Case Based Case Based PresentationPresentation

Severe Acute Pancreatitis,Or

How I Spent My Christmas Vacation

S. Mountain

January 8, 2009

The CaseThe Case

The patient is a 25-year-old obese woman The patient is a 25-year-old obese woman with a history of non-insulin-dependent with a history of non-insulin-dependent diabetes mellitus (NIDDM) and diabetes mellitus (NIDDM) and hypercholesterolemia who presents to the hypercholesterolemia who presents to the emergency department for evaluation of emergency department for evaluation of the acute onset of abdominal pain. The the acute onset of abdominal pain. The patient describes the pain, which she says patient describes the pain, which she says began 12 hours before her evaluation, as began 12 hours before her evaluation, as a constant epigastric cramping associated a constant epigastric cramping associated with nausea and vomiting. with nausea and vomiting.

She denies fever, chills, change in bowel habits, She denies fever, chills, change in bowel habits, or alteration in the character of her stool or or alteration in the character of her stool or urine. The patient's past medical history is urine. The patient's past medical history is significant for obesity, NIDDM, significant for obesity, NIDDM, hypercholesterolemia, and depression. She is hypercholesterolemia, and depression. She is uncertain of the names of the oral hypoglycemic uncertain of the names of the oral hypoglycemic and antilipidemic drugs that had been prescribed and antilipidemic drugs that had been prescribed to her. She does not use tobacco or alcohol. to her. She does not use tobacco or alcohol. There has been no recent travel. Laboratory There has been no recent travel. Laboratory studies performed 3 months before her studies performed 3 months before her admission revealed an elevated cholesterol level admission revealed an elevated cholesterol level of 597 mg/dL, with an HDL level of 42 mg/dL, of 597 mg/dL, with an HDL level of 42 mg/dL, and an elevated triglyceride level of 3034 mg/dL.and an elevated triglyceride level of 3034 mg/dL.

The physical examination is The physical examination is significant for morbid obesity (weight, significant for morbid obesity (weight, 301 lb); temperature, 37°C; blood 301 lb); temperature, 37°C; blood pressure, 100/50; pulse, 110/min; pressure, 100/50; pulse, 110/min; respiratory rate, 16/min; regular heart respiratory rate, 16/min; regular heart rate; clear lungs on auscultation; and rate; clear lungs on auscultation; and a diffusely tender abdomen without a diffusely tender abdomen without rebound or guarding. The stool is rebound or guarding. The stool is guaiac negative.guaiac negative.

Laboratory studies:Laboratory studies:– White blood cell countWhite blood cell count 11.6 x 1011.6 x 1033

– HemoglobinHemoglobin 13.7 g/dL13.7 g/dL– HematocritHematocrit 40.4%40.4% (normal: 37%-47%)(normal: 37%-47%)– SodiumSodium 135 mmol/L135 mmol/L– PotassiumPotassium 4 mmol/L4 mmol/L– ChlorideChloride 101 mmol/L101 mmol/L– BicarbonateBicarbonate 11.2 mmol/L11.2 mmol/L– Blood urea nitrogenBlood urea nitrogen 7 mg/dL7 mg/dL– CreatinineCreatinine 0.7 mg/dL0.7 mg/dL– CalciumCalcium 7.3 mg/dL7.3 mg/dL

Laboratory studies:Laboratory studies:– GlucoseGlucose 219 mg/dL219 mg/dL– AlbuminAlbumin 2.6 g/dL2.6 g/dL – AmylaseAmylase 222 U/L222 U/L– LipaseLipase 5562 U/L5562 U/L (normal: 25-300 U/L)(normal: 25-300 U/L)– Aspartate aminotransferase (AST)Aspartate aminotransferase (AST) 48 U/L48 U/L– Alanine aminotransferase (ALT)Alanine aminotransferase (ALT) 28 U/L28 U/L– Alkaline phosphataseAlkaline phosphatase 88 U/L88 U/L– Total bilirubinTotal bilirubin 0.8 mg/dL0.8 mg/dL– CholesterolCholesterol 784 mg/dL784 mg/dL (normal: 190-260 mg/dL)(normal: 190-260 mg/dL)– TriglyceridesTriglycerides 5250 mg/dL5250 mg/dL (normal: 10-160 mg/dL)(normal: 10-160 mg/dL)

Figure 1.Figure 1. The patient's serum, which is  The patient's serum, which is lipemic, is compared with normal serum.lipemic, is compared with normal serum.

Figure 2.Figure 2. The abdominal CT scan reveals phlegmonous  The abdominal CT scan reveals phlegmonous changes of the pancreas in the perirenal space, changes of the pancreas in the perirenal space, transverse mesocolon, and small bowel mesentery.transverse mesocolon, and small bowel mesentery.

1. What is the diagnosis? Define severe acute pancreatitis (SAP). Todd

Diagnosis:Diagnosis: Pancreatitis (of the severe acute variety)Pancreatitis (of the severe acute variety)

– Evidenced by clinical syndrome, laboratory Evidenced by clinical syndrome, laboratory studies and imaging.studies and imaging.

Definition: Pancreatitis associated with other Definition: Pancreatitis associated with other end organ failure, and/or complications .end organ failure, and/or complications .– NecrosisNecrosis– AbscessAbscess– Pseudocyst formationPseudocyst formation– Radiographic: evidence of previous 3 Radiographic: evidence of previous 3

complications, rather than degree of inflammatory complications, rather than degree of inflammatory changes.changes.

Severity of Illness scores (i.e. APACHE II > 8Severity of Illness scores (i.e. APACHE II > 8

2. What are the most common etiologies of SAP in developed countries? How about in North America (i.e. the USA)? What are some other causes of pancreatitis? What is the most likely cause in this patient? Noemie

Acute PancreatitisAcute Pancreatitis

Annual incidence 4.9 to 35 per Annual incidence 4.9 to 35 per 100,000100,000

Mortality of acute pancreatitis 10% Mortality of acute pancreatitis 10% and in severe AP up to 30%and in severe AP up to 30%

Two most common causes of AP are Two most common causes of AP are gallstones and alcohol (70%)gallstones and alcohol (70%)

Etiologies of severe acute Etiologies of severe acute pancreatitispancreatitis

Gallstones (35%)Gallstones (35%) Alcohol (35%)Alcohol (35%) TraumaTrauma HypertriglyceridemiaHypertriglyceridemia DrugsDrugs InfectionInfection TumorTumor

Pancreas DivisumPancreas Divisum Post ERCP Post ERCP HypercalcemiaHypercalcemia Idiopathic (10%)Idiopathic (10%) Autoimmune (PAN, Autoimmune (PAN,

SLE)SLE)

Gallstone pancreatitisGallstone pancreatitis

Most common cause in most areas of the Most common cause in most areas of the worldworld

Only 3% to 7% of pts with gallstones dvp Only 3% to 7% of pts with gallstones dvp pancreatitispancreatitis

More common in women vs menMore common in women vs men Dx: Dx:

– UltrasoundUltrasound– ALT > 3 x normal has a 95% PPVALT > 3 x normal has a 95% PPV11 – Bili and ALP does not influence dxBili and ALP does not influence dx

30 to 50% recurrence rate without definitive 30 to 50% recurrence rate without definitive therapytherapy

1. Am J Gastroenterol. 1994 Oct;89(10):1863-6.

Acute Alcoholic PancreatitisAcute Alcoholic Pancreatitis

Most common dx in USMost common dx in US ETOH might ETOH might the production of the production of

digestive and lysosomal enzymesdigestive and lysosomal enzymes Can present as acute on chronic Can present as acute on chronic

pancreatitis pancreatitis calcifications on CT calcifications on CT Lipase:amylase ratio > 2 Lipase:amylase ratio > 2

– 91% sensitivity and 76% specificity91% sensitivity and 76% specificity

What is the most likely cause in What is the most likely cause in this patient?this patient?

chol 15.44, HDL 1.09, trig 34.27 HypertriglyceridemiaHypertriglyceridemia

– Accounts for 1 to 4% of Acute PancreatitisAccounts for 1 to 4% of Acute Pancreatitis– Trig > 11 mmol/L can precipitate attacksTrig > 11 mmol/L can precipitate attacks– Acquired causes in adults:Acquired causes in adults:

Alcohol, Obesity, DM, Hypothyroidism, pregnancy, Alcohol, Obesity, DM, Hypothyroidism, pregnancy, Steroid, BBB, nephrotic syndromSteroid, BBB, nephrotic syndrom

– Trig > 11mmol/L Trig > 11mmol/L opalescent and milky serum opalescent and milky serum– Amylase may be falsely low Amylase may be falsely low – Goal is to lower their Trig<2.2mmol/LGoal is to lower their Trig<2.2mmol/L

3. What is the pathogenesis of SAP? Neil

PathogenesisPathogenesis

Premature intrapancreatic activation Premature intrapancreatic activation of digestive enzymesof digestive enzymes– Autodigestion of pancreatic structureAutodigestion of pancreatic structure– Ischemia Ischemia

Inflammatory responseInflammatory response– Cytokine release (IL-6, TNF-alpha, IL-Cytokine release (IL-6, TNF-alpha, IL-

1B)1B)– NeutrophilsNeutrophils– Platelet Activating Factor (PAF)Platelet Activating Factor (PAF)

Pathogenesis (2)Pathogenesis (2)

Increased vascular permeability and Increased vascular permeability and microcirculation impairmentmicrocirculation impairment– Constriction of arterioles and stasis of Constriction of arterioles and stasis of

neutsneuts– Ischemia results in rupture of lysosomes Ischemia results in rupture of lysosomes

and release of cytokinesand release of cytokines– Increased vascular permeability and NO Increased vascular permeability and NO

releaserelease Infection and necrosisInfection and necrosis

4. How is pancreatitis diagnosed? What are the roles and timing of amylase and lipase elevation, and how do they differ depending on the underlying etiology? What is the appropriate role and timing of imaging? Marios

Diagnosing pancreatitisDiagnosing pancreatitis

Diagnosis is usually made on the Diagnosis is usually made on the basis of: basis of:

– Clinical presentationClinical presentation

– Elevated pancreatic enzymesElevated pancreatic enzymes

– Radiologic evidence of inflammation Radiologic evidence of inflammation

Pancreatic enzymesPancreatic enzymes

Most common and available are serum Most common and available are serum amylase and lipaseamylase and lipase

Both are released into the circulation as Both are released into the circulation as their production continues in the face of their production continues in the face of reduced or absent secretionreduced or absent secretion

Levels do Levels do not not correlate with severity correlate with severity

Serum AmylaseSerum Amylase

Rises within 6-12 hours of onsetRises within 6-12 hours of onset

Elevated for 3 to 5 days in Elevated for 3 to 5 days in uncomplicated attacksuncomplicated attacks

May be May be lower lower in cases of in cases of hypertriglyceridemia-associated hypertriglyceridemia-associated pancreatitis or in chronic alcoholicspancreatitis or in chronic alcoholics

Serum AmylaseSerum Amylase

Not specific to pancreatic disease:Not specific to pancreatic disease:

– Also produced by salivary glands and Also produced by salivary glands and fallopian tubesfallopian tubes

– Can be absorbed from the gut in intestinal Can be absorbed from the gut in intestinal inflammation/infarction or from the inflammation/infarction or from the peritoneum in cases of perforated bowelperitoneum in cases of perforated bowel

– Clearance is reduced in renal failure or with Clearance is reduced in renal failure or with macroamylasemia (eg from pentaspan)macroamylasemia (eg from pentaspan)

Serum LipaseSerum Lipase

Thought to be more specific than Thought to be more specific than amylaseamylase

Can also be elevated in renal failure and Can also be elevated in renal failure and in intestinal inflammationin intestinal inflammation

Appears earlier and stays elevated Appears earlier and stays elevated longer than serum amylaselonger than serum amylase

Lipase VS AmylaseLipase VS Amylase

ROC curves for amylase and ROC curves for amylase and lipaselipase

Enzyme levels over timeEnzyme levels over time(actual figures from the paper)(actual figures from the paper)

Role and timing of Role and timing of imaging in imaging in pancreatitispancreatitis

Abdominal seriesAbdominal series

Usually part of the initial work-up in ERUsually part of the initial work-up in ER

Can be normal, or show non-specific Can be normal, or show non-specific findings such as an ileus and air-fluid findings such as an ileus and air-fluid levelslevels

More specific findings include the More specific findings include the colon-colon-cut-off sign,cut-off sign, and a and a sentinel loopsentinel loop

Colon Cutoff signColon Cutoff sign

Colon Cutoff SignColon Cutoff Sign

UltrasonographyUltrasonography

No role in the diagnosis or staging of No role in the diagnosis or staging of severe pancreatitissevere pancreatitis– Bowel gas often obscures view of pancreasBowel gas often obscures view of pancreas– Cannot identify necrosis Cannot identify necrosis

Should be performed in all patients with Should be performed in all patients with first attacks of pancreatitis to rule-out first attacks of pancreatitis to rule-out gallstonesgallstones

Contrast-enhanced CTContrast-enhanced CT Unless there is diagnostic uncertainty, Unless there is diagnostic uncertainty,

admission CTs are not usually necessary.admission CTs are not usually necessary.

Can be performed after 48-72 hours of Can be performed after 48-72 hours of conservative management if there is lack conservative management if there is lack of improvement or worsening of clinical of improvement or worsening of clinical status. status.

Intravenous contrast is preferred in order Intravenous contrast is preferred in order to show areas of necrosis, which will to show areas of necrosis, which will appear as unenhanced areas (< 50 HU)appear as unenhanced areas (< 50 HU)

5. What are some of the prognostic scoring systems used to predict severity of pancreatitis? Please discuss both clinical and radiographic scoring systems, but focus on those that are clinically relevant and useful for an intensivist. Naisan

Clinical Scoring Clinical Scoring SystemsSystems

Scoring systemsScoring systems Despite traditional measures, including Despite traditional measures, including

scoring systems, serum measurements and scoring systems, serum measurements and radiological evaluation, acute pancreatitis radiological evaluation, acute pancreatitis patients remain challenging to risk stratifypatients remain challenging to risk stratify

Serum lipase and amylase levels are poorly Serum lipase and amylase levels are poorly correlated with disease severitycorrelated with disease severity

CRP is a good discriminator between CRP is a good discriminator between severe and mild disease 48 h after the severe and mild disease 48 h after the onset of symptoms. A cut-off level of 150 onset of symptoms. A cut-off level of 150 mg/l is acceptedmg/l is accepted

a BMI above 30, is a reliable predictor of a BMI above 30, is a reliable predictor of severe outcome independently of agesevere outcome independently of age

Lab MarkersLab Markers

Predicting SeverityPredicting Severity

In a meta-analysis of 399 patients In a meta-analysis of 399 patients presenting with acute pancreatitis, a serum presenting with acute pancreatitis, a serum haematocrit above 44mg/dl, BMI above 30 haematocrit above 44mg/dl, BMI above 30 kg/m2, and pleural effusion on chest X-ray, kg/m2, and pleural effusion on chest X-ray, were the most sensitive predictors of were the most sensitive predictors of overall severity in acute pancreatitis. In the overall severity in acute pancreatitis. In the same paper, these criteria were validated same paper, these criteria were validated in a prospective cohort of 238 American in a prospective cohort of 238 American patients, as the ‘panc 3 score’patients, as the ‘panc 3 score’

Brown A, James-Stevenson T, Dyson T, et al. The panc 3 score: a rapid and accurate test for predicting severity on Brown A, James-Stevenson T, Dyson T, et al. The panc 3 score: a rapid and accurate test for predicting severity on presentation in acute pancreatitis. J Clin Gastroenterol 2007; 41:855–858.presentation in acute pancreatitis. J Clin Gastroenterol 2007; 41:855–858.

Clinical ScoringClinical Scoring

Ranson Criteria Ranson Criteria distinguish distinguish between mild and severe between mild and severe pancreatitis with about 80% pancreatitis with about 80% accuracy. The Ranson criteria, accuracy. The Ranson criteria, however, require evaluation of 11 however, require evaluation of 11 parameters over 48 hours. parameters over 48 hours.

The The APACHE II APACHE II scale scale has advantages in has advantages in that it can be that it can be performed on performed on admission, can be admission, can be reevaluated at any reevaluated at any time during the time during the patient’s patient’s hospitalizaton. It is hospitalizaton. It is cumbersome to use cumbersome to use clinically thoughclinically though

MPM IIMPM II

Lemeshow S et al. Mortality probability models (MPM II) based on an international cohort of intensive care patients. JAMA 1993;270:2478-86

Severe PancreatitisSevere Pancreatitis

Severe acute pancreatitis is Severe acute pancreatitis is diagnosed if 3 or more of diagnosed if 3 or more of Ranson’s criteria are present, if Ranson’s criteria are present, if the APACHE II score is 8 or more, or if the APACHE II score is 8 or more, or if one or more of the following are one or more of the following are present: shock, renal insufficiency, present: shock, renal insufficiency, and pulmonary insufficiencyand pulmonary insufficiency– Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol

1997;92:377-86.1997;92:377-86.

Practical approach to predicting Practical approach to predicting severity requiring admission to an severity requiring admission to an

ICU: ICU: a BMI above 30, anda BMI above 30, and left-sided or bilateral effusion on CXR left-sided or bilateral effusion on CXR

within 24 h of admission, within 24 h of admission, An APACHE II score of at least 8 at 24 h An APACHE II score of at least 8 at 24 h

after admission, and a CRP above 150 mg/l after admission, and a CRP above 150 mg/l or a Ranson score above 3 at 48 h after or a Ranson score above 3 at 48 h after

admission. admission. The development of organ failure or The development of organ failure or

pancreatic necrosis (i.e., SAP by definition) pancreatic necrosis (i.e., SAP by definition) also warrants immediate transfer to an also warrants immediate transfer to an ICU.ICU.– A. Wilmer / European Journal of Internal Medicine 15 (2004) 274–280A. Wilmer / European Journal of Internal Medicine 15 (2004) 274–280

Imaging CriteriaImaging Criteria

CT Severity IndexCT Severity Index

Copyright © 2006 by the American Roentgen Ray Society

Mortele, K. J. et al. Am. J. Roentgenol. 2004;183:1261-1265

--74-year-old man with acute pancreatitis

Radiological ScoringRadiological Scoring

Gurleyik et al found a sensitivity of 85% Gurleyik et al found a sensitivity of 85% and a specificity of 98% in predicting and a specificity of 98% in predicting severe pancreatitis based solely on CT severe pancreatitis based solely on CT severity index.severity index.– Computed tomography severity index, APACHE II score, serumCRP concentration for Computed tomography severity index, APACHE II score, serumCRP concentration for

predicting the severity of acute pancreatitis. JOP 2005; 6(6):562–7.predicting the severity of acute pancreatitis. JOP 2005; 6(6):562–7.

severity index less than 3 had a 4% severity index less than 3 had a 4% morbidity rate and no mortality, morbidity rate and no mortality, whereas patients who had a SI of more whereas patients who had a SI of more than 6 had a 92% morbidity rate and a than 6 had a 92% morbidity rate and a 17% mortality17% mortality– Balthazar EJ, Robinson DL, Megibow AJ, et al. Acute pancreatitis: value of CT in Balthazar EJ, Robinson DL, Megibow AJ, et al. Acute pancreatitis: value of CT in

establishing prognosis. Radiology 1990;174(2):331–6.establishing prognosis. Radiology 1990;174(2):331–6.

CT severity indexCT severity index

patients who had a CT severity index patients who had a CT severity index greater than 5 were eight times more greater than 5 were eight times more likely to die, 17 times more likely to likely to die, 17 times more likely to have a prolonged hospital course, have a prolonged hospital course, and 10 times more likely to require and 10 times more likely to require necrosectomy than patients who had necrosectomy than patients who had a severity index less than 5a severity index less than 5

6. What is the appropriate initial management approach for a patient with SAP? Yoan

Non ICU ptNon ICU pt– NPO,FluidsNPO,Fluids– Analgesia,Analgesia,– No ATBxNo ATBx– Abdo U/S: R/O gallstoneAbdo U/S: R/O gallstone– Feed low fat when anorexia goneFeed low fat when anorexia gone

Management, ICU patientManagement, ICU patient Shock, pulmonary failure, renal failure, gastrointestinal bleeding, Shock, pulmonary failure, renal failure, gastrointestinal bleeding,

multiorgan system failuremultiorgan system failure Initially NPOInitially NPO Aggressive fluid resuscitation and monitoring (up to 500cc/hr + Aggressive fluid resuscitation and monitoring (up to 500cc/hr +

bolus)bolus) ATBXATBX

– Give if infected pancreatic necrosis (CT guided aspiration)Give if infected pancreatic necrosis (CT guided aspiration)– Do not give for fever only (inflammatory)Do not give for fever only (inflammatory)

Abdo U/S: R/O gallstone-ERCP if gallstone pancreatitis-Abdo U/S: R/O gallstone-ERCP if gallstone pancreatitis-Cholecystect in same hospitCholecystect in same hospit

NJ feeds initiated early (after initial ressuc- possibly NG)NJ feeds initiated early (after initial ressuc- possibly NG) TPN = 2TPN = 2ndnd line if feeds not tolerated line if feeds not tolerated CT C+: early if doubt and for baseline, then at 2-5d, then PRN vs CT C+: early if doubt and for baseline, then at 2-5d, then PRN vs

q1weekq1week

7. When should the patient with SAP be monitored in an ICU or step-down unit? Todd

Indications for ICU/stepdown Indications for ICU/stepdown admission:admission:

Shock (hypovolemic/distributive in setting of SIRS)Shock (hypovolemic/distributive in setting of SIRS)– Need for invasive cardiovascular monitoring.Need for invasive cardiovascular monitoring.– Hemodynamic support (pressors).Hemodynamic support (pressors).– Massive volume resuscitation, usually “too heavy” for Massive volume resuscitation, usually “too heavy” for

standard ward care, with resuscitation taking too long for standard ward care, with resuscitation taking too long for typical busy ER.typical busy ER.

Organ failureOrgan failure– Lung injuryLung injury– Renal failureRenal failure

Specific patient characteristics: elderly, morbid Specific patient characteristics: elderly, morbid obesity (BMI > 30), extensive pancreatic necrosis obesity (BMI > 30), extensive pancreatic necrosis (>30%)(>30%)

The patient was admitted to the intensive care unit and was treated with intravenous fluids, narcotic analgesia, and insulin for her diabetes. Twenty-four hours after admission, the patient was noted to be tachypneic and dyspneic, requiring oxygen administration.

8. What is the frequency of lung injury in SAP? What is the proposed mechanism? Discuss the main preventive and therapeutic strategies. Noemie

Lung injury and Acute Lung injury and Acute PancreatitisPancreatitis

30% of pts with acute pancreatitis dvp ALI/ARDS30% of pts with acute pancreatitis dvp ALI/ARDS Responsible for 60% of all deaths in 1st weekResponsible for 60% of all deaths in 1st week Mechanism:Mechanism:

– Autodigestion of pancreas --> extravasation of Autodigestion of pancreas --> extravasation of proteolytic enzymes and vasoactive mediatorsproteolytic enzymes and vasoactive mediators

– Systemic activation of inflammatory cells (Neutrophils)Systemic activation of inflammatory cells (Neutrophils)

– Endothelial hyperpermeability and leakEndothelial hyperpermeability and leak

Current Opinion in Critical Care 2002,8:158-163

Prevention and treatment:Prevention and treatment:– Low tidal volume ventilationLow tidal volume ventilation– Inhibition of proinflammatory cascadeInhibition of proinflammatory cascade

Experimental/Animal modelsExperimental/Animal models Antibodies against neutrophil Antibodies against neutrophil

chemoattractantschemoattractants Hypertonic salineHypertonic saline

– Attenuates neutrophil activation Attenuates neutrophil activation

– NutritionNutrition Enteral feeding shown to have better Enteral feeding shown to have better

outcome (ICAM)outcome (ICAM)

Lung injury and Acute Lung injury and Acute PancreatitisPancreatitis

Current Opinion in Critical Care 2002,8:158-163

Forty-eight hours after admission, the patient was found to have marked hypocalcemia (calcium, 0.7 mmol/L) and hypophosphatemia (phosphorus, 0.52 mmol/L), requiring supplementation. On rounds, you need to make a decision on nutrition, as the patient has not yet been fed.

9. What is the etiology of the hypocalcemia and hypophosphatemia? Neil

What is the etiology of the What is the etiology of the hypocalcemia and hypocalcemia and

hypophosphatemia? hypophosphatemia? PTHPTH

– Suppressed secretionSuppressed secretion– InactivitatedInactivitated

Cytokines result in intracellular shift Cytokines result in intracellular shift of phosphateof phosphate

10. What is the optimal mode and timing of nutritional support for the patient with SAP? Are there any specific nutritional supplements that are beneficial in SAP? Are probiotics useful? Marios

Nutrition in Nutrition in pancreatitispancreatitis

What is the optimal mode and What is the optimal mode and timing of nutritional support timing of nutritional support

for the patient with SAP?for the patient with SAP?

Total infectious Total infectious complicationscomplications

MortalityMortality

Nutritional Nutritional supplements in SAPsupplements in SAP

Are probiotics useful?Are probiotics useful?

www.thelancet.com Vol 371 February 23, 2008

On the seventh hospital day, the patient develops a leukocytosis (white blood cell count, 13.35 x 103) with 32% bands. Panculturing is performed. You are concerned about the possibility of a secondary pancreatic infection.

11. What is the frequency of infectious complication in SAP? What is the impact on prognosis? Naisan

IncidenceIncidence

20% of patients develop pancreatic necrosis 20% of patients develop pancreatic necrosis 15-50% pts that have pancreatic necrosis 15-50% pts that have pancreatic necrosis

develop infected necrosis from translocation develop infected necrosis from translocation of gut-derived micro-organismsof gut-derived micro-organisms

The highest risk group is those with 30% or The highest risk group is those with 30% or more necrosismore necrosis

infection might occur within the 1st week, infection might occur within the 1st week, but its incidence tends to peak in the third but its incidence tends to peak in the third weekweek

PrognosisPrognosis

death occurs in 10 to 20% of patients death occurs in 10 to 20% of patients with infected necrosis. with infected necrosis.

Infectious complications account for Infectious complications account for 80% of deaths from SAP, as well as 80% of deaths from SAP, as well as the majority of late complicationsthe majority of late complications

12. Should patients with SAP receive prophylactic antibiotics? What is the evidence? What about selective decontamination of the digestive tract (SDD)? Yoan

Question 12Question 12

Should patients with SAP receive Should patients with SAP receive prophylactic antibiotics? What is the prophylactic antibiotics? What is the evidence? What about selective evidence? What about selective decontamination of the digestive decontamination of the digestive tract (SDD)? tract (SDD)? YoanYoan

Nathens et al. Management of the critically ill Nathens et al. Management of the critically ill patient with severe acute pancreatitis. CCM 2004patient with severe acute pancreatitis. CCM 2004

Cochrane Data Review/Metaanalysis 2006Cochrane Data Review/Metaanalysis 2006

Meta Analysis on ATBX in Meta Analysis on ATBX in SAPSAP

Am J Gastroenterol 2008

US RCT MulticentricUS RCT Multicentric

100pts100pts Proved Pancreatic necrosisProved Pancreatic necrosis Meropenem/placeboMeropenem/placebo No decrease in IxNo decrease in Ix No change in hard outcomesNo change in hard outcomes

Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo controlled study. Ann Surg 2007; 245:674–683.

We recommend against the routine use of prophylactic systemic antibacterial or antifungal agents in patients with necrotizing pancreatitis in light of inconclusive evidence and divided expert opinion

Nathens et al. Management of the critically ill patient with severe acute pancreatitis. CCM 2004

We recommend against the routine We recommend against the routine use of selective decontamination of use of selective decontamination of the digestive tract in the the digestive tract in the management of necrotizing management of necrotizing pancreatitis. Further investigation of pancreatitis. Further investigation of this promising strategy in SAP is this promising strategy in SAP is warrantedwarranted

Nathens et al. Management of the critically ill patient with severe acute pancreatitis. CCM 2004

Cultures all come back negative, and the empiric antibiotic therapy you initiated is discontinued. A repeat abdominal CT scan reveals worsening phlegmonous changes of the pancreas. The WBC continues to rise, as do the lipase and amylase.

13. What are the indications for surgery in acute pancreatitis and what is the optimal timing for intervention? What are the roles for less invasive approaches, including percutaneous drainage and laparoscopy? Are there any specific approaches that need to be considered with this etiology? Todd

Indications for Surgery in Indications for Surgery in SAP:SAP:

Cholecystectomy (stone-associated Cholecystectomy (stone-associated disease)disease)

Necrosectomy:Necrosectomy:– Infected necrotic tissue (up to 40% of patients Infected necrotic tissue (up to 40% of patients

with SAP).with SAP).– Possibly in sterile necrotic pancreatitis, in Possibly in sterile necrotic pancreatitis, in

setting of recalcitrant SIRS/clinical setting of recalcitrant SIRS/clinical deterioration, or failed attempts at enteral deterioration, or failed attempts at enteral refeeding after 2-4 weeks.refeeding after 2-4 weeks.

– Abdominal compartment syndrome in setting Abdominal compartment syndrome in setting of pancreatitis.of pancreatitis.

TimingTiming

Key is allowing necrotic pancreas to Key is allowing necrotic pancreas to demarcatedemarcate– Early in abdominal compartment Early in abdominal compartment

syndrome, possibly in gallstone-related syndrome, possibly in gallstone-related disease with cholecystitis.disease with cholecystitis.

– Delayed, i.e. >2 weeks, for Delayed, i.e. >2 weeks, for necrosectomy (barring uncontrolled necrosectomy (barring uncontrolled SIRS), cholecystectomy.SIRS), cholecystectomy.

Other toolsOther tools

Less invasive options:Less invasive options:– Percutaneous drainage (also useful for Percutaneous drainage (also useful for

obtaining gram stain/culture to guide obtaining gram stain/culture to guide surgical decision and antimicrobial surgical decision and antimicrobial choice).choice). May add continuous peritoneal lavage (no May add continuous peritoneal lavage (no

planned re-laparotomy)planned re-laparotomy)

– Percutaneous necrosectomy.Percutaneous necrosectomy.– Laparoscopy/Video-assisted Laparoscopy/Video-assisted

retroperitoneal debridement (VARD).retroperitoneal debridement (VARD).

Endoscopic Retrograde Endoscopic Retrograde CholangiopancreatographyCholangiopancreatography

To decompress ducts and drain To decompress ducts and drain infected biliary sludge in patients infected biliary sludge in patients with choledocholithiasis.with choledocholithiasis.– This is an early intervention (< 72 hrs) This is an early intervention (< 72 hrs)

in setting of obstructive jaundice or in setting of obstructive jaundice or biliary sepsis.biliary sepsis.

MiscellaneousMiscellaneous

Plasma Exchange (PLEX)Plasma Exchange (PLEX) If lipemic plasma is the problem, get rid If lipemic plasma is the problem, get rid

of it (at least temporarily)…of it (at least temporarily)… Described in Described in Therapeutic ApheresisTherapeutic Apheresis 2002 2002

Dec. 6 (6) 454-58.Dec. 6 (6) 454-58.– 2 patients in Japan with necrotizing 2 patients in Japan with necrotizing

pancreatitis in setting of pancreatitis in setting of hypertriglyceridemia.hypertriglyceridemia. Early PLEX--> survival after 60-day hospital courseEarly PLEX--> survival after 60-day hospital course Delayed (20 days after onset of illness) --> death Delayed (20 days after onset of illness) --> death

from multiorgan failure and sepsis.from multiorgan failure and sepsis.

14. Under what circumstances should patients with gallstone pancreatitis undergo interventions for clearance of the bile duct? Noemie

Gallstone AP and interventions for Gallstone AP and interventions for clearance of the bile duct?clearance of the bile duct?

CBD stones cause 35-40% of SAPCBD stones cause 35-40% of SAP 1998 UK guidelines:1998 UK guidelines:

– In SAP with u/s proven stone with obstructive In SAP with u/s proven stone with obstructive jaundice, urgent ERCP+ES is recommendedjaundice, urgent ERCP+ES is recommended

– In mild suspected gallstone pancreatitis, In mild suspected gallstone pancreatitis, conservative management is recommended. If pt’s conservative management is recommended. If pt’s condition fails to improve in 24-48H, ERCP is condition fails to improve in 24-48H, ERCP is indicatedindicated

European Journal of Internal Medicine 2004;15:274-280

Ann Surg 2006;243: 154-168.

Studies compared emergency ERCP+ES vs Studies compared emergency ERCP+ES vs conservative Txconservative Tx

ERCP+ES significantly reduced overall ERCP+ES significantly reduced overall complication rate (41% vs 31%)complication rate (41% vs 31%)

Trend toward mortality benefitTrend toward mortality benefit Does not influence the course of mild biliary Does not influence the course of mild biliary

APAP

Primary Cholecystectomy vs Primary Cholecystectomy vs early ERCPearly ERCP

One level I trial comparing ERC+ES vs One level I trial comparing ERC+ES vs cholecystectomy for mild biliary APcholecystectomy for mild biliary AP Hospital stay and overall cost for Hospital stay and overall cost for

cholecystectomy groupcholecystectomy group Three level I trials looking at symptomatic Three level I trials looking at symptomatic

CBD stones CBD stones – suggested less recurrent biliary sxsuggested less recurrent biliary sx– Late mortality in ERC group was Late mortality in ERC group was in one trial in one trial

Recommend that mild biliary AP be Recommend that mild biliary AP be treated with cholecystectomy + intraop treated with cholecystectomy + intraop cholangio. cholangio.

Ann Surg 2006;243: 154-168.

15. Is there a role for therapy targeting the inflammatory response in patients with SAP? Neil

Is there a role for therapy Is there a role for therapy targeting the inflammatory targeting the inflammatory

response in patients with SAP? response in patients with SAP? OctreotideOctreotide

– Benefit in meta-analysisBenefit in meta-analysis– Big RCT = no benefitBig RCT = no benefit

Antioxidants vs placebo in SAP Antioxidants vs placebo in SAP Siriwardena et al.Siriwardena et al. – no difference in organ functionno difference in organ function

Lexipafant (PAF antagonist)Lexipafant (PAF antagonist)– No improvement in DBRCTNo improvement in DBRCT

The patient's abdominal pain and laboratory values stabilize and improve slightly with medical management, and surgical intervention is withheld. However, on day 11, the patient’s hemoglobin drops to 85 from 110 the day before.

16. List at least 4 potential causes of GI bleeding in SAP. Which are most common; which are least? Yoan

Jury et al. Review Surg Tx Pancreatitis. MedClinNAm 2008Jury et al. Review Surg Tx Pancreatitis. MedClinNAm 2008

Cappel et al. Review Pancreatitis MedClinNAm 2008

Left colic artery pseudoaneurysm from pancreatitis presenting as upper gastrointestinal hemorrhage. Marichal DA, Savage C, Meler JD, Kirsch D, Rees CR. J Vasc Interv Radiol. 2009 Jan;20(1):133-6. Epub 2008 Nov 22.

Acute necrotizing pancreatitis complicated with pancreatic pseudoaneurysm of the superior mesenteric artery: A case report.He Q, Liu YQ, Liu Y, Guan YS. World J Gastroenterol. 2008 Apr 28;14(16):2612-4

During the remainder of her hospitalization, the patient's abdominal pain and laboratory values continue to improve. She recovers with conservative medical management and does not require surgical intervention.On hospital day 20, the patient is discharged in good condition. She is followed by her primary care physician and is compliant with gemfibrozil therapy and continues without reported recurrent episodes of pancreatitis for more than 1 year.