VIMS Journal: December 2016

Review Article

Management of Acute Pancreatitis: Current Trend

Dr. Gunjan Shoor, Dr. K. A. Mukherjee, Dr. A. K. Saraf

Clinical Significance :
Acute pancreatitis (AP) is one of the mostcommon diseases of the gastrointestinal tract,leading to tremendous emotional, physical, andfinancial human burden[1,2] Yet, no prevalencedata are available from India. Only some idea ofincidence can be obtained from patients admittedin tertiary care centers.
An extensive meta-analysis by Scott Tenner,John Baillie et al published in Americal journalof gastroenterology, June 2013 laid set guidelinesclassifying them to different strength ofrecommendations, which has considerablychanged the local protocols to approach a patientwith acute pancreatitis.

Diagnosis :
The diagnosis of AP is most often establishedby the presence of two of the three followingcriteria:
i) Clinical- abdominal pain consistent with thedisease

A patient with AP typically presents with aconstant severe pain in the epigastric or left upperquadrant. Other characteristics of pain such asradiation to chest, flanks or back are not veryspecific. The pain intensity and location doesnot necessarily with severity. Pain described asdull, colicky, or located in the lower abdominalregion is not consistent with AP and suggests analternative etiology.

ii) Laboratory- serum amylase and/or lipase

Low sensitivity, specificity, and positive andnegative predictive value renders the use ofserum amylase alone not reliable for thediagnosis of AP and serum lipase is preferred[3,4]

iii) Characteristic findings from abdominalimaging (strong recommendation, moderatequality of evidence)

Choice of imaging : CECT provides over 90%sensitivity and specificity for the diagnosis ofAP[5]

Candidates for imaging : Routine use of CECTin patients with AP is not warranted, as thediagnosis is apparent in many patients and mosthave a mild, uncomplicated course. CECT and/or magnetic resonance imaging (MRI) of thepancreas should be reserved for patients in whomthe diagnosis is unclear or who fail to improveclinically within the first 48 - 72 h after hospitaladmission to assess local complications such aspancreatic necrosis [6-8] (strong recommendation,low quality of evidence).

Etiology :
Gallstones and alcohol are the most commoncauses of AP, gallstones being about twice ascommon as alcohol in our population. Othercauses include hypertriglyceridemia,hypercalcemia, postendoscopic retrogradecholangiopancreatography (ERCP) and druginducedpancreatitis, but they are much lesscommon. Microlithiasis is perhaps also fairly common especially in those who present withrecurrent AP[9]. Among toxin-induced pancreatitis,smoking is being increasingly incriminated asan important causative factor[10,11]

Identifying etiology :

1) Transabdominal ultrasound should beperformed in all patients with acutepancreatitis (strong recommendation, lowquality of evidence). Because of the highprevalence and importance of preventingrecurrent disease, abdominal ultrasound toevaluate for cholelithiasis should beperformed on all patients with AP.[12-14].

2) Alcohol-induced pancreatitis often manifestsas a spectrum, ranging from discrete episodesof AP to chronic irreversible silent changes.The diagnosis should not be entertainedunless a person has a history of over 5 yearsof heavy alcohol consumption.[15]

3) Medications, infectious agents, and metaboliccauses such as hypercalcemia andhyperparathyroidism are rare causes, oftenfalsely identified as causing AP.[16,17,18]Although some drugs such as 6-mercaptopurine, azathioprine can clearlycause AP, there are limited data supportingmost medications as causative agents[16]Primary and secondary hypertriglyceridemiacan cause AP; however, these account foronly 1 - 4 % of cases.[16]

4) In the absence of gallstones and / or historyof significant history of alcohol use, Serumtriglycerides should rise above 1,000 mg / dlto be considered the cause of AP.[19,20](conditional recommendation, moderatequality of evidence)

5) In a patient older than 40 years, a pancreatictumor should be considered as a possiblecause of acute pancreatitis. (conditionalrecommendation, low quality of evidence)

6) Idiopathic acute pancreatitis is defined aspancreatitis with no etiology establishedafter initial laboratory (including lipid andcalcium level) and imaging tests(transabdominal ultrasound and CT in theappropriate patient). [21]

7) Patients with idiopathic pancreatitis shouldbe referred to centers of expertise.(conditional recommendation, low qualityof evidence)

8) Endoscopic investigation in patients withacute idiopathic pancreatitis should belimited, as the risks and benefits ofinvestigation in these patients are unclear.(conditional recommendation, low qualityof evidence) [22]

9) Genetic testing may be considered in youngpatients (< 30 years old) if no cause isevident and a family history of pancreaticdisease is present. (conditionalrecommendation, low quality of evidence)[23]

Initial assessment and risk stratification :

1) Hemodynamic status should be assessedimmediately upon presentation andresuscitative measures begun as needed.(strong recommendation, moderate qualityof evidence)

2) Most episodes of AP are mild and selflimiting,needing only brief hospitalization.Mild AP is defined by the absence of organfailure and / or pancreatic necrosis [10,11] By48 h. after admission, these patients typicallywould have substantially improved andbegun feeding.

3) Severe AP occurs in 15-20% of patients[24].Severe AP is defined by the presence ofpersistent (fails to resolve within 48 h) organfailure and / or death [11]. Local complications include peripancreatic fluid collections andpancreatic and peripancreatic necrosis.(sterile or infected)

Definitions of Severity in Acute Pancreatitis: Comparison of Atlanta and Recent Revision

Atlanta criteria (1993) Atlanta Revision (2013)
Mild acute pancreatitis Mild acute pancreatitis
Absence of organ failure Absence of organ failure
Absence of local complications Absence of local complications
Severe acute pancreatitis Moderately Severe acute pancreatitis
Local complications AND / OR Local complications AND / OR
Organ failure Transient organ failure ( < 48 h)
GI bleeding ( > 500 cc/24 hr) Severe acute pancreatitis
Shock – SBP- 90 mm Hg Persistent organ failure > 48 h
PaO 2 - 60 %
Creatinine -2 mg / dl

Patients with organ failure should be admittedto an intensive care unit or intermediary caresetting whenever possible (strongrecommendation, low quality of evidence)
1) Risk assessment should be performed tostratify patients into higher- and lower-riskcategories to assist triage, such as admissionto an intensive care setting (conditionalrecommendation, moderate quality ofevidence)
2) Clinicians have been largely unable to predictwhich patients with AP will develop severedisease. Uniformly, severity scoring systemsare cumbersome, typically require 48 h tobecome accurate [25-27]

Clinical findings associated with a severe coursefor initial risk assessment
Patient Characteristics :

Age > 55 years [24,27]Obesity (BMI > 30 kg / m2) [28]
Altered mental status [29]
Comorbid disease [24]
The systemic inflammatory response syndrome(SIRS) [11,24,30,31]
Presence of > 2 of the following criteria:
- pulse > 90 beats / min
- respirations > 20/min or PaCO2 > 32 mm Hg
- temperature > 38°C or < 36° C
- WBC count > 12,000 or < 4,000 cells / mm3
or > 10 % immature neutrophils (bands)

Laboratory findings :BUN > 20 mg/dl[32]
BUN > 20 mg/dl[32]
Rising BUN [32]
HCT > 44 % [33]
Rising HCT [33]
Elevated creatinine [34]

Radiology findings :
Pleural effusions [35]
Pulmonary infiltrates [24]
Multiple or extensive extrapancreaticcollections[36]

Initial management :

1) Aggressive hydration, defined as 250-500 mlper hour of isotonic crystalloid solutionshould be provided to all patients, unlesscardiovascular and / or renal comorbiditesexist. Early aggressive intravenous hydrationis most beneficial the first 12 - 24 h, andmay have little benefit beyond (strongrecommendation, moderate quality ofevidence).

2) In a patient with severe volume depletion,manifest as hypotension and tachycardia,more rapid repletion (bolus) may be needed(conditional recommendation, moderatequality of evidence).

3) Lactated Ringer's solution may be thepreferred isotonic crystalloid replacementfluid (conditional recommendation, moderatequality of evidence).

4) Fluid requirements should be reassessed atfrequent intervals within 6h of admission andfor the next 24 - 48h. The goal of aggressivehydration should be to decrease the bloodurea nitrogen (strong recommendation,moderate quality of evidence).

Role of ERCP in acute pancreatitis

1) Patients with acute pancreatitis andconcurrent acute cholangitis should undergoERCP within 24 h of admission (strongrecommendation, moderate quality ofevidence) [37]

2) ERCP is not needed in most patients withgallstone pancreatitis who lack laboratoryor clinical evidence of ongoing biliaryobstruction (strong recommendation, lowquality of evidence) [38]

3) In the absence of cholangitis and / orjaundice, MRCP or endoscopic ultrasound(EUS) rather than diagnostic ERCP shouldbe used to screen for choledocholithiasis ifhighly suspected (conditional recommendation,low quality of evidence)[39,40]

4) Pancreatic duct stents [22] and / or postprocedure rectal non steroidal antiinflammatorydrug (NSAID) suppositories,[41]should be utilized to prevent severe post-ERCP pancreatitis in high-risk patients(conditional recommendation, moderatequality of evidence).

The role of antibiotics in acute pancreatitis

1) Infectious complications, both pancreatic(infected necrosis) and extrapancreatic(pneumonia, cholangitis, bacteremia, urinarytract infections, and so on), are a major causeof morbidity and mortality in patients withAP. Many infections are hospital acquiredand may have a major impact on mortality[42]

2) Fever, tachycardia, tachypnea, andleukocytosis associated with SIRS that mayoccur early in the course of AP may beindistinguishable from sepsis syndrome. Thus,When an infection is suspected, antibioticsshould be given while the source of theinfection is being investigated.[24]

3) Antibiotics should be given for anextrapancreatic infection, such as cholangitis,catheter-acquired infections, bacteremia,urinary tract infections, pneumonia (strongrecommendation, high quality of evidence).

4) Routine use of prophylactic antibiotics inpatients with severe acute pancreatitis is notrecommended (strong recommendation,moderate quality of evidence). Although earlyunblinded trials suggested that administrationof antibiotics may prevent infectiouscomplications in patients with sterilenecrosis[43,44] subsequent, better-designed trialshave consistently failed to confirm anadvantage[45,46].

5) The use of antibiotics in patients with sterilenecrosis to prevent the development of infectednecrosis is not recommended (strongrecommendation, moderate quality ofevidence). There is one successful randomizedcontrolled, clinical trial that used selectivedecontamination of the bowel, targeting bothbacteria and fungi, in order to prevent infectednecrosis[47]. Because of the decreasedmorbidity and mortality in this trial in patientswith severe AP who had undergone selectivedecontamination, further study in this area isneeded.

6) Infected necrosis should be considered inpatients with pancreatic or extrapancreaticnecrosis who deteriorate or fail to improveafter 7 - 10 days of hospitalization.

7) In these patients, either initial CT-guided fineneedle aspiration (FNA) for Gram stain andculture to guide use of appropriate antibioticsor empiric use of antibiotics without CT FNAshould be given (strong recommendation, lowquality of evidence).

8) In patients with infected necrosis, antibioticsknown to penetrate pancreatic necrosis, suchas carbapenems, quinolones, andmetronidazole, may be useful in delaying orsometimes totally avoiding intervention, thusdecreasing morbidity and mortality(conditional recommendation, low quality ofevidence).

9) Routine administration of antifungal agentsalong with prophylactic or therapeuticantibiotics is not recommended (conditionalrecommendation, low quality of evidence).

Nutrition in acute pancreatitis
Historically, despite the absence of clinical data,patients with AP were kept NPO (nothing bymouth) to rest the pancreas[48]. The need toplace the pancreas at rest until completeresolution of AP no longer seems imperative.The long-held assumption that the inflamedpancreas requires prolonged rest by fastingdoes not appear to be supported by laboratoryand clinical observation [49]. Clinical andexperimental studies showed that bowel restis associated with intestinal mucosal atrophyand increased infectious complicationsbecause of bacterial translocation from thegut.

1) In mild AP, oral feedings can be startedimmediately if there is no nausea andvomiting, and abdominal pain has resolved(conditional recommendation, moderatequality of evidence). Multiple studies haveshown that patients provided oral feedingearly in the course of AP have a shorterhospital stay, decreased infectiouscomplications, decreased morbidity, anddecreased mortality [50]

2) In mild AP, initiation of feeding with a lowfatsolid diet appears as safe as a clear liquid diet (conditional recommendations, moderatequality of evidence) [51]

3) In severe AP, enteral nutrition is recommendedto prevent infectious complications. Parenteralnutrition should be avoided unless the enteralroute is not available, not tolerated, or notmeeting caloric requirements (strongrecommendation, high quality of evidence).As enteral feeding maintains the gut mucosalbarrier, prevents disruption, and prevents thetranslocation of bacteria that seed pancreaticnecrosis, enteral nutrition may prevent infectednecrosis. [52]

4) Nasogastric delivery and nasojejunal deliveryof enteral feeding appear comparable inefficacy and safety although the use of anasojejunal route has been traditionallypreferred to avoid the gastric phase ofstimulation. (strong recommendation,moderate quality of evidence)[50]

The role of surgery in acute pancreatitis :

1) In patients with mild AP, found to havegallstones in the gallbladder, acholecystectomy should be performed duringthe initial hospitalization to prevent arecurrence of AP (strong recommendation,moderate quality of evidence)[53]

2) In a patient with necrotizing biliary AP, inorder to prevent infection, cholecystectomyis to be deferred until active inflammationsubsides and fluid collections resolve orstabilize (strong recommendation, moderatequality of evidence).

In these patients, cholecystectomy is typicallydelayed until
i) a later time in prolonged hospitalization
ii) as part of the management of the pancreaticnecrosis if present
iii) after discharge [53]

3) The presence of asymptomatic pseudocystsand pancreatic and / or extrapancreaticnecrosis do not warrant intervention,regardless of size, location, and / or extension(strong recommendation, moderate qualityof evidence). Early open debridement forsterile necrosis was abandoned decades agodue to high morbidity and mortality.[48]

4) In stable patients with infected necrosis,surgical, radiologic, and / or endoscopicdrainage should be delayed preferably formore than 4 weeks to allow liquefication ofthe contents and the development of a fibrouswall around the necrosis (walled-off necrosis)(strong recommendation, low quality ofevidence) but unstable patients with infectednecrosis should undergo urgentdebridement[11]. The concept that infectedpancreatic necrosis requires prompt surgicaldebridement has been challenged by multiplereports and case series showing thatantibiotics alone can lead to resolution ofinfection and, in select patients, avoid surgeryaltogether.[11]

5) In symptomatic patients with infectednecrosis, minimally invasive methods ofnecrosectomy are preferred to opennecrosectomy (strong recommendation, lowquality of evidence). Minimally invasivenecrosectomy by endoscopic, radiologic,video-assisted retroperitoneal, laparoscopicapproach, or combination thereof, or opensurgery is recommended once the necrosisis walled-off [54,55]. The concept of step upapproach whereby staged debrimentperformed using minimally invasivetechniques first followed by open approach when required has been widely accepted bysurgeons and gastroenterologists to minimizemorbidity. [54]

Conclusion :
Acute pancreatitis being a common and seriousdisease with its undoubted increasing incidenceover the past decade cannot be dealt withcasually. Established treatment protocols andguidelines such as above, with or without localmodifications for the Indian scenario may helpus providing adequate treatment to the patientand also overcome many long lastingmisconceptions regarding the disease.

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