Drainage for Infected Pancreatic Necrosis –Earlier Is Not Better
Shria Kumar, MD, MSCE and Sunil Amin, MD, MPH
Assistant Professors, Division of Digestive and Liver Diseases, University of Miami,.Miller School of Medicine, Miami, Florida
This article reviews Boxhoorn L, van Dijk SM, van Grinsven J, et al. Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis. N Engl J Med. 2021 Oct 7;385(15):1372-1381. doi: 10.1056/NEJMoa2100826.
Correspondence to Shria Kumar, MD, MSCE, Associate Editor. Email: EBGI@gi.org
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STRUCTURED ABSTRACT
Question: Is early catheter drainage of infected pancreatic necrosis superior to delayed drainage (after necrosis is walled-off)?
Design: Patients with infected pancreatic necrosis were randomized to immediate (within 24 hours of diagnosis) percutaneous or endoscopic drainage versus postponed drainage (after necrosis is encapsulated or walled-off).
Setting: Twenty-two centers in the Netherlands, in collaboration with the Dutch Pancreatitis Study Group.
Patients: Hospitalized acute pancreatitis patients with infected necrosis diagnosed within 35 days of onset of acute pancreatitis. Infected necrosis
confirmed by gram stain/culture from fine needle aspirate or gas collections on imaging in first 14 days of hospitalization. On hospitalization days 15-35, clinical signs of infection, persistent organ failure or persistent elevation of 2 inflammatory variables (temperature, C-reactive protein, leukocyte count) for 3 consecutive days were also diagnostic of infected necrosis. Key exclusion criteria included previous intervention for necrotizing pancreatitis, inability to undergo percutaneous or endoscopic drainage, or acute pancreatitis symptoms for more than 35 days.
Interventions: Patients were assigned to immediate (within 24 hours) drainage by percutaneous or endoscopic modality versus supportive care with drainage postponed until after the development of walled-off pancreatic necrosis. Patients in the postponed group could undergo drainage earlier if clinical decompensation occurred. If catheter drainage was unsuccessful, necrosectomy was performed (either endoscopic transluminal necrosectomy or videoscopicassisted retroperitoneal debridement). All study patients received antibiotics immediately after diagnosis of infected necrosis.
Outcomes: The Comprehensive Complication Index, which is a validated tool that incorporates all complications over the course of 6 months of follow-up and is weighted based on severity of complication, was the primary outcome. It was originally developed to assess postoperative complications, but is used in nonsurgical interventional fields as well.1 Secondary endpoints included death, organ failure, and health care utilization, such as number of procedures, length of stay, and cost.
Data Analysis: Intention to treat analysis with reported relative risks and mean differences.
Results: Of 932 patients assessed for eligibility, 104 underwent randomization: 55 to the immediate drainage group, 49 to postponed drainage. The mean time after pancreatitis to the first intervention was 24 days in the immediate drainage group, and 34 days in the postponed group. In the intention to treat analysis, there was no significant difference between the groups when evaluating the Comprehensive Complication Index, mortality, or organ failure (Table 1). Secondary endpoints evaluating health care utilization found that more persons in the immediate drainage group underwent necrosectomy at a future date, 51% vs 22% (relative risk [RR] 2.27; 95% confidence interval [CI] 1.27–4.06). Those in the immediate drainage group underwent numerically higher mean surgical, endoscopic, and radiologic interventions vs the postponeddrainagegroup (4.4 vs 2.6; mean difference, 1.8; 95% CI, 0.6 to 3.0), and numerically more total catheter drainages (3.1 vs 1.9; mean difference 1.2; 95% CI 0.3 to 2.2). There was no difference in cost or length of stay between the groups. Importantly, in the postponed group, 39% (19/49) improved with antibiotics alone and no drainage or necrosectomy was indicated.
Funding: None.
Table 1. Summary of Findings
COMMENTARY
Why Is This Important?
Necrotizing pancreatitis can develop in up to 30% of acute pancreatitis cases, and subsequent infection frequently requires procedural intervention.2,3 Infection can be hard to differentiate from the pancreatitis itself, due to the systemic inflammatory response syndrome, but the distinction becomes apparent 2 to 4 weeks after the onset of disease, when the incidence of infected necrosis peaks. Signs of infection include clinical instability, gas bubbles within the pancreatic fluid collection, or a positive gram stain or culture from a fluid collection.
Currently, the recommended approach to infected necrotizing pancreas is a stepup algorithm, with institution of antibiotics that penetrate pancreatic tissue: carbapenems, quinolones, and metronidazole.4 This is frequently followed by either percutaneous or endoscopic catheter drainage and/or debridement if symptoms such as abdominal pain, nausea, and vomiting persist, or if there are complications, such as gastric outlet obstruction, biliary obstruction, or ongoing clinical symptoms.5 If minimally invasive retroperitoneal necrosectomy failed, open necrosectomy was performed.4 It is important to note that this approach is based on the era when open surgical necrosectomy, which has a high morality, was performed.6
However, the timing of catheter drainage for infected pancreatic necrosis is unclear. Prior research from the surgical management era indicated that open surgical necrosectomy/drainage of infected necrosis should be delayed until clearly demarcated walled-off pancreatic necrosis developed, which usually occurred after 4 weeks of developing pancreatitis. Since we can now use a minimally invasive approach to drain infected necrosis (via endoscopy or percutaneous approach), it is unknown if we should initiate this drainage as soon as infection is identified or if patients have better clinical outcomes if drainage is delayed until the collection is walled-off.
Key Study Findings
This is a well-designed randomized control trial to evaluate the hypothesis that earlier catheter drainage of infected pancreatic necrosis leads to better outcomes than postponed drainage (i.e., after walled-off pancreatic necrosis developed). The trial shows no difference in the primary outcome, the Comprehensive Complication Index. There was also no difference between groups regarding mortality or organ failure, and no difference in outcomes including length of stay or hospital costs. In fact, those in the postponed drainage group underwent fewer interventions, and almost 40% of those in the postponed drainage group were able to be treated with antibiotics alone (Figure 1).
Figure 1. Outcomes in the immediate vs postponed drainage groups
Caution
Prior to randomization, 37 patients died, underlining the potential for rapid deterioration and high mortality associated with infected necrotizing pancreatitis. Thus, postponed drainage may not be suitable for all patients. There was cross-over of 1 patient from the postponed drainage group, also highlighting the need for close attention to clinical status. Additionally, the trial was unable to include those persons in whom catheter drainage was not feasible, and excluded those with previous drainage.
This underscores that management of pancreatitis is a nuanced issue, and depending on clinical status, accessibility of infected collections, and specialist availability, the approach may still need to be tailored to each patient. This study primarily evaluated timing of intervention, not method of intervention. There are marked differences between percutaneous, endoscopic, and surgical techniques, including efficacy and risk. The timing difference should also be highlighted: immediate catheter drainage occurred at 24 days after symptom onset, while postponed drainage occurred 34 days after symptoms.
My practice
This study supports our own practice patterns, where we attempt to delay drainage until the collection has walled off. At the time of suspicion of infected necrotizing pancreatitis, we initiate antibiotics, preferring those that can penetrate pancreatic necrosis: carbapenems, quinolones, and metronidazole.4 We attempt to delay drainage for 4 weeks, then proceed with an endoscopic transluminal approach to facilitate drainage and, if necessary, debridement. For infected necrosis that is not amenable to endoscopic drainage (either in location or if <4 weeks from pancreatitis onset), we proceed with percutaneous catheter drainage. Additionally, if a patient has clinical deterioration and the collection is not yet mature enough for endoscopic drainage, we proceed with percutaneous catheter drainage, which is supported by the results of this trial.
For Future Research
The benefit of early endoscopic drainage in collections that are <4 weeks old should be assessed in comparison to percutaneous drainage, as this could be a practice changing paradigm. Additionally, in this study, there was no difference in healthcare utilization, but in a different setting, and perhaps in the US itself, there may be differences in the cost-effectiveness of immediate vs postponed drainage.
REFERENCES
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- Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus Gut 2013;62(1):102-111.
- van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome.
Gastroenterology 2011;141(4):1254-1263. - Baron TH, DiMaio CJ, Wang AY, Morgan KA. American Gastroenterological Association Clinical Practice Update: Management of Pancreatic Necrosis. Gastroenterology 2020;158(1):67-75 e61.
- Arvanitakis M, Dumonceau JM, Albert J, et al. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guidelines. Endoscopy 2018;50(5):524-546.
- Baron TH. Drainage for Infected Pancreatic Necrosis—Is the Waiting the Hardest Part? N Engl J Med. 2021;385(15):1433-1435.