This study reports risk factors and outcome for IPN in ICU-treated patients with necrotizing SAP. Infected pancreatic necrosis presented in more than a quarter of patients. We report here evidence of an increased risk of IPN in patients with wide anatomical spread of necrotic collections, postinterventional etiology of pancreatitis, preceding bacteremia, and open abdomen treatment. IPN was associated with significant morbidity compared to patients without IPN.
The proportion of patients with IPN that we report here is within the range of previous studies.1 The strength of the present study was to include only patients with persistent organ failure and admission to ICU in the early disease course. We observed significant morbidity related to IPN in terms of length of stay, need for ICU resources, and need for necrosectomy. We also observed that around half of ICU-treated patients with necrotizing SAP die without documented IPN. Recent results from a large prospective multicenter study support our study findings, as IPN was associated with significant morbidity, but not mortality, compared to patients with sterile necrotic collections, when adjusting for persistent organ failure.18 Preceding health status and disease severeness were associated with late death risk of patients in our study.
In the present study, around 60% of IPN occurred within the first 4 weeks after symptom debut of SAP, and almost half of all cases of IPN were diagnosed during the third or fourth week of the disease. In line with these findings, previous studies have shown that a significant portion of patients develop IPN within the first weeks of disease.19 Although postponing intervention up to 4 weeks is generally advocated in guidelines,8,9 it should be individually evaluated if persisting physiological disturbances or deterioration is presumed to be maintained by early IPN. Especially as encapsulation of necrotic collections seems to occur earlier in a significant percentage of patients.20
Institutional protocol mandated short antibiotic prophylaxis within the study period. With this treatment policy, we observed that IPN occurred in less than 30% of patients. A markedly higher percentage of patients with IPN has been reported from studies using total parenteral nutrition21,22 and in some studies without prophylactic antimicrobials.2,23 In contrast, lower or corresponding frequencies of IPN have been found in some studies using on-demand or similar antibiotic protocol to ours, but these studies also included patients with mainly a less severe degree of acute pancreatitis.24,25,26 The present study was not designed to evaluate the effects of prophylactic antibiotic treatment in necrotizing SAP. However, the observed high number of infections despite the use of prophylactic antibiotics raises questions about the utility of a prophylactic antibiotic protocol. The authors recommend following the existing treatment guidelines recommending against the use of antibiotic prophylaxis.8,9,10
This study reports an independent association between postoperative or post-endoscopic etiology and the risk of IPN. Although post-ERCP pancreatitis rarely becomes severe,27 IPN is common in severe post-ERCP pancreatitis according to results from the present study. Necrotizing SAP in this subgroup of patients might be fuelled by bacterial infection; however, magnitude of the odds ratio should be interpreted very cautiously due to the low number of events.
As our results show, wide anatomical spread of necrotic collections increases the risk of IPN. We found three previous studies reporting an association between measured extra-pancreatic necrosis volume and IPN in acute pancreatitis28,29,30 that included patients with mild edematous pancreatitis,28,29,30 interpreted certain edematous radiological findings as necrotic,29 or defined infection unconventionally.28 A recent analysis of patients with only necrotic SAP found the number of necrotic collections independently associating with the risk of IPN.31 Results from these previous reports and those of the present study warrant clinician to consider widespread necrotic collections as if they are infected with low threshold. An increased proportion of pancreatic parenchymal necrosis has previously been associated with an increased risk of IPN, but our study failed to show such association.2,32
Open abdomen treatment was associated with an increased risk of IPN. The association between preceding open abdomen treatment and increased risk of IPN in SAP has not been previously reported. Open abdomen treatment due to refractory abdominal compartment syndrome is a last but unavoidable measure preserved for patients that suffer from the severest form of acute pancreatitis. Presumably the severe disease itself is a leading cause of the increased susceptibility of IPN. Shattering the sterile intraperitoneal space might increase the risk of direct or indirect bacterial translocation to the retroperitoneal space.
As is shown by our study, IPN results in an increasingly morbid outcome for the patient. In attempting to decrease the rate of IPN, efforts to identify and treat incipient organ failure with subsequent low threshold for admission to ICU becomes essential. Adequate and early treatment of hypovolemia and developing shock is best accomplished in ICU settings with enough monitoring and treatment capacity of developing organ failures. Optimization of patient outcome should include early preventive conservative management of intra-abdominal hypertension, as abdominal compartment syndrome with consequent open abdomen treatment was significantly associated with IPN in the present study. Empirical early antibiotic treatment is justifiable in the most severely ill patients (e.g., patients with high SOFA score) if clinical suspicion of possible underlying concurrent infectious etiology of shock arises.
This study has weaknesses. The retrospective setting with a prospectively uncontrolled patient cohort, non-standardized treatment protocol, and possible differences in the specifics regarding antibiotic treatment might introduce some bias to this study. In the present study, a reliable evaluation of potential difference in mortality between patients with and without IPN cannot be performed because of the study design. In fact, patients with IPN had to survive until IPN was developed, whereas patients without IPN included those who died early (and did not even had chance to develop IPN). This is known as survival bias. Therefore, those with and without IPN differed by their risk of death already before IPN was developed. This study cannot provide a reliable estimate of the difference in mortality attributable to IPN itself. Another weakness is that for some of the studied potential risk factors there were quite small number of patients who presented with these conditions of interest. Thus, it is possible that some of the observed associations are due to chance only or some of the observed differences are under- or overestimated.