Shock: Volume Management and Hemodynamic Monitoring
Hemodynamic failure in AP has been defined as systolic blood pressure of less than 90 mmHg despite adequate volume administration [4]. In clinical practice, shock in a patient with AP is usually a consequence of two different situations that may coexist: a hypovolemic state (hypovolemic shock), and systemic arteriolar vasodilation (distributive shock). Cardiac damage and dysfunction have been described in patients with the most severe forms of AP [20,21] but are less frequent; it should be considered if an important hemodynamic impairment is present.
1 Hypovolemic shock. A hypovolemic state is frequent in patients with AP, especially in patients with moderate‐to‐severe disease [22]. There are several factors determining this hypovolemia: reduction in oral intake, fluid sequestration due to the development of an important third space (interstitial edema, retroperitoneal collections, pleural effusion, paralytic ileus), and increased losses (vomiting, diaphoresis, tachypnea) [22]. Vascular leak syndrome, an increase in vascular permeability due to mediators like angiopoietin‐2, may be important in this regard [23]. Much less frequently, patients with local complications may have retroperitoneal or gastrointestinal bleeding, which can be life‐threatening.
2 Distributive shock. Arteriolar tone may decrease due to uncontrolled secretion of proinflammatory mediators. As stated, it can result from the initial aseptic inflammation of the pancreas, or be due to infections.
It has been hypothesized that early and accurate volume replacement could stabilize the permeability of the capillary membrane and support the macro‐ and micro‐circulation, prevent the cascade of events leading to pancreatic necrosis, maintain the function of the intestinal barrier, and modulate the inflammatory response [24], but evidence about the optimal volume and rate of fluid resuscitation from randomized controlled trials is lacking [25]. Studies addressing fluid resuscitation in severe AP are scarce, and most of them are retrospective with small sample sizes. Two randomized controlled studies from the same group investigated the effect of a more aggressive versus a moderate fluid resuscitation rate, and both showed decreased survival in patients receiving the aggressive strategy [26,27]. For this reason, aggressive fluid resuscitation in patients with established severe AP should be avoided, unless strictly needed. According to two randomized controlled trials, lactated Ringer’s solution has an anti‐inflammatory effect [28,29], but these studies were underpowered to detect improved survival or decreased incidence of organ failure.
Bearing in mind the limited evidence from the literature, we recommend lactated Ringer’s solution‐based fluid resuscitation, with an initial bolus of 10–20 ml/kg and a subsequent infusion of 1.5 to 3 ml/kg per hour, monitored with hematocrit (maintained between 35 and 44%), blood urea nitrogen plasma levels (an increase in serial blood tests may indicate the need for a more aggressive strategy), and urine output (>1 ml/kg per hour) [26,27,30]. These parameters should be monitored every 8–12 hours. Although the study of Wu et al. [28] did not demonstrate significant differences between standard and goal‐directed fluid resuscitation, the study was underpowered. In the case of organ failure, the patient should be monitored in an ICU setting. In the article of Sun et al. [31], patients monitored with pulse indicator continuous cardiac output (PiCCO) received more volume infusion, with lower need for renal replacement therapy and shorter ICU length of stay, but without differences in mortality. In the absence of higher‐quality studies, it seems logical to recommend strict hemodynamic monitoring in patients with shock or renal failure, using thermodilution and/or ultrasound techniques [32].
Once adequate volume replacement is completed, if hemodynamic impairment persists, norepinephrine infusion should be started in order to normalize peripheral vascular resistances. Once again, strict hemodynamic monitoring is recommended in the management of these cases. The use of corticosteroid therapy has been tested in several randomized trials involving small sample sizes. According to a meta‐analysis, corticosteroid therapy for AP with shock and high norepinephrine requirements may be associated with reductions in length of hospital stay, need for surgical intervention, and mortality rate [33], but further research is needed before recommending this treatment.
Acute Renal Failure: Early Detection and Management
Acute renal failure is another common type of organ failure associated with severe AP. Factors related to the development of acute kidney injury (AKI) are male sex, sepsis and septic shock, respiratory failure, age, development of abdominal compartment syndrome, and comorbidities according to a propensity score‐matched analysis [34]. In a study trying to develop a prediction rule for mortality in patients with AP in ICU and at least one organ failure [35], the presence of renal failure was not an independent predictor of mortality, but the need for continuous renal replacement therapy (CRRT) was an important mortality predictor.
The mechanisms of acute renal failure in AP patients are not well studied and the resulting kidney injury is likely multifactorial. Proposed mechanisms include hypovolemia (pre‐renal component, see preceding sections), hypoxemia‐driven injury to the renal tubular epithelial cells, impairment of renal microcirculation due to released pancreatic amylase, release of apoptotic molecules including cytokines from the inflamed pancreas leading to renal cellular injury, and abdominal compartment syndrome that may develop in patients with severe AP and lead to decreased renal perfusion pressure causing ischemic injury [36].
If a patient with AP develops renal failure, a global evaluation should be performed and volume infusion should be started in order to correct the hypovolemic state and the pre‐renal etiology of kidney injury. IAP should be continuously monitored in patients with AP and renal failure. It is worth bearing in mind that an increase in serum chloride and chloride exposure could also be associated with AKI [37], and thus the composition of replacement fluid, in addition to the volume infused, could be important. Normal saline is associated with a higher chloride concentration than balanced solutions such as lactated Ringer’s solution [29].
When renal failure is more severe, depuration techniques are needed. Conventional dialysis uses diffusion as the depuration mechanism and is performed over a short time period (3–4 hours), so it could be deleterious in hemodynamically unstable patients. CRRT offer two advantages in comparison to conventional dialysis: (i) the option for continuous management over 24 hours, with better hemodynamic tolerance; and (ii) the use of dispersion, convection and adsorption mechanisms to remove endotoxin and inflammatory mediators, to correct disorders in acid–base balance, adjust immune stability, and maintain stability of the internal environment. CRRT promotes good hemodynamic stability for patients with excessive load and high catabolism, which improves prognosis [38].
The optimal timing for initiation of CRRT in patients admitted to the ICU with AKI remains uncertain. Conventionally accepted indications include volume overload, hyperkalemia, metabolic acidosis, overt uremia, and even progressive azotemia in the absence of specific symptoms; however, precise definitions for these indications are lacking [39]. The optimal timing of initiation of renal replacement therapy for non‐life‐threatening indications of AKI also remains to be determined. There is a debate as to whether different strategies for initiation of renal replacement therapy (early vs. delayed) confer a survival benefit [40].
The concept of immunomodulation in AP, using CRRT, is very exciting, but results are not clear. Pulses of high‐volume hemofiltration can reduce levels of tumor necrosis factor (TNF)‐α, interleukin (IL)‐4, IL‐6, IL‐8 and IL‐10, but there are no data about the clinical impact on mortality or other relevant outcomes [41,42].
A recent meta‐analysis [43] of patients with AP and continuous blood purification showed that, compared with conventional treatment, continuous blood purification could reduce the incidence of organ