CONTENTS

• Rapid Reference 🚀
• Diagnosis
• Evaluating the cause of pancreatitis
• Risk stratification- who needs ICU?
• Treatment
  • General principle: pancreatoseptic equivalence
  • Treatment of causative factors
  • ERCP?
  • Resuscitation
  • Nutrition
  • Analgesia
  • Prophylactic & early antibiotics
  • Fluid collections & infected necrosis
  • Abdominal compartment syndrome
  • Hemorrhage
• Podcast
• Questions & discussion
• Pitfalls

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rapid reference

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Pancreatitis management checklist ✅

Evaluation to guide etiology & management 📖

• RUQ ultrasound.
• Calcium level.
• Triglyceride level.
• Liver function tests.
• Review of medication list for potentially causative drugs.

Resuscitation 📖

• Same resuscitative strategy as for septic shock (e.g., moderate fluid, early vasopressors).
• Avoid large-volume resuscitation (which causes abdominal compartment syndrome).

ERCP 📖

• Not routinely indicated.
• May be considered if evidence of ascending cholangitis or choledolithiasis (e.g., markedly elevated bilirubin, dilation of the common bile duct).

Nutrition 📖

• Non-intubated:  Low-fat diet, as tolerated.
• Intubated:  Start enteral nutrition as soon as hemodynamically stabilized.

Pain control 📖 

• Start with scheduled acetaminophen 💉 (e.g., 1 gram Q6hr) and pain-dose ketamine infusion 💉 (0.1-0.3 mg/kg/hr).
• Opioids may worsen ileus, limit them as able.

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diagnosis

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diagnostic criteria for acute pancreatitis

• At least two of the following are required:
  • (1) Elevation of lipase >3 times upper limit normal (i.e., >~500 U/L).
  • (2) Characteristic abdominal pain.
  • (3) Imaging evidence of pancreatitis on CT, MRI, or ultrasound.
• Patients not meeting these criteria don't have pancreatitis and should not be treated for it.

clinical findings

• Pain:
  • Typically in epigastrum or left upper-quadrant, may radiate to the back, may be relieved by sitting.
  • Epigastric tenderness on exam is usually present.
• Persistent nausea/vomiting.
• Hemorrhagic pancreatitis may cause Cullen Sign and Grey Turner Signs:

lipase

• Sensitivity and specificity are ~90% for acute pancreatitis.
• Causes of elevated lipase include:
  • Pancreatic disease of any sort (e.g., pancreatitis, pseudocyst, cancer).
  • Intestinal obstruction/pseudo-obstruction, perforation, duodenal ulceration, ischemia.
  • Biliary disease (cholecystitis, cholangitis, choledocholithiasis).
  • Renal failure.
  • Heparin therapy (through activation of lipoprotein lipase).(33556276)
• Elevations of lipase due to diseases other than pancreatitis tend to be under three times the upper-limit normal.
  • Very high lipase values are more specific for a diagnosis of pancreatitis.
  • Higher lipase values don't correlate with worse prognostic outcome.  So severely elevated lipase values may seem scary, but they shouldn't actually be.
• Lipase has replaced amylase for the diagnosis of pancreatitis.  There is no point in checking an amylase level.

CT scan

• Early CT if necessary to clarify the diagnosis:
  • CT is sensitive and specific for pancreatitis, also providing information about severity.
  • If the patient definitely has pancreatitis (based on typical history, exam, and labs), then there is no reason to get an early CT scan (it won't affect management).
  • For patients in shock, CT scan is often sensible to exclude a focus of intra-abdominal sepsis.
• Late CT scan for complications:
  • The primary role of CT scan in pancreatitis is to look for complications if the patient deteriorates later in their course (after several days).   For example, CT scan may help evaluate for infected necrosis and pseudocyst.

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evaluating the cause of pancreatitis

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common causes of acute pancreatitis

• Gallstones (~40%).(30243452)
• Alcoholism (~30%).
• Metabolic abnormalities:  hypertriglyceridemia, hypercalcemia.
• Medications include:(29736167)
  • Antibiotics:  tetracyclines, sulfonamides, pentamidine, HIV medications, isoniazid, metronidazole.
  • Immunosuppressives:  azathioprine, sulfasalazine, aminosalicylates, 6-mercaptopurine.
  • Cardiac:  amiodarone, losartan, furosemide, pravastatin, simvastatin.
  • Valproic acid.
  • All-trans-retionic acid (ATRA).
  • Glucagon-like peptide-1 agonist therapy for diabetes.
• Posterior penetrating ulcer, trauma.
• Iatrogenic: ERCP, surgery, radiation therapy, post CABG.
• Pancreatic malignancy.
• Cystic fibrosis.

labs to evaluate the cause of pancreatitis:

• Calcium:  Rarely, hypercalcemia is a rare cause of pancreatitis.  More commonly, pancreatitis may cause hypocalcemia (which can occasionally be symptomatic).
• Triglyceride level:>1,000 mg/dL or >11.2 mM suggests hypertriglyceridemic pancreatitis. 📖
• Liver function tests:  Significantly elevated bilirubin and alkaline phosphatase suggest obstruction, raising a possible concern of simultaneous ascending cholangitis.

right upper quadrant ultrasonography

• This should be obtained on all pancreatitis patients.(10580962)
• Gallstones may suggest gallstone pancreatitis.
• The most important finding is size of the common bile duct.

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risk stratification-  who needs ICU?

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Most pancreatitis patients have mild disease and can be admitted to the ward, but some require ICU admission.  This is tricky because pancreatitis patients may look OK initially, but deteriorate later.

edematous vs. necrotizing pancreatitis

• Pancreatitis can be divided into two categories:
  • Interstitial edematous pancreatitis (90%) – diffuse inflammation of the pancreas, tissue remains viable.
  • Necrotizing pancreatitis (10%) – areas of pancreatic tissue become necrotic.
• The diagnosis of necrotizing pancreatitis is generally made based on contrast CT scan, which shows a lack of blood flow to necrotic areas.  (Note, however, that CT scan shouldn't be obtained solely for this purpose.)
• Necrotizing pancreatitis is more worrisome, as these patients are at risk for developing multiorgan failure or superinfection of the devitalized pancreatic tissue (infected pancreatic necrosis).  The mortality rate of necrotizing pancreatitis is 17%, much higher than the mortality of interstitial edematous pancreatitis at 3%.(29736167)

definition of severe acute pancreatitis (SAP)

• Severe Acute Pancreatitis (SAP) is defined as acute pancreatitis causing organ failure that persists for >48 hours (including shock, renal failure, and hypoxemic respiratory failure).  Severe acute pancreatitis describes ~15% of all patients with acute pancreatitis, who are at increased risk of mortality.(33230385)
• Defining the severity of pancreatitis in terms of organ failure is a clinically useful approach at the bedside.  This has the advantage that it doesn't require advanced imaging or comprehensive laboratory analysis.

scoring systems

• Numerous scoring systems are available to predict outcomes.  However, it's unclear whether scoring systems add substantively to clinical judgement.
• APACHE-II score might be the best scoring system, with scores >7 predicting severe acute pancreatitis.  Unfortunately, its performance is far from perfect (with sensitivity of 65% and specificity of 76%).🧮
• The Ranson score can't be calculated until after 48 hours, so it plays no role in up-front risk stratification.

neutrophil/lymphocyte ratio (NLR)

• NLR is a global indicator of physiological stress which is easily calculated from an admission blood count.🌊  Higher NLR values predict severe pancreatitis (area under ROC curve of ~0.75) and mortality (area under ROC curve ~0.8).(27631223, 28638228, 28878366, 29030078, 28348184)  NLR seems more accurate than C-Reactive Protein (CRP), a lab test which is occasionally recommended for prognostication in pancreatitis.(28348184, 29370777)
• The table below provides a rough guide to interpreting NLR in this context.(27631223)   Prognostication shouldn't be based solely on NLR, but this may provide another bit of information that contributes to the global assessment.

possible indications for ICU admission?

• Organ failure(s), including:(33464002)
  • Acute kidney injury, including substantially reduced urine output.
  • Marked delirium.
  • Hypotension, bradycardia, or tachycardia.
  • Significant tachypnea or increased work of breathing.
  • Hypoxemic respiratory failure.
• Hypertriglyceridemic pancreatitis (triglyceride >1,000 mg/dL or >11.2 mM) should be considered for insulin infusion in the ICU. 📖

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general principle- pancreatoseptic equivalence

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Historically, pancreatitis has been treated as a unique disease.  It was feared by intensivists, who skittishly deferred management to gastroenterologists and surgeons.  Pancreatitis was treated with vast quantities of fluid, bowel rest, nasogastric tube drainage, parenteral nutrition, and prophylactic antibiotics – a wholly bizzare potpourri of therapies inconsistent with basic principles of critical care.  Only recently have we begun the hard work of dispelling these harmful treatments.

principle of pancreatoseptic equivalence 

• Severe pancreatitis and septic shock are extremely similar processes (both vasodilatory shock states involving profound systemic inflammation and endothelial dysfunction).
• The treatment for severe pancreatitis should follow the same principles as the treatment of septic shock.
• Evidence gaps regarding how to manage severe pancreatitis can be filled with experience gained from the treatment of septic shock.

This is probably not entirely accurate, but it's a huge advance compared to the bizarre ways in which pancreatitis has been treated over the past few decades.

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treatment of causative factors

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• Hypertriglyceridemic pancreatitis:  Discussed further here.📖
• Medication-induced:  Stop potentially offending medications.
• Hypercalcemia:  Treat this aggressively (e.g., with bisphosphonate & calcitonin).📖  
• Gallstone-induced:  Ideally, delayed cholecystectomy later on during the patient's admission for acute pancreatitis.

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ERCP?

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• The American Gastroenterological Association recommends against routine urgent ERCP in patients with acute biliary pancreatitis without cholangitis.   Most studies of ERCP have failed to show benefit.
• The strongest indication for ERCP is definite or suspected ascending cholangitis (which sometimes occurs simultaneously with pancreatitis, serving as a focus of septic shock).   Evidence of cholangitis may include:
  • Dilation of the common bile duct.
  • Significantly elevated & rising bilirubin.
• ERCP may also be considered for patients with evidence of choledocholithiasis (e.g., persistently elevated bilirubin, impacted stone visualized radiographically).
• When in doubt about the need for ERCP, possible approaches are:
  • Follow the patient clinically, with serial monitoring of liver function tests and overall picture.
  • Magnetic Resonance Cholangiopancreatography (MRCP) – a noninvasive imaging modality to better define the anatomy of the biliary tract.

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resuscitation

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traditional dogma:  large volume fluid resuscitation

• Traditionally patients have been treated with massive fluid resuscitation (e.g., 250-500 ml/hr, resulting in ~8-14 liters fluid administration over the first day).  This is insanity.
• There is no evidence to support massive volume administration.  Available prospective studies show that more aggressive fluid administration increases rates of infection, abdominal compartment syndrome, ARDS, and death.(19187641, 20819621)

reasonable approach?

• Nobody knows the best approach.  There is little high-quality prospective data to guide this.
• A reasonable approach to resuscitation is probably similar to a septic shock resuscitation:
  • Give fluid based on hemodynamic assessment (e.g., with ultrasonography).  Most patients may benefit from a moderate amount of fluid initially (e.g., ~2 liters total over the first day).
  • Don't give much fluid after the initial resuscitation (e.g., beyond 12-24 hours).  Following stabilization, it's generally wise to target an even fluid balance.
  • Use vasopressors (e.g., norepinephrine) early, as needed to maintain an adequate MAP.  This may reduce the amount of fluid given, thereby reducing the risk of abdominal compartment syndrome.
• Be careful about the use of fluid-responsiveness in these patients.  Even if the patient is fluid-responsive, administered fluid will rapidly leak out of the vascular space.  Pancreatitis patients will often be fluid-responsive regardless of how much fluid they are given.
• Patients will often develop renal failure due to acute tubular necrosis.  This doesn't respond to additional fluid administration.

lactated ringers (LR) is preferred

• Lactated Ringers might be the fluid of choice, given one RCT in pancreatitis that found reduced inflammation when using LR compared to normal saline.(21645639)
• LR is a terrific resuscitative fluid, so it's a good choice regardless.🌊

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nutrition

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the concept of “pancreatic rest” is dangerously misleading dogma

• Traditionally there was a concept that nutrition would stimulate pancreatic secretions and thereby worsen pancreatitis.
• Not only is this wrong, it's probably backwards.(29409760)  Early enteral nutritional support (ideally within 24 hours) may improve outcomes, for example
  • Improved intestinal function (reduced rate of ileus, decreased bacterial translocation into the bloodstream).
  • Reduced risk of infected pancreatic necrosis.
  • Reduced hospital length of stay.
  • Decreased gastrointestinal symptoms.(30243452)

nutritional support for the non-intubated patient

• Oral diet may be started immediately.
• It's fine to start with a low-fat diet (rather than a clear-liquid diet).
• Some patients are unable to tolerate food (e.g., due to pain or emesis).  This may be observed for a couple days.  If the patient still isn't eating after 3-5 days, a small-bore nasal feeding tube may be placed to provide nutrition.(25409371)  It's ideal to place this in a post-pyloric location, but gastric feeding is also fine.

nutritional support for the intubated patient

• Enteral tube feeding should be started immediately after the initial resuscitation.  Start feeds at a low level (10-20 ml/hr) and advance as tolerated.
• It is controversial whether to feed the stomach (e.g. via nasogastric/orogastric tube) or to use a post-pyloric tube.
  • RCTs show no differences in outcome, so either route is fine.
  • Among intubated patients it's usually easier to place an orogastric tube, so this route is often used initially.
  • If the patient has problems with gastroparesis or vomiting, then switching to a post-pyloric tube may be helpful.
• 💡Intubated patients with pancreatitis can generally be fed in the same fashion as other critically ill patients.📖  The only exception to this is hypertriglyceridemic pancreatitis, who should receive fat-free enteral nutrition.📖
• Pancreatitis causes exocrine pancreatic dysfunction in a majority of patients initially, leading to malabsorption.(33464002)  This may be managed using pancreatic enzyme supplements or semi-elemental tube feeding formulations.

total parenteral nutrition should be avoided

• RCTs in pancreatitis have shown harm from parenteral nutrition.  This has been shown to increase the risk of infected pancreatic necrosis and multi-organ failure.(29409760)
• Parenteral nutrition should be used only as a last resort, when enteral nutrition is impossible.📖

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analgesia

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• Opioids may promote ileus, interfering with nutrition and potentially increasing the risk of abdominal compartment syndrome.  Most patients will need some amount of opioid, but this should be kept to a minimum.  Opioid infusions in particular should be avoided.
• Pain-dose ketamine infusions 💉 (e.g., 0.1-0.3 mg/kg/hr) may be helpful to control pain while avoiding opioids.(28713597, 29870457, 29760856)
• Scheduled acetaminophen 💉 shouldn't be forgotten, as this may also be opioid-sparing.
• Non-steroidal anti-inflammatory agents should be avoided, given the tendency of pancreatitis patients to develop acute tubular necrosis.
• Epidural analgesia may be an excellent option if available.
• More on multimodal analgesia in critical care here.📖

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prophylactic & early antibiotics

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avoid antibiotics in the first week 

• There are many parallels between sepsis and pancreatitis.  These will cause the pancreatitis patient to look infected upon arrival (e.g. pancreatitis commonly causes fever, leukocytosis, hypotension, and vasodilatory shock).   However, this is generally a reflection of sterile inflammation rather than true infection.
• Historically there was a concept that prophylactic antibiotics could prevent the development of infected pancreatic necrosis.  This has been debunked and should not be used.  Up-front antibiotics will select out resistant organisms, which cause problems later on (when true infection actually does occur).
• Antibiotics should generally be avoided during the first week, with the following exceptions:
  • (1) The diagnosis of pancreatitis is unclear and there is concern for septic shock with a focus of infection elsewhere.
  • (2) The patient has coexisting ascending cholangitis (which is a true bacterial infection and requires decompression & antibiotics).
• Infectious complications of pancreatitis (e.g., infected necrosis) are rare during the first week.  During this time frame, inflammatory symptoms (e.g., fever, leukocytosis) likely reflect sterile pancreatic inflammation.

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fluid collections & infected necrosis

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Necrotizing pancreatitis can cause acute necrotic collections, infected pancreatic necrosis, and walled-off necrosis.  Alternatively, interstitial edematous pancreatitis may cause acute peripancreatic fluid collections and pseudocysts.  

acute peripancreatic fluid collection (APFC)

• Defined as a homogeneous fluid collection occurring adjacent to the pancreas within four weeks of interstitial edematous pancreatitis (i.e., not necrotizing pancreatitis).🌊
• Unlike a pseudocyst, there is no wall encapsulating the fluid.
• Superinfection can occur, but this is rare.
• Most collections resolve spontaneously without intervention.  If the collection persists, it may mature into a pseudocyst (see below).

pancreatic pseudocyst 

• Defined as encapsulated fluid collections with an inflammatory wall, usually occurring >1 month after interstitial edematous pancreatitis.  On CT imaging, they should appear homogeneous, without any solid component.
• Pseudocysts will usually resolve spontaneously.  If asymptomatic, pseudocysts may be observed with serial imaging.
• Complications resulting from pseudocysts may include: (31791953)
  • Gastric or duodenal obstruction (most common).
  • Biliary obstruction.
  • Infection of the cyst.
  • Rupture leading to pancreatic ascites.
  • Bleeding, including erosion of surrounding vessels (e.g., splenic or gastroduodenal arteries).
• Symptomatic pseudocysts may be drained endoscopically, surgically, or percutaneously.   Endoscopic drainage is generally preferred if technically possible.  However, percutaneous drainage may be preferred for fragile patients who cannot tolerate any other procedure – despite an increased risk of fistula formation.(31192242)

acute necrotic collection (ANC)

• Defined as fluid collections adjacent to necrotizing pancreatitis that occur within the first four weeks.  Unlike acute peripancreatic fluid collections:
  • These may contain some heterogeneous, non-liquified material.
  • Collections can be intrapancreatic and/or extrapancreatic.
• The risk of infection may be higher than with acute peripancreatic fluid collection (see section below on infected pancreatic necrosis).
• If a sterile necrotic collection persists, it may mature into walled-off necrosis (WON) after about a month.
• Most collections are sterile and will resolve with conservative management.(31192242)   Acute necrotic collections may develop into infected pancreatic necrosis or walled-off sterile necrosis (with management described below).

infected pancreatic necrosis

• This peaks about 10-14 days after the onset of pancreatitis.  The classic presentation would be a patient who initially improves, but subsequently deteriorates with worsening sepsis.
• Investigation typically begins with repeat CT scan.  Occasionally, radiologic features may be diagnostic (e.g., air within pancreatic tissue implies infection).
• Fine-needle aspiration to determine whether infection is present is routinely used at some centers and recommended in the Canadian guidelines for acute pancreatitis.(27007094)  However, empiric antibiotics are favored at some centers due to fear of introducing infection into the pancreas during fine-needle aspiration.(28857624)
• Traditionally a carbapenem (e.g., meropenem) as used for improved penetration of the pancreas.  However, other antibiotics also penetrate the pancreas well (e.g., cefepime/metronidazole and probably piperacillin-tazobactam).(18333238, 18809943)  Given that these patients often remain in the ICU for some weeks, using piperacillin-tazobactam initially (instead of a carbapenem) could delay the selection of resistant pathogens.
• A team approach is required, including pancreatic surgeons, interventional radiologists, and invasive gastroenterologists.  Ideally this should be managed at a large center which offers a range of minimally invasive debridement techniques.(29736167)
  • The PANTER trial supported a strategy of beginning with percutaneous drainage, and stepping up to more invasive therapy if needed.  Notably, solely percutaneous drainage was required in a third of patients.(20410514)  However, endoscopic strategies may result in a lower risk of pancreatic fistula formation.(31791953)

walled-off necrosis (WON)

• Defined as an encapsulated collection of pancreatic and/or peripancreatic necrosis with a well-defined inflammatory wall.  Maturation usually requires >4 weeks.
• Aside from the presence of a wall, this has similar features compared to an acute necrotic collection:
  • May contain heterogeneous contents, including liquid and solid components.
  • May be intrapancreatic and/or extrapancreatic.
• Sterile necrosis can resolve without intervention.  Alternatively, management may include percutaneous drainage, endoscopic drainage, or surgical drainage.  Minimally invasive techniques are increasingly being utilized.(31791953)  

procalcitonin in pancreatitis

• Although procalcitonin is often conceptualized as a test for bacterial sepsis, it can be elevated in pancreatitis as well (as might be expected based on similarities between these two conditions).  Procalcitonin may potentially be used for two purposes:
• (1) Risk stratification 
  • Greater procalcitonin elevation reflects more severe inflammation, which may predict a more severe disease course.
  • Elevation of procalcitonin >0.5 ng/mL predicts severe pancreatitis with moderate reliability (sensitivity 73%, specificity 87%).(19541012)
• (2) Diagnosis of infected pancreatic necrosis
  • Pancreatitis alone generally doesn't cause profound elevation in procalcitonin.  Therefore, a markedly elevated procalcitonin level (e.g. >3.5 ng/ml) is suggestive of infected pancreatic necrosis.(17457167, 18470712)
  • Other causes of procalcitonin elevation include renal failure and other foci of nosocomial infection (e.g., line infection, pneumonia).
  • The value of procalcitonin for infected pancreatic necrosis is likely as a rule-out test (e.g., a low procalcitonin argues against infected necrosis, whereas an elevated value is nonspecific).  This might be useful in avoiding unnecessary antibiotic courses or invasive procedures in patients at low risk for true infection.  Further prospective evidence is needed to validate this.

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abdominal compartment syndrome

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• Compartment syndrome can cause deterioration and multi-organ failure.📖
• This is largely an iatrogenic complication, due to the use of excessive volumes of crystalloid.   As we are moving away from large-volume resuscitation of pancreatitis, this seems to be less of a problem.

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hemorrhage

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• Hemorrhage may result from erosion of arteries near the pancreas (especially the splenic or gastroduodenal arteries).
• Front-line investigation is CT angiography, which may be able to identify the bleeding vessel.  For patients with active hemorrhage, angiographic embolization is the preferred treatment.(31791953)  

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podcast

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

• #1 most common error is administration of excessive volumes of fluid, causing ARDS and abdominal compartment syndrome.  Unfortunately, this strategy continues to be recommended by many sources.
• Delayed initiation of nutrition, due to a desire to “rest” the pancreas.
• Fear-induced initiation of antibiotics during the first week of therapy, when superinfection is uncommon.
• Meropenem isn't required to penetrate pancreatic tissue, piperacillin-tazobactam also has good penetration.

Guide to emoji hyperlinks 

•  = Link to online calculator.
•  = Link to Medscape monograph about a drug.
•  = Link to IBCC section about a drug.
•  = Link to IBCC section covering that topic.
•  = Link to FOAMed site with related information.
•  = Link to supplemental media.

Going further

• Pancreatitis overview
  • Acute pancreatitis (Anand Swaminathan, RebelEM)
  • Pancreatitis (Chris Nickson, LITFL)
• Resus & abdominal compartment syndrome
  • Pancreatitis: please stop the drowning (PulmCrit)
  • Killer resuscitation:  Abdominal hypertension as a cause of multiorgan failure (PulmCrit)
• Hypertriglyceridemic pancreatitis (PulmCrit)
• New guidelines simplify ICU nutrition (PulmCrit)
• Analgesic ladder for pain control in critically ill patients (PulmCrit)