Editing Acute pancreatitis

''Pancreatic inflammation secondary to inappropriate activation of enzymes and autodigestion''

== '''Epidemiology''' ==

* Increasing since 2000
* Up to 80% caused by gallstones/alcohol

== '''Natural history''' ==

* 10-20% have a rapidly progressive inflammatory response - prolonged hospital stay, morbidity, mortality
* Risk of death in severe pancreatitis 10-50%, especially with MODS
* Mortality in the first two weeks is due to MODS
* Mortality after two weeks is from sepsis

== '''Aetiology''' ==
GET SMASHED

* Gallstones
** Biliary sludge or gallstones on imaging
** Dilated CBD (>=8mm in patients <75, >=10mm patients >75)
** ALT>2x upper limit normal (PPV >95% for biliary aetiology, when pancreatitis has been diagnosed)
* Ethanol
** Look for LFTs consistent with alcohol liver disease
* Trauma 
** Blunt abdo trauma 
** Bile duct injury
* Steroids
* Mumps + Viruses
** HIV, coxsackie, CMV, mumps
* Autoimmune/anatomical
* Scorpions and other venoms/splenic embolisation 
* Hypercalcaemia
* Hyperlipidaemia
** Need lipids >11.3mmol/L
** Suspect with trigs >25, and confirmed with trigs >50
** Can see a pseudohyponatraemia in this setting
** Consider risks
*** Primary hypertriglyceridaemia - familial syndromes
*** Secondary
**** Diabetes
**** Meds - tamoxifen etc, clomiphene, protease inhibitors, antiretroviral agents, propofol, olanzapine, mirtazapine, retinoids, thiazide diuretics, betablockers
**** Pregnancy
**** Alcohol
**** Hypothyroidism
*** Note that hypertriglyceridaemia secondary to hypothyroidism, DM or alcohol does not typically cause pancreatitis
* ERCP/surgery
** 3% if surveillance, 5% if removal of stone, 25% if procedure on Sphincter of Oddi
** More common in young females and prior history of ERCP pancreatitis
** More common with multiple attempts at cannulation
** Mild in 95% of patients
** May be possible to prevent with use of indomethacin
* Drugs
** Sulfonamides, metronidazole, erythromycin, tetracyclines, didanosine, thiazides, furosemide, statins, azathioprine, 6-mercaptopurine, 5-aminosalicyclic acid, sulfasalazine, valproic acid, HIV antiretroviral agents.

== '''Pathophysiology''' ==

* Likely the result of inappropriate activation of proenzymes inside acinar cells
* Leads to autodigestion of normal pancreatic parenchyma, which triggers acinar cells releasing proinflammatory cytokines, propagating the response locally and systemically
* In severe cases, the local inflammatory response causes local haemorrhage and pancreatic necrosis
* SIRS can also worsen injury due to pancreatic ischaemia
* 80-90% of patients with acute pancreatitis have a self-limited inflammatory cascade -> mild pancreatitis
* Gallstones
** Caused by either increased pancreatic duct back pressure, or bile salt reflux into the pancreas
** Injury to acinar cells, triggering a cascade of pro-inflammatory changes
* Alcohol
** Only seen in 5-10% of heavy drinkers
** Risk factors - >100g/day for at least 5 years, smoking (RR 4.9), genetic predisposition
** Alcohol probably causes pancreatic injury via a number of mechanisms, although it has not been fully delineated
*** '''Pancreatic processing of alcohol leads to damaging metabolites''' through both oxidative and non-oxidative pathways, such as acetaldehyde and fatty acid ethyl esters
*** Increased synthesis of digestive and lysosomal enzymes
*** Possible chronic sensitisation of acini to CCK
*** '''Precipitation and increased viscosity of pancreatic secretions''' - protein plugs in small ducts - progressive inflammation and fibrosis, leading to loss of acinar, islet and ductal cells
*** Premature activation of trypsinogen and other digestive and lysosomal enzymes
* Anatomical
** Obstructed flow of pancreatic juice, secondary to tumour (uncommon), parasites, or congenital defects (pancreas divisum or annular pancreas)
* Hypercalcaemia - activation of trypsinogen, and intra-ductal precipitation of calcium leading to ductal obstruction
* Lipase release leads to fat necrosis and digestion, with subsequent reaction of fatty acids and calcium to create soaps, or 'saponification'

== '''Presentation''' ==

* Epigastric or periumbilical pain, constant, radiating through to back (cardinal symptom)
* Nausea or vomiting that does not relieve pain
* Hypovolaemia
* Retroperitoneal bleeding:
** Grey Turner sign - flank ecchymosis
** Cullen sign - periumbilical ecchymosis
* Jaundice - can be choledocholithiasis or oedematous pancreatic head causing CBD obstruction
* Pleural effusion - most commonly left

== '''Diagnosis:''' ==

* Two of the following (Atlanta criteria)

# Clinical history/examination consistent with pancreatitis
# Lipase/amylase >3 times upper limit of normal (lipase rises within 4-8 hours and peaks at 24 hours, and often stays high for 1-2 weeks. Lipase is better in EtOH pancreatitis, and has a slightly longer half-life (7-13.5 hours))
## Amylase rises within 6-12 hours of symptoms, and returns to normal in 3-5 days. It can also be elevated in PUD, mesenteric ischaemia, salpingitis and macroamylasaemia.
# Radiological evidence pancreatitis

== '''Imaging''' ==

* USS - useful to identify gallstones, not particularly good for seeing the pancreas
* CT portal venous phase
* MRCP indications: acute pancreatitis with no known aetiology to rule out pancreas divisum, IPMN, or a small ductal tumour

== '''Scoring systems''' probably don't have clinical relevance ==

* Lots of systems, conflicting evidence
* The most useful approach:
** During admission, use a three-dimensional approach to predict risk:
*** Risk factors (age, comorbidity, BMI)
*** Clinical risk stratification (persistent SIRS)
*** Monitoring response to initial therapy (persistent SIRS, BUN, creatinine)
** Use BISAP, Atlanta or even just SIRS criteria
** Apache II can be useful if patient is in ICU
** Ignore Ranson/Glasgow
* SIRS criteria
** Persistent SIRS from admission = mortality 25%
** SIRS at admission but not persistent 8%
** No SIRS 0%
**[[File:SIRS.png|frameless|468x468px]]
* BISAP predicts mortality, quite simple, easy to use, performs on par with more extensive scores
** Factors at admission (one point for each): BISAP
*** BUN: Urea >8.92mmol/L
*** Impaired mental status
*** SIRS criteria >=2
*** Age >60
*** Pleural effusion present
** 0-2 points: mortality <2%
** 3 or more points: mortality >15%
* Modified Atlanta:
** [[File:Revised-Atlanta-Criteria-for-Severity-of-PEP.png|frameless]]

* Atlanta radiographic classification:
** Interstitial oedematous
** Necrotising
** Acute peripancreatic fluid
** Pancreatic pseudocyst

* CT severity index
**[[File:CTSI.png|frameless|409x409px]]
* APACHE II
** Predicts ICU mortality, really only useful with ICU-style investigations e.g. arterial BP
* Glasgow-Imrie criteria (1984) predicts severity, but requires values from 48 hours after admission
** Similar to Ranson
** Not used any more
* Ranson predicts mortality (published 1974)
** Disadvantage - needs scores at 0 and 48 hours post admission
** Mainly used to rule out severe pancreatitis, but low PPV
**[[File:Ranson non-gallstone.png|frameless]]
**[[File:Ranson gallstone.png|frameless]]

*

== '''Initial medical management:''' ==

* Analgaesia:
** Don't give NSAIDs. ?PUD
** Paracetamol probably IV if vomiting
** Initial trial of endone + fluid resus, however often need PCA
** No evidence opioids worsen outcomes, despite supposed sphincter of Oddi contraction
* Antiemetics
* IV PPI - prevent stress ulceration
* Early enteral feeding, unless ileus, pain or intubation
** 20% of severe AP patients get recurrent pain after restarting diet
** Enteral feeding reduces the need for surgery, but TPN can be considered if failing to meet requirements
** NJT feeds if gastric outlet obstruction is present (according to Schein, if gastric aspirates are >250mL/6 hours). Start at 10mL/hr and increase gradually until 40mL/hr is reached)
* Investigate cause
** USS vs MRCP to rule out biliary pathology
** FBE, UEC, LFT, Lipase, CRP, CMP, fasting lipids (don't need to do it unless suspicious this is the cause - see above)
** Consider INR if liver derangement
** Erect CXR - rule out perf ulcer, plus check for ARDS
** CT - only if unclear diagnosis or severe abdominal pain where perforated viscus or bowel ischaemia may be considered
* Strict FB - may need IDC if severe or does not respond to resuscitation
* Supplemental oxygen (to try and optimise perfusion)
* Correct fluids with CSL (vomiting, poor oral intake, increased resp losses, diaphoresis, oedema)
** 5-10ml/kg/hr until HR<120, MAP 65-85, normal lactate and UO 0.5-1ml/kg/hr
** Going to need a lot. Remember pancreatitis pain is worse if dehydrated. Be aggressive.
** CSL better than saline with pancreatitis
* Correct electrolytes
* VTE prophylaxis
* ?Thiamine
* ?ICU if persistent shock for vasopressors after initial resuscitation
* Grade severity - Atlanta - mild/mod/severe - or use SIRS criteria on admission and again at 48/24
* Antibiotics if acute pancreatitis and an active infection (cholangitis, UTI, pneumonia, catheter-related infections, bacteraemia, infected necrosis)

== '''Investigation for aetiology''' ==

* USS - to look for gallstones
* Trigs/calcium
* LFTs
* IgG4 - although UTD says don't need to do this, it seems to be standard of care in Australia if no other obvious cause
* Genetic testing in young (<35) or FHx - PRSS1, SPINK1, CFTR, CTRC, CASR, Claudin-2
** But these would all be organised by geneticist, I think
** Costs $300 and requires referral with justification
** HPB surgeon says test it in young patients with recurrent presentations
* Consider cancer if other suggestions of it
* MRCP +/- secretin
* EUS - microlithiasis, ductal abnormalities, small tumours near ampulla

== '''Course:''' ==

* Daily bloods including CRP
** Don't repeat lipase
** CRP >150 at 48 hours is reasonably predictive for severe course (sp 80%, se 76%)
* Early deaths - MODS from SIRS
* Late deaths - MODS from necrotic sepsis
* Feed early (once pain is better) in mild disease
* Consider enteral tube feeding around 72 hours in for severe AP (NGT and NJT are comparable, either is ok)
* CT 3-5 days after symptom onset if no improvement or deterioration (pancreatic necrosis typically becomes apparent 72 hours after onset)

== '''Gallstone pancreatitis''' ==

=== Indications for ERCP: ===

** Cholangitis
*** Cholangitis = fever + any of: CBD stones OR dilated CBD OR progressive cholestasis (bili >40). If cholangitis is suspected, aim ERCP within 24 hours.
** Persistent CBD obstruction
*** Dilated CBD
*** Obstructing stone in CBD on MRCP (consider at 72 hours)
*** Increasing LFTs without cholangitis (do MRCP first - usually do it after 24-48 hours - give them a chance to improve on their own - could be just pancreatic head oedema)
* Urgent ERCP doesn't make a difference in patients with severe acute gallstone pancreatitis if they don't have cholangitis or significant cholestasis - might as well treat conservatively and take out GB after a few days if possible - Lancet article. Cholangitis will happen more often in conservatively-managed patients, but just do an ERCP at that point.
* ERCP and sphincterotomy effectively prevents recurrent biliary pancreatitis and is especially useful in elderly patients (according to Schein)
[[File:GSP algorithm.png|right|frameless|530x530px]]

=== Cholecystectomy ===

** If no cholecystectomy is done, there's a 25% risk of recurrence
** Cholecystectomy in ALL medically fit patients once pancreatitis settled - during index admission if mild. Traditionally this has meant once pain and LFTs have normalised, but evidence is now suggesting we can do it at 48 hours or even earlier
** Unclear at this time what the best thing to do is with moderate or severe pancreatitis - retrospective data says slightly higher risk profile if done during index admission, but no good evidence
** Usual practice is, if complicated or severe disease, wait until all inflammation has resolved, and all pockets of fluid resolve or stabilise

=== In pregnant patients: ===

** Can lead to complications: preterm labour, prematurity, in utero fetal death
** First trimester is worst - low rate of term pregnancies, high rate of recurrence in same pregnancy - aim conservative treatment then lap chole
** Second trimester - safest time to operate - can operate +/- ERCP
** Third trimester - conservative treatment +/- ERCP, aim lap chole post-partum

== '''Hypertriglyceridaemia pancreatitis:''' ==

* A patient with epigastric pain and high triglycerides (>20 or so) probably has hypertriglyceridaemia pancreatitis, even if their lipase is normal or only mildly elevated. The lipaemic blood can mess with the results and probably underestimates the true lipase level.
* Lipotoxicity caused by pancreatic metabolization of trigs into free fatty acids by pancreatic enzymes
* Most common in south Asian patients
* Anyone with triglycerides >11mmol/L is high-risk
** 5% risk of developing it with trig > 11.3, 10-20% with trig > 22.6
* If 'worrisome features' (lactic acidosis, end-organ dysfunction, >= 2 SIRS criteria, or hypocalcaemia) need apharesis
* Otherwise treat with insulin infusion until triglycerides <5.6 mmol/L
** BD triglycerides and K+
** Set rate insulin infusion - generally 3 units per hour is reasonable, with concurrent 5% glucose, target BSL 6-15
** Check BSL and ketones prior
** NBM or clear fluids to start with
** Once triglycerides down <10, common practice to cease infusion (sometimes switch to subcut insulin) and start fenofibrate/fish oil)
* Needs long-term follow-up with endocrinologist and medical r/v while inpatient for long-term lipid control

== '''Autoimmune pancreatitis''' ==

* Uncommon overall
* Not commonly a cause of ACUTE pancreatitis
* Suspect in those with painless obstructive jaundice (most common) or diffusely enlarged pancreas on imaging, who have other autoimmune conditions
* Type 1
** Associated with high IgG4 levels and obstructive jaundice in older men
** Often seen as part of an IgG4-related disease syndrome
*** Sclerosing cholangitis
*** Retroperitoneal fibrosis
*** Sclerosing sialadenitis
* Type 2
** Pancreas-specific disease - often presents with acute pancreatitis
** Often have normal IgG4
** Requires tissue sampling, as no biomarker
** 'idiopathic duct-centric pancreatitis'
** Often seen with IBD
* Diagnosis
** Histology in the setting of supportive serologic studies
** EUS and MRCP if suspected (also need to exclude pancreatic cancer)
* Treatment
** Glucocorticoid - typically dramatic response - if no response you need to suspect cancer

[[Category:Pancreas]]
[[Category:Intern education]]