#327 Acute Pancreatitis

April 4, 2022 | By Matthew Watto, MD

Video

Rapidly treating Acute Pancreatitis might change its course! Learn what you really need to diagnose pancreatitis, when to use imaging sources and what is most important in management! We’re joining Dr. Kaveh Sharzehi @sharzehi of Oregon Health & Science University (@OHSUNews).

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Credits

• Producer & Scriptwriters: Monee Amin MD and Meredith Trubitt MD
• Show Notes & Infographics: Andréa Perdigão 
• Cover Art: Monee Amin MD
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP   
• Reviewer: Molly Heublein MD
• Executive Producer: Beth Garbitelli
• Showrunner: Matthew Watto MD, FACP
• Editor: Clair Morgan of nodderly.com
• Guest: Kaveh Sharzehi MD, MS 

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Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner
• Case from Kashlak
• Risk factors for severe course
• Use of Scoring Systems 
• Requirements to make the diagnosis 
• Rational use of imaging 
• Initial management: fluids, analgesia, and nutrition
• When to use antibiotics 
• When to perform cholecystectomy 
• Most common complications and interventions 
• How to follow up in the outpatient setting

Acute Pancreatitis Pearls

1. Acute Pancreatitis is more severe in patients with higher BMI or Metabolic Syndrome. 
2. Patients with comorbidities are at high risk for organ dysfunction and we should have a lower threshold for sending them to the ICU. 
3. Early resuscitation is key to prevent necrotizing pancreatitis.
4. CT scan is not needed at time of admission and may be more useful after 72 hours to assess complications.
5. It is important to investigate the etiology of pancreatitis because it might change initial management.
6. Prolonged bowel rest is not recommended. Early enteral nutrition prevents bacterial translocation and reduces infection. 
7. Fever and leukocytosis at an early stage doesn’t mandate empiric antibiotic use, as acute pancreatitis alone does not warrant prophylactic antibiotics. Antibiotics may be useful for alternative known infections (i.e. cholangitis, aspiration pneumonia, etc.)  
8. During transition of care, the provider needs to consider complications of long term endocrine and exocrine dysfunctions.

Acute Pancreatitis Show Notes 

How To Diagnose

The diagnosis of acute pancreatitis (AP) requires two out of three of the following diagnostic criteria: (1) characteristic abdominal pain (acute, persistent, and severe epigastric pain that can radiate to the back); (2) serum pancreatic enzymes (lipase or amylase) greater than three times the upper limit of normal (ULN); (3) common AP findings on imaging – computed tomography (CT) scan, magnetic resonance imaging (MRI) or transabdominal ultrasound (Banks 2013).

Although elevation of serum pancreatic enzymes is a component of the diagnostic criteria, lipase level does not indicate severity of disease (Lankisch 1999, Holmes 2011). Also, improvement of the value does not correspond to an improvement of clinical condition, as taught by Dr. Sharzehi. 

It is Dr. Sharzehi’s expert opinion that cross-section imaging/CT scan within the first 48 hours has very limited value on patient management. It might help if symptomatology or pancreatic enzymes are equivocal, and you need the third item to help make the diagnosis (Boxhoorn 2020). Delayed presentation can cause the serum amylase and lipase to present below three times ULN, requiring imaging to confirm the diagnosis (Banks 2013).

Although some literature endorses contrast enhanced CT scan as the standard for establishing severity, it might not be the best early resource, since it best evaluates peri-pancreatic inflammation and pancreatic necrosis, which tends be detectable 72-96 hours after beginning of the symptoms (Boxhoorn 2020; Chatila 2019; Leppaniemi 2019).

The transabdominal ultrasound is the only early imaging that might change the initial management, once it assesses possible biliary tract causes of AP, visualizing obstructing gallstones, sludge, or biliary tract dilation. It should be considered if there are signs of hepatic involvement, such as liver enzyme elevation. Also, the ultrasound is a reasonable first choice because it is available at bedside, does not need contrast and is inexpensive (Goodchild 2019). As Dr. Sharzehi says, there is no utility for an early cross-sectional imaging if the ultrasound already shows signs of biliary tract etiology for AP! 

MR cholangiopancreatography (MRCP) is recommended when the patient presents with signs of cholangitis. But Dr. Sharzehi emphasizes that there is no need to rush to a MRCP! Even if there are signs of gallstones, we have the option to monitor clinical status and liver function tests within 24 to 48 hours. If the patient improves clinically and LFTs are down trending after 48 hours, we can presume that the stone has passed or was not obstructing. On the other hand, if LFTs and clinical status deteriorate, a MRCP and a consultation with the gastroenterologist should be obtained. MRCP might be recommended early on to assess obstructive stone disease with signs of cholangitis (right upper quadrant tenderness, fever, jaundice).

Scoring Systems 

A wide variety of scoring systems try to predict the course of acute pancreatitis. They intend to classify the severity of the disease and, based on severity, determine the appropriate treatment regimen, and avoid complications (Chatila 2019). Though they are frequently used for research purposes, their high false positive rate, low specificity, and low positive predictive value limited their clinical use (Boxhoorn 2020; Forsmark 2016). 

One of the most reliable and the best metrics to assess acute pancreatitis, according to Dr. Sharzehi, is the revised Atlanta Classifications (RAC), which simplifies classification of AP into two buckets – type and severity (Boxhoorn 2020; Banks 2013).

RAC classifies AP into two types: interstitial edematous pancreatitis and acute necrotizing pancreatitis. The differentiation of those two types is based on contrast enhanced CT scan. The interstitial edematous pancreatitis has a homogeneous enhancement associated with a diffuse or partial expansion of pancreatic parenchyma due to edematous inflammation. While necrotizing pancreatitis presents areas of impaired enhancement, evidence of necrosis on the tissue should be identified after the first week of the symptoms begin (Banks 2013).

This classification helps distinguish and plan a treatment approach for the different local complications any of those types might develop (Boxhoorn 2020; Leppäniemi 2019).

In terms of severity, AP is classified as: mild, when there is no organ failure nor local complications; moderate, when there is transient organ failure (resolves within 48 hours), local complications or exacerbation of co-morbid disease; or severe, presenting persistent organ failure (more than 48 hours) (Leppäniemi 2019; Chatila 2019). The Lancet Seminar (2020) approaches classification differently: it classifies as moderately severe AP as presenting with local and/or systemic complications with transient organ failure; and severe as presenting with local and/or systemic complications with persistent one or multiple organ failure (Boxhoorn 2020).

Dr. Sharzehi states that organ failure can be defined using the Marshall Score System (MSS), establishing that a score of 2 or higher in each category defines organ failure. The advantage of the MSS use is to assess possibly damaged organ systems – cardiac, respiratory, renal – and repeat the evaluation periodically, enabling verification of improvement of organ failure (Banks, 2013). 

Etiologies and risk factors

Etiologies  

Different etiologies may determine management or risk of recurrence. According to Dr. Sharzehi, there are few etiologies that might change initial management. Evaluation of the history, physical exam and imaging can help to narrow the possible causes of AP and as such, choose the best management option (Boxhoorn 2020; Chatila 2019; Leppäniemi 2019).

Biliary tract disease is the most common cause of AP, ranging from 28% to 45% of all causes of pancreatitis. (Boxhoorn 2020; Chatila 2019). They can be caused by gallstones or sludge duct obstruction and high pressure, causing the accumulation of enzymes inside pancreatic ducts. Early identification of gallstones defines etiology and helps establish future treatment plan, that might include Endoscopic retrograde cholangiopancreatography (ERCP) and Cholecystectomy. (Boxhoorn 2020; Leppäniemi 2019; Forsmark 2016). 

Alcohol-induced pancreatitis is the second most common cause of AP. The pathophysiology is complex, but acute pancreatitis most likely is the consequence of a chronic pancreatitis caused by long term and heavy alcohol use (Chatila, 2019; Forsmark, 2016). Dr. Sharzehi states that alcohol related AP does not change initial management. But it is important to encourage cessation to avoid recurrence (Chatila, 2019; Boxhoorn, 2020; Forsmark, 2016). 

Beyond that, hypercalcemia and hypertriglyceridemia are rare causes of AP. Hypercalcemia seems to induce pancreatitis by the disruption of intracellular signaling and cell damage. Hypertriglyceridemia can cause damage to vasculature and acinar cells of the pancreas when there is high concentration of free fatty acids released during hydrolysis of triglyceride rich lipoproteins. It causes ischemia and an acidic environment. Those etiologies might be linked to other conditions, like hyperparathyroidism or Cystic Fibrosis, predisposing to acute pancreatitis (Chatila, 2019; Forsmark, 2016). Dr. Sharzehi advises checking serum calcium and triglycerides as potential reversible causes of AP.

Idiopathic Pancreatitis is defined as AP with no identified etiology after laboratory and imaging findings. After the acute phase, the endoscopic ultrasound (EUS), CE-CT or MRI might be performed to exclude microlithiasis, neoplasm, or chronic pancreatitis. Further investigation may help prevent recurrence (Leppäniemi, 2019; Goodchild, 2019; Chatila, 2019).

There are other possible causes for pancreatitis, some of those causes are identified during history, such as history of Cystic Fibrosis or trauma, others are visualized on imaging, like anatomical abnormalities or signs of malignancy (Chatila, 2019; Forsmark, 2016). Other rare causes of pancreatitis, as autoimmunity, should not be investigated at acute phase of the disease, as clarified by Dr. Sharzehi. 

Risk Factors  

Elevated BMI, diabetes mellitus, and tobacco use are risk factors for severe pancreatitis. Obesity and diabetes are risk factors for chronic pancreatitis and pancreatic cancer (Forsmark, 2016; Leppäniemi, 2019).  Dr. Sharzehi warns that those conditions might predispose to organ failure. He recommends a low threshold for sending these patients to the ICU, based on the previous health conditions that might decompensate or the possible organ failure they might already have. 

Management   

Initial management  

The primary goal of the initial management of Acute Pancreatitis is to prevent complications and reduce symptoms. Basically, it is composed by fluid correction, pain management, bowel rest. Management should be multidisciplinary (Goodchild, 2019). 

Fluid management 

Early fluid resuscitation is the most important aspect of initial management because it prevents ischemia, local complications, and organ failure (Goodchild, 2019). The intense inflammatory response AP causes a great amount of fluid shifting into the third space, which causes intravascular volume depletion, hypoperfusion and organ failure (Boxhoorn, 2020). Therefore, early and adequate fluid restitution is necessary to avoid complications, such as pancreatic necrosis and organ failure, which are mainly caused by diminished organ perfusion. Intravenous fluid therapy rate should be around 5-10 ml/kg per hour most importantly during the first 12 – 24h of the beginning of the symptoms. 

Clinical and laboratory findings should guide the volume repletion. This regimen should be continued until heart rate less than 120 per minute, mean arterial pressure between 65 – 85 mmHg, urinary output over 0.5 – 1.0 ml/kg per hour. Blood pressure, heart rate, urine output, BUN, creatinine, hematocrit, lactate, and signs of hypoperfusion or congestion should be monitored to detect insufficient fluid reposition or signs of volume overload (Chatila, 2019; Goodchild, 2019; Leppäniemi, 2019). 

Though, it is still controversial if Ringer’s Lactate (RL) leads to better outcomes than Normal Saline (NS). Some studies recommend RL, as it might lower the chance of progressing to Systemic Inflammatory Response Syndrome (SIRS), reduce inflammatory markers (such as C-reactive protein concentration), and correct hypokalemia (Boxhoorn, 2020; Goodchild, 2019; Forsmark, 2016). Dr. Sharzehi states that RL should not be used when there is a history of hypercalcemia induced AP. But, more important than the type of crystalloid used, he emphasizes that the key point is the effective resuscitation of fluids within 24h to prevent complications. Dr. Sharzehi even says the correct amount of early fluid resuscitation within 24h might prevent evolving from an interstitial pancreatitis into a necrotizing pancreatitis, because the AP pathologic process increases intrapancreatic pressure, which contributes to ischemia and necrosis of the tissue, an irreversible outcome. 

Pain management 

Dr Sharzehi emphasizes that early pain relief is important, not only for patient’s comfort, but to reduce triggering catecholamine release, which causes vasoconstriction and worsening of pancreatic ischemia. Opioids, like morphine and fentanyl, are commonly used, but no medication showed superior benefit (Goodchild, 2019; Boxhoorn, 2020). Epidural anesthesia might be considered for severe acute pancreatitis that demands high doses of analgesics (Leppäniemi, 2019). 

Nutrition  

Early enteral nutrition (within 24h after admission) is recommended for mild to moderate cases, if patients can tolerate it. Complete resolution of abdominal pain or lowering of serum pancreatic enzymes is not necessary to introduce diet (Forsmark, 2016; Goodchild, 2019). Low-fat diets are recommended, but the consistency is not a major concern (Forsmark, 2016). If the patient cannot tolerate oral nutrition, nasoenteric feeding can be started about 72h after insufficient oral intake, using a nasoduodenal feeding (Dobhoff) tube (Forsmark, 2016). 

Total parenteral nutrition (TPN) should be avoided even for severe AP patients in the ICU, according to Dr. Sharzehi. TPN should be limited to the patients that cannot tolerate enteral nutrition or achieve nutritional goals (Forsmark, 2016; Boxhoorn, 2020; Goodchild, 2019). 

Enteral nutrition is preferred because it helps maintain gastrointestinal mucosal barrier, reducing bacterial translocation and, consequently, lowering chance local infection or SIRS (Boxhoorn, 2020; Forsmark, 2016). Dr. Sharzehi even recommends a low threshold to place post pyloric enteral access and start nutrition within 48h even in severe cases. 

Antibiotic use 

Antibiotics should only be used in pancreatitis if it is treating a complication. Confirmed pneumonia, bacteremia, or cholangitis are common complications within early AP and should be treated with antibiotics (Boxhoorn, 2020). 

Dr. Sharzehi’s expert opinion: Fever, leukocytosis, and other positive serum inflammatory markers within the first 7 to 10 days of pancreatitis should not indicate antibiotic therapy. Only if there are signs of known infection (i.e. pneumonia, cholangitis). Persistent or worsening of symptoms after 7-10 days should raise suspicion of local complications, such as infected walled-off necrosis or infected necrosis. To confirm, imaging tests must be repeated.  

Necrotic collections usually get infected after 2 weeks of the disease’s course (Forsmark, 2016). Differentiation between infection or inflammation on imaging can be challenging, not always showing the pattern of gas within the necrotic collection indicative of infection (Leppäniemi, 2019). CT-guided fine-needle aspiration of necrotic areas for Gram stain and culture may solve diagnostic uncertainties and guide antibiotic therapy. However, it may be controversial due to its high false negative rate (Boxhoorn, 2020; Leppäniemi, 2019). 

Secondary prevention  

Almost 20% of patients with Acute Pancreatitis have recurrent episodes. Cholecystectomy should be considered for all biliary acute pancreatitis. In mild AP, cholecystectomy should be performed during index admission to prevent recurrence, which occurred in 18% of patients with mild cases who did not undergo surgery within 6 weeks (Goodchild, 2019). Same-admission cholecystectomy reduced to 5% the related gallstones-related complications and mortality when compared to delayed elective procedure (17%) (Boxhoorn, 2020; Forsmark, 2016). 

AP complicated necrotic collections should delay cholecystectomy until collection resolution (Boxhoorn, 2020). Dr Sharzehi instructs that more severe disease, with multiple organ failure or necrosis, should wait 6 weeks after the hospitalization.

Local Complications 

Local complications should be suspected when there is persistence of abdominal pain, worsening organ dysfunction (increasing liver or pancreatic enzymes, signs of gastric or intestinal obstruction) or clinical signs of sepsis (Banks, 2013). 

The different patterns of pancreatitis tend to develop different complications. Interstitial edematous pancreatitis can develop peripancreatic fluid collections during the early phase of the disease, which commonly resolves on its own and does not need intervention if the patient remains asymptomatic.  Rarely, if the collection persists for 4 weeks, it becomes a pseudocyst, which is a fluid collection delineated by a well-defined wall and without any solid masses or necrosis. They may develop from disruptions of pancreatic ducts filled up with pancreatic secretions (Banks, 2013).

On the necrotizing pathway, you can have gland parenchymal necrosis or/and peripancreatic necrosis, which is the surrounding fatty tissue developing fat necrosis.  Usually, we see evidence of necrosis on imaging after 5 to 7 days.  Acute necrotic collections may  involve pancreatic tissue and surroundings, being visualized as a fluid collection with solid necrotic parts. Necrotic tissue mixed with fluid can be encapsulated by a well-defined inflammatory wall, forming a walled-off necrosis.  Differentiation of those complications can be made by clinical signs and imaging (Banks, 2013).  

Dr. Sharzehi makes it clear that infected necrosis tends to be more severe and unstable. They might be identified using clinical worsening signs and findings like gas on imaging.  Sterile collections are usually just painful due to enlargement, which may cause organ compression, like gastral obstruction.

Dr. Sharzehi’s recommendations intervention on fluid collections are when there is: 

Evidence of infection – consider if the patient is clinically worse, febrile, with leukocytosis after 2 weeks, and there is a suspicion that fluid collections may be infected.  A CT-guided aspiration may be performed for Gram stain and culture, and broad-spectrum antibiotic treatment should be started. It is often not recommended to perform an endoscopic procedure during the early phase because the collections are not well-defined (Boxhoorn, 2020; Forsmark, 2016).

High risk of collection contamination – if there is a great concern for infection, it might be important to undergo percutaneous drainage to avoid further infection. If it is too early and it is not well encapsulated, drainage should be postponed more than 3 weeks. 

Causing symptoms – If the collection is enlarged, causing pain, difficulty eating, or organ obstruction, this can be an indication for drainage. Possible compression of duodenum and gallbladder can cause bile obstruction(Leppäniemi, 2019).

Partial or complete pancreatic ducts disconnection can be a complication of pancreatic necrosis. Its integrity may be evaluated using secretin-enhanced MR- cholangiopancreatography. Even though there are no guidelines for the treatment, endoscopic transluminal drainage of collections with double-pigtail stents or transpapillary bridging might be reasonable choices (Boxhoorn, 2020).

Post Discharge Follow-up   

Acute Pancreatitis outpatient follow-up can be made by a gastroenterologist, internist, or the family doctor. Routine imagining is not usually recommended, unless there is recurrence of AP,  history of worsening of symptoms or signs of focal complication, to assess the size and evaluate the need for an endoscopic or percutaneous treatment. There is no need for imaging follow-up to evaluate reduction of collections or mild and resolving symptoms (Expert opinion). 

However, follow-up of Acute Pancreatitis patients should be made within 6 to 12 months to assess endocrine or exocrine dysfunction, which can occur related to pancreatic injury. Clinical and laboratory findings that suggest exocrine pancreatic insufficiency are weight loss, steatosis stools, fat soluble vitamin deficiency. 

Endocrine pancreatic dysfunction, represented by prediabetes and diabetes mellitus (DM) were observed in almost 40% of the patients after the first episode of AP. In severe AP cases, prevalence of diabetes goes up to 30% and prediabetes 20%, and the risk increases over time(Das, 2014). For that reason, Dr. Sharzehi indicated the routine check for high blood sugar during discharge and HbA1c in an outpatient setting. Follow-up does not change between necrotic or non-necrotic pancreatitis. 

Links

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Goal

Listeners will acknowledge the nuance and complexity of treating acute pancreatitis in the hospital.

  Learning objectives

After listening to this episode listeners will…

1 – List potential etiologies of acute pancreatitis

2 – Discuss initial management of acute pancreatitis

3 – Define complications of acute pancreatitis

4 – Identify appropriate treatment for specific complications of acute pancreatitis

5 – Manage outpatient follow-up after acute pancreatitis 

Disclosures

Dr. Kaveh Sharzehi reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Amin M, Trubitt, M, Sharzehi K, Perdigão A, Williams PN, Watto MF. “#327 Acute Pancreatitis”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list April 4, 2022.