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New developments in understanding of pathophysiology, diagnosis and treatment of severe acute pancreatitis
Jurnalul Român de Anestezie Terapie Intensivã 2012 Vol.19 Nr.1, 39-50
ACTUALIZÃRI
New developments in understanding of pathophysiology,
diagnosis and treatment of severe acute pancreatitis
A. Izakson1, T. Ezri2*, Dana Weiner3, Diana Litmanovich4, E.V. Khankin4
Department of Anesthesia, Rebecca Sief Medical Center, Zefat, Faculty of Medicine, Bar Ilan University, Galille, Israel
Department of Anesthesia, Wolfson Medical Center, Holon, Affiliated with Tel Aviv University, Israel
3
Department of Nutrition, Rambam Health Care Campus, Haifa, Affiliated with Technion Medical School, Haifa, Israel
4
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA, USA
* Outcomes research Consortium, Cleveland OH, USA
1
2
Abstract
Severe acute pancreatitis (SAP) remains being a clinical challenge, carrying significant burden of
morbidity, mortality and patient related cost. In general, acute pancreatitis may vary in severity, from mild,
self-limiting pancreatic inflammation to life-threatening pancreatic necrosis. Gallstone induced obstruction
and alcohol abuse are the most common causes of pancreatitis in adults. Continuing interest in new
biological markers and predictive models for timely identification of severe acute pancreatitis cases emphasizes clinical importance of early severity prediction. Among those markers, IL-6, IL-10, procalcitonin,
and trypsinogen activation peptide are most likely to be used in clinical practice. Although all scoring
systems had reliable accuracy in predicting pancreatitis severity and outcome, SOFA score performed.
The treatment of mild disease is mainly supportive, while severe episodes require management by a
multidisciplinary team including gastroenterologists, interventional radiologists, intensive care specialists,
and surgeons. There are some unresolved issues pertinent to treatment, including indications for antibiotic
prophylaxis, optimal route for nutritional support, selective intestinal decontamination and surgical management of pancreatic infection. The purpose of this review is to present advances in pathophysiology,
diagnosis, and management of SAP.
Keywords: severe acute pancreatitis, pathophysiology, diagnosis, management
J Rom Anest Terap Int 2012; 19: 39-50
The incidence of acute pancreatitis has increased
dramatically over the last two decades. At present,
only in USA, acute pancreatitis accounts for more than
200,000 hospital admissions per year. In 80% of cases,
acute pancreatitis is relatively mild; nevertheless, almost
20% of patients eventually develop severe disease
associated with local and extrapancreatic complications. The mortality rate associated with SAP remains
between 10 and 30 percent, despite recent advances
in the management of the disease [1].
Adresa pentru corespondenþã: Alexander Izakson MD
Department of Anesthesiology
Zafed Medical Center
Rambam St 13100, Zafed, Israel
E-mail: [email protected]
According to the Atlanta Symposium (1992), SAP
is defined as pancreatitis associated with organ failure
and/or local complications (e.g. pancreatic tissue necrosis, pseudocyst, or abscess formation) [2]. Important risk factors for the development of pancreatitis in
adults are: presence of gallstones (38% of cases) and
excessive alcohol consumption (36%). Hypertigliceridemia, defined as serum triglyceride concentrations
higher than 11 mmol/L, may be both a precipitating
factor or worsen acute pancreatitis induced initially by
other condition. Hypercalcemia is another, though
relatively inconsistent, cause: incidence of pancreatitis
is generally low in patients with chronic hypercalcemia
so additional factors are probably required to induce
the disease. Additional, relatively rare causes include:
mechanical obstruction of pancreatic duct (e.g. related
to neoplasm or pancreas divisum), drugs (e.g. azathio-
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Izakson et al.
prine, thiazides, estrogens etc.) and direct trauma to
pancreas [3-5].
Pathophysiologic complexity of the disease precludes identification of a specific cause/s for each and
every episode of SAP.
Clinical features
Severe acute pancreatitis develops in two phases.
The initial phase is dominated by the systemic inflammatory response syndrome (SIRS) that usually evolves
during the first week of the disease and may either
resolve spontaneously or culminate in SAP development. The second phase (progression of SAP) is dominated by features of necrotizing pancreatitis, the most
significant of which is infected variant of pancreonecrosis complicated with multiple organ dysfunction
(MOD) syndrome. Approximately 50% of the patients
developing infected pancreo-necrosis do so within the
first 21 days of the disease.
Pathophysiology
The pathogenesis of acute pancreatitis has been
classically related to inappropriate conversion of trypsinogen to its active form (trypsin) along with lack of
prompt quenching of active trypsin inside the pancreas
itself. This, in turn leads to autodigestion of the gland
tissue and local inflammation. Consequently, acute
pancreatitis develops, though, only in cases when intracellular protective mechanisms utilized to prevent
trypsinogen activation or reduce trypsin activity are
overwhelmed. These mechanisms include synthesis of
trypsin as inactive pro-enzyme trypsinogen, autolysis
of trypsin, enzyme compartmentalization, synthesis of
specific trypsin inhibitors such as serine protease inhibitor Kazal type 1 (SPINK1), as well as relatively low
intracellular ionized Ca²+ concentrations [6]. Tumor
necrosis factor á (TNFá) is released by macrophages
localized within the pancreatic tissue. This acute
inflammatory response per se causes substantial tissue
damage and may progress beyond the pancreatic injury,
leading to a SIRS, MOD or death. In severe acute
pancreatitis, monocytes show impaired nuclear factor
kB and STAT1 activation, which may increase susceptibility to secondary infections. Monitoring of monocyte
signaling profiles may aid in finding new therapeutic
approaches and predictors of outcome of severe acute
pancreatitis [7].
Diagnosis
The initial clinical presentation of SAP is manifested
by upper-abdominal pain and vomiting combined with
elevated serum levels of pancreatic enzymes. In
gallstone pancreatitis, the pain is typically sudden, sharp
and epigastric. In SAP related to hereditary or metabolic abnormality or alcohol abuse, the onset may be
less abrupt and the pain on many occasions is poorly
localized. Extension of inflammatory exudates from
the peripancreatic region to the diaphragm can lead to
shallow respiration.
A rise in concentration of serum amylase is expected in acute pancreatitis, but this increase is not
always obvious and easily identified, especially early
in the course of the disease or in relatively mild cases.
Pancreatic lipase levels are also elevated. The levels
of both enzymes remain elevated with ongoing pancreatic inflammation, with amylase typically returning
to normal shortly prior to lipase, in the resolution phase.
Serum amylase concentrations may be high in the
absence of acute pancreatitis as happens in macroamylasemia, in patients with reduced glomerular filtration
rate, diseases involving salivary glands, as well as in
extrapancreatic abdominal inflammatory pathologies
such as acute appendicitis, cholecystitis, intestinal
obstruction, ischemia or perforation, peptic ulcer, and
gynecological conditions [8]. Thus, serum lipase
concentration is a preferential diagnostic tool in patients
with delayed presentation of SAP [9]. An increase in
liver enzymes in a patient without history of alcohol
abuse is the best single laboratory predictor of biliary
pancreatitis: a level of more than three times the upper
limit of normal has a positive predictive value of 95
percent. Unfortunately, normal liver enzymes do not
reliably rule out the diagnosis and 15-20% of patients
with acute pancreatitis of biliary origin will have normal
liver function tests [10].
Imaging studies
Abdominal imaging either by computed tomography
(CT), magnetic resonance imaging (MRI), or transabdominal ultrasonography are all useful in confirming
the diagnosis of pancreatitis. Each technique has its
own advantages and pitfalls. Transabdominal ultrasonography (US) is more sensitive than both CT and
MRI for identifying gallstones and biliary sludge as
well as for detecting bile duct dilatation, but it is less
useful for detecting stones in the distal bile duct [11].
Endoscopic ultrasonography (EUS) supersedes that
caveat and is probably the most accurate test for diagnosing or ruling out biliary causes of acute pancreatitis
also enabling emergency endoscopic retrograde cholangiopancreatography (ERCP) [12]. If the suspicion
of gallstone pancreatitis remains high despite a normal
percutaneous ultrasonography or CT scan, endoscopic
ultrasonography should be performed whenever possible, since it enables the best view of entire bile duct.
On the other hand, contrast-enhanced CT has 8790% sensitivity and 90-92% specificity in confirming
New developments in understanding of pathophysiology, diagnosis and treatment of severe acute pancreatitis
the diagnosis of SAP in its early stages or for later
assessing of complications such as, fluid collections,
abscesses, pseudocysts, pseudoaneurysms of adjacent
arteries, peripancreatic vein thrombosis and pancreatic
necrosis (Fig 1, panels D and E). Diagnostic potential
of magnetic resonance cholangiopancreatography
(MRCP) is now almost as good as ERCP, with pancreatic MRI as the main imaging technique to investigate bilio-pancreatic pain, chronic pancreatitis, and
cystic pancreatic tumors at many institutions.
validation [15]. Several other markers of inflammation
have been investigated in this regard, including serum
procalcitonin, soluble IL-2 receptors, and soluble Eselectin [16], yet the clinical value of these prognostic
markers requires further thorough investigation.
A growing body of evidence suggests that assays
for trypsinogen activation peptide (TAP) may serve
as a useful marker of disease severity [17, 18]. Recent
reports of high sensitivity and specificity of elevated
urinary TAP values in SAP [19, 20] are quite promising;
similarly, a recent report focusing on plasma TAP levels
suggested that SAP could be recognized with sensitivity
and specificity of 70% and 78% [21, 22].
CT scan has upmost value in estimating the prognosis of disease. The severity of acute pancreatitis
by the degree of changes is classified into five grades
(0-4) on unenhanced CT scan, whereas the degree of
pancreatic necrosis is measured by contrast-enhanced
CT scan. The sum of these two scores is used to
calculate the CT severity index for acute pancreatitis
(Table 2) [17, 23]. There are no specific radiologic
features that identify infection of pancreatic tissue
except the rare presence of air bubbles within the necrotic pancreas on CT scan [24].
Pancreatic necrosis is the most devastating local
complication of acute pancreatitis. Pancreatic necrosis
is defined as areas of devitalized parenchyma and is
usually associated with peripancreatic fat necrosis.
Approximately 15% of cases of acute pancreatitis are
necrotizing and the remaining 85% are interstitial.
Diffuse or focal areas of non-viable parenchyma are
initially sterile but may become infected by bacteria of
gut intestinal origin. The condition is associated with
late additional complications and death if the necrotic
tissue becomes infected. The use of dynamic contrastenhanced CT is perhaps most useful in its ability to
Clinical course
It is critical to identify patients at high risk for severe
disease, since they require close monitoring and prompt
intervention. Recognized markers of the risk for severe
acute pancreatitis include, but are not limited to: specific
laboratory tests aimed at evaluating the systemic inflammatory response (i.e. C-reactive protein), scoring
systems that assess inflammation or organ failure (i.e.
Ranson’s score, sequential organ failure assessment
(SOFA) score, etc.) and imaging abnormalities. It is
imperative to identify the patients at risk within 24 hours
of presentation. In a prospective study Juneja et al.
had shown that SOFA score (Table 1) had a greater
efficacy for predicting severity and 30-day mortality
than the other scores employed by the authors [13].
The incidence of pulmonary complications is high in
severe pancreatitis, ranging from 15 to 55% [14].
A number of biological parameters have been evaluated as prognostic markers in both laboratory and
clinical settings. For instance: C-reactive protein (CRP)
is readily available and rises with disease severity.
Inflammatory mediators such as interleukin (IL)-8 and
IL-6 show promise as early indicators of severe disease but await general availability and further clinical
Table 1. Sequential Organ Failure Assessment score (SOFA score)
Parameter
Respiration
(PaO2/FiO2[mmHg])
Coagulation
Platelets (x103/µL)
Liver
Bilirubin (mg/dL)
Cardiovascular
Hypotension
Central nervous system
Coma scale
Renal
Creatinine (C) (µmol/L) or Urinary
Output (UO) (ml/day)
0
1
2
3
4
> 400
< 400
< 300
< 200 with respiratory support
< 100 with respiratory
support
> 150
< 150
< 100
< 50
< 20
0-1.2
1.3-1.9
2.0-5.9
6.0-11.9
> 12.0
No
hypotension
MAP < 70
mmHg
Dopamine < 5, or
Dobutamine
(any dose)
Dopamine > 5, or Epinephrine
< 0.1, or Norepinephrine < 0.1
Dopamine > 15 or
Epinephrine > 0,1 or
Norepinephrine > 0.1
15
14-13
12-10
9-6
6 and >
< 110
(C)
111-170
(C)
171-299
(C)
300-440 (C) or
< 500 (UO)
> 440 (C) or
< 200 (UO)
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Table 2. CT severity index score
Unenhanced CT scan
Pancreatic Changes
Contrast-enhanced CT scan
Score
Normal Pancreas
Pancreatic enlargement
Pancreatic and peripancreatic changes
Single fluid collection
Two or more fluid collections
0
1
2
3
4
Percentage of Necrosis
Score
0%
< 30%
30-50%
> 50%
0
2
4
6
CT scan based severity index for acute pancreatitis. Accumulated score > 7 predicts high
morbidity and mortality
demonstrate pancreatic necrosis. CT diagnosis of
pancreatic necrosis requires identification of distinct
areas of non-enhanced pancreatic parenchyma being
at least 3 cm in size or involving more than 33% of the
pancreas [25] (Figure 1). Recent data support the use
of MRI as an alternative: MRI and CT have been
shown to have comparable sensitivity and specificity
for SAP evaluation and diagnosis [26]. No data support
the use of CT to diagnose necrosis or to predict severity
within the first 24 hours, while sensitivity of pancreatic
necrosis identification approaches 100%, four days
after pancreatitis commenced [27]. Patients with
clinical and biochemical features of acute pancreatitis
who do not improve with conservative management
must undergo an abdominal CT scan with oral and
intravenous contrast.
Up to 57% of patients hospitalized with acute pancreatitis will have fluid collections. If those collections
continue to enlarge they will cause pain, become
infected (as suggested by the presence of not otherwise
explained fever, leukocytosis, or gas) or compress
adjacent organs. Fluid collections with very high levels
of pancreatic enzymes are usually associated with pancreatic-duct disruptions and may eventually lead to
pseudocyst formation (usually over a period of several
weeks), ascites, or pleural effusions [28]. The natural
course of pancreatic pseudocysts after acute
pancreatitis and the reasons for their spontaneous
Fig. 1. 64 year old male with abdominal pain. Axial and coronal Contrast Enhanced CT images demonstrate diffusely decreased density of
the pancreatic gland with spearing of pancreatic head representing subtotal pancreatic necrosis (panels A and C, arrowheads). Common
manifestations of acute pancreatitis such as extensive retroperitoneal and mesenteric fat stranding (panels B and C, white arrows) and
anteriorly located flegmonous collection (panel B, asterisk) are prominent in this case.
Evolution of pancreatitis. 55 years old male has presented originally with acute pancreatitis with relatively minimal radiological changes: fat
stranding in the peripancreatic fat limited to body and tail of the pancreas (panels D, white arrows). Clinical deterioration was followed by
subsequent imaging that has shown pancreatic pseudocyst in the distal pancreas (panel E, white arrows), as well as additional adjacent
pseudocyst in the anterior abdomen posterior to the stomach (panel E, arrowheads). Free ascites and subcutaneous fat stranding (panel E,
white asterisk) are noted.
New developments in understanding of pathophysiology, diagnosis and treatment of severe acute pancreatitis
resolution remain unknown. In his prospective study
of 369 patients Lankisch investigated the prognostic
factors for development of pancreatic pseudocysts and
for their spontaneous resolution after a first episode of
acute pancreatitis [29]. Follow-up examination 3 and
6 months after discharge, showed pancreatic pseudocysts in 36 (10%) patients (30 with and 6 without prior
fluid collection), and in 27 (7%) patients (25 with and
2 without pancreatic pseudocyst after 3 months),
respectively. The prognostic factors for their development were alcohol abuse and an initial severe course
of the disease. Spontaneous complete resolution of the
pancreatic pseudocysts occurred in 11 (31%) of the
36 patients. Prognostic factors for the spontaneous
resolution were no or mild symptoms (nausea, vomiting,
abdominal pain) and a maximal cyst diameter of < 4
cm [29].
Pancreatic infection
Infection of necrotic pancreas tissue must be suspected in case of unexplained fever, leukocytosis, and
a lack of patient’s condition improvement or unexpected
deterioration – usually after the first week of illness.
Pancreatic infection occurs typically in the setting of
pancreatic necrosis and, rarely, in association with
extrapancreatic fluid collections and/or pancreatic
pseudocysts. Mortality in infected necrosis is nearly
25%. Approximately 50% of patients who have necro-
tizing pancreatitis develop organ failure, compared with
less than 10% of patients who have purely interstitial
pancreatitis [30].
Diagnosis of infected pancreatic necrosis
Unfortunately there are no reliable clinical parameters capable of distinguishing between sterile and
infected pancreatic necrosis. Clinical markers of systemic inflammation are usually present in infected
necrosis, but may as well be present in patients with
severe sterile necrosis [31]. Elevated procalcitonin
levels seem to be promising as a marker for infection
in necrotizing pancreatitis, with several small studies
reporting 75% to 94% sensitivity and 83% to 91%
specificity [32, 33].
The ability to use image-guided percutaneous aspiration to diagnose infection in patients with pancreatic
necrosis has therefore been a major advance (Figure
2). Positive cultures obtained by fine needle aspiration
(FNA) are the gold standard for confirming infection
in necrotic pancreas. More specifically, CT-guided fine
needle aspiration has been reported to have a sensitivity
and specificity for diagnosis that exceed 95% [34],
while ultrasound guidance achieves a sensitivity and
specificity of 88% and 90%, respectively [35]. Samples have to be evaluated for aerobic, anaerobic, and
fungal growth. The interval from initial presentation to
the development of pancreatic infection can take up
Fig. 2. Pancreatic necrosis diagnosis and treatment work-flow
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to 3 weeks. For this reason, repeated CT-guided aspirations may often be necessary [36]. Even if the patient
continues with clinical picture of sepsis/SIRS the
intervention is usually delayed until after the first 7 to
10 days of illness and there are two reasons for that.
Approximately one half of pancreatic infections are
documented during the second and third week of illness.
A second reason is that during the initial 7 to 10 days
of acute pancreatitis, fever, leukocytosis, and organ
failure are caused by a severe inflammatory response
and cytokine release.
Microbiology of pancreatic infection
Gut-derived gram-negative bacteria, including
Escherichia coli, Klebsiella, and Pseudomonas, are
the most common pathogens identified in pancreatic
infections. Gram-positive organisms, including
Staphylococcus aureus and S. enterococcus species,
are also found at infected pancreatic necrosis sites.
Resistant gram-positive cocci, along with fungi, are an
increasing concern in patients who are exposed to
broad-spectrum antibiotics [37, 38].
Management of SAP
Besides specific treatment (mostly for gallstoneinduced pancreatitis), the early therapeutic strategies
are identical in all patients with acute pancreatitis.
a. Medical treatment options
An algorithm for the diagnosis and management of
acute pancreatitis is suggested in Figure 3. The cornerstone of initial management is aggressive extracellular
fluid (ECF) volume expansion to replenish the often
massive third-space losses. Inadequate fluid resuscitation not only predisposes to systemic complications,
particularly acute kidney injury, but also has recently
been shown to pose a significant risk for further pancreatic injury [39].
Determination of cause of pancreatitis is of paramount importance for guiding immediate management
and preventing recurrence.
Persistent biliary obstruction worsens the outcome
and increases the severity of acute pancreatitis and
predisposes the patient to bacterial cholangitis. When
Fig. 3. Acute pancreatitis severity assessment and treatment work-flow
New developments in understanding of pathophysiology, diagnosis and treatment of severe acute pancreatitis
the diagnosis of biliary pancreatitis is established,
endoscopic retrograde cholangiopancreatography
(ERCP) must be immediately performed combined
with endoscopic sphincterotomy in order to extract
impacted gallstones and drain infected bile. If suspicion
of gallstone pancreatitis remains high despite a normal
percutaneous ultrasonography or CT scan, endoscopic
US must be performed, as a gold standard diagnostic
procedure for bile duct stones. Although early ERCP
is not routinely recommended in relatively mild pancreatitis cases, its importance in acute biliary pancreatitis with biliary obstruction or cholangitis is undisputed.
More controversial is the utilization of early ERCP and
papillotomy in acute biliary pancreatitis without obstruction. Both Neoptolemos et al. [40] and Fan et al.
[41] demonstrated a significant reduction in morbidity
with trend towards lower mortality when patients with
acute pancreatitis underwent “early” ERCP. On the other
hand, a recent multicenter randomized trial by Fölsch et
al. [42], designed to exclude patients with proven biliary
sepsis or obstruction, demonstrated increased complications and mortality in the ERCP group. Therefore, it
was suggested that early ERCP might be harmful in the
absence of ongoing obstruction and there is insufficient
evidence to recommend ERCP in acute biliary pancreatitis
in the absence of biliary obstruction or infection. Recent
advances in diagnostic radiology suggest that MRCP is a
valid diagnostic alternative.
SIRS that causes organ failure in SAP is similar to
that caused by severe sepsis, because of that the use
of recombinant human activated protein C (rhAPC) in
the management of SAP has been investigated in
experimental and clinical studies. The experimental
evidence of disease amelioration in SAP following
intervention with rhAPC has not been revealed in the
small clinical trials [43].
Nutritional support in SAP patients
Clinical and experimental studies show that bowel
rest is strongly associated with intestinal mucosal
atrophy leading to infectious complications as a result
of bacterial translocation from the gut. In recent years,
increasing evidence suggests that enteral nutrition (EN)
may be feasible and safe even in cases of severe pancreatitis [44]. Enteral nutrition helps to avoid alterations
in intestinal barrier function observed with total
parenteral nutrition (TPN) [45], additionally avoiding
the cost of and catheter-related complications associated with TPN and should be implemented sooner
than later after adequate fluid resuscitation. Moreover,
TPN is known to be associated with enhanced proinflammatory response. Although mortality rate is not
substantially different in patients treated with parenteral
or enteral nutrition, the incidence of infections [46, 47],
surgical interventions [47], and non-infectious com-
plications [47] is clearly reduced in the enteral nutrition
treatment group. However, TPN should still be reserved for patients who cannot obtain sufficient caloric
intake via enteral nutrition or in whom enteral access
cannot be maintained [48].
The type of EN (gastric vs. jejunal) is also a matter
of ongoing debate [49]. Recently published studies
show no significant clinical difference between early
nasogastric and nasojejunal feeding [46, 50, 51]. In
relation to formulations, polymeric as compared with
elemental or semielemental did not increase the risk
of infections, feeding intolerance, or mortality in acute
pancreatitis [52].
However, noncompliance in adhering to guidelines
was documented in Davies’s study and is a revelation
that guidelines and actual practice defer in many
situations. Nutrition in SAP has been discussed and
researched over the years and still there is dominance
of what treating doctors think rather than follow
protocols and evidence [53].
Selective digestive tract decontamination
Selective digestive tract decontamination (SDD)
and selective oropharyngeal decontamination (SOD)
are infection-prevention measures used in the treatment
of some patients in intensive care, but reported effects
on patient outcome are conflicting [54]. Breakdown
of enteral barrier integrity, systemic and local immunosuppression and bacterial overgrowth due to the decrease in intestinal motility are postulated as important
factors in the mechanism of bacterial translocation
(BT) in SAP [55] providing rationale for SDD. Topical
oropharyngeally administered non-absorbed
antimicrobials (i.e. polymyxin B, tobramycin or amphotericin B) cover a wide range of gram-negative and
fungal infections and is combined for the first 3-4 days,
with a broad-spectrum systemic antibiotic, (i.e. cefotaxime). Bowel treatment to prevent infectious
complications has attracted interest, and SDD and EN
therapies have been introduced in patients with SAP.
De Jonge and colleagues assessed the effects of SDD
in an intensive care population [56] showing substantial
reduction in mortality (24 % vs. 31%) and a shorter
length of ICU stay (6.8 vs. 8.5 days) in patients treated
with SDD. It did not increase bacterial resistance on
follow-up of more than 2 years. Luiten et al. [57] randomized patients with SAP to oral and rectal administration of non-absorbable antibiotics. Mortality was
decreased in the selective decontamination group, predominantly due to late mortality reduction and decrease
in gram-negative pancreatic infection.
Since the effect of SDD in avoiding the breakdown
of intestinal integrity is uncertain, the adoption of
definitive recommendations regarding the use of gut
decontamination in SAP requires further investigation.
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Izakson et al.
Antibiotic treatment
Infection of necrotic pancreas generally involves
aerobic and anaerobic bacteria of GI origin, and may
be mono- or polymicrobial.
The benefit of antibiotic prophylaxis is seriously
debated. Since pancreatic infection is the leading cause
of morbidity and mortality in SAP, early prevention of
infected necrosis seems to be reasonable treatment
option. Unfortunately, prospective and randomized
trials as well as meta-analyses showed at best, only
weak benefit. In some cases the treatment might be
even disadvantageous due to the risk of bacterial resistance and fungal superinfection development [58]. A
recent meta-analysis of randomized controlled trials
concludes that prophylactic antibiotics do not prevent
infections in patients with pancreatic necrosis nor they
decrease mortality [59]. When infection is suspected
and fine-needle aspiration of the pancreas for bacteriology is performed, the accepted treatment is to start
with antibiotics, usually with intravenous imipenem or
meropenem, a treatment continued for 14 days [60].
This treatment is rapidly stopped if infection is not
confirmed. However, given the availability of other
agents with adequate pancreatic tissue penetration,
there is no sufficient evidence to support the use of
intravenous carbapenems as a first-line treatment [61].
Consequently, carbapenems should be reserved for
pancreatic infections proven to be secondary to multiresistant organisms [61].
Treatment of microbiologically confirmed pancreatic infection is guided by the results of culture and
sensitivity. Fluoroquinolones and carbapenems
provide excellent gram-negative coverage and achieve
adequate tissue concentration in the pancreas, compared to ampicillin and gentamicin [62, 63]. Since the
prevalence of gram-positive organisms seems to be
increasing, with S enterococcus and S aureus
accounting for 30% of isolates in at least one recent
review paper [64], appropriate coverage which will
include these organisms taking into consideration the
possibility of resistant strains, is strongly advised.
b. Surgical treatment options
Although recent years have brought increasingly
conservative trends in the management of sterile
pancreatic necrosis, infection remains an absolute
indication for intervention [65].
In the majority of patients with acute pancreatitis,
the process is limited to parenchymal edema without
necrosis. In these patients, surgical therapy is largely
limited to the delayed treatment of local complications,
such as pseudocysts, and to the use of cholecystectomy
to prevent recurrent episodes. In 10% and 30% of
patients, a progress to severe illness is observed, including pancreatic and peripancreatic necrosis, and systemic
inflammatory response syndrome (SIRS). This latter
group of patients may require debridement or other
surgical interventions during the acute phase of the
disease.
While some authors believe that patients with severe
disease benefit from debridement regardless of the
status of infection [66], others, recently adopted a more
conservative surgical approach in patients with sterile
necrosis [67]. Büchler et al. [68] followed 86 conservatively treated necrotizing pancreatitis patients and
reported a surprisingly low mortality rate of 10% and
the need for operation in the absence of documented
infection in only one patient. Non-randomized series
suggest better outcomes with delayed versus early
debridement, when “organized pancreatic necrosis” –
a process of maturation of the inflammatory tissue with
clear demarcation from healthy pancreatic and peripancreatic tissue has already occurred.
Patients with infected pancreatic necrosis account
for the majority of the deaths from acute pancreatitis,
and the absolute need for debridement is widely
accepted, since mortality in these cases without debridement is virtually 100%. The correct timing of
debridement has not been established [69]. Some
authors intervene within 24 h of the diagnosis, irrespective of the patient’s clinical condition. Others postpone intervention, allowing the areas of necrosis to
organize and demarcate, even in the presence of organ
failure, since organ failure can frequently be stabilized
by conservative, intensive care therapy [69]. A delay
in surgical debridement may allow encapsulation of
the necrotic tissue as organized necrosis which can be
removed more easily and safely sometimes via less
invasive laparoscopic or endoscopic approaches.
The three major technical drainage approaches
include open transabdominal debridement followed by
drainage placement and closure (closed suction or
Penrose drains), open transabdominal debridement with
placement of several soft drains in the retroperitoneum
for continuous lavage, or open transabdominal debridement with open packing and planned re-exploration. If
debridement is thought to be inadequate, postoperative
closed, high-volume lavage via large drains in the lesser
sac has been described with some success in avoiding
residua of necrotic tissue [70, 71].
Recently, minimally invasive approaches to the
treatment of infected peripancreatic and/or pancreatic
necrosis such as percutaneous endoscopic and laparoscopic techniques have been described [72-75].
Minimally invasive retroperitoneal necrosectomy uses
percutaneous insertion of an operating nephroscope
to access the area of pancreatic necrosis, followed by
debridement, and irrigation, and the placement of drains
for continuous retroperitoneal lavage [76].
New developments in understanding of pathophysiology, diagnosis and treatment of severe acute pancreatitis
In a meta-analysis published by Heinrich et al. [46]
it was concluded that single necrosectomy and
continuous postoperative lavage (CPL) with large-bore
surgical drains without planned re-laparotomies is the
preferred strategy for surgical treatment of infected
(peri-) pancreatic necrosis.
This strategy is also supported by a recent national
Dutch survey demonstrating that single necrosectomy
and CPL results in lower (25%) mortality (13/53
patients) [77].
Patients with infected necrosis and organ failure
and/or significant comorbidity may benefit from radiologically guided placement of percutaneous drainage
(PCD) catheters. The goal of percutaneous catheter
placement before the organized necrosis stage is to
drain necrotic material as a temporary measure. In
some cases, percutaneous catheter drainage of organized infected necrosis may be ineffective owing to
the inability to eliminate semisolid materials. The results
of Z. Tong’s study show that the mean computed tomographic density and distribution range of infective
pancreatic necrosis could significantly influence the
success rate of PCD. Higher values indicate them less
appropriate for PCD; and because of that it should be
considered seriously before the treatment decision
[78].
Endoscopic necrosectomy is another emerging
therapeutic avenue. Unlike surgical and percutaneous
approaches that can be used before or after organized
necrosis formation, endoscopic therapy is usually
reserved for the treatment of organized necrosis only.
Endoscopic ultrasonography is used to guide the site
of puncture through the gastric or duodenal wall, to
avoid injury to the blood vessels and to enter the cystic
structure accurately. Multiple pigtail catheters are
inserted to create a drainage pathway from the cyst to
the stomach or duodenum. Endoscopic therapy has
the advantage of being less invasive than surgery, but
it requires considerable expertise. The main limitation
of the endoscopic treatment is the difficulty to achieve
a complete evacuation of the necrotic tissue, with the
possible persistence of infection within the cavity.
c. Imaging guided approach to treatment of
complications of pancreatitis
The most frequent complications treated by percutaneous image guided procedures are pancreatic
pseudocyst and pancreatic abscess, followed by embolisation of pseudoaneurysms and debridement of
liquefied necrosis.
Pancreatic pseudocyst would require drainage if
more than 5 cm at time of diagnosis, enlarging over
time, painful, infected or causing local mass effect
exempli gratia biliary obstruction. Transperitoneal
approach with utilization of CT guidance is most
commonly used. Alternatively, transgastric approach
can be used, especially when pseudocyst is communicating with the pancreatic duct. Presence of such a
communication would require prolong drainage up to
6-8 weeks, but the duration can be decreased with
the use of somatostatin analog octreotide. The success
rate of percutaneous drainage currently stands at
approximately 90%.
Pancreatic abscess drainage by percutaneous
approach is overall challenging given its generally
multilocular nature and extremely viscous content, thus
large bore catheters (14 to 26 French) are preferred.
CT guided procedure is the common approach since
the ileus associated with the condition in most cases
renders US imaging unsuitable.
Pseudoaneurysms of peripancreatic arteries is a
well recognized late complication of SAP being a result
of erosion by pancreatic enzymes. The most commonly
affected arteries are: splenic artery, gastroduodenal
artery, and arteries comprising pancreaticoduodenal
arcades. Rapture of a pseudoaneurysm is life threatening event and carries a mortality rate of approximately 37%. Percutaneous intervention in a form of
embolization can serve as a temporary (till surgery) or
permanent solution.
Complications of severe acute pancreatitis
Elevated intra-abdominal pressure (IAP) with progression to abdominal compartment syndrome (ACS)
has been described in a wide variety of clinical conditions
[79, 80] including SAP [81]. Intra-abdominal hypertension (IAH) may develop due to pancreatic and
retroperitoneal inflammation, paralytic ileus and peripancreatic fluid collections with third-space loss. De
Waele et al. [82] had shown a 51% frequency of IAH
in a group of 44 patients with SAP. This prompts earlier,
more aggressive monitoring of IAP to facilitate the
institution of corrective/preventive measures before
full-blown ACS develops. Percutaneous drainage of
fluid collections represent a less invasive abdominal
decompression option [83], while the definitive treatment for fully manifested ACS is surgical decompression via laparotomy [84, 85].
Conclusions
The majority of patients admitted with acute pancreatitis have a benign course, however approximately
20% will develop SAP with significantly increased
mortality. Supportive care, including fluid management,
analgesia, and nutritional support, ideally via the enteral
route remains the cornerstone of therapy. Repeated
clinical, radiological and biochemical assessment is
47
48
Izakson et al.
essential for the timely diagnosis of pancreatic necrosis
and infection. Patients with confirmed pancreatic
necrosis should receive prophylactic antibiotics. For
biliary pancreatitis, early ERCP should be performed
and infected pancreatic necrosis should be evacuated.
Although the overall incidence of acute pancreatitis
is rising, recent data suggest that the mortality associated with SAP is falling. Large scale trials could help
to further elucidate the pathophysiology and management SAP and further lead to improvements in
outcome.
Conflict of interest
Nothing to declare
References
1. Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J
Med 2006; 354: 2142-2150
2. Bradley EL 3rd. A clinically based classification system for acute
pancreatitis. Summary of the International Symposium on Acute
Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch
Surg 1993; 128: 586-590
3. Delhaye M, Engelholm L, Cremer M. Pancreas divisum:
congenital anatomic variant or anomaly? Contribution of
endoscopic retrograde dorsal pancreatography. Gastroenterology
1985; 89: 951-958
4. Gelrud A, Sheth S, Banerjee S, et al. Analysis of cystic fibrosis
gener product (CFTR) function in patients with pancreas divisum
and recurrent acute pancreatitis. Am J Gastroenteroll 2004; 99:
1557-1562
5. Whitcomb DC. Pancreatitis: acute and chronic. In: Walker WA,
Kleinman RE, Sherman PM, Shneider BL, Sanderson IR (ed).
Pediatric gastrointestinal disease: pathophysiology, diagnosis,
management. B. C. Decker, Hamilton, CA, 2004, p. 15841597
6. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet
2008; 371: 143-152
7. Oiva J, Mustonen H, Kylänpää ML, et al. Patients with acute
pancreatitis complicated by organ failure show highly aberrant
monocyte signaling profiles assessed by phospho-specific flow
cytometry. Crit Care Med 2010; 38: 1702-1708
8. Swensson EE, Maull KI. Clinical significance of elevated serum
and urine amylase levels in patients with appendicitis. Am J Surg
1981; 142: 667-670
9. Sternby B, O’Brien JF, Zinsmeister AR, DiMagno EP. What is
the best biochemical test to diagnose acute pancreatitis? A
prospective clinical study. Mayo Clin Proc 1996; 71: 1138-1144
10. Dholakia K, Pitchumoni CS, Agarwal N. How often are liver
function tests normal in acute biliary pancreatitis? J Clin
Gastroenterol 2004; 38: 81-83
11. Lévy P, Boruchowicz A, Hastier P, et al. Diagnostic criteria in
predicting a biliary origin of acute pancreatitis in the era of
endoscopic ultrasound: multicentre prospective evaluation of
213 patients. Pancreatology 2005; 5: 450-456
12. Romagnuolo J, Currie G. Noninvasive vs. selective invasive biliary
imaging for acute biliary pancreatitis: an economic evaluation by
using decision tree analysis. Gastrointest Endosc 2005; 61: 8697
13. Juneja D, Gopal PB, Ravula M. Scoring systems in acute pancreatitis: which one to use in intensive care units? J Crit Care
2010; 25: 358.39-358.e15
14. Berry AR, Taylor TV, Davies GC. Pulmonary function and fibrinogen metabolism in acute pancreatitis. Br J Surg 1981; 68: 870873
15. Pezzilli R, Billi P, Miniero R, et al. Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity
of acute pancreatitis. Comparison with serum C-reactive protein.
Dig Dis Sci 1995; 40: 2341-2348
16. Kylänpää-Bäck ML, Takala A, Kemppainen EA, et al. Procalcitonin, soluble interleukin-2 receptor, and soluble E-selectin
in predicting the severity of acute pancreatitis. Crit Care Med
2001; 29: 63-69
17. Balthazar EJ. Acute pancreatitis: assessment of severity with
clinical and CT evaluation. Radiology 2002; 223: 603-613
18. Closa D, Bardaji M, Hotter G, et al. Hepatic involvement in
pancreatitis-induced lung damage. Am J Physiol 1996; 270: G6G13
19. Neoptolemos JP, Kemppainen EA, Mayer JM, et al. Early
prediction of severity in acute pancreatitis by urinary trypsinogen
activation peptide: a multicentre study. Lancet 2000; 355: 19551960
20. Tenner S, Fernandez-del Castillo C, Warshaw A, et al. Urinary
trypsinogen activation peptide (TAP) predicts severity in patients
with acute pancreatitis. Int J Pancreatol 1997; 21: 105-110
21. Kemppainen E, Mayer J, Puolakkainen P, Raraty M, Slavin J,
Neoptolemos JP. Plasma trypsinogen activation peptide in
patients with acute pancreatitis. Br J Surg 2001; 88: 679-680
22. Mayer J, Rau B, Schoenberg MH, Beger HG. Mechanism and role
of trypsinogen activation in acute pancreatitis. Hepatogastroenterology 1999; 46: 2757-2763
23. Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute
pancreatitis: value of CT in establishing prognosis. Radiology
1990; 174: 331-336
24. Casas JD, Díaz R, Valderas G, Mariscal A, Cuadras P. Prognostic
value of CT in the early assessment of patients with acute
pancreatitis. AJR Am J Roentgenol 2004; 182: 569-574
25. Banks PA, Freeman ML, Practice Parameters Committee of
the American College of Gastroenterology. Practice guidelines
in acute pancreatitis. Am J Gastroenterol 2006; 101: 23792400
26. Arvanitakis M, Delhaye M, De Maertelaere V, et al. Computed
tomography and magnetic resonance imaging in the assessment
of acute pancreatitis. Gastroenterology 2004; 126: 715-723
27. Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective
assessment of severity, and management of acute pancreatitis.
Santorini consensus conference. Int J Pancreatol 1999; 25:
195-210
28. Kozarek RA. Endoscopic therapy of complete and partial pancreatic duct disruptions. Gastrointest Endosc Clin N Am 1998;
8: 39-53
29. Lankisch PG, Weber-Dany B, Maisonneuve P, Lowenfels AB.
Pancreatic pseudocysts: prognostic factors for their development
and their spontaneous resolution in the setting of acute pancreatitis. Pancreatology 2012; 12: 85-90
30. Perez A, Whang EE, Brooks DC, et al. Is severity of necrotizing
pancreatitis increased in extended necrosis and infected necrosis?
Pancreas 2002; 25: 229-233
31. Gerzof SG, Banks PA, Robbins AH, et al. Early diagnosis of
pancreatic infection by computed tomography-guided aspiration.
Gastroenterology 1987; 93: 1315-1320
New developments in understanding of pathophysiology, diagnosis and treatment of severe acute pancreatitis
32. Oláh A, Belágyi T, Issekutz A, Makay R, Zaborszky A. Value of
procalcitonin quick test in the differentiation between sterile
and infected forms of acute pancreatitis. Hepatogastroenterology
2005; 52: 243-245
33. Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Beger
HG. The potential role of procalcitonin and interleukin 8 in the
prediction of infected necrosis in acute pancreatitis. Gut 1997;
41: 832-840
34. Banks PA, Gerzof SG, Langevin RE, Silverman SG, Sica GT,
Hughes MD. CT-guided aspiration of suspected pancreatic infection: bacteriology and clinical outcome. Int J Pancreatol
1995; 18: 265-270
35. Rau B, Pralle U, Mayer JM, Beger HG. Role of ultrasonographically
guided fine-needle aspiration cytology in the diagnosis of infected
pancreatic necrosis. Br J Surg 1998; 85: 179-184
36. Werner J, Feuerbach S, Uhl W, Büchler MW. Management of
acute pancreatitis: from surgery to interventional intensive care.
Gut 2005; 54: 426-436
37. Gloor B, Müller CA, Worni M, et al. Pancreatic infection in
severe pancreatitis: the role of fungus and multiresistant organisms. Arch Surg 2001; 136: 592-596
38. 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
39. Brown A, Baillargeon JD, Hughes MD, Banks PA. Can fluid
resuscitation prevent pancreatic necrosis in severe acute pancreatitis? Pancreatology 2002; 2: 104-107
40. Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA, James
D, Fossard DP. Controlled trial of urgent endoscopic retrograde
cholangiopancreatography and endoscopic sphincterotomy versus
conservative treatment for acute pancreatitis due to gallstones.
Lancet 1988; 2: 979-983
41. Fan ST, Lai EC, Mok FP, Lo CM, Zheng SS, Wong J. Early
treatment of acute biliary pancreatitis by endoscopic papillotomy.
N Engl J Med 1993; 328: 228-232
42. Fölsch UR, Nitsche R, Lüdtke R, Hilgers RA, Creutzfeldt W.
Early ERCP and papillotomy compared with conservative
treatment for acute biliary pancreatitis. The German Study Group
on Acute Biliary Pancreatitis. N Engl J Med 1997; 336: 237242
43. Miranda CJ, Babu BI, Siriwardena AK. Recombinant human
activated protein C as a disease modifier in severe acute pancreatitis: systematic review of current evidence. Pancreatology 2012;
12: 119-123
44. Lobo DN, Memon MA, Allison SP, Rowlands BJ. Evolution of
nutritional support in acute pancreatitis. Br J Surg 2000; 87:
695-707
45. Buchman AL, Moukarzel AA, Bhuta S, et al. Parenteral nutrition
is associated with intestinal morphologic and functional changes
in humans. JPEN J Parenter Enteral Nutr 1995; 19: 453-460
46. Heinrich S, Schäfer M, Rousson V, Clavien PA. Evidence-based
treatment of acute pancreatitis: a look at established paradigms.
Ann Surg 2006; 243: 154-168
47. Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition
versus enteral nutrition in patients with acute pancreatitis. BMJ
2004; 328: 1407
48. McClave SA, Dryden GW. Issues of nutritional support for the
patient with acute pancreatitis. Semin Gastrointest Dis 2002;
13: 154-160
49. Meier R, Ockenga J, Pertkiewicz M, et al. ESPEN Guidelines on
Enteral Nutrition: Pancreas. Clin Nutr 2006; 25: 275-284
50. Eatock FC, Chong P, Menezes N, et al. A randomized study of
early nasogastric versus nasojejunal feeding in severe acute
pancreatitis. Am J Gastroenterol 2005; 100: 432-439
51. Kumar A, Singh N, Prakash S, Saraya A, Joshi YK. Early enteral
nutrition in severe acute pancreatitis: a prospective randomized
controlled trial comparing nasojejunal and nasogastric routes. J
Clin Gastroenterol 2006; 40: 431-434
52. Petrov MS, Loveday BP, Pylypchuk RD, McIlroy K, Phillips AR,
Windsor JA. Systematic review and meta-analysis of enteral
nutrition formulations in acute pancreatitis. Br J Surg 2009; 96:
1243-1252
53. Davies AR, Morrison SS, Ridley EJ, et al. Nutritional therapy in
patients with acute pancreatitis requiring critical care unit management: a prospective observational study in Australia and
New Zealand. Crit Care Med 2011; 39: 462-468
54. de Smet AM, Kluytmans JA, Cooper BS, et al. Decontamination
of the digestive tract and oropharynx in ICU patients. N Engl J
Med 2009; 360: 20-31
55. Sawa H, Ueda T, Takeyama Y, et al. Treatment outcome of
selective digestive decontamination and enteral nutrition in
patients with severe acute pancreatitis. J Hepatobiliary Pancreat
Surg 2007; 14: 503-508
56. de Jonge E, Schultz MJ, Spanjaard L, et al. Effects of selective
decontamination of digestive tract on mortality and acquisition
of resistant bacteria in intensive care: a randomised controlled
trial. Lancet 2003; 362: 1011-1016
57. Luiten EJ, Hop WC, Lange JF, Bruining HA. Controlled clinical
trial of selective decontamination for the treatment of severe
acute pancreatitis. Ann Surg 1995; 222: 57-65
58. Berzin TM, Rocha FG, Whang EE, Mortele KJ, Ashley SW,
Banks PA. Prevalence of primary fungal infections in necrotizing
pancreatitis. Pancreatology 2007; 7: 63-66
59. Bai Y, Gao J, Zou DW, Li ZS. Prophylactic antibiotics cannot
reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis: evidence from a meta-analysis of randomized
controlled trials. Am J Gastroenterol 2008; 103: 104-110
60. 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: 113-118; discussion 118-120
61. Baron MJ. Pancreatic infections. In: Mandell GL, Douglas RG
(ed). Principles and practice of infectious diseases. Elsevier,
London, 2005, p. 959-966
62. Bassi C, Pederzoli P, Vesentini S, et al. Behavior of antibiotics
during human necrotizing pancreatitis. Antimicrob Agents
Chemother 1994; 38: 830-836
63. Büchler M, Malfertheiner P, Friess H, et al. Human pancreatic
tissue concentration of bactericidal antibiotics. Gastroenterology
1992; 103: 1902-1908
64. Beger HG, Rau B, Isenmann R, Schwarz M, Gansauge F, Poch B.
Antibiotic prophylaxis in severe acute pancreatitis. Pancreatology
2005; 5: 10-19
65. Banks PA. Acute pancreatitis: medical and surgical management.
Am J Gastroenterol 1994; 89: S78-85
66. Rattner DW, Legermate DA, Lee MJ, Mueller PR, Warshaw AL.
Early surgical débridement of symptomatic pancreatic necrosis
is beneficial irrespective of infection. Am J Surg 1992; 163:
105-109; discussion 109-110
67. Bradley EL 3rd, Allen K. A prospective longitudinal study of
observation versus surgical intervention in the management of
necrotizing pancreatitis. Am J Surg 1991; 161: 19-24; discussion
24-25
49
50
Izakson et al.
68. 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
69. Connor S, Raraty MG, Neoptolemos JP, et al. Does infected
pancreatic necrosis require immediate or emergency debridement?
Pancreas 2006; 33: 128-134
70. Beger HG. Operative management of necrotizing pancreatitis –
necrosectomy and continuous closed postoperative lavage of the
lesser sac. Hepatogastroenterology 1991; 38: 129-133
71. Beger HG, Isenmann R. Surgical management of necrotizing
pancreatitis. Surg Clin North Am 1999; 79: 783-800
72. Castellanos G, Piñero A, Serrano A, et al. Translumbar
retroperitoneal endoscopy: an alternative in the follow-up and
management of drained infected pancreatic necrosis. Arch Surg
2005; 140: 952-955
73. Chang YC, Tsai HM, Lin XZ, Chang CH, Chuang JP. No
debridement is necessary for symptomatic or infected acute
necrotizing pancreatitis: delayed, mini-retroperitoneal drainage
for acute necrotizing pancreatitis without debridement and
irrigation. Dig Dis Sci 2006; 51: 1388-1395
74. Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M.
Percutaneous CT-guided catheter drainage of infected acute
necrotizing pancreatitis: techniques and results. AJR Am J
Roentgenol 1998; 170: 969-975
75. van Santvoort HC, Besselink MG, Horvath KD, et al. Videoscopic
assisted retroperitoneal debridement in infected necrotizing
pancreatitis. HPB (Oxford) 2007; 9: 156-159
76. Connor S, Ghaneh P, Raraty M, et al. Minimally invasive retroperitoneal pancreatic necrosectomy. Dig Surg 2003; 20: 270277
77. Besselink MG, de Bruijn MT, Rutten JP, Boermeester MA, Hofker
HS, Gooszen HG. Surgical intervention in patients with
necrotizing pancreatitis. Br J Surg 2006; 93: 593-599
78. Tong Z, Li W, Yu W, et al. Percutaneous catheter drainage for
infective pancreatic necrosis. Is it always the first choice for all
patients? Pancreas 2012; 41: 302-305
79. Burch JM, Moore EE, Moore FA, Franciose R. The abdominal
compartment syndrome. Surg Clin North Am 1996; 76: 833842
80. Eddy VA, Key SP, Morris JA Jr. Abdominal compartment syndrome: etiology, detection, and management. J Tenn Med Assoc
1994; 87: 55-57
81. Uomo G, Miraglia S. Indications for surgery in severe acute pancreatitis. Could it also be a “manometric” question? JOP. J
Pancreas (Online) 2008; 9: 240-243
82. De Waele JJ, Hoste E, Blot SI, Decruyenaere J, Colardyn F. Intraabdominal hypertension in patients with severe acute pancreatitis.
Crit Care 2005; 9: R452-457
83. Reckard JM, Chung MH, Varma MK, Zagorski SM. Management
of intraabdominal hypertension by percutaneous catheter
drainage. J Vasc Interv Radiol 2005; 16: 1019-1021
84. De Waele JJ, Hoste EA, Malbrain ML. Decompressive laparotomy
for abdominal compartment syndrome – a critical analysis. Crit
Care 2006; 10: R51
85. Hunter JD, Damani Z. Intra-abdominal hypertension and the
abdominal compartment syndrome. Anaesthesia 2004; 59: 899907
Progrese în descifrarea fiziopatologiei,
diagnosticului ºi tratamentului
pancreatitei acute severe
Rezumat
Pancreatita acutã severã rãmâne o provocare
clinicã, întrucât creeazã o mare responsabilitate în
privinþa relaþiei dintre morbiditate, mortalitate ºi costuri
impuse de starea pacientului. În general, pancreatita
acutã poate varia în severitate, de la o inflamaþie pancreaticã uºoarã, auto-limitantã, la necroza pancreaticã
cu risc vital. La adulþi, cele mai frecvente cauze ale
pancreatitei sunt litiaza biliarã ºi abuzul de alcool.
Interesul în creºtere pentru noi markeri biologici ºi
posibilitãþile de identificare în timp util a pancreatitei
acute severe subliniazã importanþa clinicã a predicþiei
precoce a severitãþii bolii. Dintre aceºti markeri, IL-6,
IL-10, procalcitonina, peptida activatoare a tripsinogenului sunt cel mai utilizate în practica clinicã. Deºi
toate scorurile prezic cu o mare acurateþe severitatea
ºi evoluþia pancreatitei, scorul SOFA este utilizat cel
mai frecvent. Tratamentul pancreatitei uºoare este mai
ales de susþinere, în timp ce episoadele severe necesitã
ca tratamentul sã fie efectuat de o echipã multidisciplinarã care sã includã gastroenterologi, radiologi intervenþionali, specialiºti în terapie intensivã ºi chirurgi.
Existã unele probleme nerezolvate privind tratamentul,
care includ indicaþia pentru profilaxia cu antibiotice,
calea optimã de administrare a suportului nutritiv, decontaminarea intestinalã selectivã ºi tratamentul chirurgical al þesutului pancreatic infectat. Scopul acestei
prezentãri este de a trece în revistã progresele recente
în domeniul fiziopatologiei, diagnosticului ºi tratamentului
pancreatitei acute severe.
Cuvinte cheie: pancratitã acutã severã, fiziopatologie, diagnostic, tratament