Evidence-based Evidence-based approach in approach in

managing acute managing acute pancreatitispancreatitis

James FungJames FungDepartment of SurgeryDepartment of Surgery

Tseung Kwan O HospitalTseung Kwan O Hospital

Topic for discussionTopic for discussion

Serum amylase – how to use it in Serum amylase – how to use it in diagnosis?diagnosis?

Severity assessmentSeverity assessment Antibiotic prophylaxis in SAP – is it Antibiotic prophylaxis in SAP – is it

useful?useful?

Serum amylase – how to Serum amylase – how to use it? use it?

Peaks within 12 – 24 hr from onset, norPeaks within 12 – 24 hr from onset, normalize within 3 – 5 daysmalize within 3 – 5 days

Pitfalls:Pitfalls: Falsely high level: intra-abdominal inflamFalsely high level: intra-abdominal inflam

mation; salivary gland pathologymation; salivary gland pathology Falsely normal level: Falsely normal level: delayed presentatiodelayed presentatio

nn; pancreatic insufficiency; hypertriglycer; pancreatic insufficiency; hypertriglyceridaemiaidaemia11

1. Spechler SJ et al. Prevalence of normal serum amylase levels in patients with acute alcoholic pancreatitis. Dig Dis Sci 1983; 28:865-9

Serum amylase – how to Serum amylase – how to use it? use it?

Sn and Sp Sn and Sp varies with diagnostic cut-off valvaries with diagnostic cut-off valueue

Cut-off Cut-off (IU/L)(IU/L)

SensitivSensitivityity

SpecificSpecificityity

Steinberg et alSteinberg et al11 326326 94.9%94.9% 86%86%

600600 92.3%92.3% 100%100%

Thomson et alThomson et al22 316316 95.6%95.6% 97.6%97.6%

10001000 60.9%60.9% 100%100%

1. Steinberg WM et al. Diagnostic assays in acute pancreatitis. A study of sensitivity and specificity. Ann Intern Med 1985;102:576-80

2. Thomson HJ et al. Diagnosis of acute pancreatitis: a proposed sequence of biochemical investigations. Scand J Gastroenterol 1987;22:719-24

Use of serum amylase – Use of serum amylase – summarysummary

Useful only when used in a correct Useful only when used in a correct clinical contextclinical context

Diagnostic accuracy depends on Diagnostic accuracy depends on thresholdthreshold

Use supplementary tools when in Use supplementary tools when in doubtdoubt

Severity assessmentSeverity assessment

Acute pancreatitis

Mild acutepancreatitis (80%)

Severe acutepancreatitis (SAP) (20%)

Severity scoring systemsSeverity scoring systems Glasgow scoreGlasgow score11

Within 48 hrsWithin 48 hrs PaO2 <60mmHgPaO2 <60mmHg Albumin <32 g/LAlbumin <32 g/L Ca++ <2mmol/LCa++ <2mmol/L WBC >15 x 109/LWBC >15 x 109/L AST/ALT >200U/LAST/ALT >200U/L LDH > 600U/LLDH > 600U/L Glucose Glucose

>10mmol/L>10mmol/L Urea >16mmol/LUrea >16mmol/L

Ranson scoreRanson score22

On admission:On admission: Age, WBC, glucose, Age, WBC, glucose,

LDH, ASTLDH, ASTWithin 48 hr:Within 48 hr: Haematocrit, BUN, eHaematocrit, BUN, e

stimated fluid shift, stimated fluid shift, PaO2, base deficit, CPaO2, base deficit, Ca++a++

1. Blamey et al. Prognostic factors in acute pancreatitis. GUT 1984; 25:1340-6

2. Ranson et al. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982;77:633-8

Severity scoring systemsSeverity scoring systems

Sn for predicting poor outcome:Sn for predicting poor outcome: Glasgow score – 61%Glasgow score – 61%11

Ranson score – 70%Ranson score – 70%22

48hr for complete scoring48hr for complete scoring

1. Corfield et al. Prediction of severity in acute pancreatitis: Prospective comparison of three prognostic indices. Lancet 1985;2:403-7

2. Ranson et al. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982;77:633-8

Severity scoring systemsSeverity scoring systems

APACHE IIAPACHE II 12 physiological / biochemical findings + a12 physiological / biochemical findings + a

ge + chronic health surveyge + chronic health survey

Sn up to 95%Sn up to 95%11

Daily / repeated scoring as reassessmentDaily / repeated scoring as reassessment Immediate scoring after admissionImmediate scoring after admission

Too complicated for use outside ICUToo complicated for use outside ICU

1. Wilson C et al. Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. BJS 1990;77:1260-4

Severity assessment – Severity assessment – CRPCRP

CRPCRP Serum level increase the degree of SIRSSerum level increase the degree of SIRS Cut-off value of 150mg/L (Sentorini ConseCut-off value of 150mg/L (Sentorini Conse

nsus)nsus)11

Sn and Sp (prediction of septic complicatiSn and Sp (prediction of septic complication) ~ 80%on) ~ 80%22

Peaks by 36hr after onsetPeaks by 36hr after onset

1. Dervenis C et al. Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini Consensus Conference. Int J Pancreatol 1999;25:195-210

2. Vesentini S et al. Prospective comparison of CRP level, Ranson score and contrast-enhanced computed tomography in the prediction of septic complications of acute pancreatitis. BJS 1993;80:755-7

Severity assessment – Severity assessment – summarysummary

Should not rely on scoring system Should not rely on scoring system for severity assessmentfor severity assessment

Frequent clinical +/- biochemical Frequent clinical +/- biochemical assessment is most importantassessment is most important Aim at early detection of organ Aim at early detection of organ

dysfunctiondysfunction

Treatment – antibiotics Treatment – antibiotics prophylaxis?prophylaxis?

Rationale:Rationale: To prevent the life threatening bacterial To prevent the life threatening bacterial

infection of pancreatic necrosisinfection of pancreatic necrosis

Concerns:Concerns: Antimicrobial resistanceAntimicrobial resistance11

Opportunistic fungal infectionOpportunistic fungal infection22

1. Bassi C et al. Controlled clinical trial of Pefloxacin versus Imipenem in severe acute pancreatitis. Gastroenterology 1998; 115:1513-17

2. Eatock FC et al. Fungal infection of pancreatic necrosis is associated with increased mortality. BJS 1999;86 supp 1:78

Treatment – antibiotics Treatment – antibiotics prophylaxis?prophylaxis?

RCTsRCTs PatiePatient nt no.no.

Prophylaxis Prophylaxis regimenregimen

Infected neInfected necrosiscrosis(Rx vs con)(Rx vs con)

MortalityMortality(Rx vs con)(Rx vs con)

Pederzoli Pederzoli (1993)(1993)

7474 ImipenemImipenem 12% vs 30%12% vs 30% 7% vs 12%7% vs 12%

Sainio (19Sainio (1995)95)

6060 CefuroximeCefuroxime 30% vs 40%30% vs 40% 3% vs 23%3% vs 23%

Schwarz Schwarz (1997)(1997)

2626 Olofloxacin Olofloxacin + metronida+ metronidazolezole

62% vs 54%62% vs 54% 0% vs 15%0% vs 15%

Nordback Nordback (2001)(2001)

5858 ImipenemImipenem 4% vs 18%4% vs 18% 8% vs 15%8% vs 15%

Treatment – antibiotics Treatment – antibiotics prophylaxis?prophylaxis?

Cochrane review 2007Cochrane review 2007 Included 5 RCTs comparing antibiotics prIncluded 5 RCTs comparing antibiotics pr

ophylaxis vs no prophylaxisophylaxis vs no prophylaxis Significant reduction of mortality in antibiSignificant reduction of mortality in antibi

otics prophylaxis group (6% vs 15%)otics prophylaxis group (6% vs 15%) Both significant reduction of infected necrBoth significant reduction of infected necr

osis (16% vs 29%)and mortality (6% vs 17osis (16% vs 29%)and mortality (6% vs 17%) in beta-lactam prophylaxis subgroup%) in beta-lactam prophylaxis subgroup

Antibiotics prophylaxis – Antibiotics prophylaxis – summarysummary

Current evidence is still not concrete Current evidence is still not concrete enough to make clear conclusionenough to make clear conclusion

Antibiotics prophylaxis probably Antibiotics prophylaxis probably gives a marginal benefit to SAP gives a marginal benefit to SAP patientspatients

Duration of treatment should last for Duration of treatment should last for at least 14 daysat least 14 days

Thank youThank you