygen is appropriate [6].

It is extremely important to follow the evolution of the patient's clinical conditions to tailor our therapies. If there is no parameter improvement but rather diuresis contracts, lactates increase, respiratory insufficiency arises, or patient becomes hemodynamically unstable despite ongoing hydration, ICU transfer is indicated.
