The Management of Acute Necrotizing Pancreatitis Stephanie Cheung Hay Man Caritas Medical Centre 25th July 2009 Joint Hospital Grand Round

Introduction Severe pancreatitis occurs in 15-20% of patients with acute pancreatitis The degree of necrosis and the presence of infection are crucial determinants of overall outcome Patients with predicted severe acute pancreatitis should be nursed in high dependency unit or ICU Close monitoring and organ support

Disease progression Early First 2 weeks Organ failure is common As a result of SIRS due to release of inflammatory mediators into the circulation Late Two weeks after onset of symptoms Dominated by septic related complications of the infected necrosis

UK Guidelines 2003 The Management of Acute Pancreatitis

Controversies Does prophylactic antibiotic help to prevent infection of the pancreatic necrosis? Management of necrosis What is the role of surgery in sterile necrosis? Which is the best treatment modality for infected necrosis?

Meta-analysis of Prophylactic Antibiotic Use In Acute Necrotizing Pancreatitis (ANP) In total 6 eligible RCT included, 329 patients in the meta-analysis with 167 received prophylactic AB and 162 in the control group. Infected necrosis reported in all studies. Of total 81 patients with infected necrosis, 34 in prophylactic group and 47 in control, Antibiotic group was not associated with significant reduction in incidence of infected necrosis, p= 0.173 44 deaths reported in all studies, 17 in prophylactic group and 27 in control. A/B use showed no significant reduction in reducing mortality p=0.404 non pancreatic infection ( Respiratory or UTI), results a/v from 4 RCTs only. Of 61 reported non pancreatic infections, 26 in prophylactic group and 35 in control. Again no significant reduction in reducing non pancreatic infection p= 0.402 Results a/v from 5 RCTs for need of surgery. 86 ( total) 39 from prophylactic group and 47 from control. Results not significant p=0.167 3 RCTS reported on hospital stay. There is significant reduction p= 0.04

Prophylactic Antibiotic in ANP On the contrary, some meta-analyses have lent support to prophylactic use Indicating reduction in the incidence of infected necrosis and mortality Villatoro et al Antibiotic Therapy for Prophylaxis Againist Infection of Pancreatic necrosis in ANP; Cochrane Database Syst Rev 2009

Is Prophylactic Antibiotic Useful In ANP? Remains controversial Imipenem is frequently used due to its good penetration to the pancreas Judicious use of antibiotic Change of Gram negative to Gram positive infection Promotion of fungal infection Buchler et al Acute Necrotizing Pancreatitis: Treatment Strategy According to The Status of Infection; Ann of Surg 2000 Whether to use prophylactic antibiotic or not remains controversial. Imipenem is frequently used due to its good penetration to the pancreas, however one should consider it use with caution

Management of Necrosis in ANP What is the optimal time for necrosectomy? What is the role of surgery in sterile necrosis ? Which surgical modality is best for treating infected necrosis?

Timing of Surgery in ANP (I) For predicted severe pancreatitis, CT helps to document the presence and degree of necrosis Early phase – multimodality approach Safe period – 4-6 weeks Surgical intervention in the early phase carries high mortality when inflammation is spreading without a clear demarcation The unorganised necrosis also leads to massive intraoperative bleeding MT Cheung Surgical Intervention in Necrotizing Pancreatitis: towards lesser and later, ANZ J Of Surg 2009 With the use of CT in dx the presence and amount of necrosis in the pancreatitis, these patients ought to be management with mutlidisciplinary approach in the early phase. The safe period suggested around 4-6 weeks due to surgery in early phase carries high mortality when inflammation is spreading without demarcation and the unorganised necrosis easily lead to massive bleeding intraoperatively

Timing Of Surgical Intervention In ANP (II) Retrospective study of 53 infected necrosis Surgery for persistant organ failure despite maximal ICU support or proven infected necrosis Open necrosectomy and post operative lavage Post operative mortality rate within 14 days – 75% 15-29 days – 45% > 30 days – 8% Besselink et al Timing of surgical intervention in necrotizing pancreatitis, Arch of Surg 2007 In this study, the authors aimed to find out the optimal timing of surgical intervention. 53 pts reviewed retrospectively, surgery indicated for persistant organ failure and proven infected necrosis. Open necrosectomy with post op larvage used . There is significant reduction in mortality when surgery performed more than 30 days p< 0.01

Does Surgery Help in The Management of Sterile Necrosis? Sterile necrosis is not an indication to surgery Reports have shown that sterile necrosis can be managed conservatively with antibiotics With the exception when persistant or progressive organ complications despite maximal ICU support Heinrich et al, Evidence Based Treatment of Acute Necrotizing Pancreatitis, Ann of Surg 2006 The decision to surgery is by clinical judgement FNA has false negative rate

Conservative Management of Sterile Necrosis 86 patients with ANP All were given imipenem Sterile necrosis Mx with antibiotic regime Mortality 1.8% Buchler et al Acute necrotizing pancreatitis: Treatment strategy according to the status of infection; Ann of Surg 2000 100% survival on conservative Management Bradley and Allen A prospective longitudinal study of observation vs surgical intervention in the management of ANP; Am J Surg 1991

Results Of Surgery In Sterile Necrosis Mortality rate is significantly higher in the surgical group than conservative treatment Meta-analysis to justify the role of surgery in sterile necrosis is not possible because these studies are not randomised controlled trials. If we compare the mortality rate of surgery vs conservative with sterile nercosis as the indication to surgery, there is significant increase in mortality in the surgical group

Management Of Infected Necrosis in ANP What Treatment Modalities Are Available?

Open Necrosectomy Open necrosectomy + continuous post- operative drainage with irrigation is commonly used for infected necrotizing pancreatitis Considerable mortality 15-43% Connor et al Early and Late Complications After Necrosectomy; Surgery 2005 Werner et al Surgery in The Treatment of Acute Pancreatitis- open pancreatic necrosectomy; Scand J Surg 2005

Minimally Invasive Necrosectomy Sometimes radiological guided drainage is used to facilitate post op drainage and to delay open necrosectomy, MIN offers advantage over radiological drainage as it enables infected necrosum debridement and avoid laparotomy

Published Series Of MIN Up To 2008 No perioperative complication Single/ double sessions Mortality rate < 20% This table shows a list of published series of MIN, the no. of patients is each study is small, MIN used due to open necrosectomy and post op drainage or just radiological drainage not enough to control sepsis

Laparoscopic Assisted Necrosectomy Removal of necrosis under direct vision Operative time ~ 87 mins 75% with complete clearance of necrosis after single session No peri or post operative complication Bucher et al Minimally Invasive Necrosectomy for Infected Necrotizing Pancreatitis; Pancreas 2008

Percutaneous Necrosectomy 8fr nephrostomy catheter placed into necrosis under CT guidance irrigation, suction and piecemeal extraction of necrotic debris No patients required open surgery Mean ~ 2 sessions Carter et al Percutaneous necrosectomy and sinus tract endoscopy in the management of infected pancreatic necrosis; Ann of Surg 2000

Which Is Better? MIN vs open necrosectomy Safe Effective Improved mortality and morbidity The PANTER trial (The Netherlands) Multicentred RCT Minimal invasive step up approach vs open necrosectomy in patients with acute necrotizing pancreatitis

Conclusion- Management of ANP Prophylactic antibiotic No definite data supporting use of A/B to improve mortality and reduce incidence of infected necrosis Judicious use of antibiotic due to trend of emerging Gram positive and fungal infection

Conclusion- Management of Necrosis Timing of necrosectomy – towards the later the better Surgery is not indicated in patients with sterile necrosis except when clinical condition continues to deteriorate despite maximal ICU care The efficacy of MIN in ANP is yet to be determined by future randomized controlled trial whether the observed improved mortality and morbidity is attributable to this surgical approach

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