Open Access

Risk management in patients with severe acute pancreatitis

Critical Care20048:430

https://doi.org/10.1186/cc3007

Published: 8 November 2004

Abstract

Primary or secondary infection of necrotized areas by enteral bacteria is considered a primary cause of mortality in patients with severe acute pancreatitis (SAP). Indeed, 20–30% of patients die during the course of the disease from multiple organ dysfunction after infection. This is why strategies such as antibiotic prophylaxis and early surgical intervention are appealing, but the controlled data that support these measures are insufficient. On the other hand, environmental risk factors (e.g. smoking, alcohol) and genetic predisposition have been identified; together, these led to SAP being considered a 'multifactorial' disease. However, this description does not help the intensivist to assess risk in the individual patient. A number of prognostic factors in SAP have been identified, and different scoring systems have been developed that include therapy-associated and patient-related factors. Nevertheless, at present no prognostic model is available that takes into account all of these predictors. Moreover, despite several attempts to create guideline-based strategies, SAP is still characterized by rapidly progressive multiple organ failure and high mortality, and both surgical and conservative therapies yield poor outcomes. This brief commentary highlights the most recent developments in risk management for patients with SAP.

Keywords

organ failure pancreatic necrosis predictors risk assessment severe acute pancreatitis

Introduction

Severe acute pancreatitis (SAP) can progress to a critical condition within a few hours or days after the onset of symptoms. Particularly during the early course of the disease, patients are at high risk for developing infections with subsequent multiple organ dysfunction syndrome. Therefore, early surgical intervention has been favoured, although evidence-based data are lacking. In this issue of Critical Care, De Waele and coworkers [1] present findings from a critical review conducted over nearly a decade. In contrast to many prior recommendations, the authors could not find any significant association between the timing of surgery and patient outcomes. Moreover, they identified patient age, severity of organ dysfunction at the time of surgery, and the presence of sterile necrosis as the main risk factors, and concluded that an early surgical intervention is not justified in the absence of proven infection when necrosis is detected after computed tomography (CT) scan [1]. These important findings once again raise the issue of risk assessment in the individual patient with SAP.

Current practice

A major problem in the treatment of patients with SAP is the lack of randomized trials. Recently, King and coworkers [2] reported results from the first pan-European survey conducted among specialists in hepato-pancreato-biliary surgery of surgical strategies for management of SAP, with the aim being to highlight areas of discordance and thus provide a rational focus for future research. A questionnaire survey of 866 surgeons was undertaken, and the response rate was 38%. Severity stratification was used by 324 respondents (99%), with the Ranson score being the most popular. Antibiotic prophylaxis was utilized by 73%, and fine needle aspiration biopsy (FNAB) was undertaken by 53% of respondents. Furthermore, the results show that there were further aspects of practice that were concordant among surgeons, such as use of early CT and agreement that infected necrosis should be treated surgically. However, there were unexpected findings that demonstrate that enclaves of heterodox practice in the treatment of SAP persist in Europe; for example, some surgeons advocated nonoperative management of FNAB-proven infected necrosis. Importantly, there was no consensus regarding the optimal timing of surgery. Chiang and coworkers [3] compared management of patients with SAP between two centres in Australia. They found that all diagnostic tests for severity stratification recommended by current practice guidelines were performed in only 38% of patients.

Prognostic models

Early deaths in patients with SAP are rare, mainly as a result of modern intensive care treatment. A retrospective analysis [4] found that nine out of 10 deaths occurred more than 3 weeks after the onset of disease. This emphasizes the importance of prognostic models, especially early in the course of disease. Several risk factors for SAP have been described. Patients with android fat distribution and higher waist circumference are at greater risk for developing SAP [5]. This finding was interpreted to be related either to the amount of abdominal fat or to an overactive systemic inflammatory response that tended to be upregulated in those with android fat distribution. A meta-analysis of the same group 2 years later [6] revealed that obesity (defined as a body mass index of =30 kg/m2) carries a significant 2.6-fold higher risk for development of SAP, and up to a 4.6-fold higher risk for complications. Pupelis and coworkers [7] found increased intra-abdominal pressure (=25 cmH2O), which is related to body weight, to be a risk factor for early organ dysfunction, and therefore they recommended monitoring of intra-abdominal pressure in patients with SAP.

Primary and secondary infections, however, are still considered the determining factors for fatal outcome in patients with SAP. In particular, Luiten and coworkers [8] reported that Gram-negative intestinal colonization (except that with Escherichia coli) carries a significantly increased risk for pancreatic infection and mortality, and De Waele and colleagues [9] found a trend toward increased risk for development of renal failure among patients with fungal infections, although no significant difference in patient outcomes was described. Halonen and coworkers [10] attempted to develop a multivariate model using new strategies involving neuronal networks. Interestingly, their optimal prediction model (logistic approach) identified four variables: age, greatest serum creatinine value within 60–72 hours from primary admission, need for mechanical ventilation, and chronic health status. In contrast, 'classic' scores (Ranson, Imrie) were inaccurate, with accuracy values of 0.65 and 0.54, respectively. However, the model was developed primarily to permit early prediction of hospital mortality and not to classify the severity of SAP over time, and so infection status was not included in the analysis.

Current trends in treatment for severe acute pancreatitis

Although the studies cited above yielded contradictory findings regarding the importance of infection status, current recommendations are clearly aimed at preventive and therapeutic measures to reduce the bacterial focus. Büchler and coworkers [11] concluded that patients with infected necrosis should be treated surgically, whereas conservative management, including early antibiotic administration, is promising in the case of sterile pancreatic necrosis. The same group formulated an algorithm including antibiotic administration as a standard in SAP [12], and repetitively stated that 'there is no doubt that pancreatic infection is the major risk factor in necrotizing pancreatitis with regard to morbidity and mortality' [13]. Recently, the validity of that statement was cast into doubt by the findings of a placebo-controlled, double-blind trial [14], which surprisingly revealed that antibiotic prophylaxis had no benefit with respect to risk for developing infected necrosis or mortality. In conclusion, antibiotic prophylaxis in SAP remains controversial. In contrast, for treatment of infected necrosis, surgical intervention with either laparotomy or ultrasound- or CT-guided drainage is widely accepted, and the International Association of Pancreatology recently reported guidelines that include recommendations for surgical techniques [15]. Altogether, in contrast to therapy-associated risk factors, the importance of patient-related variables in SAP remain undetermined and merits further attention.

Conclusion

Data from different groups of investigators lead to the following conclusion; assessment of individual risk and optimal treatment in SAP remain areas of uncertainty. A major reason for this uncertainty is misleading statistics, or at least questionable interpretation of them, which often take only single variables into consideration. However, several studies using multivariate strategies [1, 10] confirmed that there is considerable coupling of variables, and that conclusions should be drawn with caution. For example, if early surgical intervention is associated with increased mortality, then this does not necessarily mean that the surgeon employed the wrong strategy. The severity of organ dysfunction at the time of surgery clearly is a major risk factor. In other words, the increased risk for death in these patients is not necessarily treatment associated, but rather it could be patient related. Hopefully, new imaging techniques [16] as well as novel approaches with which to assess genetic predisposition [17] may lead to improved risk management in patients with SAP. Future studies should focus on the identification of individual risk factors, which might permit application of specific, evidence-based guidelines rather than general recommendations.

Abbreviations

CT: 

computed tomography

FNAB: 

fine needle aspiration biopsy

SAP: 

severe acute pancreatitis.

Declarations

Authors’ Affiliations

(1)
Professor and Director, Department of Anesthesiology, Critical Care Medicine, and Pain Management, Vivantes – Klinikum Neukoelln

References

  1. De Waele JJ, Hoste E, Blot SI, Hesse U, Pattyn P, de Hemptinne B, Decruyenaere J, Vogelaers D, Colardyn F: Perioperative factors determine outcome after surgery for severe acute pancreatitis. Crit Care 2004, 8: R504-R511. 10.1186/cc2991PubMed CentralView ArticlePubMedGoogle Scholar
  2. King NK, Siriwardena AK: European survey of surgical strategies for the management of severe acute pancreatitis. Am J Gastroenterol 2004, 99: 719-728. 10.1111/j.1572-0241.2004.04111.xView ArticlePubMedGoogle Scholar
  3. Chiang DT, Anozie A, Fleming WR, Kiroff GK: Comparative study on acute pancreatitis management. ANZ J Surg 2004, 74: 218-221. 10.1111/j.1445-2197.2004.02958.xView ArticlePubMedGoogle Scholar
  4. Gloor B, Müller CA, Worni M, Martignoni ME, Uhl W, Büchler MW: Late mortality in patients with acute pancreatitis. Br J Surg 2001, 88: 975-979. 10.1046/j.0007-1323.2001.01813.xView ArticlePubMedGoogle Scholar
  5. Mery CM, Rubio V, Duarte-Rojo A, Suazo-Barahona J, Peláez-Luna M, Milke P, Robles-Díaz G: Android fat distribution as predictor of severity in acute pancreatitis. Pancreatology 2002, 2: 543-549. 10.1159/000066099View ArticlePubMedGoogle Scholar
  6. Martínez J, Sánchez-Payá J, Palazón JM, Suazo-Barahona J, Robles-Díaz G, Pérez-Mateo M: Is obesity a risk factor in acute pancreatitis? A meta-analysis. Pancreatology 2004, 4: 42-48. 10.1159/000077025View ArticlePubMedGoogle Scholar
  7. Pupelis G, Autrums E, Snippe K, Melbarde-Gorkusa I: Increased intra-abdominal pressure: an important risk factor of early organ dysfunction in severe acute pancreatitis. Zentralbl Chir 2002, 127: 982-986. 10.1055/s-2002-35762View ArticlePubMedGoogle Scholar
  8. Luiten EJ, Hop WC, Endtz HP, Bruining HA: Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis; results of a controlled clinical trial of selective decontamination. Intensive Care Med 1998, 24: 438-445. 10.1007/s001340050593View ArticlePubMedGoogle Scholar
  9. De Waele JJ, Vogelaers D, Blot S, Colardyn F: Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Clin Infect Dis 2003, 37: 208-213. 10.1086/375603View ArticlePubMedGoogle Scholar
  10. Halonen KI, Leppäniemi AK, Lundin JE, Puolakkainen PA, Kemppainen EA, Haapiainen RK: Predicting fatal outcome in the early phase of severe acute pancreatitis by using novel prognostic models. Pancreatology 2003, 3: 309-315. 10.1159/000071769View ArticlePubMedGoogle Scholar
  11. Büchler MW, Gloor B, Müller CA, Friess H, Seiler CA, Uhl W: Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann Surg 2000, 232: 619-626. 10.1097/00000658-200011000-00001PubMed CentralView ArticlePubMedGoogle Scholar
  12. Gloor B, Schmidtmann AB, Worni M, Ahmed Z, Uhl W, Büchler MW: Pancreatic sepsis: prevention and therapy. Best Pract Res Clin Gastroenterol 2002, 16: 379-390. 10.1053/bega.2002.0313View ArticlePubMedGoogle Scholar
  13. Werner J, Uhl W, Hartwig W, Hackert T, Müller C, Strobel O, Büchler : Modern phase-specific management of acute pancreatitis. Dig Dis 2003, 21: 38-45. 10.1159/000071338View ArticlePubMedGoogle Scholar
  14. Isenmann R, Rünzi M, Kron M, Kahl S, Kraus D, Jung N, Maier L, Malfertheimer P, Goebell H, Beger HG, The German Antibiotics in Severe Acute Pancreatitis (ASAP) Study Group: Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial. Gastroenterology 2004, 126: 997-1004. 10.1053/j.gastro.2003.12.050View ArticlePubMedGoogle Scholar
  15. Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG, Carter R, Di Magno E, Banks PA, Whitcomb DC, et al.: IAP guidelines for the surgical management of acute pancreatitis. Pancreatology 2002, 2: 565-573. 10.1159/000071269View ArticlePubMedGoogle Scholar
  16. Arvanitakis M, Delhaye M, De Maertelaere V, Bali M, Winant C, Coppens E, Jeanmart J, Zalcmann M, Van Gansbeke D, Devière J, et al.: Computed tomography and magnetic resonance imaging in the assessment of acute pancreatitis. Gastroenterology 2004, 126: 715-723. 10.1053/j.gastro.2003.12.006View ArticlePubMedGoogle Scholar
  17. Sahin-Toth M: The pathobiochemistry of hereditary pancreatitis: studies on recombinant human cationic trypsinogen. Pancreatology 2001, 1: 461-465. 10.1159/000055848View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2004