Acute Pancreatitis – NEJM Review notes

Causes

  • Gallstones (40%)
    • Migrating gallstones -> transient obstruction
    • No convincing data showing that Sphincter of Oddi or Pancreas Divisum play a role in AP
  • ETOH (30%)
    • 4-5 drinks per day x 2-5 years — overall lifetime risk 2-5%
      • Type of ETOH consumed does not affect risk
      • Binge drinking in absence of chronic, heavy ETOH use does not precipitate AP
    • Typically flares superimposed on chronic pancreatitis
    • Mechanism: direct toxicity and immunologic mechanisms
  • Drugs (< 5%)
    • Hundreds implicated — notables are Azathioprine, 6-MP, didanosine, valproic acid, ACE-i, mesalamine
    • “Exceedingly difficult to determine whether drug is responsible”
      • Evidence of drug allergy (ex. rash) in rare cases
  • Genetics
    • Cationic trypsinogen (PRSS1), serine protease inhibitor Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin C, calcium-sensing receptor, claudin-2
      • claudin-2 mutation interacts synergistically with ETOH
  • Hypertriglyceridemia (2-5%)
    • Fasting triglycerides > 1000 mg/dl
  • ERCP (5-10%)
  • Autoimmune (< 1%)
    • Type 1: obstructive jaundice, elevated serum IgG4 levels, response to glucocorticoids
      • Systemic disease involving pancreas, salivary glands, kidneys
    • Type 2: possible presentation as AP, occurrence in younger patients, no IgG4 elevation, response to glucocorticoids
      • Only pancreas is affected
  • Associated Conditions: Smoking, Obesity, DM (increases risk of AP by factor of 2-3)

Epidemiology

  • Admissions increased by 20% over past 10 years – tracks with obesity epidemic and increasing rate of gallstones
  • Mortality, decreased over time to 2% cases
    • 80% cases are mild, self-limited disease
    • Risks for mortality include: 1) elderly 2) numerous/severe coexisting conditions (i.e. obesity) 3) hospital-acquired infection 4) severe acute pancreatitis (multi-organ failure)

Diagnosis and Classification

  • 2 of 3 diagnostic criteria must be met:
    • 1) Abdominal pain consistent with AP
    • 2) Serum Lipase or Amylase levels at least 3 x ULN
    • 3) Findings of AP on cross-sectional imaging (CT or MRI)
  • Moderately Severe and Severe AP defined by presence of systemic complications, local complications or both
    • Systemic Complications: failure of organ system, exacerbation of preexisting disorder (i.e. COPD, heart failure, chronic liver disease)
    • Local Complications: peripancreatic fluid collections or pseudocysts, pancreatic/peripancreatic necrosis (either sterile or infected)
    • Persistent failure of organ system (i.e. lasting > 48 hours) is the prime determinant of poor outcome — mortality approaches 30% in these patients

Predicting Severity

  • Clinical factors increasing risk of complications or death:
    • 1) Advanced age (> 60 years old)
    • 2) numerous & severe coexisting conditions (score >/= 2 on Charlson comorbidity index)
    • 3) Obesity (BMI >/= 30)
    • 4) Long-term, heavy ETOH use (4-5 drinks/day)
  • Laboratory Measurements
    • Primarily act as measurements of volume depletion due to third space losses or markers of inflammation
    • Most useful predictors:
      • 1) Elevated BUN + Creatinine
      • 2) Elevated hematocrit
        • Especially if these do not return to normal after fluid resuscitation
    • The DEGREE of serum lipase or amylase level has NO PROGNOSTIC VALUE
  • Imaging
    • CT evidence of severe AP lags behind clinical findings
      • Early CT studies may underestimate severity
  • Scoring Systems
    • Include: APACHE II, APACHE-O (obesity), Glasgow, HAPS, PANC 3
      • High false positive rates
      • Generally cumbersome and not routinely used
  • SIRS
    • SIRS persisting longer than 48 hours is indicative of poor prognosis
    • During first 48-72 hours, rising Hct or BUN or Cr levels, persistent SIRS after adequate fluid resus or presence of pancreatic or peripancreatic necrosis on imaging constitutes evidence of evolving severe pancreatitis

Management

  • Fluid Resuscitation
    • Aggressive hydration in first 24 hours reduces morbidity and mortality
      • 1) Balanced crystalloid solution at 200 – 500 cc/hour, or 5-10 ml/kg/hr
        • Comes out to 2500-4000 cc/24 hr in first 24 hours
        • One trial indicates LR superior to NSS for reducing inflammatory markers
        • Tailor fluid therapy to degree of IV volume depletion and cardiopulmonary reserve that is available to handle the fluid and prevent fluid overload
        • RCTs needed to assess type of fluid, rate and goals of therapy – most recs are made on expert opinion alone without RCTs to back them up
  • Feeding
    • Mild AP: no need to hold feeds until resolution of pain or normalization of enzyme levels
      • Low-fat or solid diet preferred over clear-liquid diet
    • Artificial, enteral feedings predicted by day 5 based on symptoms
      • Nasogastric or nasoduodenal feedings are clinically equivalent to nasojejunal feeds
    • Early initiation of NG feeding (w/n 24h) is NOT SUPERIOR to waiting 72h until initiation – even with patients predicted to have severe or necrotizing pancreatitis
      • Don’t bother with TPN
  • Antibiotics
    • No benefit of prophylactic antibiotics – not recommended for any type of AP unless infection is suspected for has been confirmed
  • Endoscopic Therapy
    • ERCP – indicated if evidence of cholangitis superimposed on gallstone pancreatitis
      • also reasonable if choledocholithiasis suspected or findings of persistent bile duct stone (ex. jaundice, progressive rise in liver enzymes or persistently dilated bile duct)
        • ERCP not beneficial in absence of these findings
  • Treatment of Fluid Collections and Necrosis
    • Acute fluid collections do NOT require therapy
      • Symptomatic pseudocysts managed with endoscopic techniques
    • Necrotizing Pancreatitis – initially mix of semisolid & solid tissue
      • Becomes more liquid and encapsulated after 4 weeks
      • Sterile necrosis does not require therapy unless obstructing nearby viscus (ex. duodenum, bile duct, gastric obstruction)
    • Infection – main indication for therapy
      • Rare in first 2 weeks of illness
        • Bugs: monomicrobial (GNR, enterobacter, gram positive including staph)
        • Clinical: fever, leukocytosis, increasing abdominal pain
        • CT scan: air bubbles in necrotic cavity
      • Therapy (Step Up Approach)
        • 1) Initiation of broad spectrum antibiotics
        • 2) Percutaneous drainage (if patient unstable and unable to wait 4 weeks for collection to wall off)
          • 60% patients with necrotizing pancreatitis can be treated non-invasively with low risk of death
          • Approximately 1/3 will avoid debridement with this approach
        • 3) Minimally invasive debridement after several weeks (if required)
          • Superior to traditional open necrosectomy

Long Term Consequences of AP

  • 20-30% develop exocrine and endocrine dysfunction and chronic pancreatitis occurs in 1/3 to 1/2 of those patients
  • Long-term heavy ETOH as cause and smoking as cofactor dramatically increase transition to chronic pancreatitis

Prevention of Relapse

  • Cholecystectomy (if gallstone pancreatitis) during INITIAL HOSPITALIZATION for MILD pancreatitis reduces rate of subsequent gallstone-related complications by 75% compared with cholecystectomy 25-30 days after discharge
    • Endoscopic biliary spincterotomy reduces (but does not eliminate) risk of recurrent biliary pancreatitis, but may not reduce risk of subsequent acute cholecystitis and biliary colic
  • ETOH use – stop
  • Smoking – stop
  • Tight control of hyperlipidemia – may reduce risk if cause is hypertriglyceridemia

 

Source: NEJM- Acute Pancreatitis

 

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