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17 Critical Care Management of Severe Acute Pancreatitis
Table 17.7 Summary of meta-analyses evaluating the use if prophylactic antibiotics in acute necrotizing pancreatitis
Decrease in infected
Year 1st author Included trials Total patients
1998 Golub 8 514 Not tested Yes
2001 Sharma 3 160 No Yes
2006 Heinrich 5 288 No Yes
2006 Villatoro 5 294 No Yes
2006 Mazaki 6 329 No No
2006 Xiong 6 338 No No
2007 Dambrauskus 10 1,279 Yes Yes
2007 De Vries 6 397 No No
2008 Hart 7 429 No No
2008 Xu 8 540 Yes No
2008 Bai 8 467 No No
2009 Jafri 8 502 No No
2010 Villatro 7 404 No No
2010 Bai 9 519 No No
2011 Wittau 14 841 No No
Bolded meta-analyses consistently show no mortality benefi t or decrease in the rate of infected necrosis
necrosis Mortality benefi t
193
Location of Enteral Feeding
Nasojejunal feeding has been routinely utilized in patients
with SAP to minimize stimulation of the pancreas. However,
recent comparisons of nasogastric and nasojejunal feeding
in patients with predicted severe acute pancreatitis have
caused this practice to be questioned [ 196 , 197 ].
Unfortunately this work is clouded by the inclusion of
patients who received duodenal feeding in the jejunal feeding group. It is known that duodenal feedings with low-fat
elemental formulas are stimulatory in nature and that feeding 20 cm and further beyond the ligament of Treitz results
in a progressive loss of pancreatic secretory stimulation
[ 198 – 200 ]. Furthermore, the development of functional
(gastric ileus) or mechanical (pancreatic infl ammation and
acute fl uid collections) gastric outlet obstruction is not
uncommon in patients with severe acute pancreatitis and
impacts their ability to tolerate gastric enteral nutrition
regardless of its stimulatory effect [ 200 ]. Considering the
signifi cant improvement in outcomes associated with the
early institution of enteral nutrition, these factors should be
taken into account when considering in which anatomic
location to begin feeding.
Antibiotics and Probiotics in the Prevention of Infected Necrosis
When compared to pancreatic necrosis that remains sterile,
those who develop infected necrosis have a higher rate of
mortality that in some series approaches 69 % [ 18 , 107 ].
While it is generally believed that infected pancreatic
necrosis occurs later in the course of the disease, there is data
that suggests that over a quarter of cases occur within the
fi rst 14 days [ 91 , 193 , 201 ]. Given the excess mortality asso-
ciated with infected pancreatic necrosis strategies that may
prevent its development are extremely important.
Prophylactic Antibiotics
There was great enthusiasm for the use of prophylactic
antibiotics for prevention of the development of infected
pancreatic necrosis based on series published in the 1980s.
However, the data of many of these studies was questioned
given their poorly designed nature. There were several randomized trials in the 1990s that continued to suggest a
positive effect for prophylactic antibiotics [ 202 – 205 ].
Since that time there have been multiple studies that have
repeatedly failed to demonstrate any benefi t of the prophylactic use of antibiotics [ 206 – 209 ]. Multiple meta-analy-
ses, including the well- designed prospective randomized
trials published since 1993, have failed to demonstrate a
mortality benefi t or a consistent decrease in pancreatic
infections (Table 17.7 ) [ 210 – 213 ]. Additionally, early pro-
phylaxis with broad-spectrum antibiotics has been associated with the subsequent development of resistant bacterial
infections (including MRSA and multi-drug-resistant
Pseudomonas and Acinetobacter ) and fungal infections
[
208 , 214 – 216 ]. Although it is possible that a subset of
patients in whom some type of antibiotic prophylaxis may
be of benefi t exists, the current literature does not support
the routine administration of prophylactic antibiotics to
prevent infection of pancreatic necrosis or to improve
outcomes.
194
R. Tesoriero and J.J. Diaz
Probiotics
Some clinical trials have suggested a benefi t of probiotics in critically ill patients, and several studies suggest that they can
enhance intestinal barrier function and stimulate the production
of antimicrobial peptides such as bactericidal/permeabilityincreasing protein [
217 ]. Given the role that intestinal bacterial
translocation is thought to play in the infection of pancreatic and
peripancreatic necrosis, there has been interest in its possible prevention with the use of probiotics [
217 , 218 ]. Multiple early
studies showed improvements in bacterial translocation, infected
pancreatic necrosis, and the need for surgical intervention in
these patients [ 219 ]. These were followed with the publication of
the randomized, double-blind, placebo-controlled PROPATRIA
trial in 2008 which demonstrated no differences in infectious
complications and showed a signifi cantly increased mortality in
patients who were treated with probiotics [ 220 ]. This has resulted
in a decline in interest in the use of probiotics in SAP and in critically ill patients in general. However, there were signifi cant
issues with the design of the trial, including the administration of
the probiotic [ 219 ]. Probiotics in the study were administered as
a bolus directly into the small bowel with a combination of soluble and insoluble fi ber. It has been proposed that the administration of large volumes of soluble fi ber and probiotics into the
small bowel led to local fermentation, stasis, localized acidosis,
and bowel wall injury [ 219 ]. Further analysis suggested that the
main mortality difference in the study appears to be related to
bowel ischemia and transmural necrosis and perforation near the
site of probiotic delivery [ 219 , 221 ]. This coupled with the results
of further RCTs and meta-analysis that demonstrate no adverse
effects of probiotic administration [ 217 ] calls into question the
results of the PROPATRIA trial. Though probiotics cannot be
currently recommended for use in the prevention of infected
necrosis in severe acute pancreatitis, they appear to be safe, and
further clinical trials are warranted.
The Role of Acute Endoscopic Therapy
Gallstones are one of the leading causes of acute pancreatitis
[ 18 , 28 – 30 ]. Generally most of the gallstones that cause
acute pancreatitis pass through into the duodenum [ 222 ]. In
a small number of patients continued choledocholithiasis or
ampullary edema can cause severe acute pancreatitis and/or
cholangitis related to ongoing pancreatic and biliary tree
obstruction. In these cases the use of ERCP and ES to remove
the obstruction could reduce the risk of progression and has
been an area of keen interest.
There have been several studies that demonstrated that the
early (within 24–72 h) routine use of ERCP in acute gallstone pancreatitis reduces the risk of progression to severe
disease and decreases the complication rate in patients with
predicted severe disease, without affecting mortality [ 223 , 224 ].
However, further studies and meta-analysis, while showing a
morbidity and mortality benefi t when ERCP is performed in
the setting of acute cholangitis and biliary obstruction, have
failed to demonstrate any benefi t in progression of disease,
complications, or mortality in their absence [
225 – 227 ].
Ongoing choledocholithiasis and biliary obstruction can be
reliably diagnosed with MRCP and endoscopic ultrasound
(EUS), rendering the use of ERCP unnecessary in establishing the diagnosis [
18 , 59 ]. When coupled with the potential
risk for the development of post-ERCP pancreatitis in
2–10 % of cases [ 18 ], ERCP and ES should not be used in the
absence of demonstrated biliary obstruction or cholangitis to
prevent the progression of disease of severe acute
pancreatitis.
Although up to 40 % of patients with acute pancreatitis
will develop some type of a peripancreatic or pancreatic
fl uid collection, only a small number of patients will go on
to develop a pancreatic fi stula [
228 ]. Although a high-qual-
ity pancreatic protocol CT can suggest the presence of a fi stula in severe acute or non-improving moderate pancreatitis
when acute fl uid collections fail to resolve, MRCP can diagnose and characterize an active leak without the administration of contrast-enhancing agents or invasive tests [
228 – 231 ].
The use of ERCP and placement of pancreatic duct stents
have been shown to be effective as part of a multidisciplinary treatment strategy for pancreatitis-induced pancreatic fi stula and fl uid collections [ 228 ]. However, its early
prophylactic use for the prevention of persistent fl uid collections in the case of acute ductal disruption has not been
investigated.
The routine use of early index hospitalization cholecystectomy has been shown to decrease the incidence of recurrent gallstone pancreatitis in mild cases of disease [ 232 – 236 ].
However, the risk of operating on patients with SAP early in
the disease course, and the technical diffi culties that can
result in increased complications when surgery is delayed 1
or 2 weeks, typically results in delays of cholecystectomy
until later times during prolonged hospitalization, as part of
the surgical management of pancreatic necrosis, or until well
after discharge [ 18 , 237 ]. Unfortunately, these delays put the
patient at an increased risk of recurrent episodes of acute
gallstone pancreatitis while they are recovering from severe
disease [ 237 ]. Although not supported in all reviews [ 235 ],
there have been multiple studies that have demonstrated a
protective effect of ERCP/ES against recurrent pancreatitis
[ 232 , 233 , 237 ]. Given these fi ndings, ERCP/ES should be
considered after the resolution of the initial acute phase of
severe gallstone-induced pancreatitis when cholecystectomy
is going to be signifi cantly delayed.
The third leading cause of acute pancreatitis is idiopathic;
however it is likely that most of these cases are related to
biliary microlithiasis [ 27 , 31 , 32 ]. When considering the data
regarding the prevention of recurrent gallstone pancreatitis
by ERCP/ES, its use should be considered with IP as well.
17 Critical Care Management of Severe Acute Pancreatitis
195
However, when cholecystectomy in IP was performed in the
absence of stones, sludge, or signifi cantly elevated liver
enzymes, it was not preventative of recurrent episodes of
acute pancreatitis [ 238 ]. Given these fi ndings the routine use
of ERCP/ES in the absence of these fi ndings cannot be recommended. The administration of ursodeoxycholic acid
decreases the viscosity of and sediment in bile and has been
shown to decrease recurrence of microlithiasis-induced and
idiopathic pancreatitis [
alternative that may play a role in reduction of symptoms and
recurrence of disease in SAP or in those with IP that do not
fi t criteria for endoscopic therapy.
32 , 33 , 239 ]. It offers a noninvasive
Management of Hypertriglyceridemia- Induced
Pancreatitis
Hypertriglyceridemia is likely the third leading cause of acute
pancreatitis accounting for at least 1–10 % of all cases [ 34 –
37 ]. It is present in more than half of acute pancreatitis cases
in pregnancy, and it likely plays a role in the pathogenesis of
alcohol-induced acute pancreatitis [ 27 , 38 , 39 ]. Serum tri-
glyceride (TG) levels greater than 1,000 mg/dL are generally
considered necessary to cause acute pancreatitis [ 18 , 21 , 27 ],
and acute pancreatitis seen in patients with lower levels
should be investigated for other causes. Secondary causes of
HTG include common endocrine disorders (hypothyroidism,
type II diabetes, Cushing’s syndrome), certain medications
(glucocorticoids, thiazide and loop diuretics, β-adrenergic
blockers, estrogens, cholestyramine, antiretrovirals, and others), alcohol intoxication, chronic kidney disease, nephrotic
syndrome, and acute hepatitis. However, the levels of HTG
needed to produce acute pancreatitis generally require an
underlying familial hyperlipidemic disorder [ 240 , 241 ].
Because secondary causes often play a role in signifi cant elevation of HTG levels in patients with familial hyperlipidemic
disorders, they should be aggressively sought out and treated
as part of the management strategy in HTG-SAP.
The underlying pathophysiologic mechanism of HTG
causing pancreatitis remains unclear, but likely includes
some combination of direct acinar cell and pancreatic capillary injury combined with impaired blood fl ow related to
chylomicron-induced increased viscosity of blood [ 35 ].
Whether or not early treatment changes outcomes is unclear
as severe HTG quickly decreases to levels in which the likelihood of further pancreatic injury is low within 48 h of the
onset of pancreatitis [ 35 , 40 ]. Given the burden of morbidity
and mortality associated with SAP, it seems prudent to rapidly reduce TG levels if they may be inducing ongoing injury
or ischemia.
The mainstays of TG management, dietary modifi cation,
and fi brates have little role in the acute management of
patients with severe acute pancreatitis due to HTG. However,
their institution should be considered when enteral nutrition
is started. Additionally, careful consideration of the type of
enteral nutrition and fat composition is important. In
instances where TPN becomes necessary, the use of intralipids should be avoided or very carefully monitored [ 35 ]. For
patients requiring sedation, agents other than propofol should
be considered.
Both heparin and insulin infusions have been utilized for
reduction of TGs in the treatment of HTG acute pancreatitis
[ 35 , 241 ]. Insulin has been shown to increase the production
and activity of peripheral lipoprotein lipase (LPL) and thus
decrease levels of TGs [ 35 , 241 , 242 ]. While it is unclear
whether the routine use of insulin is helpful, it is particularly
useful in patients with poorly controlled diabetes- precipitated
HTG-AP who present with both HTG and hyperglycemia
[ 243 ]. Heparin infusion increases serum LPL activity result-
ing in an initial decrease in TG. Unfortunately, this effect is
transient due to depletion of LPL on the surface of endothelial cells, and TG levels later rise [ 35 , 241 , 242 ]. This com-
bined with the possibility of hemorrhage into areas of
pancreatic necrosis [ 244 ] has led to a signifi cant decrease in
the use of heparin for HTG management.
There has been enthusiasm for the use of plasmapheresis
to reduce levels of TG. The available studies demonstrate its
ability to decrease serum TG between 49 and 80 % after a
single session [ 245 – 251 ]. This could signifi cantly limit the
ability of HTG to cause further injury in cases of severe
acute pancreatitis. However, the lack of randomized and controlled trials and the unknown optimal start time, duration,
and technique, combined with its lack of availability, limit its
routine use [ 35 ].
Overall Management Strategy in the First Week
Management in the fi rst week of severe acute pancreatitis
includes the completion of goal-oriented resuscitation and
ongoing support of any developing or non-transient organ
failure. Additionally, continued monitoring of IAP is necessary as fl uid shifts and ongoing resuscitation needs may lead
to the delayed development of ACS.
Early enteral nutrition has been the only therapy shown to
consistently improve outcomes and decrease infectious risks
and mortality in pancreatitis and it should be aggressively
started within 48 h of onset of disease. It is unclear whether
the location of delivery of enteral nutrition impacts worsening
of disease, but given that early enteral nutrition is so important, it must be administered someplace where it will be tolerated. While gastric and duodenal feeding is reasonable,
frequent assessments for tolerance are necessary and those
unable to tolerate should have early conversion to jejunal
feeds. Considering the multiple competing interests in these
196
R. Tesoriero and J.J. Diaz
patients, it may be better to just begin with jejunal feeding to
assure adequate delivery early in the disease process.
Antibiotics given prophylactically do not reduce morbidity,
local complications, pancreatic infections, or mortality. Infection
of pancreatic necrosis in the fi rst week, though possible, is
extremely uncommon. However, extra-pancreatic infections are
common, related to ICU management and the infl ammatory
state, and should be investigated aggressively. The use of antibiotics should be reserved for treatment of strongly suspected or
proven extra-pancreatic and pancreatic infections.
Whether there is any role of probiotic in the management
of SAP is unclear, although when administered appropriately
they do not negatively affect outcomes. Their use should be
reserved for clinical trials or if other clear indications for
administration in the critically ill become available.
The acute use of endoscopic therapy with ERCP/ES
should be reserved for cases where cholangitis or ampullary
obstruction is present. As ERCP/ES has been shown to
reduce recurrence of gallstone pancreatitis, it should be considered after the early acute phase of management in patients
with gallstone-induced SAP and in cases of idiopathic pancreatitis when biliary microlithiasis or sludge is identifi ed,
when early cholecystectomy is unable to be performed.
There may be a role for prevention of pancreatic collections,
pseudocysts, and fi stula with early pancreatic stent placement when ductal disruption is diagnosed, but further investigation is needed.
Patients who present with HTG-induced AP should have
potential secondary causes evaluated and managed. The
acute management of HTG-AP patients with type 2 diabetes
and hyperglycemia should include an insulin infusion.
Plasmapheresis should be considered in patients presenting
with severe acute pancreatitis and TG levels >1,000 mg/
dL. In severe cases of HTG-AP, insulin and glucose infusion
should be considered in nondiabetic patients when plasmapheresis is unavailable.
ICU Management After the First Week
(Identifi cation and Management of Local Complications)
After the fi rst week of severe acute pancreatitis patients
often remain critically ill related to persistent organ failure,
need for mechanical ventilation, and renal replacement
therapy support. Management includes ongoing support for
organ failure and continued enteral nutritional support.
Continued vigilance in evaluation for extra-pancreatic
infections associated with ICU care (VAI, CR-BSI, CAUTI)
is necessary as they are common in this patient population
and their development signifi cantly impacts morbidity and
mortality [ 18 ]. It is during this later phase of the disease
process that local complications of acute pancreatitis begin
to occur and contribute to worsened outcomes. Any patient
that has failure to improve or an acute decompensation
after previously improving should be carefully investigated
for the development of infected necrosis or other local
complications.
Management of Sterile and Infected Necrosis
Pancreatic and peripancreatic necrosis occurs in about 15 %
of patients with acute pancreatitis [ 252 ]. However, the likeli-
hood of having pancreatic necrosis goes up signifi cantly in
patients who present with SAP and persistent organ failure.
In the past open necrosectomy was the treatment of choice,
early debridement was considered to be important to improve
outcomes for symptomatic sterile necrosis, and immediate
urgent debridement was felt to be mandatory in cases of
infected necrosis [
retrospective studies have demonstrated that reoperation
rates, morbidity, and mortality are signifi cantly improved
when surgical debridement of infected necrosis can be
delayed to more than 28–30 days [
patients with fulminant severe acute necrotizing pancreatitis
in the fi rst week of disease who are deteriorating despite
maximal medical and intensive care unit therapy are sometimes offered early surgical therapy for sterile necrosis, these
patients’ prognosis remains poor and does not appear to be
improved with surgical intervention, with the possible exception of surgical decompression for ACS [ 7 , 201 , 252 ].
18 , 107 , 253 ]. However, carefully done
201 , 254 , 255 ]. While
Classifi cation and Diagnosis
Acute (peri)pancreatic fl uid collections and acute necrotic
collections may occur early after the development of acute
pancreatitis. However, the appearance of necrosis is often
delayed until several days (up to 5) after presentation [ 13 , 58 ,
59 , 74 , 96 , 252 ]. When present for greater than 4 weeks with-
out resolution, necrosis may organize into a liquid and
necrotic collection, become encapsulated, and is termed
walled-off necrosis (Fig.
(Fig.
17.2 ) are uncommon after acute pancreatitis and are
fl uid collections that persist for more than or develop after
4 weeks, lack signifi cant non-liquid material, and are encapsulated [ 13 , 252 ]. They may cause symptoms related to com-
pression and rarely lead to pseudoaneurysm and hemorrhage
(Fig. 17.3 ).
Contrast-enhanced CT is the standard imaging test to
detect pancreatic and peripancreatic necrosis, determine its
extent, and diagnose local complications. MRI is likely
equivalent to CT for the diagnosis of necrosis, even in the
absence of intravenous contrast. It has the advantage of
improved imaging of the biliary and pancreatic ducts and can
diagnose retained stones and disruptions, as well as avoid
exposure to radiation [ 252 ]. As they are rarely required to
make the diagnosis of acute pancreatitis, and severity can be
17.1 ) [ 13 , 252 ]. Pseudocysts
17 Critical Care Management of Severe Acute Pancreatitis
ab
197
Fig. 17.1 ( a ) Area of walled-off necrosis (WON) characterized by a
thickened organizing wall ( arrows ) surrounding a collection of fl uid
and necrosis that usually occurs more than 4 weeks after the onset of
necrotizing pancreatitis. The presence of gas within the necrosis sug-
a
gests infection, which in this case was previously drained. ( b ) A drain
( arrow ) can be seen traversing the left retroperitoneum and fl ank in
anticipation of a video-assisted retroperitoneal debridement/necrosectomy (VARD)
b
Fig. 17.2 Coronal ( a ) and axial ( b ) views of a large pancreatic
pseudocyst, characterized by a well-formed encapsulated wall ( white
arrows ) surrounding a fl uid collection. They are uncommon after acute
pancreatitis but when present typically develop more than 4 weeks after
the acute episode. They may cause early satiety or nausea related to
compression of the stomach and duodenum and are frequently associated with pain. The proximity to mesenteric, peripancreatic, and splenic
vessels ( black arrows ) may lead to hemorrhage due to compression and
erosion into the vessels
198
ab
R. Tesoriero and J.J. Diaz
Fig. 17.3 Portosplenomesenteric thrombosis secondary to acute pancreatitis. ( a ) Axial view demonstrating nearly occlusive thrombus in the
portal vein ( white arrow ) with extension into the splenic vein ( black arrow ). ( b ) Coronal view of thrombus within the portal vein ( arrow )
predicted equally well with other methods, pancreatic imaging studies should not be routinely utilized in the early phase
of acute pancreatitis. Instead they should be reserved for
making the diagnosis of necrosis and local complications of
severe acute pancreatitis.
Noninfected asymptomatic pancreatic and extra- pancreatic
necrosis does not require intervention and generally resolves
over time [ 18 , 252 ]. Most patients with symptomatic sterile
necrosis (gastric outlet obstruction or biliary obstruction) will
be manageable with supportive care. Although some may
require intervention, they are generally treatable with percutaneous or endoscopic drainage therapies [ 252 ]. In contrast,
chronically infected necrosis may be present in up to 40 % of
patients who are persistently unwell (ongoing inability to
tolerate oral feedings, persistent pain, nausea, or vomiting,and
persistent low-grade fever) [ 254 ]. When any of these develop,
the patient should be carefully investigated with cultures,
radiologic evaluation, and when indicated interventional
evaluation. Often the causative infections will be extrapancreatic and hospital acquired and can have a signifi cant
impact on mortality rates [ 18 ]. Infection should be strongly
considered when there is gas documented in necrotic collections on abdominal imaging, especially when coupled with
the correct clinical scenario.
some type of intervention will be required in nearly all cases
of infected necrosis, although there are reports of successful
treatment with antibiotics alone [ 13 , 252 , 256 , 257 ].
Infection of pancreatic and peripancreatic necrosis is rare
in the fi rst week after the development of acute pancreatitis.
Though its development peaks between the second and
fourth weeks [ 252 ], up to a quarter of all cases of infected
necrosis may occur within 14 days, and infection may occur
at any time during the course of the disease [
193 ]. Diagnosis
of infection should be strongly considered in patients who
develop a worsening or new onset of SIRS, sepsis, or organ
failure after the fi rst week of the disease [ 107 , 121 , 252 ,
258 ]. This is particularly true if the patient was previously
improving and evidences a precipitous decline. Additionally,
Utility of Fine Needle Aspiration
CT-guided fi ne needle aspiration (FNA) to diagnose infected
pancreatitis has been used for the past several decades.
Unfortunately, in up to 25 % of cases FNA may not identify
all of the causative organisms of infection [ 259 ], and the
false-negative rate may be as high as 25 % [ 254 ]. Given the
frequent misleading results, the ability to diagnose most
cases of infected necrosis with clinical scenario and imaging
studies, the potential for treatment with antibiotics alone,
and the opportunity for potentially defi nitive minimally invasive percutaneous or endoscopic drainage, the role of FNA
has been diminishing [ 252 ]. The current role for FNA is
likely limited to cases of suspected necrosis that are not
17 Critical Care Management of Severe Acute Pancreatitis
199
responding to initially selected antibiotic therapy and have
no area amenable to indwelling external drainage.
Antibiotic Therapy for Infected Necrosis
When a patient is suspected of having infected necrosis
and has signifi cant clinical deterioration, antibiotics
should be started without delay in advance of interventional treatment or diagnostic techniques. Few intravenous
antibiotics have the ability to penetrate into pancreatic and
peripancreatic necrosis. Ones that have been shown to
penetrate in clinical trials (carbapenems, high-dose cephalosporins, quinolones, metronidazole) should be selected
for initial empiric therapy [ 18 , 102 , 260 – 262 ]. For patients
that develop infected necrosis later in the course of disease (3–4 weeks) and who have received previous treatment for extra-pancreatic hospital- acquired infections,
coverage for fungal infection, MRSA, and resistant gramnegative organisms should be considered [ 208 , 214 – 216 ].
There is suggestion that infected necrosis can be successfully treated with antibiotics alone or as a bridge to allow
more successful intervention after the demarcation and
liquefaction of necrosis, in stable patients [ 256 , 257 , 263 ,
264 ]. However, patients with suspected infected necrosis
who have severe sepsis, develop clinical deterioration, or
fail to respond to antibiotic therapy require interventional
therapy [ 252 ].
Interventional Treatment for Infected Necrosis
Several series have shown that most cases of infected pancreatic necrosis are amenable to, and nearly 50 % of patients
can be managed with, antibiotics and percutaneous therapy
alone [ 92 , 252 , 265 , 266 ]. There does not appear to be a
worsened mortality when percutaneous therapy is utilized
as primary management, and it has the benefi t of a lower
complication rate than open and other minimally invasive
techniques of management. Percutaneous drainage of pancreatic or peripancreatic necrosis can be achieved via a
transabdominal or retroperitoneal approach (Fig.
17.1b ).
The retroperitoneal approach is preferred in order to avoid
peritoneal contamination, enteric injury and subsequent fi stula, and to facilitate a step-up approach to minimally invasive necrosectomy when indicated [
252 , 266 ]. There is
suggestion that a dedicated interventional radiology team
and a multidisciplinary approach are needed to achieve the
good outcomes seen in several studies as multiple catheters
and frequent catheter exchanges are often necessary [ 265 ,
266 ]. The optimal number and size of catheters remain
unknown, but one study suggested that a single 14-French
drain was adequate for most patients [ 92 ]. When percutane-
ous management alone is unsuccessful, further minimally
invasive techniques are available. These include minimally
access retroperitoneal necrosectomy and endoscopic
necrosectomy.
Minimally invasive retroperitoneal necrosectomy
(MARPN) is generally achieved with video assistance and is
referred to as video-assisted retroperitoneal debridement
(VARD). Several series comparing a step-up approach to
VARD after percutaneous drainage versus open surgical
debridement have shown decreased morbidity, including a
reduction in postoperative organ failure, bleeding events,
enterocutaneous fi stula, enteric perforation, pancreatic fi stula, incisional hernia, and development of pancreatic exocrine and endocrine insuffi ciency [ 92 , 267 , 268 ]. Some
studies suggest a longer hospital course and no difference in
mortality in patients treated with MARPN, while others
demonstrate reductions in both mortality and hospital length
of stay [ 268 ]. Overall the need for open necrosectomy for
infected necrosis can be reduced from more than 90 % to less
than 10 % in centers experienced with percutaneous drainage
and MARPN [
252 ]. Unfortunately, the disadvantage of both
percutaneous drainage and MARPN/VARD is the greater
than 20 % development of pancreaticocutaneous fi stula that
may have diffi culty with closure related to associated disruptions in the pancreatic duct [
252 ].
Various reports of endoscopic drainage for pancreatic
pseudocysts have been described for over a quarter century,
but the fi rst report of endoscopic transluminal necrosectomy
for walled-off necrosis (Fig. 17.1a ) was in 2000 [ 269 ]. The
procedure generally requires endoscopic ultrasound (EUS)
guidance for success and to decrease complications [ 252 ].
When compared to open and MARPN techniques, it has the
potential benefi ts of a decreased infl ammatory response and
a decreased risk of external pancreatic fi stula due to the
nature of its internal drainage. In one series comparing it to
surgical necrosectomy (VARD or open), there was a statistically signifi cant reduction in new post-intervention organ
failure and pancreatic fi stula and a non-statistically signifi cant reduction in mortality [ 270 ]. However, the procedure is
limited by the availability of expertise, the presence of
WON within 2 cm of the gastric or duodenal wall, the size
and complexity of the necrotic fl uid collections, and the frequent need for multiple repeated procedures [ 252 ]. A com-
bination of endoscopic and percutaneous approaches is
often feasible and may decrease the need for multiple interventions, the number of drains required, the number of CT
scans, the time to drain removal, and length of hospitalizations [ 252 ].
Given the overall improvement in morbidity and the
potential improvement in mortality that minimally invasive
techniques offer, open necrosectomy is reserved for cases
that fail these management techniques or when they are not
available. Necrosectomy is performed in an organ-sparing
non-resectional blunt fashion to avoid removal of normal
pancreatic tissue in order to decrease the incidence of pancreatic endocrine and exocrine insuffi ciency and to minimize
the risk of bleeding and fi stula. There are four basic available
200
R. Tesoriero and J.J. Diaz
techniques for management after initial open necrosectomy:
open packing and serial surgical debridement with subsequent closure, open packing and serial dressing changes until
closure by secondary intent, closed packing and drainage,
and closed drainage and continuous lavage [
data suggests that closed packing or continuous lavage is
superior to open techniques and results in a decreased incidence of bleeding events, pancreatic and enteric fi stula, and
ventral incisional hernia [ 9 , 254 ].
9 ]. The available
Disconnected Pancreatic Duct Syndrome and Pancreatic Fistula
Up to 40 % of patients with pancreatic necrosis will have disconnected pancreatic duct syndrome [ 252 ]. These disruptions
can lead to persistent or recurrent pancreatic and peripancreatic fl uid collections and the development of pancreatic ascites or pancreaticopleural fi stula. Additionally they can
contribute to the development of pancreaticocutaneous fi stulas in patients who have undergone interventional drainage.
The diagnosis is made by either direct evaluation of the duct
through ERCP or MRCP, identifi cation of amylase-rich fl uid
collections, or persistent drainage of pancreatic fl uid through
externalized catheters or drains [ 252 , 271 , 272 ]. Though
small bridgeable disruptions may be treated with external
drainage and endoscopic placement of pancreatic stents
across the area of disruption, true disconnected duct syndrome generally requires either internal transmural drainage
into the GI tract or distal pancreatectomy [ 252 ]. Internal
drainage may be achieved either endoscopically or surgically.
Although endoscopic internal drainage is less invasive, it
generally requires that transmural stents be left in place indefinitely as routine removal leads to recurrent pancreatic fl uid
collections in up to 40 % of patients [ 252 , 273 ]. Overall,
endoscopic transmural drainage appears to be most successful when it is accompanied by placement of a bridging transpapillary pancreatic stent [
distal pancreatectomy and internal drainage of either the duct
(Roux-en-Y pancreaticojejunostomy) or walled-off fl uid collection (cyst gastrostomy or cyst jejunostomy). When possible, internal drainage is preferred over distal pancreatectomy
due to decreased operative blood loss and the preservation of
pancreatic parenchyma that may minimize the development
of endocrine and exocrine insuffi ciency.
274 ]. Surgical alternatives include
Gastrointestinal Complications of Severe Acute Pancreatitis
The most common GI manifestations of severe acute pancreatitis, gastric ileus and gastroduodenal outlet obstruction, are
generally self-limited and manageable with nasogastric
drainage, placement of distal naso-enteric feeding access,
and when necessary drainage of pancreatic fl uid
collections.
Colonic complications are rare (3.3 %) in acute pancreatitis, but may occur in up to 15 % of cases of severe acute
pancreatitis [
necrosis, fistula, and stricture, all of which significantly
increase morbidity in this patient population. The development of colonic necrosis is associated with a mortality
of 54 % [
in the fourth week (median: 25 days), there are multiple
reports of its development within the first few days of
severe acute pancreatitis [ 275 , 276 ]. The transverse colon
and splenic flexure are most commonly affected, due to
their proximity to the body and tail of the pancreas. The
most common pathogenic mechanism is thought to be a
combination of (1) hypotension and inflammatoryinduced mesenteric vascular thrombosis with resultant
ischemia at watershed areas and (2) direct retroperitoneal
spread of pancreatic enzymes to the mesocolon and colon
leading to colitis and transmural necrosis [ 276 – 279 ].
Erosion of a pseudocyst or walled-off necrosis into the
colon is a less common etiology [ 280 ]. The diagnosis is
frequently obscured by the ongoing inflammatory process
in fulminant cases of severe acute pancreatitis [ 275 , 281 ].
Patients with worsening clinical status despite aggressive
therapy in the first week of severe acute pancreatitis, and
patients with secondary decompensation thereafter,
should increase clinical suspicion and aggressive investigation with CT and fluoroscopic imaging should follow.
Surgical resection and proximal diversion remains the
mainstay of therapy. Overall, gastrointestinal perforation
and fistula are far more common as a result of interventional therapy and open debridement in the management
of necrosis then as a primary result of severe acute pancreatitis [ 282 ].
275 ]. Complications of the colon include
275 ]. While most cases of necrosis are diagnosed
Vascular Complications of Acute Pancreatitis
Up to 25 % of patients with acute pancreatitis will develop
arterial or venous vascular complications, most occurring in
those with severe disease [ 283 ]. While most cases of venous
thrombosis will have a benign clinical course [ 284 ], the
development of arterial pseudoaneurysm and hemorrhage is
associated with signifi cant morbidity and a 40–90 % mortality [ 285 ].
Portosplenomesenteric Venous Thrombosis
Portosplenomesenteric venous thrombosis (PSMVT) is the
most common vascular manifestation of acute pancreatitis
present in up to 22.6 % of cases [
the absence of necrosis, it occurs in over 50 % of cases
286 ]. Though it is rare in
17 Critical Care Management of Severe Acute Pancreatitis
201
where pancreatic necrosis is present [ 284 ]. Thrombosis is
most common in the splenic vein (86 %), followed by the
portal (36 %) and superior mesenteric veins (27 %), and it
may be present in more than one location (Fig. 17.3 ) [ 284 ].
The occurrence of venous thrombosis in acute pancreatitis
is likely related to a combination of factors, including the
release of procoagulant infl ammatory mediators, vascular
spasm, and compression from (peri)pancreatic edema and
acute fl uid collections [
287 ]. Although PSMVT may be
acutely associated with ischemia and infarction of the
bowel, spleen (which may lead to spontaneous rupture), or
liver and chronically associated with left-sided (sinistral)
portal hypertension, complications related to its presence
are uncommon [ 284 , 286 , 288 ]. Resolution without antico-
agulation is infrequent, and when vascular thrombosis is
complete, delays in anticoagulation after the fi rst week of
diagnosis result in a signifi cant decrease in recanalization
(69 % vs. 25 %) [ 284 , 287 , 289 ]. Despite the low rate of
resolution of PSMVT with delays in treatment, early anticoagulation in critically ill patients with severe acute pancreatitis seems unwise given the risk of hemorrhagic
complications and the infrequent rate of complications due
to thrombosis. However, patients should be evaluated for
treatment at the earliest possible time as the subsequent
development of left-sided port-venous hypertension may
lead to gastric varices and acute GI bleeding events in up to
12.3 % [ 286 ].
Hemorrhage and Pseudoaneurysm
Life-threatening hemorrhage after acute pancreatitis is
rare affecting only 1–3 % of patients [ 9 ]. Massive hemor-
rhage is usually the result of a ruptured arterial pseudoaneurysm (Fig. 17.4 ), but may also occur due to diffuse
bleeding from necrosis, hemorrhage from pseudocysts,
and erosion into small peripancreatic veins (or more rarely,
erosion into the portosplenomesenteric venous system) [ 9 ,
285 , 290 ]. Additionally, some patients develop GI hemor-
rhage related to erosion of acute pancreatitis into the GI
track.
The incidence of pseudoaneurysm formation after acute
pancreatitis has not been well established but is within a
range of 1.3–10 % in most case series [ 285 ]. They occur
either due to arterial wall autodigestion and arteritis from
proteolytic enzymes released during acute pancreatitis or
from direct extension and erosion of pseudocysts into the
arterial tree (Fig. 17.4 ) [ 9 , 285 ]. Pseudocysts are a signifi cant
risk factor as up to 40 % of patients with pseudoaneurysms
have concomitant pseudocysts [ 291 ]. Large pseudoaneu-
rysms are most often the result of pseudocyst erosion into a
vessel with resultant decompression into the pseudocyst
[ 292 , 293 ]. Pseudoaneurysm formation is uncommon prior
to the third week of acute pancreatitis, and patients may not
present with symptoms until years after their acute disease
Fig. 17.4 Development of pseudoaneurysms ( white arrows ) of the
splenic artery with secondary hemorrhage ( black arrows ) into a large
pseudocyst. Most pseudoaneurysms due to severe acute pancreatitis can
be controlled with interventional techniques and embolization with an
overall improvement in outcomes compared to open surgical
management
process is completed [ 285 , 294 , 295 ]. The most commonly
affected mesenteric vessels are the splenic (50 %), gastroduodenal (20–22 %), and pancreaticoduodenal (10–25 %) arteries, and the remainder occur in the superior mesenteric and
hepatic arteries [ 285 , 296 ]. The most useful tool for diagno-
sis is computed tomography angiography (CTA), as it is
rapid and readily available and has a sensitivity of more than
95 % [ 285 ]. However, small pseudoaneurysms may only be
visible on digital subtraction angiography (DSA) and
patients presenting with retroperitoneal, peripancreatic,
intra-abdominal hemorrhage, or gastrointestinal bleeding
with a negative CTA should have further investigation with
DSA [ 285 ].
Rupture of pseudoaneurysms associated with acute
pancreatitis have a high morbidity and a reported historic
mortality between 40 and 90 % [ 285 ]. Mortality rates are
higher when pancreaticoduodenal arteries are involved,
likely related to their rich collateral blood supply and diffi culty with defi nitive catheter-based treatment [ 285 , 297 ]. In
the past, pseudonaeurysms were surgically repaired or
resected with rates of mortality reported between 10 and
50 % [ 285 ]. The availability of interventional catheter-based
techniques has seen an improvement in the outcomes in these
cases and has become the current fi rst-line therapy [
285 ].
These techniques, which may include embolizaition (coil,
balloon, or foam) and covered stent placement, have a success rate of between 80 and 100 % and are associated with a
reduction of mortality to around 10 % [
285 , 298 – 300 ].
Complications of embolization may occur in up to 25 % of
202
R. Tesoriero and J.J. Diaz
patients and include splenic infarction, coil migration, and
intestinal necrosis [
285 , 296 , 299 ]. Recurrent hemorrhage
may occur in approximately 12 % of those who undergo
interventional treatment and 37 % of those who undergo surgical repair [ 296 ]. When it occurs, repeat angiography as
either primary therapy or as a bridge to surgical intervention
is warranted. Occasionally, patients may be too unstable to
pursue angiography, and emergent surgical therapy becomes
necessary. When the appropriate expertise is available, resuscitative endovascular balloon occlusion of the aorta (REBOA)
may be life saving for the patient in extremis from hemorrhage and offers a bridge to either interventional or surgical
therapy [ 301 ].
Strategy for Management After the First Week
Patients with severe acute pancreatitis will continue to
require nutritional support and management of organ failure,
after the fi rst week in the ICU. They should begin to show
gradual resolution in SIRS and recovery of organ dysfunction. However, when a patient fails to improve, is persistently
unwell, or has a clinical decompensation after a period of
improvement, aggressive investigation into the possibility of
a hospital-acquired non-pancreatic infection or a local complication of pancreatitis is imperative. Cultures and investigation to rule out typical non-pancreatic infections should be
performed, and a careful investigation for local complications with a CT of the abdomen and pelvis with oral and IV
contrast should occur. In cases where hemorrhage is suspected, the study should be protocolized as a CTA.
Most cases of symptomatic sterile necrosis can be managed with supportive care. Patients will often require nasogastric decompression and naso-enteric feeding access for
nutritional support. Occasionally percutaneous drainage can
facilitate the resolution of gastroduodenal obstruction, but
should be carefully considered when necrosis is sterile as
secondary infection can occur.
When signifi cant deterioration occurs and there is a strong
clinical suspicion of infected necrosis, broad-spectrum
antibiotics with good pancreatic penetration should be
started without delay for diagnostic studies. Otherwise, antibiotics should be reserved for cases where CT features are
consistent with infected necrosis or cultures from necrosis
are positive. Given the high false-negative rate and imprecision of FNA, its use should be reserved for cases of suspected infected necrosis that are not responding to initially
selected antibiotics and have no areas amenable to drainage.
Infected necrosis with associated fl uid collections or
walled-off necrosis that is not responding to antibiotics
should undergo percutaneous drainage. In general, a left retroperitoneal approach should be utilized, if anatomically
possible, to facilitate a possible step-up approach to a
VARD. Up to 50 % of patients will be manageable with
percutaneous drainage and antibiotics alone. Those who fail
to initially improve with drainage and appropriate antibiotic
therapy should be considered for repeat percutaneous drainage or upsizing of drains. When possible, surgical therapy
should be delayed until the fourth week to decrease morbidity and mortality. Nearly all outcomes appear to be improved
when a minimally invasive approach to debridement (VARD
or endoscopic necrosectomy) is used. Open necrosectomy is
warranted when a minimally invasive approach is not anatomically possible or local expertise is not available, and outcomes appear best with closed rather than open techniques.
Persistent pancreatic and peripancreatic fl uid collections
after the fi rst week or the presence of pancreatic ascites or
pancreaticopleural fi stula should raise the suspicion of disconnected pancreatic duct syndrome. Patients should be
evaluated with either MRCP or ERCP and if diagnosed a
transpapillary pancreatic stent should be considered.
Defi nitive management may require internal drainage or distal pancreatectomy if fl uid collections persist and develop
into a pseudocyst.
The most common gastrointestinal manifestations of
severe acute pancreatitis are gastric ileus and gastroduodenal
outlet obstruction which are generally manageable with supportive care. Colonic complications, while rare, almost
always require surgical intervention. Colonic necrosis and
perforation tend to occur in the fourth week, though they may
develop acutely in the fi rst week of the disease. Patients with
clinical deterioration should undergo CT, but the diagnosis
may be obscured by the local infl ammatory process and
infected necrosis and may require the addition of fl uoroscopic
studies to establish its presence. There should be a strong
clinical suspicion of erosion and colonic peroration in patients
who develop gastrointestinal hemorrhage. Progressive fi brosis and stricture with obstruction tend to occur much later in
the disease process. The mainstay of treatment of all colonic
complications is resection and proximal diversion, though
these cases are often technically challenging related to the
intense local infl ammatory process in the mesentery.
CTs performed to evaluate for local complications should
be carefully scrutinized for vascular complications. PSMVT
is relatively common, and patients should be considered for
treatment with anticoagulation due to the potential for the
subsequent long-term development of sinistral hypertension,
gastric varices, and gastrointestinal hemorrhage. When possible, treatment should be started early in cases of total
occlusion as the rate of recanalization decreased signifi cantly
for delays in treatment. However, many patients with severe
acute pancreatitis will have a signifi cant risk of hemorrhage
early in the disease process. Given the overall low complication rate with PSMVT, a careful risk-benefi t analysis should
occur in each patient, and frequently therapy will need to be
delayed.