Acute Pancreatitis Management Conference LTC J. David Horwhat, MD Assistant Chief, GI WRAMC

Demographics Incidence 17 per 100,000 Mortality 2-3% overall mortality from acute pancreatitis Tertiary centers report rates of 5-15%, high of 30% Skew towards series with more severe pancreatitis Interstitial pancreatitis (1%) Necrotizing pancreatitis/organ failure (30%) Physician office visits 911,000 per year Hospitalizations 230,000 in 2002 Deaths 2500 per year

Incidence

17 per 100,000

Mortality

2-3% overall mortality from acute pancreatitis

Tertiary centers report rates of 5-15%, high of 30%

Skew towards series with more severe pancreatitis

Interstitial pancreatitis (1%)

Necrotizing pancreatitis/organ failure (30%)

Physician office visits

911,000 per year

Hospitalizations

230,000 in 2002

Deaths

2500 per year

More Demographics The median age at onset depends on the etiology AIDS-related - 31 years Vasculitis-related - 36 years Alcohol-related - 39 years Drug-induced etiology - 42 years ERCP-related - 58 years Trauma-related - 66 years Biliary tract–related - 69 years

The median age at onset depends on the etiology

AIDS-related - 31 years

Vasculitis-related - 36 years

Alcohol-related - 39 years

Drug-induced etiology - 42 years

ERCP-related - 58 years

Trauma-related - 66 years

Biliary tract–related - 69 years

Terminology of Acute Pancreatitis Acute interstitial pancreatitis (~80%) Necrotizing pancreatitis (~20%) Sterile necrosis Infected necrosis Pancreatic fluid collection Sterile Infected Pancreatic pseudocyst Sterile Infected Pancreatic abscess Collection of pus with little or no pancreatic necrosis Terms no longer used Hemorrhagic pancreatitis Phlegmon

Acute interstitial pancreatitis (~80%)

Necrotizing pancreatitis (~20%)

Sterile necrosis

Infected necrosis

Pancreatic fluid collection

Sterile

Infected

Pancreatic pseudocyst

Sterile

Infected

Pancreatic abscess

Collection of pus with little or no pancreatic necrosis

Terms no longer used

Hemorrhagic pancreatitis

Phlegmon

Clinical Presentation Pain (95%) Acute onset Mid-abdominal or mid-epigastric Radiates to the back (50%) Peak intensity in 30 minutes Lasts for several hours Nausea and vomiting (80%) Abdominal distension (75%) Abdominal guarding and tenderness (50%) Restlessness and agitation

Pain (95%)

Acute onset

Mid-abdominal or mid-epigastric

Radiates to the back (50%)

Peak intensity in 30 minutes

Lasts for several hours

Nausea and vomiting (80%)

Abdominal distension (75%)

Abdominal guarding and tenderness (50%)

Restlessness and agitation

Laboratory Diagnosis Increased amylase and/or lipase >3 times ULN <3 ULN does not rule out diagnosis in right clinical context Amylase levels rise w/in 2 to 12h of sxs Peak w/in first 48h Remain elevated 3-5d before return to baseline ↑ TGs interferes with assay (false negative) Lipase much more specific Causes for < 3x elevation Perforated ulcer, mesenteric ischemia, CRF (CrCl < 20 ml/min) Height of elevation does not correlate with severity No utility in following daily levels after the diagnosis

Increased amylase and/or lipase

>3 times ULN

<3 ULN does not rule out diagnosis in right clinical context

Amylase levels rise w/in 2 to 12h of sxs

Peak w/in first 48h

Remain elevated 3-5d before return to baseline

↑ TGs interferes with assay (false negative)

Lipase much more specific

Causes for < 3x elevation

Perforated ulcer, mesenteric ischemia, CRF (CrCl < 20 ml/min)

Height of elevation does not correlate with severity

No utility in following daily levels after the diagnosis

Lab studies Other causes for  amylase SBO mesenteric ischemia tubo-ovarian disease renal insufficiency macroamylasemia brain injury/brain trauma LTFs ALT > 3x ULN = 95% PPV for biliary etiology Calcium  Ca as a cause  Ca as a complication saponification of fats in retroperitoneum TG Can be falsely low during an attack

Other causes for  amylase

SBO

mesenteric ischemia

tubo-ovarian disease

renal insufficiency

macroamylasemia

brain injury/brain trauma

LTFs

ALT > 3x ULN = 95% PPV for biliary etiology

Calcium

 Ca as a cause

 Ca as a complication

saponification of fats in retroperitoneum

TG

Can be falsely low during an attack

Differential Diagnosis Mesenteric ischemia Perforated peptic ulcer Intestinal obstruction Biliary colic Inferior wall MI Ectopic pregnancy

Mesenteric ischemia

Perforated peptic ulcer

Intestinal obstruction

Biliary colic

Inferior wall MI

Ectopic pregnancy

Causes OBSTRUCTION -GB Stones : 30 to 75% *ALT > 3x ULN = 95% PPV -Tumors TOXINS - EtOH : ~30% -Scorpion bites Tityus trinitatis & T. serrulatus -Insecticides METABOLIC -  TG ~ 4% -> 1000 mg/dl -  PTH < 0.5% TRAUMA -Surgery -Post-ERCP -MVAs etc . INFECTION -Viral -HIV/EBV/Coxsackie/Mumps -CMV/Varicella/Hep A&C -Parasitic -Ascariasis, clonorchiasis -Bacterial -Mycoplasma, C. jejuni, TB -MAI, Leptospirosis, Legionella VASCULAR -Ischemia -Embolic -Vasculitis MISC -Hereditary -Cystic Fibrosis - Idiopathic : 10 to 30% - 70% microlithiasis P. divisum Annular pancreas SOD -Crohn’s Dz -Post Perf DU Drugs -Imuran -Estrogens -TCN -Flagyl -Thiazides -Lasix -DDI -Sulfa drugs -Depakote -Pentamidine 80%

MISC

-Hereditary

-Cystic Fibrosis

- Idiopathic : 10 to 30%

- 70% microlithiasis

P. divisum

Annular pancreas

SOD

-Crohn’s Dz

-Post Perf DU

Management questions When should patients admitted with AP be monitored in an ICU or step-down unit? When do I order a CT scan? Should patients with SAP receive prophylactic abx? What is the optimal mode and timing of nutritional support for the patient with SAP? Under what circumstances should patients with gallstone pancreatitis undergo interventions to clear the bile duct? What are the indications for surgery in AP; optimal timing for intervention, and roles for less invasive approaches including percutaneous drainage and laparoscopy?

When should patients admitted with AP be monitored in an ICU or step-down unit?

When do I order a CT scan?

Should patients with SAP receive prophylactic abx?

What is the optimal mode and timing of nutritional support for the patient with SAP?

Under what circumstances should patients with gallstone pancreatitis undergo interventions to clear the bile duct?

What are the indications for surgery in AP; optimal timing for intervention, and roles for less invasive approaches including percutaneous drainage and laparoscopy?

Tityus trinitatus Tityus serrulatus

When Do I Transfer to the Unit ? Severe pancreatitis Multi-organ failure Pulmonary Renal Consider it if you are placing the patient on antibiotics and/or ordering a CT to evaluate non-improvement

Severe pancreatitis

Multi-organ failure

Pulmonary

Renal

Consider it if you are placing the patient on antibiotics and/or ordering a CT to evaluate non-improvement

Determining severity Clinical criteria early development/persistence of organ dysfnx Ranson criteria Atlanta criteria POP score Clinical assessment frequent VS, fluid status/UOP, pulse oximetry Radiographic criteria CT severity index necrosis may not be evident until 48-72h

Clinical criteria

early development/persistence of organ dysfnx

Ranson criteria

Atlanta criteria

POP score

Clinical assessment

frequent VS, fluid status/UOP, pulse oximetry

Radiographic criteria

CT severity index

necrosis may not be evident until 48-72h

Ranson Criteria Admission Age > 55 years White blood cells > 16,000/mm 3 Glucose > 200 mg/dL LDH > 350 IU/L AST > 250 U/L During Initial 48 Hours Hct decrease of > 10 mg/dL BUN increase of > 5 mg/dL Base deficit > 4 mEq/L Fluid sequestration > 6 L Ca++ < 8 mg/dL Pa O 2 < 60 mm Hg Directly related to fluid resuscitation Independent predictors of mortality ** Caveat ** Valid at 48h after onset of symptoms and not at any other time during the disease

Admission

Age > 55 years

White blood cells > 16,000/mm 3

Glucose > 200 mg/dL

LDH > 350 IU/L

AST > 250 U/L

During Initial 48 Hours

Hct decrease of > 10 mg/dL

BUN increase of > 5 mg/dL

Base deficit > 4 mEq/L

Fluid sequestration > 6 L

Ca++ < 8 mg/dL

Pa O 2 < 60 mm Hg

Directly related to fluid resuscitation

Independent predictors of mortality

Ranson et al. Radiology, 1990;174:331 † Sn 73%, Sp 77% * > 7 d in ICU MORTALITY † MORBIDITY *

Pancreatitis Outcome Prediction (POP) Score Data collected within 24hr of ICU admission 2,462 patients from 159 ICUs in the UK Logistic regression model with area under the ROC curve of 0.838 (needs prospective validation)

Data collected within 24hr of ICU admission

2,462 patients from 159 ICUs in the UK

Logistic regression model with area under the ROC curve of 0.838

(needs prospective validation)

Pancreatitis Outcome Prediction Score

TAP? CRP? Hct? Trypsinogen activation peptide CRP Latency of 24-48hr  not useful for EARLY determination Hematocrit Admission Hct ≥50% significant predictor of severe pancreatitis, necrosis, LOS, need for ICU LR 7.5 for severe AP

Trypsinogen activation peptide

CRP

Latency of 24-48hr

 not useful for EARLY determination

Hematocrit

Admission Hct ≥50%

significant predictor of severe pancreatitis, necrosis, LOS, need for ICU

LR 7.5 for severe AP

Famous people who have had pancreatitis Alexander the Great Ludwig von Beethoven Dizzie Gillespie Maximilian Schell Matthew Perry John Ashcroft

Alexander the Great

Ludwig von Beethoven

Dizzie Gillespie

Maximilian Schell

Matthew Perry

John Ashcroft

Acute Pancreatitis INTERSTITIAL (Edematous) 80% NECROTIZING 20% INFECTED NECROSIS 70% INFLAMMATORY MASS STERILE NECROSIS 30% HEALING CHRONIC PSEUDOCYST PANCREATIC ABSCESS

Severe Pancreatitis Atlanta criteria Organ Failure i.e. systolic blood pressure <90 mm Hg, PaO 2 <60 mm Hg, serum creatinine >2 mg/dL, >500 mL/24 h GI bleeding OR Local Complications Necrosis Abscess Pseudocyst OR Unfavorable Early Prognostic Signs  3 Ranson's signs OR  8 APACHE-II points

Organ Failure

i.e. systolic blood pressure <90 mm Hg, PaO 2 <60 mm Hg, serum creatinine >2 mg/dL, >500 mL/24 h GI bleeding OR

Local Complications

Necrosis

Abscess

Pseudocyst OR

Unfavorable Early Prognostic Signs

 3 Ranson's signs OR

 8 APACHE-II points

Organ Failure Cardiovascular Hypotension Septic physiology  HR, CO and  SVR Respiratory Hypoxemia Pleural effusions Renal ATN Oliguria Hematologic DIC Thrombocytosis Hepatic Encephalopathy  T bili (3 mg/dl)  AST/ALT 2X nl GI Stress ulcer Acalculous cholecystitis

Cardiovascular

Hypotension

Septic physiology

 HR, CO and  SVR

Respiratory

Hypoxemia

Pleural effusions

Renal

ATN

Oliguria

Hematologic

DIC

Thrombocytosis

Hepatic

Encephalopathy

 T bili (3 mg/dl)

 AST/ALT 2X nl

GI

Stress ulcer

Acalculous cholecystitis

When Do I Order A CT? If the patient has….. Signs of severe acute pancreatitis No signs of clinical improvement after several days Diagnostic dilemma Infection suspected T > 101 o F Positive blood cultures What kind of CT? Dynamic with rapid bolus IV contrast What are you looking for? Necrosis: Lack of enhancement with contrast Fluid Collections Alternate diagnosis

If the patient has…..

Signs of severe acute pancreatitis

No signs of clinical improvement after several days

Diagnostic dilemma

Infection suspected

T > 101 o F

Positive blood cultures

What kind of CT?

Dynamic with rapid bolus IV contrast

What are you looking for?

Necrosis: Lack of enhancement with contrast

Fluid Collections

Alternate diagnosis

CT Findings Pancreas Pancreatic enlargement Decreased density due to edema Intrapancreatic fluid collections Blurring of gland margins due to inflammation Peripancreatic Fluid collections and stranding densities Thickening of retroperitoneal fat * It may take up to 72h for inflammatory changes to become apparent on CT *

Pancreas

Pancreatic enlargement

Decreased density due to edema

Intrapancreatic fluid collections

Blurring of gland margins due to inflammation

Peripancreatic

Fluid collections and stranding densities

Thickening of retroperitoneal fat

CT Findings Tail Indistinct Intraperitoneal fluid PANC LIVER

CT Findings Severe Pancreatitis Peripancreatic edema and inflammation Unenhancing Necrosis PANC LIVER GB

Normal Pancreas

POINTS Grade of Acute Pancreatitis A = Normal pancreas 0 B = Pancreatic enlargement 1 C = Pancreatic/peripancreatic inflammation 2 D = Single peripancreatic fluid collection 3 E = Multiple fluid collections 4 Grade E = 50% chance of developing an infection and 15% chance of death Degree of Necrosis No necrosis 0 Necrosis of one third of pancreas 2 Necrosis of one half of pancreas 4 Necrosis of more than one half 6 CT Severity Index = Grade + Degree of necrosis

* > 7 days in the ICU CT Severity Index = Grade of Panc. + Degree of Necrosis per Balthazar MORTALITY MORBIDITY*

Cullen’s sign

Management Mild-Moderate NPO with IVF (crystalloid) Colloid (blood if Hct <25, albumin if serum alb <2) Closely follow I/Os, UOP UOP 0.5cc/kg body wt per hr in absence of renal failure Generous narcotics PCA MSO4 OK no evidence in humans of worsening Ac Panc d/t sphincter of Oddi Scheduled not PRN NGT decompression if frequent emesis or evidence of ileus on plain films Start clear liquids when pain/anorexia resolve DO NOT follow amylase and lipase levels

NPO with IVF (crystalloid)

Colloid (blood if Hct <25, albumin if serum alb <2)

Closely follow I/Os, UOP

UOP 0.5cc/kg body wt per hr in absence of renal failure

Generous narcotics

PCA

MSO4 OK

no evidence in humans of worsening Ac Panc d/t sphincter of Oddi

Scheduled not PRN

NGT decompression

if frequent emesis or evidence of ileus on plain films

Start clear liquids when pain/anorexia resolve

DO NOT follow amylase and lipase levels

When Do I Start Antibiotics? Acute pancreatitis is c/b infection ~ 10% 30-50% of those with necrosis get infection Prophylactic antibiotics Controversial No benefit in mild EtOH pancreatitis Imipenem or meropenem in necrotizing pancreatitis Selective gut decontamination may be beneficial Abx do not appear to promote fungal infection General recommendations for use: Biliary pancreatitis with signs of cholangitis > 30% necrosis on CT scan

Acute pancreatitis is c/b infection ~ 10%

30-50% of those with necrosis get infection

Prophylactic antibiotics

Controversial

No benefit in mild EtOH pancreatitis

Imipenem or meropenem in necrotizing pancreatitis

Selective gut decontamination may be beneficial

Abx do not appear to promote fungal infection

General recommendations for use:

Biliary pancreatitis with signs of cholangitis

> 30% necrosis on CT scan

Antibiotics - EBM Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database of Systematic Reviews. 3, 2005 Despite variations in drug agent, case mix, duration of treatment and methodological quality (especially the lack of double blinded studies), there was strong evidence that intravenous antibiotic prophylactic therapy for 10 to 14 days decreased the risk of super-infection of necrotic tissue and mortality in patients with severe acute pancreatitis with proven pancreatic necrosis at CT

Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis.

Cochrane Database of Systematic Reviews. 3, 2005

A final word on antibiotics Do not use empirically early in mild pancreatitis Fever early in the disease process is almost universally secondary to the inflammatory response and NOT an infectious process

Do not use empirically early in mild pancreatitis

Fever early in the disease process is almost universally secondary to the inflammatory response and NOT an infectious process

When can he eat ? Nutritional issues in AP TPN vs. enteral feeding Not TPN per meta-analysis but …* NJ not NG Early initiation of enteral nutrition in severe AP tube feed if anticipate NPO > 1 week may be unnecessary for mild AP Reduce microbial translocation Enhance gut mucosal blood flow Promote gut mucosal surface immunity Reduce incidence of infected necrosis * 6 older studies, relationship b/w glycemic control and infectious risk may confound vs. TPN

TPN vs. enteral feeding

Not TPN per meta-analysis but …*

NJ not NG

Early initiation of enteral nutrition in severe AP

tube feed if anticipate NPO > 1 week

may be unnecessary for mild AP

Reduce microbial translocation

Enhance gut mucosal blood flow

Promote gut mucosal surface immunity

Nutrition Mild pancreatitis Calories from IVF (D5W) are sufficient No benefit from additional nutritional support Oral intake advancing to low fat diet once pain/anorexia resolve Moderate/Severe Begin nutritional support as early as possible NJ tube preferred TPN only if : Can’t maintain adequate jejunal access Unable to meet caloric demands enterally

Mild pancreatitis

Calories from IVF (D5W) are sufficient

No benefit from additional nutritional support

Oral intake advancing to low fat diet once pain/anorexia resolve

Moderate/Severe

Begin nutritional support as early as possible

NJ tube preferred

TPN only if :

Can’t maintain adequate jejunal access

Unable to meet caloric demands enterally

When Do I Consult GI ? Evidence of biliary pancreatitis Elevated LFTs + pancreatitis No matter what the US shows Severe pancreatitis Recurrent unexplained pancreatitis Rule out infected necrosis EUS FNA sampling of fluid collections Endoscopic treatment of necrosis/abscess

Evidence of biliary pancreatitis

Elevated LFTs + pancreatitis

No matter what the US shows

Severe pancreatitis

Recurrent unexplained pancreatitis

Rule out infected necrosis

EUS FNA sampling of fluid collections

Endoscopic treatment of necrosis/abscess

Biliary pancreatitis Q: When should I suspect it ? A: Always Q: How do I evaluate for it ? A: (E)US and LFTs Q: When is ERCP indicated ? A: 3 studies looked at emergency (within 24-72h) ERC with ES vs standard therapy in biliary AP

Q: When should I suspect it ?

A: Always

Q: How do I evaluate for it ?

A: (E)US and LFTs

Q: When is ERCP indicated ?

A: 3 studies looked at emergency (within 24-72h) ERC with ES vs standard therapy in biliary AP

Fan Neoptolemus Fölsch Meta-analysis Emergency ERC (with ES & stone extraction when stones present) benefits severe AP but not mild

Emergency ERC (with ES & stone extraction when stones present)

benefits severe AP but not mild

Management of Pancreatic Complications Acute fluid collections Occur early, seen not felt No defined wall  usually resolve spontaneously NO routine percutaneous or operative drainage may infect otherwise sterile tissue Infected pancreatic necrosis Pancreatic abscess Pseudocysts

Acute fluid collections

Occur early, seen not felt

No defined wall  usually resolve spontaneously

NO routine percutaneous or operative drainage

may infect otherwise sterile tissue

Infected pancreatic necrosis

Pancreatic abscess

Pseudocysts

Grey-Turner’s sign

Management of Pancreatic Complications Infected necrosis Organisms on gram stain after aspirate Surgical drainage Trans-gastric drainage Try to delay necrosectomy 2-3wk for demarcation of necrosis Pancreatic abscess CT or EUS guided drainage Walled collection of pus Similar to management of pseudocyst

Infected necrosis

Organisms on gram stain after aspirate

Surgical drainage

Trans-gastric drainage

Try to delay necrosectomy 2-3wk for demarcation of necrosis

Pancreatic abscess

CT or EUS guided drainage

Walled collection of pus

Similar to management of pseudocyst

Pseudocysts Collection of pancreatic fluid enclosed by non-epithelialized wall of granulation tissue Complicates 5-10% cases of AP ~ 4 weeks after insult 25-50% resolve spontaneously

Collection of pancreatic fluid enclosed by non-epithelialized wall of granulation tissue

Complicates 5-10% cases of AP

~ 4 weeks after insult

25-50% resolve spontaneously

Complications of Pseudocyst Infection - 14% Rupture - 6.8% Hemorrhage - 6.5% Common bile duct obstruction - 6.3% GI obstruction - 2.6%

Infection - 14%

Rupture - 6.8%

Hemorrhage - 6.5%

Common bile duct obstruction - 6.3%

GI obstruction - 2.6%

Pseudocyst Management Old thought Pseudocysts > 5 cm that have been present > 6 weeks must be drained Current practice Asymptomatic pseudocysts , regardless of size, do not require treatment

Old thought

Pseudocysts > 5 cm that have been present > 6 weeks must be drained

Current practice

Asymptomatic pseudocysts , regardless of size, do not require treatment

Pseudocyst Drainage Techniques Endoscopic Surgical Radiologic Liver PC PC Stom

Endoscopic

Surgical

Radiologic

Endoscopic Pseudocyst Management Pseudocyst classification Communicating Non-communicating

Pseudocyst classification

Communicating

Non-communicating

Endoscopic Pseudocyst Management

Percutaneous Pseudocyst Drainage Open Cystgastrostomy

Laparoscopic Cyst Gastrostomy

Closing Points 4 out of 5 patients have mild uneventful pancreatitis If the patient is not getting considerably better in 36-48 hrs, start thinking about that “5th patient” A CT is that 5th patient’s friend If you are thinking about antibiotics, you should be thinking about a CT and a few consults The pancreas is mean organ….respect it

4 out of 5 patients have mild uneventful pancreatitis

If the patient is not getting considerably better in 36-48 hrs, start thinking about that “5th patient”

A CT is that 5th patient’s friend

If you are thinking about antibiotics, you should be thinking about a CT and a few consults

The pancreas is mean organ….respect it

Questions?