Evidence-based approach in managing acute pancreatitis James Fung Department of Surgery Tseung Kwan O Hospital

Topic for discussion Serum amylase – how to use it in diagnosis? Serum amylase – how to use it in diagnosis? Severity assessment Severity assessment Antibiotic prophylaxis in SAP – is it useful? Antibiotic prophylaxis in SAP – is it useful?

Serum amylase – how to use it? Peaks within 12 – 24 hr from onset, normalize within 3 – 5 days Peaks within 12 – 24 hr from onset, normalize within 3 – 5 days Pitfalls: Pitfalls: Falsely high level: intra-abdominal inflammation; salivary gland pathology Falsely high level: intra-abdominal inflammation; salivary gland pathology Falsely normal level: delayed presentation; pancreatic insufficiency; hypertriglyceridaemia 1 Falsely normal level: delayed presentation; pancreatic insufficiency; hypertriglyceridaemia 1 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 use it? Sn and Sp varies with diagnostic cut-off value Sn and Sp varies with diagnostic cut-off value Cut-off (IU/L) SensitivitySpecificity Steinberg et al %86% %100% Thomson et al %97.6% %100% 1.Steinberg WM et al. Diagnostic assays in acute pancreatitis. A study of sensitivity and specificity. Ann Intern Med 1985;102: 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 – summary Useful only when used in a correct clinical context Useful only when used in a correct clinical context Diagnostic accuracy depends on threshold Diagnostic accuracy depends on threshold Use supplementary tools when in doubt Use supplementary tools when in doubt

Severity assessment

Severity scoring systems Glasgow score 1 Glasgow score 1 Within 48 hrs PaO2 <60mmHg PaO2 <60mmHg Albumin <32 g/L Albumin <32 g/L Ca++ <2mmol/L Ca++ <2mmol/L WBC >15 x 109/L WBC >15 x 109/L AST/ALT >200U/L AST/ALT >200U/L LDH > 600U/L LDH > 600U/L Glucose >10mmol/L Glucose >10mmol/L Urea >16mmol/L Urea >16mmol/L Ranson score 2 On admission: Age, WBC, glucose, LDH, AST Within 48 hr: Haematocrit, BUN, estimated fluid shift, PaO2, base deficit, Ca++ 1.Blamey et al. Prognostic factors in acute pancreatitis. GUT 1984; 25: Ranson et al. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982;77:633-8

Severity scoring systems Sn for predicting poor outcome: Sn for predicting poor outcome: Glasgow score – 61% 1 Glasgow score – 61% 1 Ranson score – 70% 2 Ranson score – 70% 2 48hr for complete scoring 48hr for complete scoring 1.Corfield et al. Prediction of severity in acute pancreatitis: Prospective comparison of three prognostic indices. Lancet 1985;2: Ranson et al. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 1982;77:633-8

Severity scoring systems APACHE II APACHE II 12 physiological / biochemical findings + age + chronic health survey 12 physiological / biochemical findings + age + chronic health survey Sn up to 95% 1 Sn up to 95% 1 Daily / repeated scoring as reassessment Daily / repeated scoring as reassessment Immediate scoring after admission Immediate scoring after admission  Too 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 – CRP CRP CRP Serum level increase the degree of SIRS Serum level increase the degree of SIRS Cut-off value of 150mg/L (Sentorini Consensus) 1 Cut-off value of 150mg/L (Sentorini Consensus) 1 Sn and Sp (prediction of septic complication) ~ 80% 2 Sn and Sp (prediction of septic complication) ~ 80% 2  Peaks 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: 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 – summary Should not rely on scoring system for severity assessment Should not rely on scoring system for severity assessment Frequent clinical +/- biochemical assessment is most important Frequent clinical +/- biochemical assessment is most important Aim at early detection of organ dysfunction Aim at early detection of organ dysfunction

Treatment – antibiotics prophylaxis? Rationale: Rationale: To prevent the life threatening bacterial infection of pancreatic necrosis To prevent the life threatening bacterial infection of pancreatic necrosis Concerns: Concerns: Antimicrobial resistance 1 Antimicrobial resistance 1 Opportunistic fungal infection 2 Opportunistic fungal infection 2 1.Bassi C et al. Controlled clinical trial of Pefloxacin versus Imipenem in severe acute pancreatitis. Gastroenterology 1998; 115: Eatock FC et al. Fungal infection of pancreatic necrosis is associated with increased mortality. BJS 1999;86 supp 1:78

Treatment – antibiotics prophylaxis? RCTs Patient no. Prophylaxis regimen Infected necrosis (Rx vs con) Mortality Pederzoli (1993) 74Imipenem 12% vs 30% 7% vs 12% Sainio (1995) 60Cefuroxime 30% vs 40% 3% vs 23% Schwarz (1997) 26 Olofloxacin + metronidazole 62% vs 54% 0% vs 15% Nordback (2001) 58Imipenem 4% vs 18% 8% vs 15%

Treatment – antibiotics prophylaxis? Cochrane review 2007 Cochrane review 2007 Included 5 RCTs comparing antibiotics prophylaxis vs no prophylaxis Included 5 RCTs comparing antibiotics prophylaxis vs no prophylaxis Significant reduction of mortality in antibiotics prophylaxis group (6% vs 15%) Significant reduction of mortality in antibiotics prophylaxis group (6% vs 15%) Both significant reduction of infected necrosis (16% vs 29%)and mortality (6% vs 17%) in beta-lactam prophylaxis subgroup Both significant reduction of infected necrosis (16% vs 29%)and mortality (6% vs 17%) in beta-lactam prophylaxis subgroup

Antibiotics prophylaxis – summary Current evidence is still not concrete enough to make clear conclusion Current evidence is still not concrete enough to make clear conclusion Antibiotics prophylaxis probably gives a marginal benefit to SAP patients Antibiotics prophylaxis probably gives a marginal benefit to SAP patients Duration of treatment should last for at least 14 days Duration of treatment should last for at least 14 days

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