Optimal management of patients with acute pancreatitis (AP) is essential in order to reduce mortality and morbidity associated with this disease.1 There was a high mortality rate among AP patients hospitalized in Spanish intensive care units (ICUs) during the 1970s. Eight of every 10 patients (81.2%) died.2 In 1974 Ranson reported a morality rate of 100% in SAP patients with more than 7 points3 and López Benito4 reported a 77.2% mortality rate in patients with necrotizing pancreatitis.

Recently, the incidence of lethal forms has been significantly reduced5,6 and this reduction has been attributed to early detection of prognostically unfavourable forms during the first three days after onset of symptoms, to treatment administered in the ICUs, to delaying the operative intervention for as long as possible,6–8 and to the introduction of minimally invasive draining techniques.9

Taking into account the recently emerged evidence in the literature, the Northern Spanish Intensive Care Society (SNMIUC) proposed the development of clinical pathways10 for AP at its meeting in Pamplona in January 2010.

The main aim of AP pathways is to improve the diagnosis and treatment of patients with AP who are hospitalized and managed by a multidisciplinary team, including but not limited to gastroenterologists, surgeons, intensive care physicians, nutritionists and radiologists. The pathways detail the recommended algorithm of actions and level of care on daily and hourly basis within the first 3days after hospital admission. The current knowledge based on scientific evidence must be applied by means of multidisciplinary “levels of care” which will include the appropriate succession of clinical management, laboratory tests, radiological investigations, and therapeutic procedures. All these aspects are focused on confirming the AP diagnosis and stratifying the severity by initiating early the most appropriate support treatment for each patient. The previous Spanish guidelines and recommendations for AP management have formed the basis11,12 for the pathways presented in this document.

All the pathways are presented using a sequential format during the first day of admission and the first three days in the Emergency, Surgery, Gastroenterology Departments or ICU.

In preparing the present pathways, we first found a new classification of severity that was proposed by Petrov and colleagues in 2010.13 This new classification significantly advances the outdated 1992 Atlanta classification.14 The definitions used for the categories of severity in the new classification are based on the characteristics of “local determinants” (absent, sterile or infected peri/pancreatic necrosis) and “systemic determinants” (an absent, transient or persistent organ failure), as well as the possibility of the determinants factors interacting during the episode of acute pancreatitis. Organ failure (OF) is defined as transient (when it is resolved in a short period of time after having applied adequate support measures, normally in less than 48h from the onset of acute pancreatitis) or persistent organ failure (when it is resolved more than 48h later).

Other clinical entities that are different from these local and systemic factors of severity should be considered as complications and are not used to classify the severity.

The definitions are as follows:

• 1.

  Mild Acute Pancreatitis is characterized by the absence of both (peri)pancreatic necrosis and organ failure.

• 2.

  Moderate Acute Pancreatitis is characterized as the presence of sterile (peri)pancreatic necrosis or transient organ failure.

• 3.

  Severe Acute Pancreatitis is characterized as the presence of infected (peri)pancreatic necrosis or persistent organ failure.

• 4.

  Critical Acute Pancreatitis is characterized as the presence of infected (peri)pancreatic necrosis and persistent organ failure.

From a practical standpoint we introduced the concept of “Early severity criteria”11 that defines a Potentially Serious Acute Pancreatitis (PSAP). A PSAP is defined as an episode of AP with one or more organ failures, i.e. with cardiovascular, respiratory or renal failure or alarm signs (Fig. 1). This is useful for providing early appropriate treatment and for designing future trials.15 The alarm signs are the symptoms/signs in a patient with AP indicating a potentially negative or severe evolution of the disease.

Each one of them has been presented in the following pathways: The AP Pathway (intended for the medical specializations involved in the first patient treatment, especially Emergency and Digestive Care or Surgery), and the PSAP Pathway (Table 2) or post-surgical phase (Table 3). The “levels of care” are shown in the first column and listed in the following order:

1°. Assessment.—2°. Medical intervention.—3°. Laboratory tests.—4°. Imaging.—5°. Catheters/Monitoring/Surveillance.—6°. Medication/Treatments.—7°. Nutrition/Fluids.—8°. Biliary AP—9°. Information/Teaching.—10°. Discharge; hospitalized.—11°. Medical Objectives/Nursing.—12°. Early Severity Criteria or Alarm signs. (They determine which patients require most detailed medical attention, where the AP algorithm is applied.)—13° ICU Call Criteria, Assessment and ICU admission. (They are based on the evaluation of three organ failure parameters.)

The other four columns correspond to initial assessment (Day 0) in Emergency, Digestive, or ICU Services, and the following columns show the chronology of the first three days in the hospital (Date: Day l, Day 2 and Day 3 in Emergency, Digestive or ICU Services). The actions, attitudes and measures conforming to the previous recommendations11 are subsequently developed.

Lastly, the algorithms for AP and PSAP are developed as a result of these pathways (Figs. 1 and 2).

Table 1 represents the pathway for acute pancreatitis. It displays the specific aspects of clinical care in the first column and how it should be implemented on the day of hospital admission (day 0) and the following 72h. This pathway is based on the best available evidence, including the new determinants-based classification of acute pancreatitis severity and a complex of therapeutic treatments known under the acronym P.A.N.C.R.E.A.S. Besides, the Alarm Signs are shown as the last two aspects of care (Table 1) and they define the patients requiring most detailed medical attention. These signs are also shown in the AP algorithm (Fig. 1).

Table 2 and Fig. 2 represent the pathway for potentially severe acute pancreatitis (PSAP) and the respective algorithm. The “ICU call criteria” are shown in the first row. The management in Intensive Care (a more detailed P.A.N.C.R.E.A.S. protocol) and the “final classification” of the PSAP patients admitted to an ICU are described in the last two rows.

Analytical panels have been designed with the appropriate laboratory tests to be ordered in patients with AP (see Attachment 1). These patients are usually admitted to the Emergency or Digestive or Surgical Department or ICU at this stage.

The pathways are designed to be used on a sheet of paper (printed on both sides) in order to be placed at the head of the patient's bed for easy consultation on the part of all the medical specialists involved in the patient's care.

Identification of unfavourable signs in patients with AP during the first three days after admission improves the prognosis and reduces the probability of death.3,8,14,17,19–22 This document presents the multidisciplinary clinical care pathways that aim to improve and standardize early management of patients with AP.

One of the most important recent developments that has been reflected in the pathway is the determinants-based classification of acute pancreatitis severity, originally proposed by Petrov in 2012.23 This new classification of AP severity is based on two fundamental principals. First, it is based on real severity factors instead of factors that predict severity. The use of systems with multi-factor scoring (for example, APACHE II, Ranson criteria, Imrie-Glasgow criteria, etc.) for predicting severity were incorporated into the original Atlanta classification and it was an important development 20–30years ago14 but time proved that all of them suffer from at least 30–40% misclassification error. The direct implication is that patients are often admitted to ICU too late, when the opportunities of intensive care to alter favourably the natural course of AP are quite limited. Therefore, it is important to identify the early markers of persistent organ failure24 and the risk factors that trigger the alarm.22 Second, the new classification defines the severity only on the basis of factors that have a causal relation to this severity. In acute pancreatitis these factors are (peri) pancreatic necrosis and organ failure. On the basis of published studies there are three organs that should be considered in diagnosing OF: cardiovascular, renal, and respiratory.25,26

When these two principles were applied, four categories of severity appeared: Mild AP (MiAP); moderate AP (MoAP); severe AP (SAP); and critical AP (CAP). The exact definitions are provided in Fig. 2 and Table 2. It is also worth mentioning that these four categories of severity have very different outcomes. In our cohort of patients admitted to ICU, the mortality was 0% among patients with moderate AP, 21.2% in SAP patients and 25% in CAP patients.2

At the same time, some of the previously published severity criteria11,14,22 could still be used as “early” criteria that predict which patients will have an unfavourable course of the disease and will require more attention. These criteria are described as “alarm signs” in the AP pathways (Figs. 1 and 2) and in Table 1.

It is also necessary to point out that this classification is dynamic and evolving, so that the accurate assignment of a severity category (particularly, SAP and CAP) will require at least 48h after hospital admission. This is a potential disadvantage of the new classification as it is impossible to “diagnose” SAP or CAP at the time of hospital admission. At most, we are able to diagnose a moderate AP only.27 For this reason, we suggest to term an AP patient who has at least one organ failure or signs of alarm upon admission and within first 48h “Potentially Serious Acute Pancreatitis” (PSAP) and this is the type of patient who may require management in the ICU, as described in Table 1 and Figs. 1 and 2.

The pathways presented in this document incorporate the acronym P.A.N.C.R.E.A.S.,28 in which all the therapeutic modalities currently advocated in patients with AP are summarized. There are “eight” easy therapeutic measures for remembering the acronym: Perfusion; Analgesia; Nutrition; Clinical; Radiology; ERCP; Antibiotics; and Surgery28:

• 1.

  Perfusion: The sequestration of fluids in the interior of the third abdominal space can become so significant that it could account for a third of the total plasma volume. Rapidly restoring and maintaining intravascular volume in the first 48h after patient admission is essential and the cornerstone for initial resuscitation. However, both excessive rehydration and the scarce supply of fluids in the first 48h are associated with an increased morbidity and mortality.29 In addition, a greater need of fluids associated with oliguria30 is a sign of alarm and consequently requires greater and continuous hemodynamic control31,32 or even the employment of vasopressor drugs in accordance with the initial severity.29 Oxygenation is needed for adjusting the saturation >95% in severe and critical AP.33

• 2.

  Analgesia: Controlled patient analgesia; or analgesia on demand, including with opioids.34

• 3.

  Nutrition: There is a growing body of evidence that mortality is reduced in those patients with acute pancreatitis who receive enteral nutrition. Enteral nutrition in the first 48h via nasojejunal tube is advocated if the gastric route is not tolerated.35,36

• 4.

  Clinical: Scores for evaluating and stratifying cases such as BISAP,37 the APACHE II38 or the APACHE-O39 are available. These scoring systems are not mandatory in most emergency and digestive care areas. This clinical evaluation should be performed especially in intensive care units according to the severity of the pancreatitis.40

• 5.

  Radiology: Ultrasound (US) for detecting gallstones, choledocholithiasis, and local complications (free peritoneal fluid). Contrast-enhanced Computed Tomography (CECT) after the first 72h following the onset of pain is useful for determining the extension and magnitude of the necrosis.41 Percutaneous catheter drainage guided by ultrasound or CT is useful for managing infected fluid collections or necrosis and also as a part of the step-up approach.9,42

• 6.

  ERCP: If cholangitis is present ERCP should be performed during the first 24h or in the case of AP with common bile duct obstruction in the first 48h.43

• 7.

  Antibiotics: There is little evidence to support the prophylactic role of antibiotics in the prevention of infected necrosis.24 As a general rule, treatment with empirical antibiotics can begin after 14days if there is suspicion of infection, following culture collection. However, the appearance of SIRS after the first week in the case of AP with necrosis raises the suspicion of infection and it would be the appropriate time to indicate an antibiotic after obtaining culture samples. The intra-abdominal pressure assessment (IAP) is essential in this sense, because it is one of the markers indicating that (peri)pancreatic inflammation has become an infected entity. It is evident that obtaining purulent material and/or culture and antibiogram of suctioned material, by means of percutaneous US or CT guided fine needle aspiration (FNA), should be useful for guiding the administration of antibiotics.44

• 8.

  Surgery: Should be considered in patients with: (a) multi-organ failure with necrosis that does not respond to conservative treatment; (b) compartmental syndrome (IAP >25mmHg) with persistent organ failure; (c) infected necrosis; and (d) mesenteric ischaemia and/or perforation of the intestine.9,33,34 In this case monitored measurements of IAP in a critical patient with AP is essential,45,46 because it indicates the evolution of process to an abdominal compartmental syndrome, regardless of whether it is infected or not, and it indicates complementary exploration (repeat CT if applicable) and surgery. Take into account the role of new surgical techniques: Minimal invasive pancreatic necrosectomy or step-up (open necrosectomy after the failure of minimal invasive surgery).9 The important message is to try to “gain time” before performing early surgery as “necrosectomy in itself could be less important than obtaining adequate drainage”.47 Pseudo-aneurysm of surrounding vessels with or without haemorrhage can be treated with embolization techniques.

To conclude, this document proposes the pathways for AP, PSAP, Peri-surgical phase and the algorithms for clinical care during the first 72 hours after hospitalization based on various approaches, levels of care, analytical tests, medical and surgical indications that are supported by current scientific evidence. The second conclusion is to propose a revision of the previous Recommendations for treatment of Severe and Critical AP.

The authors have no conflicts of interest to declare.