Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Книга_683_Библиотеки_им_академика_М_И_Перельмана

.pdf

Скачиваний:

Добавлен:

30.08.2026

Размер:

56 Мб

Скачать

☆

<<< < Предыдущая 14 15 16 17 18 19 20 21 22 23 24 2526 / 5026 27 28 29 30 31 32 33 34 35 36 37 38 > Следующая >>>

238

Downloaded from https://onlinelibrary.wiley.com/doi/ by Universität Bern, Wiley Online Library on [22/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

https://t.me/medicina_free

Clinical Course andMedical Treatment ofAcute Pancreatitis— Use ofAntibiotics inSevere Acute Pancreatitis: Indications andLimitations

Rainer Isenmann1 and Mathias Wittau

Department of Surgery, St.- Anna- Virngrund- Klinik, Ellwangen, Jagst, Germany

Department of General and Abdominal Surgery, University of Ulm, Ulm, Germany

Introduction

Although 85% of the patients with acute pancreatitis experience an uneventful recovery, this disease bears a high risk for severe and even lethal complications. Cardiocirculator y, pulmonary, or renal failure, alone or in combination are common problems in patients with severe acute pancreatitis. The treatment is conservative, including mechanical ventilation, hemofiltration or hemodialysis as well as cardiocirculatory support, if required. The majority of patients respond to such an approach. Nevertheless, mortality of severe acute pancreatitis remains at about 10%.

The poorest prognosis is observed in patients with necrotizing pancreatitis who develop local bacterial infection. Surgical or interventional management is generally required in these cases and mortality rates exceeding 30% been reported [1,2]. Despite progress in our understanding of the pathology of pancreatic sepsis and in intensive care treatment, the mortality rates of infected pancreatic necrosis have not changed in recent decades. Recent attempts with nonsurgical or interventional treatment have been promising[1,3] but there is no doubt that bacterial infection will remain a lifecation in patients with necrotizing pancreatitis.

The recently revised Atlanta classification of acute pancreatitis discriminates between mild acute pancreatitis, moderately severe acute pancreatitis, and severe disease, depending on the occurrence of organ failure and/or local and systemic complications[4]. In contrast to former classification systems, where the term “infected pancreatic necrosis” has been used for all locally infected pancreatic entities, the revised classification distinguishes between morphologically different local infectious complications.

threatening compli-

Infectious Complications

During the course of acute pancreatitis, either systemic or local pancreatic infections may occur. The incidence of these complications varies widely, depending on definition and patient selection.

Local Pancreatic Infection

In approximately 30–40% of the patients with necrotizing pancreatitis local infections of the necrotic areas develop[5]. Bacterial infection of pancreatic necrosis is the most important determinant of outcome [6]. The revised Atlanta classification discriminates between different morphological entities and comprises acute peripancreatic fluid collections (APFC), pancreatic pseudocysts, acute necrotic collections (ANC), and walled- off necrosis (WON). These morphologic entities have a variable potential for bacterial infection (Table26.1) with pancreatic necrosis and WON bearing the highest risk. For our understanding of relevance of infectious complications and the role of antibiotics in the treatment algorithm, discrimination between these morphologies is therefore important. Irrespective of the morphologic differences, bacterial infection is a phenomenon of the later phase of acute pancreatitis, commonly observed after the third or fourth week after onset of the disease. This might be one of the reasons why all efforts to reduce the infection rate by prophylactic antibiotics have failed. There is a wide time frame for infection and it is difficult to impossible to define the exact period when prophylactic antibiotics might be effective.

The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Fourth Edition. Edited by Hans G. Beger, Markus W. Büchler, RalphH. Hruban, Julia Mayerle, John P. Neoptolemos, Tooru Shimosegawa, Andrew L. Warshaw, David C. Whitcomb, and Yupei Zhao. © 2023 John Wiley & Sons Ltd. Published 2023 by John Wiley & Sons Ltd. Companion website: www.wiley.com/go/beger/thepancreas4e

Rationales forAntibiotics inAcute Pancreatitis 239

https://t.me/medicina_free

Table26.1 Complications of severe acute pancreatitis with the potential risk of bacterial infection, according to the current revised

Atlanta classification[4].

Estimated potential

Characterization

for infection

Necrotizing acute pancreatitis Inflammation associated with pancreatic parenchymal necrosis

Walled-

off necrosis (WON) Necrotic tissue surrounded by a wall of tissue, usually >4weeks

Acute necrotic collection (ANC) Collection of necrosis and fluid during the first 4weeks of AP Moderate

Pancreatic pseudocyst Walled-

Acute peripancreatic fluid collection (APFC)

AP: acute pancreatitis.

Systemic Bacterial Infection

Extra- abdominal bacterial infection is a common finding during severe acute pancreatitis. Its incidence varies widely in different studies. In a multinational European study, more than 40% of the patients had extraabdominal infections, with respiratory tract infections being the most frequent (28%), followed by bloodstream infections (14%), and catheter- related infections as well as genito- urinary tract infections (4%)[7]. In the authors’ own investigation, 25% of the patients of the control group (not treated with antibiotics) had extrapancreatic infection, with pneumonia being the most frequent[8].

The clinical relevance of extrapancreatic infection has been clearly demonstrated: it increases mortality and adversely affects the outcome of acute pancreatitis [9]. Whether its relevance is equal to that of pancreatic sep-

and/or peripancreatic necrosis

after onset of pancreatitis

off fluid collection weeks after AP. May require surgical

drainage if persistent

During the early phase of AP, resolve spontaneously Low

spectrum beta- lactamase (ESBL)- producing gram- negative germs. In one recent study, 63% of the patients with infected pancreatic necrosis were infected with multiresistant germs [12]. As in other infectious pathologies, these multiresistant germs are of therapeutic and prognostic importance. Their isolation should prompt treatment with an adequate antibiotic drug according to the tested bacterial susceptibilities.

In addition, a considerable percentage of patients with necrotizing pancreatitis develop fungal infection. Its prognostic impact has been a matter of discussion over the past decade. Most often, fungal infection is caused by Candida species and is considered to be a predictor of worse outcome. It is generally accepted that antibiotic treatment promotes overgrowth of unaffected or resistant pathogens and is thus considered to be a risk factor for both fungal and multiresistant infection[13,14].

High

Low- moderate

sis is subject to discussion.

Spectrum ofBacteria

In the first description of infected pancreatic necrosis in the 1980s, the bacterial spectrum of infection was dominated by gram- negative enteric germs [5]. During the past three decades, there has been some change, but gram- negative bacteria still play a predominant role in the bacterial spectrum. Nevertheless, gram- positive microorganisms, especially staphylococci and enterococci are increasingly coming into focus. The bacterial spectrum is polymicrobial and comprises anaerobic bacteria, as well (Table26.2).

The role of multidrug resistance among these germs has been recently addressed. Many gram- positive species are resistant to methicillin, as are many extended

Rationales forAntibiotics inAcute Pancreatitis

The use of antibacterial agents in acute pancreatitis has been debated since the 1970s. At first, antibiotics were regarded as a part of the treatment regime without clear definition of their indication. Our increasing knowledge about the impact and relevance of infection has defined two potential settings for the use of antibiotics.

Prevention ofInfection

The clinical relevance of bacterial infection with its poor prognosis supports treatment algorithms for its prevention. This led to the idea of prophylactic administration of antibiotics with the intention of preventing bacterial

Clinical Course and Medical Treatment of Acute Pancreatitis—Use of Antibiotics in Severe Acute Pancreatitis

https://t.me/medicina_free

240

Table26.2 Development ofthe bacterial spectrum ofinfected pancreatic necrosis over thepast 30 years. Given are selected strains

fromdifferent studies. Note theincrease inthe incidence ofenterococci andfungi.

Beger 1986[5] Isenmann 2004[6] Dellinger 2007[10] Schmidt 2014 [11]

No. of isolates 75 19 30 88

Percentage of strains

Enterococci 8% 11% 23% 28%

E. coli 32% 32% 7% 26% (Enterobacteriaceae)

Pseudomonas 7% – 10%

Anaerobic bacteria 7% – 3% n.d.

Fungi 4% 10% 10% 14%

n.d.: no data.

superinfection. In recent years there has been considerable scientific effort to prove such a concept as discussed later in this chapter.

Treatment ofInfection

In combination with surgical debridement, antibiotic treatment is the mainstay in the treatment of any intraabdominal infection, including infected pancreatic necrosis. It is well known that inappropriate antibiotic treatment in severe sepsis results in a fivefold increase in mortality[15]. For acute pancreatitis a selective uptake of antibiotics into the pancreas has been described [16], which should be taken into account. As a consequence the antibiotics for treatment of pancreatic infection should not only be chosen according to the bacterial spectrum and their antibacterial activity, but also according to their ability to penetrate into the infectious focus[16,17].

Clinical Studies withAntibiotics

During the past 20 years, there have been numerous controlled and uncontrolled, blinded and unblinded studies addressing the issue of whether early administration of antibiotics in severe acute pancreatitis could reduce the incidence of local bacterial infection and consequently could improve the prognosis of the disease (Table26.3). Among those, four had adequate scientific power for meaningful conclusions [10,18,19]. None of them has been able to give a definite answer to this question and according to the latest meta- analyses, there is no evidence to support the routine use of prophylactic antibiotics in patients with severe acute pancreatitis[20,21,22].

Consequently, the overwhelming majority of current

guidelines and expert reviews do not recommend the

routine administration of broad- spectrum antibiotics in patients with severe acute pancreatitis or pancreatic necrosis [34,35,36].

What are the reasons for our inability to demonstrate a beneficial effect of prophylactic antibiotics on the infection rate in acute pancreatitis? First, acute pancreatitis is a heterogeneous disease with a highly variable course ranging from mild and self- limiting to devastating with severe septic complications. The majority of patients with acute pancreatitis will never develop infectious complications. To date, there are no reliable parameters that allow the identification of patients at risk for developing pancreatic sepsis. Second, pancreatic infection is a phenomenon of the later course of the disease. Thus the ideal timing and optimal duration of antibiotic administration as prophylaxis is not clear. Antibiotics given too early and too long may be ineffective and promote bacterial resistance. Third, new concepts in the therapy of acute pancreatitis such as early enteral nutrition and treatment of organ dysfunctions may directly or indirectly affect the incidence of septic complications.

These facts, together with others, make it unlikely that we will ever be able to elaborate pathways for the prophylactic use of antibiotics in severe acute pancreatitis[37].

Indications forAntibiotic Treatment

The main indications for initiation of antibiotic treatment in acute pancreatitis are evidence or strong suspicion of local and/or systemic bacterial infection. Therefore, all current guidelines aim at the timely identification of infected necrosis. The recommended standard comprises close monitoring of infectious parameters, imaging by contrast- enhanced computed tomography and, in cases with strongly suspected bacterial infection, the fineneedle aspiration for Gram- stain and culture [35].

Indications forAntibiotic Treatment 241

https://t.me/medicina_free

Table26.3 Studies onantibiotic prophylaxis insevere acute pancreatitis. Note that only afew had adequate scientific power

formeaningful conclusions.

Effect on

Author Double- blind Patients

infected necrosis Effect on mortality

Pederzoli[23] 1993 Imipenem vs. none No 41/33 Reduction in

Delcenserie[24] 1996 Ceftaz idime

Schwarz[25] 1997 Ofloxacin

Nordback[26] 2001 Early imipenem vs.

Spicak[27] 2002 Ciprofloxacin

Spicak[28] 2003 Meropenem vs. meropenem

Rokke[29] 2007 Imipenem vs. none No 36/37 No No

Barreda[30] 2009 Imipenem vs. none No 24/34 No No

Xue[31] 2009 Imipenem vs. none No 29/27 No No

Yang[32] 2009 Imipenem vs. none No 28/26 No No

Randomized/placebo-

Sainio[18] 1995 Cefuroxime vs. none No 30/30 No Reduction in the

Bassi[19] 1998 Pefloxacin vs. imipenem No 30/30 Reduction in the

Isenmann[13] 2004 Ciprofloxacin + metronidazol

Dellinger[10] 2007 Meropenem vs. placebo Yes 50/50 No No

Garcia-

Barrasa[33] 2009 Ciprofloxacin vs. placebo Yes 22/19 No No

Poropat[41] 2019 Imipenem vs. placebo Ye s 49/49 No No

controlled with the best scientific power

metronidazol vs. none

none

imipenem delayed

vs. ciprofloxacin on demand

on demand

vs. placebo

+ amikacin +

+ metronidazol vs.

+ metronidazol

No 11/12 Reduction in

No 13/13 no No

No 25/33 Reduction in early

No 33/30 No No

No 20/21 No No

Yes 58/56 No No

imipenem group

antibiotic group

treatment group

imipenem group

cefuroxime group

Pancreatic infection should be suspected in patients with pancreatic or extrapancreatic necrosis and clinical deterioration or failure to improve over 7–10days.

Antibiotic Treatment onDemand

The experience from the ASAPantibiotic treatment was initiated in a considerable percentage of patients with clinical deterioration. The criteria for initiating this so- called “antibiotic treatment on demand” in this study were:

● newly developed sepsis/SIRS;

● newly developed organ failure (pulmonary, renal,

cardiocirculatory);

● increase in serum C- reactive protein and strongly sus-

pected/proven extrapancreatic infection;

study [8] showed that

● increase in serum C- reactive protein and strongly sus-

pected/proven pancreatic infection.

In 37% of the patients of this study, the double- blind study medication was terminated and switched to open antibiotic treatment. The low rate of infected pancreatic necrosis (10.5%) as well as the favorable outcome (mortality 6% in the overall study) can be taken as rationale to initiate antibiotic treatment at these given indications. In patients fulfilling these criteria, sepsis and bacterial infection (pancreatic and/or extrapancreatic) are most likely present and they should thus be candidates for antibiotic treatment[22].

Choice ofAntibiotics

For the choice of antibiotics in necrotizing pancreatitis, the following should be taken into consideration:

Clinical Course and Medical Treatment of Acute Pancreatitis—Use of Antibiotics in Severe Acute Pancreatitis

https://t.me/medicina_free

242

● the bacterial spectrum,

● the antibiotic concentrations at the site of infection,

● the results of clinical studies.

Based on these criteria, carbapenems, chinolones, and broad- spectrum cephalosporins are first- choice drugs for the initial treatment of pancreatic infection. The last two should be combined with metronidazole as they lack sufficient antibacterial activity in the anaerobic spectrum. Based on their pharmacokinetic properties, acylaminopenicillins beta- lactamase inhibitor combinations can also be regarded as effective, although there are no clinical studies with these drugs.

Following initiation of an empirical antibiotic therapy, a step down should be followed as soon as the results of bacterial susceptibility testing are available.

Up to now, there is no rationale to initiate a “blind” antifungal therapy. Antifungal agents should only be given when bacterial smears yield fungal infection.

Limitations ofAntibiotic Treatment

Antibiotic treatment is an essential part of the therapeutic regime in patients with infected pancreatic necrosis, but it is not enough on its own for successful treatment of these critically ill patients. The mainstay for success is source control of the infectious focus, and debridement of the infectious material is an essential part of the treatment regime.

Today open or laparoscopic surgical debridement and interventional drainage are subject to debate. Scientific evidence suggests that a “step-

up approach” might provide favorable results as the best surgical approach in pancreatic infection[1]. Following such an approach, the patient is managed by conservative treatment for as long as possible. In case of strongly suspected or proven pancreatic infection percutaneous drainage is used as an initial approach for source control. If this fails surgical necrosectomy (minimally invasive or open) follows[38].

Whether or not pancreatic infection can be treated with antibiotics alone and without debridement is under current investigation. The first studies following such an approach have been criticized [39], but a recent metaanalysis shows that in selected patients this can be safely done with low mortality[3]. Nevertheless it is necessary to define criteria that characterize the group of patients who are eligible for such a conservative approach.

A global overview on the use of antibiotics among physicians indicated that their use, both as prophylaxis and as treatment in acute pancreatitis is widespread [40]. Irrespective of the national treatment guidelines of the disease, antibiotics are frequently given without clear indication, even in mild pancreatitis or when pyrexia is present. This overuse poses not only healthcare problems in terms of unnecessary expense, but also risks for the patients: antibiotic-

associated side effects and a

selection of multiresistant bacteria.

References

1 Van Santvoort HC, Besselink MG, Bakker OJ etal.; Dutch

Pancreatitis Study Group. A stepnecrosectomy for necrotizing pancreatitis. N Engl J Med 2010;362:1491–1502.

2 Petrov MS, Shanbhag S, Chakraborty M, Phillips AR,

Windsor JA. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology 2010;139:813–820.

3 Mouli VP, Sreenivas V, Garg PK. Efficacy of conservative

treatment, without necrosectomy, for infected pancreatic necrosis: a systematic review and meta- analysis. Gastroenterology 2013;144:333–340.

4 Banks PA, Bollen TL, Dervenis C etal.; Acute Pancreatitis

Classification Working Group. Classification of acute pancreatitis- - 2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62:102–111.

5 Beger HG, Bittner R, Block S, Büchler M. Bacterial

contamination of pancreatic necrosis. A prospective clinical study. Gastroenterology 1986;91:433–438.

6 Isenmann R, Rau B, Beger HG. Bacterial infection and

extent of necrosis are determinants of organ failure in

up approach or open

patients with acute necrotizing pancreatitis. Br J Surg 1999;86:1020–1024.

7 de Waele JJ, Rello J, Anzueto A etal. Infections and use of

antibiotics in patients admitted for severe acute pancreatitis: data from EPIC II Study. Surg Inf 2014;15:394–398.

8 Isenmann R, Rünzi M, Kron M etal.; German Antibiotics

in Severe Acute Pancreatitis Study Group. Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo- controlled, double- blind trial. Gastroenterology 2004;126:997–1004.

9 Uomo G. Extra- pancreatic infections in acute pancreatitis:

supporting or main actor into the disease´s outcome? J Pancreas [online] 2013;14:469–470.

10 Dellinger EP, Tellado JM, Soto NE etal. Early antibiotic

treatment for severe acute necrotizing pancreatitis: a randomized, double- blind, placebo- controlled study. Ann Surg 2007;245:674–683.

11 Schmidt PN, Roug S, Hansen EF, Knudsen JD, Novovic S.

Spectrum of microorganisms in infected walled- off pancreatic necrosis impact on organ failure and mortality. Pancreatology 2014;14:444–449.

References 243

https://t.me/medicina_free

12 Lee HS, Lee SK, Park do H etal. Emergence of multidrug

resistant infection in patients with severe acute pancreatitis. Pancreatology 2014;14:450–453.

13 Isenmann R, Schwarz M, Rau B, Trautmann M, Schober

W, Beger HG. Characteristics of infection with Candida species in patients with necrotizing pancreatitis. World J Surg 2002;26:372–376.

14 Trikudanathan G, Navaneethan U, Vege SS. Intra- abdominal

fungal infections complicating acute pancreatitis: a review. Am J Gastroenterol 2011;106:1188–1192.

15 Kumar A, Ellis P, Arabi Y etal.; Cooperative Antimicrobial

Therapy of Septic Shock Database Research Group. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;136:1237–1248.

16 Büchler M, Malfertheiner P, Friess H etal. Human

pancreatic tissue concentration of bactericidal antibiotics. Gastroenterology 1992;103:1902–1908.

17 Bassi C, Pederzoli P, Vesentini S etal. Behavior of

antibiotics during human necrotizing pancreatitis. Antimicrob Agents Chemother 1994;38:830–836.

18 Sainio V, Kemppainen E, Puolakkainen P etal. Early

antibiotic treatment in acute necrotising pancreatitis. Lancet 1995;346:663–667.

19 Bassi C, Falconi M, Talamini G etal. Controlled clinical

trial of pefloxacin versus imipenem in severe acute pancreatitis. Gastroenterology 1998;115:1513–1517.

20 Villatoro E, Mulla M, Larvin M. Antibiotic therapy for

prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2010;CD002941.

21 Wittau M, Mayer B, Scheele J, Henne- Bruns D, Dellinger

EP, Isenmann R. Systematic review and meta-

analysis of antibiotic prophylaxis in severe acute pancreatitis. Scand J Gastroenterol 2011;46:261–270.

22 Mourad MM, Evans RPT, Kalidindi V, Navaratnam R,

Dvorkin L, Bramhall SR. Prophylactic antibiotics in acute pancreatitis: endless debate. Ann R Coll Surg Engl 2017;99:107–112.

23 Pederzoli P, Bassi C, Vesentini S, Campedelli A. A

randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet 1993;176(5):480–483.

24 Delcenserie R, Yzet T, Ducroix JP. Prophylactic antibiotics

in treatment of severe acute alcoholic pancreatitis. Pancreas 1996;13(2):198–201.

25 Schwarz M, Isenmann R, Meyer H, Beger HG. Antibiotika

bei nekrotisierender Pankreatitis– Ergebnisse einer kontrollierten Studie. Dtsch Med Wochenschr 1997;122(12):356–361.

26 Nordback I, Sand J, Saaristo R, Paajanen H. Early

treatment with antibiotics reduces the need for surgery in acute necrotizing pancreatitis— a single- center randomized study. J Gastrointest Surg 2001; 5(2):113–118.

27 Spicak J, Hubaczova M, Antos F etal. Antibiotics in the

treatment of acute pancreatitis— randomized multi-

center prospective study. Ces Slov

findings from a

Gastroent Hepatol 2002;56:183–189.

28 Spicak J, Hejtmankova S, Hubaczova M etal. Antibiotic

prophylaxis of infectious complications of acute pancreatitis-

the results of a randomised study by

meropenem. Ces Slov Gastroent Hepatol 2003;57:222–227.

29 Røkke O, Harbitz TB, Liljedal J etal. Early treatment of severe

pancreatitis with imipenem: a prospective randomized clinical trial. Scand J Gastroenterol 2007;42:771–776.

30 Barreda L, Targarona J, Milian W etal. Is the prophylactic

antibiotic therapy with Imipenem effective for patients with pancreatic necrosis? Acta Gastroenterol Latinoam 2009;39(1):24–29.

31 Xue P, Deng LH, Zhang ZD etal. Effect of antibiotic

prophylaxis on acute necrotizing pancreatitis: results of a randomized controlled trial. J Gastroenterol Hepatol 2009;24(5):736–742.

32 Yang X, Deng LH, Xue P, Zhao L, Jin T, Wan M. Non-

preventive use of antibiotics in patients with severe acute pancreatitis treated with integrated traditional Chinese and Western therapy: a randomized controlled trial. JChion Interg Med 2009;7:330–333.

33 García- Barrasa A, Borobia FG, Pallares R etal. A double-

blind, placebo- controlled trial of ciprofloxacin prophylaxis in patients with acute necrotizing pancreatitis. JGastrointest Surg 2009;13(4):768–774.

34 Working Group IAP/APA Acute Pancreatitis Guidelines.

IAP/APA evidence-

based guidelines for the management of

acute pancreatitis. Pancreatology 2013;13(4 Suppl 2):e1–15.

35 Tenner S, Baillie J, DeWitt J, Vege SS; American College of

Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterology 2013;108:1400–1415.

36 Baron TH, DiMaio CJ, Wang AY, Morgan KA. American

Gastroenterological Association clinical practice update: management of pancreatic necrosis. Gastroenterology 2020;158:67–75.

37 De Waele JJ. A role for prophylactic antibiotics in

necrotizing pancreatitis? Why we may never know the answer.... Crit Care 2008;12:195.

38 da Costa DW, Boerma D, van Santvoort HC etal. Staged

multidisciplinary step-

up management for necrotizing

pancreatitis. Br J Surg 2014:101:e65–e79.

39 Ruenzi M, Niebel W, Goebell H, Gerken G, Layer P. Severe

acute pancreatitis: nonsurgical treatment of infected necroses. Pancreas 2005;30:195–199.

40 Baltatzis M, Jegatheeswaran S, O´Reilly DA, Siriwardena

AK. Antibiotic use in acute pancreatitis: global overview of compliance with international guidelines. Pancreatology

2016. Epub ahead of print.

41 Poropat G, Radovan A, Peric M etal. Prevention of

infectious complications in acute pancreatitis: results of a single- center, randomized, controlled trial. Pancreas 2019;48:1056–1060.

244

https://t.me/medicina_free

Indications forInterventional andSurgical Treatment ofNecrotizing Pancreatitis

Lily V. Saadat and Thomas E. Clancy

Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Introduction

Whereas interstitial acute pancreatitis is typically a selflimited disease process that usually responds to supportive care, more severe necrotizing pancreatitis can be seen in approximately 20% of patients. This is characterized by necrosis of the pancreatic parenchyma or peripancreatic tissue, manifestations of the systemic inflammatory response syndrome (SIRS), with risks for infection and multiorgan failure[1]. High rates of morbidity are associated with mortality of up to 15% in the setting of necrotizing pancreatitis and as high as 30% in the subset of patients who develop infected pancreatic necrosis[2,3]. A variety of surgical and interventional approaches have been used in an attempt to limit the substantial morbidity and mortality of necrotizing pancreatitis.

Over the last few decades, there has been a significant change in the indications for intervention in necrotizing pancreatitis, timing of intervention, and methods of surgical, minimally invasive, radiologic, and endoscopic intervention. Revision of the 1992 Atlanta classification of acute pancreatitis[4] to describe the clinical behavior and imaging characteristics more precisely [5] has occurred in parallel with a progressively less interventional and less invasive approach to necrotizing pancreatitis. Although no universally accepted management algorithm exists to guide management, evidence-

based

consensus continues to develop[6,7].

Interventions forPancreatic Necrosis: Historical Perspective

Just a few decades ago, the association of pancreatic necrosis with systemic inflammation and secondary infection led to the goal of surgically removing all necrotic

pancreas regardless of the presence of infection[8–10]. In 1991, Bradley and Allen published a small series of 11 patients successfully managed nonoperatively with sterile pancreatic necrosis[11]. The general acceptance of nonoperative management for sterile pancreatic necrosis was facilitated by the publication of a large series demonstrating favorable overall mortality and complications[12,13]. In this new paradigm, intervention was primarily limited to surgical debridement for cases of infected pancreatic necrosis as demonstrated by computed tomography (CT)- guided fine- needle aspiration (FNA) of the pancreas. Banks etal. showed a sensitivity and specificity of

96.2% and 99.4%, respectively, for detection of infected necrosis, with a positive predictive value of 99.5% and a negative predictive value of 95.3%[14]. The presence of infection or positive Gram stain on CT- guided pancreatic aspiration was considered an absolute indication for debridement, as superinfection of the necrotic parenchyma had been associated with a mortality of virtually 100% without debridement[15].

The absolute necessity of surgical debridement for infected necrosis was subsequently questioned with the demonstration of successful nonoperative management in some patients. Runzi etal.[16] showed in a series of over 80 patients with documented infected pancreatic necrosis that initial conservative therapy can be instituted, including antibiotic therapy and maximal supportive care. Mortality in patients managed with surgery was identical to that in those managed nonoperatively. Surgical therapy, when required, was often delayed to a later stage of disease, when the systemic inflammatory response stabilized, and necrotic pancreas had become demarcated. In other patients, surgical therapy was avoided altogether. Subsequent studies have confirmed this strategy: Garg etal. describe a 10- year series of 80 patients with infected pancreatic necrosis in whom 47 were treated with

Pancreatic Necrosis withInfection 245

https://t.me/medicina_free

antibiotics alone [17]. The paradigm of urgent surgical debridement for all patients with infected pancreatic necrosis is therefore no longer considered valid.

Definitions andClassification ofPancreatic Necrosis

A classification system for acute pancreatitis was first proposed at the Atlanta Symposium in 1992. This system defined acute pancreatitis as an acute inflammatory process, associated with elevated pancreatic enzymes, with variable involvement of other organ systems[4]. A further distinction was made between acute interstitial pancreatitis and sterile or infected necrotic collections [18]. Unlike the prior delineation of pancreatic necrosis to infected and sterile versions, the revised Atlanta classification, introduced in 2012[5], divided collections associated with necrotizing pancreatitis according to time of disease onset. A collection that develops early and lacks a discrete wall is referred to as an acute necrotic collection (ANC), whereas a collection that persists after 4weeks is referred to as walled- off necrosis (WON). Both forms may be sterile or infected, although no correlation exists between extent of necrosis and risk of infection[5].

hospitalization (37 vs. 26days, P = 0.01) and higher mortality (13% vs. 4%, P = 0.02), compared to delayed (≥4weeks) treatment[19]. A randomized trial has shown that early surgical intervention is associated with higher morbidity and mortality, compared to intervention at least 12 days after onset[20]. Other reviews have confirmed lower mortality with delayed surgical intervention[21,22] with data suggesting that early surgery is an independent predictor of poor outcome in necrotizing pancreatitis [23]. More recently, a randomized, multicenter, superiority trial (POINTER), comparing immediate and postponed intervention in patients with infected pancreatic necrosis, observed more interventions in the immediate drainage group, compared to the postponed drainage group, with no difference in adverse events[24].

Significant retroperitoneal inflammation, mediated by cytokine release, is hypothesized to contribute to these observed differences in outcomes. Moreover, early debridement may lead to incomplete excision of necrotic tissue and increased risk of injury to surrounding normal tissues, with associated increases in morbidity and mortality. Conversely, increasing time for clinical stabilization and decreased inflammatory response by delaying debridement improves outcomes for these patients.

Indications andTiming ofIntervention

In principle, interventions for pancreatic necrosis intend to control organ damage by removing necrotic tissue while maintaining functional pancreas. These interventions may be considered in patients with infected pancreatic necrosis or symptomatic sterile necrosis. Although the presence or absence of infection is crucial for prognosis and affects management decisions, the presence of clinical symptoms rather than suspicion of infection is considered paramount for intervention. It should be noted that the management of pancreatic necrosis requires a multidisciplinary approach with tise from gastroenterologists, surgeons, interventional radiologists, critical care physicians, and dietitians. As such, clinical guidelines recommend transfer to a tertiary care center for management of these patients.

Timing of intervention is dependent on patient factors and clinical stability. Early resuscitative efforts, including fluid resuscitation, initiation of enteral nutrition, and reversal of organ failure, are critical, with most data and practice guidelines recommending delaying intervention for 3–4weeks after onset of acute pancreatitis. In one retrospective series of 305 patients with necrotizing pancreatitis, early intervention (defined as <4 weeks from disease onset) was associated with longer

clinical exper-

Pancreatic Necrosis withInfection

Mortality rates for patients with pancreatic necrosis and superimposed infection approach 30%. Pancreatic infection occurs via bacterial translocation or seeding from bacteremia, and is most commonly caused by gut bacteria, including Escherichia coli, Enterobacter, Enterococcus faecalis and faecium, and anaerobes [25]. Infected necrosis is suspected with clinical deterioration of a previously stable patient with pancreatic necrosis. These patients may present with one of the following clinical features: fever, bacteremia, worsening leukocytosis or organ failure, or hemodynamic deterioration. Abdominal imaging in these patients may demonstrate gas within necrotic debris due to the presence of gasisms or via a fistula to the colon, small bowel, or stomach. Alternatively, infection may be proven by culture or Gram stain obtained by image- guided FNA [26]. Although a Gram stain positive for organisms was previously thought to mandate early surgical intervention[12], patients with suspected infection are increasingly managed with antibiotics and supportive care to allow less invasive and delayed management of a walled- off collection [3]. Diagnostic FNA is therefore used less routinely in the management of suspected infection.

Currently, first- line treatment for patients with

infected pancreatic necrosis includes the initiation of

forming organ-

Indications forInterventional andSurgical Treatment ofNecrotizing Pancreatitis

https://t.me/medicina_free

246

broad- spectrum antibiotics with high penetration into the pancreas, such as carbapenems, quinolones, and metronidazole. Empiric fungal coverage is not routinely recommended. Notably, while antibiotics are critical in the management of pancreatic necrosis with infection, empiric use of antibiotics for prevention of infected necrosis is not supported. Multiple prospective, randomized trials have concluded that the administration of prophylactic broad- spectrum antibiotics does not impact rates of developing infected necrosis, systemic complications, or mortality[27,28]. As such, prophylactic use of antibiotics is discouraged.

Despite demonstrated success with nonsurgical management for infected necrosis, many if not most patients with infected pancreatic necrosis require some form of intervention. Some series suggest that clinically stable and relatively asymptomatic patients with infected necrosis can be managed w ith antibiotics alone[16,17,29]. Nonetheless, patients with infection are prone to clinical decline and require surgical, endoscopic, or radiographic intervention with the onset of clinical signs not responding to medical management. As mentioned above, in the era of surgical management, delayed intervention is far preferable to early surgery for patients with infected necrosis. Expedited intervention may be required in patients demonstrating progressive systemic sepsis or hemodynamic instability. In the absence of such systemic signs, clinically stable patients may generally be managed at least temporarily with antibiotics to allow further organization of the inflammatory process. Delayed surgical, endoscopic, or radiologic management may then proceed if clinical symptoms do not improve[6].

Delayed surgical intervention of infected pancreatic necrosis has been facilitated by the use of percutaneous catheter drains. A 1998 series by Freeney etal.[30] demonstrated that some patients with infected pancreatic necrosis might have surgical management delayed or potentially avoided altogether with the use of large-

bore percutaneous catheters placed under CT guidance. This strategy was validated in a multicenter trial in which patients were randomized to standard pancreatic debridement versus a “step- up” approach in which debridement was used only if necessar y[31]. Using a “step- up” approach, complications were significantly lower, and about onethird of patients were treated with catheter drainage alone.

Sterile, but Symptomatic, Pancreatic Necrosis

The precise role of radiographic drainage, endoscopic or surgical debridement in sterile pancreatic necrosis is less clear. Although most patients with sterile pancreatic necrosis respond to supportive care without the need

for intervention, others will experience clinical decline, including organ failure despite the absence of demonstrable infection. Historically, some authors had therefore suggested the need for surgical debridement in patients with progression of disease or failure to improve, regardless of the status of infection [32,33]. Unfortunately, no uniform criteria have defined which patients with sterile pancreatic necrosis might benefit from debridement. In the era of surgical debridement as the primary intervention for necrotizing pancreatitis, some authors suggested criteria for intervention including the extent of necrosis of more than 50% of the pancreatic parenchyma [32], rapid clinical deterioration with multiple organ failure[34], or the presence or persistence of organ failure [35,36]. However, evidence is lacking to support the use of these criteria as an absolute indication for debridement or drainage. Close analysis of one study of 89 patients with severe sterile necrosis identified only two patients who died that might have theoretically benefitted from earlier surgical debridement, though no clinical parameters were able to easily differentiate these patients from others with severe sterile necrosis[13].

As noted above, in the absence of clinical confirmation of infection by image guided FNA or suggestive imaging, intervention is typically based on the clinical course and trajectory. Patients are therefore often brought to intervention for not just documented infection, with positive pancreatic FNA, but also for suspected infection based on persistent sepsis or progressive clinical deterioration[36]. Given the additional morbidity and mortality associated with open surgery, radiologic or endoscopic drainage is used prior to surgical intervention[37].

The process of walled-

off pancreatic necrosis recognized in the revised Atlanta classification was previously described by Baron as “organized pancreatic necrosis”[38]. In this condition, an intrapancreatic or extrapancreatic heterogeneous semisolid collection develops in the context of acute necrotizing pancreatitis and has an encapsulated wall[5]. A subset of patients with WON may experience a prolonged clinical course marked by persistent pain, malaise, and inability to eat. This symptom complex was described by Warshaw as “persistent unwellness”[39]. The precise indications and timing of intervention are not precisely defined for these patients.

Asymptomatic WON does not require intervention regardless of the size of the collection and may resolve with conservative management (Fig.27.1). Symptomatic WON, however, can be marked by pain, intestinal, or biliary obstruction, or later infection. In one series, approximately 10% of patients with sterile pancreatic necrosis underwent surgery for persistent pain and organized necrosis at a mean of 29 days after initial presentation[13].

Figure27.1 Walled- off necrosis. A 55- year- old man presented

https://t.me/medicina_free

with severe acute pancreatitis and an acute necrotic collection. Hewas managed conservatively, and imaging 6weeks after presentation revealed a large area of walled- off necrosis involving the entire body and tail of the pancreas. The patient remained asymptomatic, and no intervention was pursued.

Preoperative Evaluation andImaging Considerations

The approach to debridement is dependent on imaging characteristics, including the extent and pattern of pancreatic necrosis. Involvement of the mesenteric root or extension down the paracolic gutter have historically been challenging to treat endoscopically. While some techniques have been described [40], wide surgical debridement and drainage is routinely employed in these cases to ensure adequate debridement. Extension of pancreatic necrosis into the mesocolon presents an additional challenge, as debridement of these tissues may compromise colonic blood flow. Patients with extensive colonic or mesenteric involvement may require partial colectomy at the time of surgical debridement.

Close examination of the pancreas on CT imaging is also key, as patients with isolated necrosis of the pancreatic neck or body may be at an increased risk for developing disconnected pancreatic duct syndrome (DPDS). In this condition, the disconnected pancreatic segment continues to secrete pancreatic fluid, which can in turn lead to the development of new pancreatic collections, fistula formation and recurrent pancreatitis[41]. In one retrospective series, fluid collections recurred in 42% of patients with DPDS, despite endoscopic drainage [42]. While rare with a reported prevalence of 10% to 31%[42], prompt diagnosis of DPDS is key to reducing morbidity. Diagnosis requires necrosis of at least 2 cm of pancreas

Surgical andInterventional Procedures 247

and viable upstream pancreatic parenchyma[41]. While imaging modalities can be suggestive of DPDS, ERCP, which may visualize extravasation of contrast from the pancreatic duct, remains the gold standard for diagnosis.

Management includes conservative therapy with nutritional optimization, endoscopic treatment, and/or surgery. The routine use of octreotide in these patients is not supported[43]. While surgery was once considered the mainstay of treatment for these patients, advances in endoscopic treatment modalities have provided lessinvasive alternatives for select patients. Transpapillary pancreatic duct stent placement has been previously described with successful outcomes[44,45]. In a series of 43 patients, 58% had resolution of the disruption after stent placement. Stents bridging the disruption and longer duration of stent therapy were associated with improved outcomes. In another series endoscopic treatment improved outcomes for patients with DPDS with a failure rate of 23% [42]. While long-

term plastic stent placement has been associated with improved outcomes, risks include stent migration and infection. The prophylactic use of pancreatic stents in acute necrotizing pancreatitis remains controversial, with data from a recent prospective randomized superiority trial suggesting a high risk of infection in these patients and advising against routine prophylactic use[46].

Although DPDS can be temporized with EUS- guided transmural stenting[47], many patients may ultimately require consideration of definitive surgical management. Surgical options include distal pancreatectomy for removal of the viable distal segment or internal drainage procedures such as cyst- gastrostomy, which may better preserve pancreatic function.

Surgical andInterventional Procedures

The use of various radiologic, surgical, and endoscopic interventions for necrotizing pancreatitis will vary among institutions [6]. Although open surgical necrosectomy was previously considered the definitive management, a number of minimally invasive techniques have been developed. As noted above, delayed intervention is preferable in all patients, if possible, particularly when open surgical management is used[48]. However, interventional radiologic techniques may be performed earlier with suspected infection[22]. Even in the setting of suspected or known infection, there is a growing trend to treat with supportive care and antibiotics unless there are signs of sepsis, until the pancreatic collection becomes walled off[3].

Owing to the efficacy of minimally invasive approaches and associated reductions in mortality, the

<<< < Предыдущая 14 15 16 17 18 19 20 21 22 23 24 2526 / 5026 27 28 29 30 31 32 33 34 35 36 37 38 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
30.08.202657 Мб0Книга_677_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202657 Мб0Книга_678_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202657 Мб0Книга_680_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_681_Библиотеки_им_академика_М_И_Перельмана.epub
#
30.08.202656 Мб0Книга_682_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_683_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_684_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_685_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_686_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_688_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202655 Мб0Книга_689_Библиотеки_им_академика_М_И_Перельмана.pdf