Acute pancreatitis resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2]; Vendhan Ramanujam M.B.B.S [3]

Definition

Acute pancreatitis is the acute inflammation of the pancreas.

Diagnostic Criteria

▸ Diagnosis is established by the presence of two of the three following criteria (strong recommendation, moderate quality of evidence):

• Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back)
• Serum lipase or amylase ≥ 3 x ULN
• Characteristic findings on contrast-enhanced CT, MRI, or transabdominal US

Types

• Interstitial Edematous Pancreatitis

▸ Acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without recognizable tissue necrosis

CECT criteria

▸ Pancreatic parenchyma enhancement by intravenous contrast agent.

▸ No findings of peripancreatic necrosis.

• Necrotizing Pancreatitis

▸ Inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis

CECT criteria

▸ Lack of pancreatic parenchymal enhancement by intravenous contrast agent

▸ Presence of findings of peripancreatic necrosis.

• Infected Pancreatic Necrosis:

▸ It should be considered in patients with necrotizing pancreatitis who deteriorate or fail to improve after 7–10 days of hospitalization.

▸ It may be presumed by the presence of extraluminal gas on CECT or when fine-needle aspiration is positive for bacteria and/or fungi on Gram stain and culture.

▸ Antibiotics are able to penetrate pancreatic necrosis (such as carbapenems, quinolones, and metronidazole) and may be useful in delaying or sometimes totally avoiding intervention.

Complications

Organ Failure

• Modified Marshall Scoring System

Modified Marshall Scoring System^†

Organ System	0	1	2	3	4
Respiratory PaO2/FiO2	>400	301-400	201-300	101-200	≤101
Renal‡ Creatinine (μmol/l) Creatinine (mg/dl)	≤134 <1.4	134-169 1.4-1.8	170-310 1.9-3.6	311-439 3.6-4.9	>439 >4.9
Cardiovascular Systolic Blood Pressure (mmHg)	>90	<90, fluid responsive	<90, not fluid responsive	<90, pH <7.3	<90, pH <7.2

^† A score of 2 or more in any system defines the presence of organ failure.
^‡ A score for patients with pre-existing chronic renal failure depends on the extent of further deterioration of baseline renal function. No formal correction exists for a baseline creatinine ≥134 μmol/l or ≥1.4 mg/dl.

▸ For non-ventilated patients, the FiO2 can be estimated from below:

Supplemental oxygen (l/min)	FiO2 (%)
Room air	21
2	25
4	30
6–8	40
9–10	50

• Transient organ failure = organ failure resolves within 48 h.
• Persistent organ failure = organ failure persists for >48 h.

Local Complications

▸ Should be suspected when there is persistence/recurrence of abdominal pain, secondary increases in pancreatic enzyme, increasing organ dysfunction, or the development of signs of sepsis.

• Acute Peripancreatic Fluid Collection (APFC)

▸ Peripancreatic fluid associated with interstitial edematous pancreatitis with no associated peripancreatic necrosis. This term applies only to areas of peripancreatic fluid seen within the first 4 weeks after onset of interstitial edematous pancreatitis and without the features of a pseudocyst.

CECT criteria

▸ Occurs in the setting of interstitial edematous pancreatitis.

▸ Homogeneous collection with fluid density.

▸ Confined by normal peripancreatic fascial planes.

▸ No definable wall encapsulating the collection.

▸ Adjacent to pancreas (no intrapancreatic extension).

• Pancreatic Pseudocyst

▸ An encapsulated collection of fluid with a well defined inflammatory wall usually outside the pancreas with minimal or no necrosis. This entity usually occurs more than 4 weeks after onset of interstitial edematous pancreatitis to mature.

CECT criteria

▸ Well circumscribed, usually round or oval.

▸ Homogeneous fluid density.

▸ No non-liquid component.

▸ Well defined wall; that is, completely encapsulated.

▸ Maturation usually requires >4 weeks after onset of acute pancreatitis; occurs after interstitial edematous pancreatitis.

• Acute necrotic collection (ANC)

▸ A collection containing variable amounts of both fluid and necrosis associated with necrotizing pancreatitis; the necrosis can involve the pancreatic parenchyma and/or the peripancreatic tissues.

CECT criteria

▸ Occurs only in the setting of acute necrotising pancreatitis.

▸ Heterogeneous and non-liquid density of varying degrees in different locations (some appear homogeneous early in their course).

▸ No definable wall encapsulating the collection.

▸ Location—intrapancreatic and/or extrapancreatic.

• Walled-off necrosis (WON)

▸ A mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that has developed a well defined inflammatory wall. WON usually occurs >4 weeks after onset of necrotising pancreatitis.

CECT criteria

▸ Heterogeneous with liquid and non-liquid density with varying degrees of loculations (some may appear homogeneous).

▸ Well defined wall, that is, completely encapsulated.

▸ Location—intrapancreatic and/or extrapancreatic.

▸ Maturation usually requires 4 weeks after onset of acute necrotizing pancreatitis

Systemic Complications

▸ Defined as exacerbation of pre-existing co-morbidity, such as coronary artery disease or chronic lung disease, precipitated by the acute pancreatitis.

Grades of Severity

The definitions of severity in acute pancreatitis according to the revised Atlanta classification is as follows.

• Mild acute pancreatitis

▸ No organ failure

▸ No local or systemic complications

• Moderately severe acute pancreatitis

▸ Organ failure that resolves within 48 h (transient organ failure) and/or

▸ Local or systemic complications without persistent organ failure

• Severe acute pancreatitis

▸ Persistent organ failure (>48 h)

– Single organ failure

– Multiple organ failure

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Acute pancreatitis is a life-threatening condition, especially if it progresses to necrotizing pancreatitis, and should be treated as such irrespective of the cause.

Common Causes

• Alcohol 30%

• Gallstones 35-40%

• Hypertriglyceridemia 1-4% cases

• Medication such as 5-mercaptopurine, azathioprine, 5-DDI

• Pancreatic tumor

• Post-ERCP

Management

Shown below is a diagram depicting the management of acute pancreatitis according to the American College of Gastroenterology (ACG).

Characterize the symptoms: ❑ Severe abdominal pain and/or ❑ Breathing difficulty and/or ❑ Nausea & vomiting and/or ❑ Hiccups sometimes

Examine the patient: ❑ Fever and/or ❑ Hypotension and/or ❑ Cullen's sign and/or ❑ Grey-Turner's sign and/or ❑ Tachypnea and/or ❑ Abdominal distension and/or tenderness

Consider alternative diagnosis: ❑ Gallstones ❑ Dissecting aortic aneurysm ❑ Pancreatic pseudocyst

Hemodynamic stability?

Stable

Unstable

Order Labs: (Urgent) ❑ CBC ❑ Hematocrit ❑ BUN ❑ Creatinine ❑ Amylase ❑ Lipase ❑ Triglyceride ❑ Total bilirubin ❑ Direct bilirubin ❑ Albumin ❑ AST ❑ ALT ❑ Alkaline phosphatase ❑ GGT ❑ Chest X-ray Order imaging studies: (Urgent) Trans abdominal USG (TAUSG)

Stabilize the patient

Diagnostic criteria: Any 2 out of 3 ❑ Abdominal pain consistent with disease ❑ Serum amylase or lipase values > 3 times normal ❑ Consistent findings from abdominal imaging

Acute Pancreatitis

Systemic inflammatory response syndrome? (Urgent)

Yes

No

Risk stratification (Marshall scoring)(Urgent)

Lower risk

Higher risk

Admit to medical ward

Admit to ICU (Urgent)

Fluids: (Urgent) ❑ Aggressive hydration at 250-500 ml/hr with Ringer's lactate in first 12-24 hrs ❑ Reassess within 6 hrs after admission and for next 24-48 hrs Analgesics: (Urgent) ❑ Opioids are preferred ❑ Mepridine & morphine may be used as IV drips/pt. controlled analgesia Nutrition: (Urgent) ❑ Immediate oral feeding as soon as pain, vomiting, nausea subside

Fluids: (Urgent) ❑ Initiate with a fluid bolus ❑ Aggressive hydration at 250-500 ml/hr with Ringer's lactate in first 12-24 hrs ❑ Reassess within 6 hrs after admission and for next 24-48 hrs Analgesics: (Urgent) ❑ Opioids are preferred ❑ Mepridine & morphine may be used as IV drips/pt. controlled analgesia Nutrition: (Urgent) ❑ Nasogastric or nasojejunal feeding may be initiated once pain, vomiting, nausea subside ❑ Consider enteral feeding if above not tolerated

Cholangitis or biliary obstruction

Yes

ERCP within 24 hrs/Cholecystectomy to prevent recurrence

No

Consider MRCP/EUS

Clinical improvement within 48-72 hrs

Yes

Assess for ability to maintain oral feeding at the end of 1 week

N o

CECT/MRI

Recovery

Pancreatic necrosis

Failure to improve clinically after 7-10 days of hospitalization

Yes

Supportive treatment

No

Suspect Infected necrosis

❑ CT guided FNA ❑ Empiric antibiotics, necrosis penetrating: ❑ Meropenem 1g IV Q8h ❑ Ciprofloxacin 400mg IV Q12h plus metronidazole 500 mg IV Q8h for 14 days

Gram stain & Culture (-)

❑ Supportive treatment ❑ Consider repeat CT FNA every 7 days if no improvement

Gram stain & Culture(+)

Infected necrosis

Clinically stable

Clinically unstable

❑ Continue antibiotics & observe ❑ If asymptomatic no debridement, else consider surgical consultation

Prompt surgical consultation (Urgent)

^†ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; CBC: Complete blood count; CECT: Contrast-enhanced computed tomography; CT: Computed tomography; ERCP: Endoscopic retrograde cholangiopancreatography; EU: Endoscopic ultrasound; FNA: Fine-needle aspiration; GGT: Gamma-glutamyl transpeptidase; ICU: Intensive care unit; IV: Intravenous; MRCP: Magnetic resonance cholangiopancreatography; MRI: Magnetic resonance imaging; Q8h: Every 8 hours; Q12h: Every 12 hours

Do's

• CECT or MRI should be reserved for (strong recommendation, low quality of evidence):

• Patients who fail to improve clinically (e.g., persistent abdominal pain, fever, nausea, unable to begin oral intake) within the first 48-72 h after admission.
• Patients in whom the diagnosis is unclear.

• Perform abdominal USG in all patients (strong recommendation, low quality of evidence).
• Check serum triglycerides if stones/alcohol not an etiology, consider etiology if serum triglycerides >1000 mg/dl (conditional recommendation, moderate quality of evidence).
• Consider pancreatic tumor if age > 40 years (conditional recommendation, low quality of evidence).
• Limit endoscopic investigation in patients with acute idiopathic pancreatitis and refer them to centers of expertise (conditional recommendation, low quality of evidence).
• Assess hemodynamic status on presentation and begin resuscitative measures as needed (strong recommendation, moderate quality of evidence).
• Asses risk and stratify patients into higher and lower risk categories in order to assist triage (conditional recommendation, moderate quality of evidence).
• Admit patients with organ failure to intensive care unit (strong recommendation, low quality of evidence).
• Administer 250-500 ml/hour of aggressive hydration with isotonic crystalloid solution within the first 12-24 hours, unless cardiovascular and/or renal comorbidites exist (strong recommendation, moderate quality of evidence). Reassess fluid requirement frequently within 6 hours of admission and for the next 24-48 hours with the goal of decreasing blood urea nitrogen (strong recommendation, moderate quality of evidence).
• Administer a rapid bolus in patient's with hypotension and tachycardia (conditional recommendation, moderate quality of evidence).
• Use Ringer's Lactate(RL) as first choice agent, use normal saline if RL not available (conditional recommendation, moderate quality of evidence).
• Do ERCP within 24 hours of admission in patients with acute pancreatitis and concurrent acute cholangitis (strong recommendation, moderate quality of evidence). In its absence, MRCP or EUS should be used for screening choledocholithiasis if highly suspected (conditional recommendation, low quality of evidence).
• Do consider the diagnosis of gallstone pancreatitis in patients with previous history of biliary colic or gallbladder related symptoms, elevated ALT, elevated AST and gallstones detected during ultrasound and for further management, please click here.
• Pancreatic duct stents or post-procedure NSAID's are recommended to prevent post-ERCP pancreatitis (conditional recommendation, moderate quality of evidence).
• Antibiotics are given for extra-pancreatic infections such as cholangitis, catheter-acquired infections, bacteremia, UTI's, pneumonia (strong recommendation, high quality of evidence).
• Use antibiotics for infected necrosis, with high penetrance such as carbapenems, quinolones & metronidazole (conditional recommendation, low quality of evidence).
• Start oral feeding with a low fat solid diet or clear liquid diet if the abdominal pain has resolved and there is no nausea and vomiting in patients with mild acute pancreatitis (conditional recommendation, moderate quality of evidence).
• Start enteral nutrition (nasogastric and nasojejunal) in patients with severe acute pancreatitis and consider parenteral nutrition if enteral route is not available, not tolerated, or not meeting caloric requirements (strong recommendation, high quality of evidence).
• Perform elective cholecystectomy for gallstones to prevent recurrences (strong recommendation, moderate quality of evidence).
• Presence of asymptomatic pancreatic necrosis or asymptomatic pseudocysts do not warrant intervention, regardless of size, location, extension (strong recommendation, moderate quality of evidence).
• Minimally invasive necrosectomy which is preferred over open necrosectomy, radiological and/or endoscopic drainage should be delayed for more than 4 weeks (strong recommendation, low quality of evidence).

Dont's

• ERCP is not needed in most patients with gallstone pancreatitis, especially if they lack clinical or laboratory evidence of ongoing biliary obstruction.
• Do not shift patients with sepsis/organ failure to general ward.
• Do not perform emergency surgery, radiologic or endoscopic drainage in stable patients with infected necrosis, wait for 3-4 weeks for the development of a fibrous wall around the necrosis.
• Routine use of antibiotics as prophylaxis is not recommended in acute pancreatitis (strong recommendation, moderate quality of evidence).
• In patients with sterile necrosis, routine antibiotics are not recommended to prevent development of infected necrosis (strong recommendation, moderate quality of evidence).
• Anti-fungal agents are not recommended for prophylaxis or therapeutic use along with routine antibiotics (conditional recommendation, low quality of evidence).
• Do not do cholecystectomy until active inflammation subsides in necrotizing biliary pancreatitis in order to prevent infection (strong recommendation, moderate quality of evidence).