The organizing committee for the new edition of the AP recommendations designed the project, organization, the subcommittee (in multidisciplinary working groups composed of specialists in Emergencies, Digestive Medicine, Radiology, General Surgery and Intensive Medicine), the reference terms and the development of an adaptation plan and the writing up of the recommendations. In addition, the Consensus Conference was presented with the collaboration of SEMICYUC at the XLVI National SEMICYUC Congress held in Santander (Spain) in 2012. Lastly, an international meeting was held, in line with the regulations of the Society, in order to officially present these recommendations in Madrid on 30th October 2012.

The group has decided to use the existing recommendations on the treatment of severe AP and adapt them to the needs of the target population, using the GRADE method in adapting the ACCP (American College of Chest Physicians)10 articles, due to their applicability and simplicity, although similar versions exist.11–14

The GRADE method (Table 1) classifies the recommendations according to:Grades of recommendation

According to the balance between benefits, risks, costs and potential workloads:

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  Grade 1: Strong recommendation, or

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  Grade 2: Weak recommendation.

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  No grade: There is no recommendation in this regard.

The system classifies the quality of the evidence in accordance with the factors that include study design, the consistency of the results, and the availability of evidence, as follows:

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  Evidence A: Higher,

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  Evidence B: moderate, or

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  Evidence C: low.

Electronic search in MEDLINE, SCOPUS and EMBASE from 2004 to September 2012 of the literature regarding “severe acute pancreatitis” and everything related to the questions that had been posed.

The working group decides to use the 2004 Pamplona Recommendations on the treatment of severe acute pancreatitis and update them to 2012 by using the GRADE method.

No limitations on conflicts of interest were identified.

(See on-line full version). The definitions and complications of the illness are summarized in each chapter and in the subsequent tables that are shown in this document and in the 2011 AP Pathways (7).

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

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

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

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

  • •

    Transitory organ failure. Data on an OF that are resolved in a short period of time after having applied adequate support measure.

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    Transitory organ failure. Data on an OF that are not resolved in a short period of time after having applied adequate support measures.

The authors of the new international multidisciplinary classification define transitory or persistent as an OF that is not resolved in less or more than 48h, although we believe that this deadline is too long for certain OFs and we adopted the definition of Sepsis Surviving Campaign.17

• Recommendation 14. Abdominal CT with IV contrast is not indicated for all AP patients, but only for PSAP patients. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 15. The following are considered severe alarm criteria of AP: the existence of pancreatic necrosis (defined as the lack of glandular enhancement with iodinated IV contrast) and/or the presence of peripancreatic collections (Grades D and E by CT of the Balthazar Index). Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 16. Abdominal CT with IV contrast is to be performed in the first 24h in those cases with an uncertain diagnosis. For an accurate assessment of pancreatic necrosis, the best option is to perform the CT between 48 and 72h from the onset of the outbreak. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 17. MRI is a good alternative to CT in patients who are allergic to iodinated contrast or who suffer from renal insufficiency. Weak grade of recommendation (2), moderate quality of evidence (B).

• Recommendation 18. If there is a suspicion of pancreatic necrosis, infection and/or of pancreatic collections abdominal fine needle puncture should be performed for diagnostic purposes, directed by either ultrasound or CT. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 19. Given that there is a 10% risk of false negatives with the use of FNA, it should be repeated if the clinical suspicion of infection persists. Weak grade of recommendation (2), low quality of evidence (C).

• Recommendation 20. We advise drainage (internal-external endoscopic drainage or percutaneous drainage) in the following cases: a) Acute fluid collections or infected pseudocysts, b) if there is clinical pain or biliary obstruction. The choice of one or another technique is based on the anatomical characteristics of the collections, the availability of personnel to perform the technique and experience in performing it. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 21. We recommend the drainage of infected collections only. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 22. In patients with high surgical risks, a percutaneous drainage of infected necrosis is recommended prior to surgery. The main objective of percutaneous drainage is control of the sepsis. It is considered a technical “bridge” until a more permanent treatment can be administered, because it can be beneficial for patients whose severe condition prevents them from having any type of necrosectomy. It is also worth mentioning that up to 50% of patients with infected necrosis who have been treated with percutaneous drainage survive without the need for subsequent surgery. Weak grade of recommendation (2), moderate quality of evidence (B).

Intra-abdominal pressure (IAP) is the pressure within the abdominal cavity. Its normal value in noncritical patients is subatmospheric (<0mmHg) and it is<12mmHg critical patients. An increase in IAP or in intra-abdominal hypertension (IAH) (PIA≥12mmHg) was detected more than a century, and it has been known to cause alterations in the functioning of the organism.48–52

The ACS is defined as IAP ≥20mmHg, which was maintained and associated with new organ dysfunctions, regardless of the etiology.53–60 AIP values of which predict OF and mortality, and recommendations for optimizing both the medical and surgical treatment of ACS61–64 have even been established.

Both the AIP values and the abdominal perfusion pressure (APP) should be considered, by taking into account that APP=MAP−IAP, when MAP is the average arterial pressure. The objective is to achieve an AAP of 50–60mmHg, and ACS is diagnosed below this figure if it is associated with organ dysfunction.

Inasmuch as our goal is to achieve a correct APP (50–60mmHg) we can act by improving the mean arterial pressure (MAP) and/or reducing the IAP. The improvement in MAP is achieved initially by volume replacement, while bearing in mind that an excessive volume can worsen ACS65,66 and, after replacement has been completed and, if necessary, we will initiate vasoactive amines.

The reduction of the AIP will be achieved by non-surgical techniques and/or surgical techniques.

If attempts to reduce and optimize AIP are unsuccessful and optimize APP, surgical management should be considered. Among the surgical techniques, percutaneous drainage should be considered (only in those cases where there is a lot of free intraabdominal fluid)67,68 and/or decompressive laparotomy.69,70 If decompressive surgery is performed and there is no suspicion of infected necrosis it is important that no necrosectomy be performed to prevent infected necrosis from occurring.

• Recommendation 27. IAP should be measured in all the patients with PSAP. PSAP is to be measured when the patient is in a supine position at the end of expiration every 6–8h and through the urinary bladder by instilling a maximum of 25ml of isotonic saline and this will be measured in mmHg. IAH is considered when the IAP≥12mmHg is sustained or repeated and ACS will be considered when IAP≥20mmHg is sustained and associated with SDMO de novo. In the case of IAH episodes and SCA development, our objective will be to achieve an APP of 50–60mmHg. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 28. ACS treatment of in PSAP should consist of increasing MAP or reducing IAP in order to improve APP. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 29. Among the non-surgical therapies used to reduce AIP aspiration of intestinal contents by means of a gastric and/or rectal probe, the administration of prokinetics (metoclopramide, erythromycin, neostigmine), sedation and relaxation and a reduction of the third space with diuretics and/or renal replacement techniques should be considered. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 30. Among the surgical therapies used to reduce AIP percutaneous drainage and/or decompression laparotomy should be considered. The pancreatic area should only be treated when it is infected. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 45. Specialized nutritional support in potentially severe acute pancreatitis, in its SAP and CAP forms, should be started early, within the first 48hours after initial resuscitation. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 46. Enteral jejunal nutrition is preferable to parenteral nutrition. Strong grade of recommendation (1), high quality of evidence (A).

• Recommendation 47. Parenteral nutrition is indicated if enteral nutrition cannot be administered, if there is intolerance to this nutrition or if it results in an exacerbation of pancreatitis. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 48. Enteral or parenteral nutritional intake shall be achieved on the basis of recommendations for specialized metabolic and nutritional support of critically ill patients. SEMICYUC-SENPE (2011) Consensus: caloric intake of 25–30 Kcal/kg/d, without exceeding an intake of >4g/kg/d of glucose, lipid intake of 0.7–1.5g/kg/d and protein intake of 1–1.8g/kg/d. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 49. Polymeric and elemental diets are equally recommendable. Weak grade of recommendation (2), moderate quality of evidence (B).

• Recommendation 50. Assessing the possibility of maintaining a minimum supply of jejunal nutrients, even in patients with impaired jejunal nutrition who are being treated with parenteral nutrition, is suggested. Weak grade of recommendation (2), low quality of evidence (C).

• Recommendation 51. The use of glutamine in patients with severe acute pancreatitis who receive parenteral nutrition is recommended. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 52. The use of prebiotics or probiotics in patients with potentially serious acute pancreatitis is not recommended. Strong grade of recommendation (1), moderate quality of evidence (B).

Role of endoscopy in the management of pancreatic pseudocysts

Intervencionist endoscopy. Role of endoscopy in the management of infected pancreatic necrosis. Recent studies show the effectiveness of endoscopic necrosectomy, which is an effective technique, but it should be performed only in specialized centers because it presents complications,92 which are equal to or greater than surgical complications; the level of safety is acceptable.93

Both the guided drainage of pancreatic collections by conventional endoscopy such as endoscopic ultrasound-guided methods can be considered first-line drainage collections which lead to extrinsic compression. However, endoscopic ultrasound-guided drainage must be the first choice in those cases in which there is no extrinsic compression.

Direct endoscopic necrosectomy of organized pancreatic necrosis may be a technique that, in experienced hands, is effective and has an acceptable level of safety compared to surgery. Endoscopic transmural drainage is a perfectly valid option for patients who cannot undergo surgery or any other drainage technique using large collections or who suffer from necrosis and/or suspected infection. In an unorganized infected necrosis, however, surgery is still the preferred option.

• Recommendation 53. ERCP-EE. When confronted with biliary AP having cholangitis data, ERCP should be performed urgently (within 24hours) with biliary drainage. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 54. When confronted with biliary AP having an obstruction of the biliary duct, performing ERCP (ERCP-EE) with early (first 72hours) cleaning of the bile duct may prove beneficial. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 55. In patients with biliary AP and predictors of severity, performing urgent ERCP is controversial if no cholangitis or biliary obstruction data are available. Weak grade of recommendation (2), moderate quality of evidence (B).

• Recommendation 56. In patients with mild or moderate biliary AP without cholangitis or persistent biliary obstruction, performing ERCP does not significantly reduce the risk of complications or death. Strong grade of recommendation (1), high quality of evidence (A).

• Recommendation 57. In centers where ERCP is not available in the first 48–72hours and the patient shows signs of cholangitis or obstructive jaundice, the patient should undergo percutaneous transhepatic drainage of the gallbladder or biliary surgery within this timeframe. Strong grade of recommendation (1), high quality of evidence (A).

• Recommendation 58. Performing ERCP with endoscopic sphincterotomy is an alternative to cholecystectomy as a prophylaxis for new episodes of biliary AP in patients with high surgical risk or who have refused to undergo surgery. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 59. Only symptomatic pseudocyst drainage is considered suitable. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 60. The endoscopic drainage route is usually the first choice. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 61. The use of ultrasound endoscopy limits the development of complications resulting from this technique and it is useful for differential diagnosis with other pancreatic cystic lesions. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 62. Infected or symptomatic pancreatic necrosis indicates the need for treatment. The approach should be performed in stages with medical treatment, radiological drainage or endoscopic or surgical or endoscopic debridement. Strong grade of recommendation (1), high quality of evidence (A).

• Recommendation 63. The ideal time to perform this treatment for an infected or symptomatic pancreatic necrosis is at least 3 or 4 weeks from the onset of pancreatitis. Strong grade of recommendation (1), low quality of evidence (C).

• Recommendation 64. Direct endoscopic necrosectomy is an alternative to surgical debridement when performed in specialized centers. It offers acceptable levels of efficacy, although it is not free of morbidity and mortality. Therapeutic/interventional ultrasound endoscopy (USE) shall be considered an option for the management of pseudocysts and/or symptomatic or complicated abscesses, as well as for performing necrosectomies in patients with infected necrosis whose baseline counter indicate the surgical option. We wish to point out that if this therapeutic option is chosen, it should be performed in centers that are especially “devoted” to this pathology and which have multidisciplinary team composed of expert endoscopists, surgeons and interventional radiologists. Strong grade of recommendation (1), moderate quality of evidence (B).

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  Does antibiotic treatment play an important role in the treatment of AP?

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  Does AP with intraabdominal fungal infection (IFI) offer a worse prognosis than intraabdominal bacterial infection (IIB)?

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  What is the role of DDS in SAP?

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  What is the next step?

• Recommendation 65. The use of prophylactic antibiotics in PSAP patients with or without pancreatic necrosis is not recommended. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 66. The analysis of individual patients may be important for identifying potential candidates who might benefit from antibiotic prophylaxis. Weak grade of recommendation (2), low quality of evidence (C).

• Recommendation 67. The role of “early antifungal treatment” (misnamed antifungal prophylaxis) with fluconazole is unclear and requires further study. But once the fungal infection appears an antifungal with a greater spectrum than fluconazole should be used as soon as possible and by extension the same criteria used in SAP and CAP with bacterial infection are applied. Weak grade of recommendation (2), moderate quality of evidence (B).

• Recommendation 68. Empiric antifungal treatment based on clinical findings without microbiological confirmation does not appear to be effective. Weak grade of recommendation (2), moderate quality of evidence (B).

• Recommendation 69. There is no conclusive evidence at present for recommending the routine use of SDD in PSAP. Weak grade of recommendation (2), moderate quality of evidence (B).

Back in the 1970s a group of pioneers suggested a change of strategy in the therapeutic approach of “reducing or mitigating the inflammatory process in the pancreas”, by initially using peritoneal lavage.94–96

HF has several features that make it suitable for the removal of these proinflammatory substances, although there are conflicting data in the literature regarding the actual effectiveness of HF for removing inflammatory mediators (TNF-alpha, IL 1, PAF, IL-6 and complementary fractions), because it has not always been possible to demonstrate that this clearing has an impact at the systemic level.97–100 However, there are consistent data that support the beneficial effect of HF on the clinical situation and recovery of patients with SIRS or MOF, which contributes especially to the stabilization of the respiratory and hemodynamic systems.101–104

The surgical technique for the treatment of AP with infected necrosis is based on a necrosectomy involving extensive debridement of the entire pancreatic and necrotic peripancreatic tissue, while preserving the viable tissue as much as possible in an attempt to prevent secondary pancreatic fistulas and limiting where possible lesions to and/or removal of adjacent organs.

Rau's study,115 where he compared the results on mortality published in the literature, between necrosectomy and declining drainage, necrosectomy and lavage by means of a closed and a necrosectomy plus programmed relaparotomy and an open or temporarily closed abdomen, indicated a mortality for different techniques of 42%, 20% and 21%, respectively.

These techniques have not been studied using well-controlled, randomized studies, so that there is no clear indication of one procedure over another.116 In this case, the experience of the surgical team, the proper management of these patients subjected to an open abdomen, temporary closure or continuous lavage by the nursing team that controls the treatment provide the principal criteria for selecting one technique or another.

Recently, Bradley113 reported that open abdomens should be reserved for those patients with acute pancreatitis and infected necrosis who present extensive collections that exceed the pancreatic cell and fill the entire retroperitoneal space behind the colon.

It is probably in these cases where the value of intra-abdominal pressure (IAP) becomes more relevant. The patients that Bradley113 described are, without doubt, patients with elevated abdominal pressure, who frequently are sick with a universal necrosis that is not confined to the pancreas and who are certainly those who should be treated by means of a temporary closure of the abdomen; proceeding to the conventional closing of the laparotomy is a clear predisposing factor for the development of abdominal compartmental syndrome (ACS) with fatal consequences.

If the patient is stable during pancreatic surgery, cholecystectomy can also be performed. If the condition of the patient undergoing surgery is unstable, and there is a vesicular plastron, the gall bladder should not be operated on and only the necrosectomy should be performed.

Pancreatic necrosis is a dynamic process that has two distinct phases, the early and late phases. The conclusive evidence that advised against surgery of sterile necrosis115,117 indicates that the best time to indicate necrosectomy is during the late phase of the disease, i.e. the phase in which the necrosis infection is common (often after three or four weeks from its onset).118

In the early or initial phase (first two weeks after its onset) surgical indication should only be established in the following cases:

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  Cases of MOF and diagnostic doubts between PSAP and mesenteric ischemia or perforation of an empty viscera.

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  Cases of intestinal ischemia or a perforation which is secondary to the extension and/or compression pancreatic necrosis produced by pancreatic necrosis, either at the level of small intestine or colon.

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  The appearance of ACS in the early days, by performing decompressive surgery without a necrosectomy.

In all patients with CAP or SAP AIP should be recorded regularly in search of the development of ACS that could make it necessary to perform decompressive surgery.

Minimally invasive pancreatic necrosectomy (MIN)119 has been developed according to two diametrically opposed philosophies. On the one hand, there is a group of surgeons who supports MIN as a complementary method of open necrosectomy, which is useful for the treatment of waste collection after conventional surgical treatment; this form of management has been referred to as “step-down” (5).

On the other hand, there is another group of surgeons who support “step-up” (5), which relegates open necrosectomy to a secondary option after the failure of a minimally invasive technique.

The transgastric route described by Baron120 is inspired by the classic surgical treatment of retrogastric pancreatic pseudocysts. By using this procedure, it has been possible to successfully debride pancreatic necrosis; however, it requires a specific localization of the necrosis: encapsulation and liquefaction of the necrosis area located in the lesser sac and therefore delimited by the stomach, duodenum and colon transverse: “walled off pancreatic necrosis”.

The retroperitoneal approach described by Carter's group in Glasgow121 is an adaptation of the classic lumbotomy for debridement of infected pancreatic necrosis basically localized on the left side of the abdomen.

The randomized, controlled study conducted in the Netherlands (5) comparing an open necrosectomy to the “step-up” technique (percutaneous drainage and, if it is insufficient, minimally invasive retroperitoneal necrosectomy) shows that 35% of patients can only be treated with percutaneous drainage and the remainder require the combination of percutaneous drainage and minimally invasive retroperitoneal necrosectomy. There are fewer complications, 69% for open necrosectomy versus 40% for the “step-up”; however, it was not possible to demonstrate a significantly lower mortality, 19% vs 16%.

The use of radiologically guided percutaneous catheters is considered a “bridge” technique until a more definitive treatment can be applied; it can be extremely useful for stabilizing patients whose condition is too serious to tolerate any type of necrosectomy.118 This technique has not been compared to surgical debridement, but in a systematic review of the literature on the usefulness of percutaneous drainage as the sole technique in the treatment of pancreatic necrosis, the use of drainage was found to be sufficient for 55.7% of patients who did not require surgical necrosectomy.

A new message has emerged from all these new techniques: necrosectomy in itself may be less important than achieving proper drainage.120

Currently endoscopic techniques, with some exceptions, have failed to demonstrate its superiority over conventional techniques; however, the future of minimally invasive techniques in the treatment of patients with infected pancreatic necrosis is promising, as long as the experience in handling it increases and the new technology needed for obtaining the best results appears.115,122

• Recommendation 77. Surgery. Indications: Infected necrosis plus clinical deterioration; Intestinal ischemia or perforation secondary to pancreatic necrosis; Intestinal obstruction or biliary stricture due to the organization of necrosis. Strong grade of recommendation (1), high quality of evidence (A).

• Recommendation 78. Surgery. Technique: Necrosectomy+drainage±temporary closure. Weak grade of recommendation (2), moderate quality of evidence (B).

• Recommendation 79. Surgery. Moment of surgery: 3–4 weeks after initiation of the PSAP as long as the patient's condition permits. Strong grade of recommendation (1), moderate quality of evidence (B).

• Recommendation 80. Surgery. New surgical techniques: Minimally invasive or not combined with percutaneous drainage; Retroperitoneal and transgastric. Weak grade of recommendation (2), low quality of evidence (C).

• Recommendation 81. In a patient with infected necrosis and organ failure, current indication is surgical necrosectomy. Treatment by means of other options which are less invasive, such as radiological or endoscopic techniques, has yet to be determined. Radiological or endoscopic techniques can be used in a patient with infected necrosis and without organ failure. When the patient's condition does not improve, surgical necrosectomy can be performed. Strong grade of recommendation (1), high quality of evidence (A).