ENDOCRINE SURGERY

Ann R Coll Surg Engl 2020; 00: 1–5

doi 10.1308/rcsann.2020.0029

Severe acute pancreatitis: eight fundamental steps

revised according to the ‘PANCREAS’ acronym
CA Gomes1, S Di Saverio2, M Sartelli3, E Segallini4, N Cilloni5, R Pezzilli6, N Pagano7,
FC Gomes8, F Catena9,10

1
Therezinha de Jesus University Hospital, Juiz de Fora, Brazil
2
Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK
3
Macerata University, Macerata, Italy
4
Maggiore Hospital Regional Emergency Surgery and Trauma Centre, Bologna Local Health
District, Bologna, Italy
5
Maggiore Hospital, Bologna Local Health District, Bologna, Italy
6
Internal Medicine, Pancreas Unit, Department of Medical and Surgical Sciences, University
of Bologna, Bologna, Italy
7
Department of Gastroenterology, Department of Medical and Surgical Sciences, University
of Bologna, Bologna, Italy
8
Hospital LifeCenter, Belo Horizonte, Brazil
9
Maggiore Hospital, Parma, Italy
10
‘Infermi’ Hospital, Rimini, Italy
ABSTRACT
Severe acute pancreatitis remains a life-threatening condition, responsible for many disorders of homeostasis and organ
dysfunction. By means of a mnemonic ‘PANCREAS’, eight important steps in the management of severe acute pancreatitis are
highlighted. These steps follow the principle of goal-directed therapy and should be borne in mind after diagnosis and during
clinical treatment.
The first step is perfusion: the goal is to reach a central venous pressure of 12–15mmHg, urinary output 0.5–1ml/kg/hour and
inferior vena cava collapse index greater than 48%. Next is analgesia: multimodal, systemic and combined pharmacological
agent and epidural block are possibilities. Third is nutrition: precocity, enteral feeding in gastric or post-pyloric position.
Parenteral nutrition works best in difficult cases to achieve the individual total caloric value. Fourth is clinical: mild, moderate
or severe pancreatitis according to the Atlanta criteria. Radiology is fifth: abdominal computed tomography on the fourth day for
prognosis or to modify management. Endoscopy is sixth: endoscopic retrograde cholangiopancreatography (cholangitis,
unpredicted clinical course and ascending jaundice); management of pancreatic fluid collection and ‘walled-off necrosis’.
Antibiotics comes next: infectious complications are common causes of morbidity. The only rational indication for antibiotics is
documented pancreatic infection. The last step is surgery: the dogma is represented by the ‘three Ds’ (delay, drain, debride).
The preferred method is a minimally invasive step-up approach, which allows for gradually more invasive procedures when the
previous treatment fails.

KEYWORDS
Necrotising acute pancreatitis – Classification – Imaging diagnosis – Complications – Surgery
Accepted 11 January 2020
CORRESPONDENCE TO
Carlos Augusto Gomes, E: [email protected]; [email protected]

Introduction surgery), eight fundamental steps in the management of

severe acute pancreatitis are highlighted.1 This acronym
We review of most important aspects of the management
could be used as a flowchart to decision making in the
of severe acute pancreatitis, based on current evidence.
emergency room. It has been written according to the
By means of a mnemonic method using the acronym
principle of goal-direct therapy, to make it easy to apply
‘PANCREAS’ (perfusion, analgesia, nutrition, clinical and
in many scenarios.
radiological assessment, endoscopy, antibiotics, and

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GOMES DI SAVERIO SARTELLI SEGALLINI CILLONI PEZZILLI SEVERE ACUTE PANCREATITIS: EIGHT FUNDAMENTAL STEPS
PAGANO GOMES CATENA REVISED ACCORDING TO THE ‘PANCREAS’ ACRONYM

The PANCREAS (eight steps) acronym approach to pain and early mobilisation are recom-
mended.10,11 Systemic and combined pharmacological
P = perfusion treatment is considered the first choice and opioids have
The goals of fluid resuscitation in severe acute pancreatitis proved to be effective and safe.
are to maintain perfusion of the pancreatic microcircula- Layer et al, in a placebo-controlled clinical trial studied
tion and to prevent systemic hypovolaemia caused by the effect of systemic administration of local anaesthesia
capillary leakage syndrome, which results in increased in the management of acute pancreatitis.12 They used con-
third-space loss and decrease in intravascular volume.2 tinuous intravenous procaine infusion for 72 hours (2g/
There is still no agreement on infusion regimens, total day). The study concluded that systemic administration of
volume, type of fluid and duration of treatment, but serum local anaesthetics can improve pain control and accelerate
creatinine and elevated haematocrit can be an indicator clinical recovery severe acute pancreatitis. The mechanism
severe dehydration and more severe disease.3,4 involves complex pharmacological pathways including
According to Monnet and Teboul,5 the haemodynamic anti-inflammatory, anti-infectious, neuroprotective and
status management cannot be ascertained using a simple motility-modulating effects.12
clinical parameter. They argue that transpulmonary The Epidural Analgesia for Pancreatitis (EPIPAN) trial is
thermodilution is the technique of choice, because it a prospective randomised multicentric study, which
provides a full haemodynamic assessment including included 148 patients in two arms. EPIPAN compared the
cardiac output. It also provides continuous monitoring of application of epidural analgesia containing a mixed
many other parameters such as end-diastolic volume of the solution of ropivacaine (2mg/ml) and sufentanil (0.5μg/ml)
cardiac cavities, a marker of cardiac preload and the in continuous infusion rate of 5–15ml/hour (six to nine
systolic function of the ventricles. Transpulmonary thermo- thoracic vertebra) for at least 72 hours, plus standard
dilution has the advantage that extravascular fluid in the analgesia (opioids plus non-opioid drugs with or without
lungs, which indicate the volume of pulmonary oedema other adjuvant drugs) compared with standard analgesia
and its vascular permeability, can be estimated at the only. The study highlights the possibility that epidural
bedside. Both parameters are useful for guiding fluid analgesia may be superior to standard analgesia alone in
therapy strategy, especially in the case of acute respiratory patients with severe acute pancreatitis in the acute care
distress syndrome.5 unit. Its use may become the standard of care in selected
Targeted therapy should be based on maintaining a centres.13
central venous pressure of 12–15mmHg, urinary output of
0.5–1ml/kg/hour and the inferior vena cava collapse index N = nutrition
greater than 48% (predicted fluid reposts, sensitivity 84%, The current evidence points to the primary pathophysio-
specificity 90%).1,8 In cases of pancreatitis-associated logic aspects in severe acute pancreatitis being the
shock, vasoactive agents and invasive haemodynamic mon- systemic inflammatory response and consequent vascular
itoring are indicated.6 leakage syndrome, which promotes significant loss of
The speed of fluid resuscitation in severe acute pan- circulating volume to the third space. These mechanisms
creatitis has been debated. The timing of fluid rehydration result in impairment of organ perfusion and subsequent
intervention (12–24 hours of onset of symptoms) seems to dysfunction. Moreover, breakdown of the intestinal
be important. Crystalloid solutions have been recom- mucosal barrier highlights the need for precocity of
mended. However, the volume to be administered is still enteral/parenteral nutrition to prevent bacterial transloca-
uncertain. Studies in favour of early and aggressive fluids tion and changes in intestinal microbiota, towards a sus-
in severe acute pancreatitis employing diverse strategies tained proinflammatory status. So, the idea of ‘pancreatic
(more or less than 33% of total fluids within 24 hours) rest’ in severe acute pancreatitis is an old paradigm that
and another administering 3.5 litres or 2.4 litres intrave- should be abandoned.14–16
nously within the first 24 hours showed that those receiv- Severe acute pancreatitis is characterised by sustained
ing more aggressive intravenous fluid volumes within the protein catabolism and increased energy requirements. All
first 24 hours tend to have improved outcomes, including patients are at risk of malnourishment and should be
improved mortality rates.7 The infusion of 200–500ml/ evaluated with attention from the start to nutritional
hour or 5–10ml/kg/hour in the first 24–48 hours (about support. Enteral nutrition is considered the gold standard
2500–4000ml/24 hours of fluid infusion) may be necessary of care; it should be given in different situations, including
until the outlined parameter is reached.8 It is further in the presence of complications. Parenteral nutrition is
suggested that the use of Ringer lactate results in a well established and should be employed only in those
significant reduction in systemic inflammation in relation patients who are unable to tolerate targeted demand. It is
to the use of saline solution.9 indicated when the gut has failed or the administration of
enteral nutrition is impossible for other reasons (eg pro-
A = analgesia longed ileus, complex pancreatic fistulae or abdominal
Abdominal pain is often the predominant symptom in compartment syndrome).17
patients with acute pancreatitis. In addition, uncontrolled The nasogastric tube has been demonstrated to be safe
pain may contribute to haemodynamic instability. The pain and useful, as has the nasojejunal tube. Studies have
should be managed in an aggressive way. A multimodal showed that there are no differences in terms of mortality,

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GOMES DI SAVERIO SARTELLI SEGALLINI CILLONI PEZZILLI SEVERE ACUTE PANCREATITIS: EIGHT FUNDAMENTAL STEPS
PAGANO GOMES CATENA REVISED ACCORDING TO THE ‘PANCREAS’ ACRONYM

tracheal aspiration, diarrhoea, exacerbation of pain and characteristic imaging findings on computed tomography
meeting energy balance between the two.18 The start of (CT) or magnetic resonance imaging (MRI).23 According
enteral nutrition in severe acute pancreatitis is crucial and to Japanese guidelines, ultrasonography and MRI should
should not be postponed. Studies have demonstrated the be requested for acute pancreatitis because it is more
benefits of enteral compared with parenteral nutrition useful than CT in diagnosing bile duct stones causing
when the enteral nutrition was introduced within the first pancreatitis and haemorrhagic necrotising pancreatitis.
48 hours of the onset of the symptoms.19 Contrast-enhanced CT is useful for the diagnosis of
Regarding non-protein caloric value, 25kcal/kg/day up active haemorrhage and thrombosis associated with
to a maximum of 30kcal/kg/day with 1.2–1.5g/kg of severe acute pancreatitis.24
protein/day has been recommended. The burden of Transabdominal ultrasound is the image of choice for
carbohydrate should be decreased to 15–20kcal/kg/day in the initial evaluation of acute pancreatitis, especially in
cases of systemic inflammatory response syndrome or gallstone aetiology. In addition, contrast-enhanced CT is
organ dysfunction. Carbohydrates and lipid intake should better done at first week (third or fourth day) from the
be 3–6g/kg/day and up to 2g/kg/day, respectively, and the onset of symptoms, because it is very difficult the complete
glycaemic rate should not exceed 10mmol/l (180mg/dl) evaluation of the extension and the pancreas and
and, if persistent (over 72 hours) hypertriglyceridaemia peripancreatic fluid collection and/or necrosis in the early
occurs (greater than 12mmol/l), lipid infusion should be days. An early CT may be needed for differential diagnosis,
temporarily discontinued.17,18 in cases with an unpredicted course or when treatment
A small peptide or peptide-based formula and medium- revision strategy is needed. MRI is necessary for planning
chain triglyceride oil are the macro elements of choice, but of the clearance of the common bile duct in the case of
the standard formula could be an option if it is well toler- common bile duct stones or other causes of bile ducts
ated.18 The use of glutamine supplementation, except in obstruction.1
parenteral nutrition (greater than 0.30g/kg alanine–gluta- Severe acute pancreatitis, according to the Japanese
mine dipeptide) is not support as routine approach.17 In severity score, is present when the prognostic contrast-
addition, immune nutrition, prebiotics or probiotics are not enhanced CT score is greater than 2. It is based on accu-
advised.20 Thus, a prompt and adequate nutritional therapy mulated points acquired with progressive extrapancreatic
may reduce the morbidity, hospital stay, costs and mortality inflammation (pararenal space = 0, root of mesocolon = 1,
in patients suffering from severe acute pancreatitis. beyond lower pole of kidney = 2). In addition, take in
account the compromised hypoenhanced segments of the
pancreas (head, body and tail). One segment or peri-
C = clinical
pancreatic = 0 point, two segments = 1 point, more than
The most practical and reproducible aspect in acute
two segments = 2. The total score is graded accordingly
pancreatic diagnosis is to recognise its severity based on
(grade 1 = score 0 or 1; grade 2 = score 2; grade 3 = score
clinical features, according to the international consensus
3 or more).25
was reached in Atlanta in 2013. The disease should
therefore be classified as mild, moderate and severe
E = endoscopy
pancreatitis, taking into account the presence of organ
Endoscopic retrograde cholangiopancreatography (ERCP)
dysfunction and whether it lasts for more than 48 hours
should be performed early (within 24–48 hours) in patients
despite resuscitative procedures in severe pancreatitis.
with severe acute pancreatitis with gallstone aetiology,
There are also severe forms with locoregional complica-
associated with bile duct obstruction or cholangitis.
tions: acute inflammatory fluid collections and/or acute
Another option in unstable patients with same condition is
necrotic collection. After four weeks this is termed ‘walled-
the placement of a percutaneous transhepatic gallbladder
off necrosis’ (sterile or infected).28 The mortality rate can
drainage tube, if ERCP is not safe. In addition, endoscopic
reach 30%, especially in patients who evolve with
ultrasonography is an alternative to drainage of pancreatic
persistent organ dysfunction and infected pancreatic
collection or pancreatic walled-off necrosis. Drainage
necrosis ‘critical’ pancreatitis.21
should be postponed until its liquefaction unless the
Simple laboratory confirmation at admission of elevated
infected necrosis is responsible for organ dysfunction.26,27
blood urea nitrogen level or its subsequent rise in the next
Endoscopic ultrasound-guided diagnosis of infection
24 hours of hospitalisation is an independent risk for
necrosis and intervention has become an important tool for
mortality.22 Interleukin-6 level also seems to be an
the management of pancreatic fluid collection and is
acceptable predictor of severe acute pancreatitis with
considered the option of first choice for most patients in
sensitivities ranging from 81.0% to 83.6% and specificities
centres of excellence. Two endoscopic procedures were
from 75.6% to 85.3% and should be employed in the first
described to manage infected walled-off necrosis: direct
72 hours.23
endoscopic necrosectomy and lumen-apposing metal
stenting. The first procedure, despite temporising patient
R = radiology recovery and treating the infected necrosis, is associated
At least two of following criteria are necessary for diagno- with very high morbidity and mortality. On the other hand,
sis of acute pancreatitis: typical pain and/or lipase amylase the second represents a significant promise of improved
levels three times greater than plasma concentration and and simplified management of these collections.28

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PAGANO GOMES CATENA REVISED ACCORDING TO THE ‘PANCREAS’ ACRONYM

A = antibiotics S = surgery
Infectious complications are common causes of morbidity Generally, the treatment for severe acute pancreatitis is a
and mortality in patients with severe acute pancreatitis. medical supportive therapy. However, serious complica-
The controversy over using antibiotics should be focused tions may affect some patients, and the rate ranges from
on pancreatic necrosis. In fact, patients with infected 10% to 30%.37 During the early phase of severe acute
necrosis have a higher mortality rate than those with pancreatitis, surgery is rarely indicated. The main reasons
sterile necrosis.40 Although early non-randomised trials for an urgent laparotomy are abdominal compartment
suggested that administration of antibiotics may prevent syndrome not responsive to clinical measures and intesti-
infectious complications in patients with sterile nal perforation. In cases of intra-abdominal bleeding,
necrosis,29,30 other better-designed trials have failed to angiography with embolisation is the first choice; surgery
confirm the advantage of antibiotic prophylaxis in acute should be expedited in case of failure.38
pancreatitis.31–33 Guidelines do not therefore recommend Interventional strategy, such as endoscopic drainage,
antibiotic prophylaxis in patients with acute pancreatitis. minimally invasive or open necrosectomy, should be
The only rational indication for antibiotics is documented delayed when possible, at least for four weeks after the
pancreatic infection and antibiotics should be always given onset of symptoms, to liquefy the necrotic tissue and to
to treat patients with infected necrosis.26,31,32 allow the collection to evolve in walled-off necrosis. Thus,
Although the diagnosis of infection in severe acute interventional strategy is indicated in cases of suspected
pancreatitis may be difficult based on clinical parameters, or confirmed infected necrosis, continuing clinical deterio-
infected necrosis should be considered in patients who ration with organ failure, despite maximum medical sup-
deteriorate or fail to improve after 7–10 days of hospitalisa- port; in case of persistent symptoms of gastric, intestinal or
tion. An empirical antibiotic regimen should be given in biliary obstruction deriving from mass effect. When an
these patients. After empirical antibiotic therapy, a targeted interventional approach is indicated, the dogma is repre-
antibiotic treatment can be based on the results of the sented by the ‘three Ds’ (delay, drain, debride), which
cultures from the necrosis. A CT-guided fine-needle aspi- summarise the contemporary strategy for the management
ration for Gram stain and culture can guide clinicians in of patients with necrotising acute pancreatitis.39
choosing a further individualised antibiotic regimen.26 The preferred method is a minimally invasive step-up
Appropriate spectrum and adequate tissue levels at the approach, which consists of gradually more invasive
site of infection are the main aspects that should be procedures, when the previous procedure fails.40 Many
considered when selecting an appropriate antimicrobial. minimally invasive techniques are available to drain and
Two factors should drive clinicians in choosing the antibi- debride infected necrotic pancreatic tissue. Percutaneous
otics: the microbiologic flora and the penetration of the catheter or endoscopic drainage should be the treatment of
antibiotic agent in the necrotic pancreatic tissue. The spec- first choice, indicated in case of infected acute necrotic
trum of empirical antibiotic regimen should include both collections or walled-off necrosis.41 The next step involves
aerobic and anaerobic Gram-negative and Gram-positive minimally invasive surgical debridement, such as minimal
microorganisms. The bacteria most frequently found were access retroperitoneal pancreatic necrosectomy (MARPN)
Escherichia coli, Enterococcus, Staphylococcus aureus, S. or video-assisted retroperitoneal debridement (VARD),
epidermidis, Klebsiella pneumoniae, Pseudomonas sp. and which are the two minimally invasive techniques for
Streptococcus sp.33,34 surgical necrosectomy. However, there is no strong
Pancreatic penetration is good for fluoroquinolones, evidence to support either as the better choice between
carbapenems, ceftazidime, cefepime, metronidazole and VARD and MARPN; the differences are small, so they are
piperacillin-tazobactam.35 When there is no or minimal interchangeable.41
residual infection following a source control procedure, a Transperitoneal laparoscopic necrosectomy and drain-
7–10-day period of antibiotic therapy may be sufficient, age should be considered as alternative procedure to
based on improvement of the patient’s condition. Candida MARPN or VARD, especially if the necrotic area is limited
infections are often present in these patients and antifungal to the lesser sac,42 or when intra-abdominal distant
therapy should be based on previous exposure to antifun- collections require minimally invasive drainage. If they are
gal agents, colonisation status of the patient and severity of multiple, located between intestinal loops and cannot be
the illness. Fluconazole remains the most widely used reached percutaneously. These minimally invasive strat-
agent for antifungal treatment. When the patient has egies aim to reduce mortality and morbidity, which classi-
already been exposed to fluconazole or is colonised with cally affect patients with severe acute pancreatitis
non-albicans candida or when the patient is haemodynami- undergoing more aggressive approaches, such as laparo-
cally unstable, therapy with echinocandins is suggested.35 tomic necrosectomy. Therefore, open necrosectomy
Routine fine-needle aspiration is not recommended due remains as the last step and it is indicated after failure of
to high rates of false negativity, although it has been the minimally invasive approaches. However, laparotomy
suggested to help direct antibiotics; prospective studies is associated with high morbidity and mortality and it
confirming the benefit of such a strategy are lacking.36 should be considered only as a last resort.

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Cholecystectomy should be performed during the index nutrition therapy in pancreatitis. JPEN J Parenter Enteral Nutr 2012; 36:
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should be delayed until clinical resolution in patients who pancreatitis: meta-analysis of individuals using a single-arm of randomised
have severe acute pancreatitis.42 Thus, the best surgical trials. Pancreatology 2014; 14: 340–346.
strategy is multimodal and tailored on the clinical condi- 20. Besselink MG, van Santvoort HC, Buskens E et al. Dutch Acute Pancreatitis
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