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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_1649_Библиотеки_им_академика_М_И_Перельмана.pdf
Severe Acute Pancreatitis: Since the Classical
91
Crystalloids
In AP hypovolemia is associated with greater risk of tissue hypo perfusion
and the development of MOF. In the initial phase of SAP with SIRS,
replacement with isotonic fluids (Hartman solution) in the first 12-24 h is the
basis of treatment. The fluid regime should be guided by the objective of
achieving 1 mL/K/h of diuresis in the initial phase, if and when organ failure is
not present. It requires broad vigilance, and some patients can require >20
litres intravenously in the first 24 h [64]. Fluid replenishment in SAP is meant
to replace blood volume deficiency, stabilize capillary permeability, maintain
the intestinal wall function, and moderate the inflammatory response [65]. The
success of this therapy is related to improving perfusion of the pancreas [66].
Since hypovolemia is an early trait of AP, the type of solution recommended
for initial fluid management has been theme for debate for many years.
However, fluid replacement without restrictions should be avoided because it
can be damaging. Current recommendations don’t specify a precise strategy
for the administration of fluids in AP [67].
Analgesia
Since pain in AP is intense, opioids are widely used; although there is
some uncertainty about secondary effects through the induction of spasms to
the ampulla of Vater that cause additional pain. Epidural anaesthesia is the
most effective pain control method, and it has a beneficial effect on the course
of the illness in improving pancreatic microcirculation and tissue oxygenation
[68]. However, its use is limited when there are coagulation disturbances and
systemic inflammation [69].
Somatostatin
Somatostatin is a peptide hormone primarily produced in the gastro-
intestinal tract that has an inhibitory effect on gastric emptying, intestinal
motility, and intestinal blood flow. Also, somatostatin strongly inhibits the
production of pancreatic enzymes (Fundamental basis of its use in AP). The
analogue of somatostatin is octreotide [70]. Despite the fact that there have
been clinical and experimental trials with somatostatin and octreotide, the
results have not shown any effect on the course of the illness, seemingly
Alejandra Guillermina Miranda-Díaz et al.
92
because the majority of clinical trials include few patients with SAP [71]. Still,
the biggest and best study performed is a randomized, multi-centric,
prospective study from Germany, with 302 patients with moderate to SAP
from 32 hospitals (Where octreotide or placebo were administered), which had
results that showed no significant differences with respect to mortality [72].
Corticosteroids
Corticosteroids are potent anti-inflammatories used in diverse
inflammatory illnesses. It must be considered that there are reports of cases
where AP is caused by an adverse effect of steroids, without a definitive, well-
established relationship [73]. Circulating pro-inflammatory cytokines take on a
predominant role in the progression of SAP on activating the vascular
endothelium, the migration of leukocytes, and increasing the systemic
capillary permeability [74]. Inhibition of the pro-inflammatory cytokines
through the use of corticosteroids could be beneficial in reducing hospital stay,
the need for surgical intervention, and mortality rate. The actual effects of
corticosteroids are still unclear and these should be investigated in well-
designed studies with adequate time, size, and follow-up [75].
Prophylactic Antibiotics
The role of antibiotics is determined by the presence of infected necrosis.
The use of prophylactic antibiotics has not been demonstrated to offer
beneficial effects in the prevention of infection in pancreatic necrosis,
although this strategy is still widely used in clinical practice. In nearly all trials
published systematic problems exist. Prospective, randomized controlled trials
with the exact definition of the illness that justifies the use of antibiotics are
required. Infections of the pancreas are diagnosed by fine-needle aspiration
(FNA) guided by imaging and through the cultivation of samples obtained
through open surgical intervention [15].
Meropenem
Meropenem 1g is administered by intravenous infusion over 15-30 min,
every 8 h. The infusion bottles and drip regulators should be opaque in color.
Severe Acute Pancreatitis: Since the Classical
93
A minimum administration for 7 days up to a maximum of 21 days is
recommended. The recommended duration is 14 days. Additional well-carried-
out studies that explore the benefits of antibiotic prophylaxis in SAP are
required; taking into account the adverse effects, variable duration, and if the
outcome of the infection is related to the etiology [76].
Drotrecogin Alpha (Activated)
Drotecogin alpha (activated), also known as Xigris, is an analogue of the
glycoprotein of the endogenous human protein C; is produced by recombinant
DNA technology, has 55 kDa of molecular weight, has anti-thrombotic, anti-
inflammatory, and fibrinolytic properties; and is capable of reducing mortality
in SAP and severe sepsis. Plasma concentration levels are 28 ± 9 L/h, and it
has a kinetic biphasic elimination (rapid phase of 13 min and slow of 1.6 h);
and an infusion of 12-30 mg/kg/h is recommended to maintain stable plasma
concentrations 2 h after the onset of infusion. The mechanism by which
Drotrecogin alpha (activated) improves survival in patients with SAP or sepsis
has not yet been entirely determined [77]. This recombinant human protein C
has been the object of controversy since 2001, when it became the first
biological agent approved for the treatment of severe sepsis and septic shock.
The PROWESS study demonstrated an absolute reduction of 6.1% in mortality
at 28 days. This medication was taken off of the market in 2011 despite
observational trials having consistently demonstrated a benefit on mortality. In
an observational study published in 2013, where 6 patients with SAP were
subjected to open necrosectomy for infected pancreatitis every 48 h, plus the
VAC system, plus Drotrecogin alpha (activated) with an infusion of 12-30
µg/Kg/h and a stable plasma concentration 2 h after the onset of the infusion;
an improvement in survival was found in 83.4% compared to 70.9% when
they were subjected to open necrosectomy plus VAC; or 37.5% when only
open necrosectomy was performed [78]. Even though it was a study that
included a small sample size, the results were uplifting. And, in the case that
the product would be available it would be convenient to perform controlled
clinical trials. However, in another study with 6 patients, it was reported that
treatment with Drotecogin alpha (activated) did not alter the course of the
systemic inflammation in SAP [79].
Alejandra Guillermina Miranda-Díaz et al.
94
Recombinant Human Soluble Thrombomodulin
In 2013, a phase III clinical trial reported using recombinant human
soluble thrombomodulin (rhTM) to treat patients with disseminated
intravascular coagulation and severe sepsis. The authors state that treatment
with rhTM can be associated with reduction in hospital mortality in
mechanically ventilated adult patients with disseminated intravascular
coagulation caused by sepsis [80]. In another retrospective study, the authors
investigated the efficacy of rhTM in preventing the development of WONP in
patients with SAP, where they report that it can prevent the progression from
pancreatic necrosis from ischemia to WONP [81]. However, some reports
indicate that rhTM is not effective in actual clinical practice, and others
mention that the administration of rhTM is significantly associated with the
reduction of mortality in high-risk patients [82]. Also, in a systematic review
it’s mentioned that the probability of finding beneficial effects is related to an
increase in baseline risk [83].
SURGICAL TREATMENT
In the management of mild biliary pancreatitis, laparoscopic
cholecystectomy is recommended during the initial hospitalization. A delay of
>4 weeks is associated with recurrent biliary pancreatitis or other
complications. The interventional therapy should be guided by the individual
characteristics of each patient, available resources, and the principle of the
minimally invasive approach [84].
Peritoneal Lavage
The name ‘pancreatic abscess’ has been given to the collection of intra-
abdominal purulent material that generates after a case of AP [85]. In SAP
sterile or infected pancreatic necrosis is produced. The treatment for pancreatic
necrosis has evolved considerably with respect to the moment of intervention
and to the development of treatment alternatives from traditional open
necrosectomy. The traditional surgical approach to infected pancreatic
necrosis is open necrosectomy with the aim of draining all the infected
compartments and completely eliminating all of the necrotic tissue with the
placement of drains for continuous postoperative lavage, closed or with
Severe Acute Pancreatitis: Since the Classical
95
marsupialization. At times, repeat laparotomy is periodically required to assure
complete debridement [86]. The fundamental disadvantage of open
necrosectomy is its association to increased mortality and increase in
perioperative mortality >50% [87].
Management with the ‘Step-Up’ Approach
Among alternatives in the management of SAP suspension of the surgical
intervention as a strategy to facilitate necrosectomy and improve prognostics,
is recommended. In the presence of infected necrosis, it is recommended to
start with the minimally invasive ‘Step-up’ approach. The first step in the
‘Step-up’ approach includes endoscopic or trans-gastric percutaneous
drainage. The preferred approach is through the left retroperitoneum. In the
case that another approach is later required, the minimally invasive
retroperitoneal necrosectomy is recommended. If after 72 h there is no
cumulative clinical improvement or the drainage of liquid proves to be
inadequate, another drainage procedure is recommended. If this is not
possible, or if there is no clinical improvement after another 72 h, video-
assisted retroperitoneal debridement (VARD) with post-operative lavage is
recommended [88]. The benefits to the ‘Step-up’ approach are the avoidance,
when possible, of the open abdomen approach and its associated complications
that cause greater morbidity and mortality [89]. A decrease in the appearance
of diabetes mellitus and incisional hernias are also made relevant by this
method [90]. The ‘Step-up’ approach contributes to economic benefits that can
be substantial in decreasing number of days in hospital (including days spent
in ICU). Despite these aforementioned benefits, complications or death are
reported in 40% of patients [91].
Open Surgical Debridement
When the least invasive method fails or when it’s not considered possible,
then open debridement can be necessary. Traditional open necrosectomy can
be performed by way of the gastro-colic ligament or the transverse mesocolon,
including directly through the stomach. When early open debridement is
performed, pancreatic necrosis is associated with high morbidity and
mortality; thus, it is recommended to wait the longest amount of time possible
of 3-6 weeks. This recommended time permits the demarcation of the necrosis
Alejandra Guillermina Miranda-Díaz et al.
96
of the pancreas from viable tissue, which permits the removal of the necrosis
with little to no bleeding [92]. The open abdomen with early debridement
approach is recommended when there is hemorrhagic pancreatitis or intestinal
ischemia with forthcoming mortality of 100% [86].
Vacuum-Assisted Closure System (VAC)
The VAC system consists of a biocompatible material that is placed in the
abdominal cavity (permeable polyurethane sponge, adhesive plastic film, and
impermeable plastic for a hermetic seal) connected to a sub-atmospheric
suction pump (between 50-150 mmHg), continuous or intermittent, that
provides continuous cleansing of the involved area and accelerates healing
[93]. The usefulness of the VAC system after necrosectomy permits the gentle
suction of the whole abdominal cavity including the pancreatic bed, and
occasionally it is recommended for programmed postoperative lavage. After
percutaneous drainage secondary to necrosectomy, controlled pancreatic
fistula can present, which will close with conservative treatment [94]. In a
recent study, the authors report that in open necrosectomy programmed every
48 h plus placement of the VAC system, in 24 patients with SAP and infected
pancreatic necrosis, they found that the combination was beneficial for
improving survival (70.9%) and the membrane fluidity in erythrocytes;
compared to 16 patients who were subjected only to open necrosectomy
programmed every 48 h, with a survival of 37.5%; although, the programmed
open necrosectomy was effective in decreasing elimination of the products of
peroxidation [95]. Figures 1B, 1C depict images of the removal of necrotic
pancreas through the open abdomen approach. Figures 1D, 1E, and 1F show
the placement of the VAC system in SAP with infected pancreatic necrosis.
Shown, as well, is the evolution in time in patients managed with the open
abdomen approach for SAP with infected pancreatic necrosis.
In conclusion, AP represents a wide range of clinical manifestations and
presentations. It also includes different diagnostic approaches and some recent
treatment alternatives for patients with AP. The management of SAP can be
excellent if all of the clinical parameters to identify sensitive populations who
could benefit from the different types of management, and considering the
individual characteristics of each patient, are controlled.
Severe Acute Pancreatitis: Since the Classical
97
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