Jurnalul de chirurgie

ACUTE PANCREATITIS - THE SEVERE FORM
Ioana Grigoras
Clinica A.T.I. Spitalul “Sf. Spiridon” Iasi
Jurnalul de chirurgie 2005; 1 (1):9-20
Full text: Format PDF

Abstract:
Acute pancreatitis is an acute inflammatory disease. Frequently it is a challenging condition for the surgeon and for the intensive care physician, taking into account that etiology is sometimes obscure, the pathophysiology is complex and incompletely understood, the timing of surgical treatment is still under debate and the general treatment is mostly supportive.

The incidence is about 30-50/100.000/year. In 80% of cases the disease is associated with interstitial edema, mild infiltration with inflammatory cells and intra- or peripancreatic fat necrosis. Evolution is benign and self-limited with proper treatment.

The severe form occurs less frequent (15-20%), results in long lasting hospitalization and is associated with high mortality (30-40%), due to infected necrosis and multiple organ failure.

ETIOLOGY: Alcoholism and biliary disease account for 80% of cases. Rare etiologies of disease include metabolic factors (hypercalcemia, hyperlipoproteinemia, drug ingestion), obstructive factors (abdominal tumors, trauma, endoscopic retrograde cholecistopancreatography, and s.o.), infections (viral, parasitic) and hemodynamic factors (table I).

Table I – Etiologic factors of acute pancreatitis [17]

Metabolic factors	Alcohol abuse Hyperlipoproteinemia Hypercalcemia Drug (furosemide, etacrinic acid, tetracycline, azathioprine, valproic acid, so. Scorpion venom
Mechanical factors	Biliary lithiasis Postoperative (gastric, biliary) Pancreas divisum Duodenal obstruction Pancreatic duct obstruction (pancreatic tumor) Duodenal ulcer Pancreatic trauma Endoscopic retrograde cholangiopancreatography
Infective factors	Mumps Coxackie B virus infection Cytomegakovirus infection Cryptococcus
Idiophathic factors	Familial disease
Pancreatic hypoperfusion	Vascular factors Periarteritis nodosa Atheroembolism Low cardiac output conditions

Postoperative pancreatitis is a complication after major abdominal surgery (abdominal aorta aneurism repair, extensive upper abdominal surgery, hepatic or cardiac transplant, so.). The common pathophysiological mechanism is pancreatic hypoperfusion. This mechanism is important not only for postoperative pancreatitis, but for any form of acute pancreatitis.

The early stages of the disease are accompanied by hypovolemia and consequently by tissue hypoperfusion. No matter the etiology, without early correction pancreatic hypoperfusion will result in aggravation of tissue necrosis and worse prognosis.

CLINICAL COURSE: Acute pancreatitis is not a stable disease, being characterized by time-dependent stages with specific morphologic and clinical patterns (figure 1).

The terminology used to designate these stages is stated in the Ulm classification (table II). Since the consensus Conference in Atlanta (1992) the severe form of acute pancreatitis is defined by the presence of organ dysfunction/failure or by the presence of local complications (table III).

Table II: Terminology (Ulm classification) and frequency of subsets of acute pancreatitis [16]

Interstitial edematous	71%
Necrotizing Sterile Infected	21% 68% 32%
Pancreatic abscess	3%
Postacute pseudocyst	5%

Table III: Definition criteria of severe acute pancreatitis (Consensus Conference Atlanta 1992)

Organ dysfunction/failure
Local complications	Sterile necrosis Infected necrosis Pancreatic abscess Postacute pseudocyst

PATHOPHYSIOLOGY: The initiating event is the premature zymogene activation and the impairment of the exocytosis process with local consequences (ongoing tissue necrosis) and general consequences (systemic inflammatory response). The inflammatory response is locally perpetuated by hypovolemia and pancreatic and intestinal hypoperfusion.

The systemic inflammatory response is present in severe acute pancreatitis and along with tissue hypoperfusion promotes the development of multiple organ dysfunction/failure syndrome (table IV).

The infection of the necrotic tissue occurs usually in the third week of evolution and is caused by enteric bacteria. The intestine plays a major role in the pathophysiology of acute pancreatitis (figure 2).

Table IV: Time course and pathophysiology of acute pancreatitis [16]

Time course	Clinical features	Pathophysiological features
Initially (day 4-10)	Hypovolemia Pulmonary dysfunction/failure Renal dysfunction/failure Gastro-intestinal tract dysfunction/ adynamic ileus Shock	Proinflammatory mediators in peripancreatic fluids and systemic circulation
Later (>2 weeks)	Septic local and systemic complications	Translocation of gram-negative bacteria from the intestine into necrosis

DIAGNOSIS: includes positive diagnosis, assessment of etiology and assessment of severity. Positive diagnosis relays on clinical, laboratory and radiological data. The clinical picture may mimic a lot of abdominal and extraabdominal condition. Most common but unspecific clinical signs are abdominal pain, nausea, vomiting, fever, anxiety and altered mental status, abdominal distension, abdominal tenderness, paralytic ileus, jaundice and clinical sings of hypovolemia.

Laboratory data with diagnostic value include serum amylase, urinary amylase, izoamylase measurements, lipase and other tests. Imaging studies (plain chest and abdominal X ray, abdominal ultrasound and computed tomography) are useful for the positive and the differential diagnosis. Computed tomography is the most useful imaging modality for diagnosis, assessment of severity and follow-up

Assessment of etiology is crucial, if biliary tract disease is the cause. Early endoscopic or surgical treatment may result in better prognosis. Abdominal ultrasound and laboratory data are useful in the diagnosis of biliary disease (table V).

Table V: Diagnostic criteria in biliary pancreatitis (Blamey) [17]

Age >50

Female gender

Laboratory data Alkali phosphatase >300UI TGP>100UI Serum amylase >4000UI/L

Abdominal ultrasound

New treatment strategies in severe acute pancreatitis result in better prognosis if early instituted. Therefore it is crucial along with the positive diagnosis to assess the severity. Early recognition of severe forms, early intensive care admission, monitoring and treatment are accompanied by better results.

Severity scoring systems, biological markers and imaging techniques are used to assess severity. The most used severity scoring systems are Ranson score, Imre score and Apache II score (table VI, VII, VIII).

Many serum and urinary biological markers were used for the assessment of severity, but the most useful are reactive protein C and procalcitonin.

Table VI: Early objective prognostic signs (Ranson score) [17]

At admission or diagnosis	Age >55 years
	White blood cell count >16.000/mm³
	Blood glucose level >200mg%
	Serum lactic dehydrogenase >350IU/l
	Serum GOT>250 u%
During initial 48 hours	Hematocrit decrease >10%
	Blood urea nitrogen increase >5mg%
	Serum calcium level <8mg%
	Arterial PO₂ <60mmHg
	Base deficit >4mEq/l
	Estimated fluid sequestration >6000ml

Table VII: Prognostic criteria in acute pancreatitis (Imre score)

Age >55years

Albuminemia <32g/l

White blood cell count >15.000/mm³

Serum lactic dehydrogenase >600IU

Blood glucose level >10mmol/l

Serum calcium level <2mmol/l

PaO₂ <60mmHg

Blood urea nitrogen >16mmol/l

TREATMENT: should be early instituted, aggressive, nonspecific, supportive and adapted to severity. Due to improvement in intensive care of severe forms, mortality decreased and the survival of fatal cases also increased (usual more than 3 weeks).

Patients with severe form of acute pancreatitis should be admitted to Intensive Care Unit for monitoring and therapy. Standard monitoring includes clinical data (heart rate, blood pressure, ECG, diuresis, central venous pressure, intraabdominal pressure), laboratory data (Hb, Ht, white cell blood count, BUN, creatinine, serum and urinary electrolytes, blood glucose, Ca, Mg, pH) and imaging tests (chest X ray, abdominal ultrasound, computed tomography).

Whenever needed patient monitoring may be supplemented (hemodynamic monitoring with pulmonary artery catheter, noninvasive monitoring of cardiac output, gastric tonometry, coagulation tests, so). Treatment strategy: etiologic treatment (whenever possible), analgesia, supportive therapy of organs and systems and correction of homeostasis, nutritional support, pathogenic treatment, antibiotics and surgical treatment.

Etiologic treatment should be performed early (72 hours of evolution) in case of biliary pancreatitis. Endoscopic sphincterotomy or laparoscopic surgery is preferred.

Analgesia may be provided by parenteral or epidural route and may be patient-controlled.

Hemodynamic support relies on early aggressive volume repletion, followed by inotropic or vasoactive support whenever needed in order to correct tissue perfusion. Metabolic correction aims maintenance of acid-base and blood glucose homeostasis. Ventilatory support is frequently needed and should be instituted early. Ventilatory assistance with lung protective strategies is indicated Renal support includes hemodynamic optimization, rational use of diuretics and early hemodialysis or hemofiltration.

Nutritional support consists of enteral and parenteral nutrition. The enteral route is preferred and should be use as early as possible (oral, nasogastric tube, nasojejunal tube or jejunostomy). Parenteral nutrition is used mainly in early stages when enteral nutrition is difficult due to paralytic ileus and so long it is needed to complete enteral nutrition.

Antibioprofilaxy should be instituted from the beginning in order to prevent necrosis infection. Best options are imipenem and ciprofloxacin. Digestive tract selective decontamination proved to be useful in prevention of infective complications.

Surgical treatment should be avoided in the early stages (at least, the first 3 weeks). Emergency surgery is performed in rare cases for diagnosis (atypical cases, in order to exclude other pathologies) or for hemostasis in case of massive bleeding. Surgical treatment is indicated in case of biliary pancreatitis, severe pancreatitis with sterile necrosis and multiple organ failure and pancreatic infection accompanied by sepsis.

Timing of the surgical procedure is a matter of debate. Avoidance of surgery in the first 3-6 weeks allows better result for excision of necrotic tissue and drainage. Necrosis infection is signaled by clinical signs (fever, increasing white cell blood count, deteriorating organ functions), imaging sings and positive culture of imaging-guided aspirates. Sometimes surgical treatment of severe pancreatitis means repeated surgical procedures, laparostomy, repeated peritoneal lavage and others.

CONCLUSIONS:
- In 80% of cases acute pancreatitis has a benign, self-limited evolution with favorable results of medical treatment.
- In 20% of cases systemic and/or local complication ensue – severe pancreatitis.
- Early recognition of severe forms is the cornerstone of therapeutic success.
- The patient should be admitted to Intensive Care Unit for clinical, laboratory and imaging monitoring and treatment.
- Early and aggressive correction of hypovolemia and hemodynamic optimization are crucial for initial survival.
- Infection prevention and control are crucial for later survival.
- Supportive therapy is essential for prevention/treatment of multiple organ dysfunction/failure syndrome.
- The surgical treatment should be performed in well defined circumstances with proper timing.
- Despite research mortality is still high (30-40%) and increases to 80% in case of infected necrosis.

KEYWORDS: SEVERE PANCREATITIS, APACHE II SCORE, RANSON SCORE, SURGICAL TREATMENT IN PANCREATITIS