management of acute, severe pancreatitis - ucsf cme · management of acute, severe pancreatitis...

Management of Acute, Management of Acute, Severe Severe PancreatitisPancreatitis

Lisa Ferrigno, MD, MPHLisa Ferrigno, MD, MPH

Management of Acute Management of Acute PancreatitisPancreatitis: : OutlineOutline

EpidemiologyEpidemiologySpectrum of DiseaseSpectrum of DiseaseEarly management controversies: Early management controversies:

NutritionNutritionRole of ERCPRole of ERCPAntibioticsAntibiotics

Surgical managementSurgical managementNew techniquesNew techniquesPrognosticationPrognosticationSFGH experienceSFGH experience

Emergency surgery for severe Emergency surgery for severe pancreatitispancreatitis

Pre 80Pre 80--Hour Work WeekHour Work Week

Eat when you canEat when you canSleep when you canSleep when you canDonDon’’t operate on the t operate on the pancreaspancreas

Post 80Post 80--Hour Work Hour Work WeekWeek

Eat three square meals a Eat three square meals a day, high fiber, low fatday, high fiber, low fatSleep 7.5 to 9 hours a Sleep 7.5 to 9 hours a nightnightWhen you can, operate When you can, operate on the pancreason the pancreas

Frey CF, Zhou H, Harvey DJ, White RH. The incidence andcase-fatality rates of acute biliary, alcoholic, and idiopathicpancreatitis in California, 1994–2001. Pancreas 2006; 33: 336–44.

Age Standardized Incidence rates of the 3 principal Age Standardized Incidence rates of the 3 principal types of types of pancreatitispancreatitis, 1994, 1994--2001. 2001.

Frey. The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994–2001. Pancreas 2006; 33: 336–44.

Incidence rates of firstIncidence rates of first--time acute time acute biliarybiliary, alcoholic, , alcoholic, or idiopathic or idiopathic pancreatitispancreatitis

in year 2000 by age. in year 2000 by age.

Acute Acute PancreatitisPancreatitis: Causes: Causes

Frossard. Acute pancreatitis. Lancet 2008; 371: 143-52.


Percentage of patients with acute Percentage of patients with acute biliarybiliary, alcoholic, , alcoholic, or idiopathic or idiopathic pancreatitispancreatitis

that died 0 to 91 days after that died 0 to 91 days after

admission. admission.


Multivariate Logistic Analysis of Predictors of Death Within Multivariate Logistic Analysis of Predictors of Death Within 14 or 91 Days of Hospitalization for First14 or 91 Days of Hospitalization for First--time Acute time Acute BiliaryBiliary, ,

Alcoholic, or Idiopathic Alcoholic, or Idiopathic PancreatitisPancreatitis

Spectrum of DiseaseSpectrum of Disease

Pancreatitis

Interstitial / Edematous 80%

Mortality=1%

Necrosis20%

Non-infectedMortality=10%

Infected necrosis(1-3 weeks)

Mortality > 25%

Pancreatic abscess(4-8 weeks)

Non-resolving sequestrum, symptomatic(4-12 weeks)

Resolving(1-16 weeks) Phlegmon = resolving necrosis

Hemorrhagic = ischemicPancreatitis---- specify Necrotizing ----includes peripancreaticnecrosis

Infected necrosis(1-3 weeks)

Mortality > 25%

Non-resolving sequestrum, symptomatic(4-12 weeks)

Pancreatic abscess(4-8 weeks)

SequelaeSequelae

/ Complications/ Complications

PseudocystPseudocyst

Pancreatic Pancreatic ascitesascites

Duct disruptionDuct disruption

FistulaFistula

BleedingBleeding

Initial / Early TherapyInitial / Early Therapy

Fluid resuscitationFluid resuscitationMonitoring: prognostic criteria helpful, but early Monitoring: prognostic criteria helpful, but early course most informativecourse most informativeAssess and reassess for ICU admission, transferAssess and reassess for ICU admission, transferNPO**NPO**+/+/-- NGT: emesis, nausea, distensionNGT: emesis, nausea, distensionStress ulcer and DVT prophylaxisStress ulcer and DVT prophylaxisGlycemicGlycemic controlcontrol

Initial / Early Therapy: Special Initial / Early Therapy: Special ConsiderationsConsiderations

NutritionNutritionGallstone Gallstone pancreatitispancreatitis: role of ERCP: role of ERCPSurgery: any role early?Surgery: any role early?Use of prophylactic antibioticsUse of prophylactic antibiotics

EnteralEnteral feeds preferential over feeds preferential over parenteralparenteralJejunalJejunal feeds do not stimulate pancreas exocrine feeds do not stimulate pancreas exocrine function (function (NathensNathens AB. AB. CritCrit Care Med Care Med 2004;32(12):25242004;32(12):2524––3636))Early nutrition prudentEarly nutrition prudentTPN is not poison, but not as good as enteric TPN is not poison, but not as good as enteric feedsfeeds

Early NJ feedsEarly NJ feeds

Early Therapy: Nutrition Early Therapy: Nutrition FactsFacts

PN vs Enteral nutrition: Risk of infection, complications other than infection, surgical intervention,and mortality

Marik PE. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ. 2004 Jun 12;328(7453):1407. Epub 2004 Jun 2

Meta Analysis Random effMeta Analysis Random effects model of risk of ects model of risk of infections associated with infections associated with enteralenteral

versus versus parenteralparenteral

nutritionnutritionSchmetaAnalysis:

Marik PE. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ. 2004 Jun 12;328(7453):1407. Epub 2004 Jun 2

Early Therapy: Nutrition Early Therapy: Nutrition ConsiderationsConsiderations

Gastric Gastric ileusileus? Nausea, emesis, large, fluid filled ? Nausea, emesis, large, fluid filled stomach on XR, CT.stomach on XR, CT.Abdominal distension?Abdominal distension?Abdominal compartment syndrome / Abdominal compartment syndrome / htnhtn??Respiratory insufficiency?Respiratory insufficiency?Fluid overload?Fluid overload?Degree of SIRS?Degree of SIRS?

PN PN vsvs

NothingNothing

Heyland, Crit Care Med 1998

PN versus nothingPN versus nothing

SandstromSandstrom et al: randomized TPN et al: randomized TPN vsvs glucose glucose postpost--op; continued until op; continued until popo intake toleratedintake toleratedMortality rate threefold higher (p < 0.15) in Mortality rate threefold higher (p < 0.15) in glucoseglucose--treated patients versus TPNtreated patients versus TPN--treated treated patients (n=2 and 6)patients (n=2 and 6)No differences in other outcomes, including No differences in other outcomes, including infectious complicationsinfectious complications

Sandstrom. Ann Surg, 1993.

ERCP in Acute ERCP in Acute PancreatitisPancreatitis: CBD : CBD ObstructionObstruction

CBD obstruction: urgent ERC (CBD obstruction: urgent ERC (NathensNathens; ; UhlUhl) ) NeoptolemosNeoptolemos: n=11 with : n=11 with cholangitischolangitis

complication rate was significantly lower after ERC complication rate was significantly lower after ERC (15% versus 60%, (15% versus 60%, P P 0.003)0.003)

CBD exploration versus ERCPCBD exploration versus ERCP

ERCP in Non Obstructing Severe ERCP in Non Obstructing Severe Gallstone Gallstone PancreatitisPancreatitis

Fan et al found a reduction in Fan et al found a reduction in biliarybiliary sepsis in patients sepsis in patients with severe with severe biliarybiliary APAPMetaMeta--analysis by Sharma and analysis by Sharma and HowdenHowden, N=4 , N=4 randomized trialsrandomized trials

demonstrated significantly lower morbidity (38.5% versus demonstrated significantly lower morbidity (38.5% versus 25%; 25%; P P 0.001) and mortality (9.1% versus 5.2%; 0.001) and mortality (9.1% versus 5.2%; P P 0.05) rates 0.05) rates following early ERC compared with interval ERC.following early ERC compared with interval ERC.

NonobstructingNonobstructing: controversial, but data supportive of : controversial, but data supportive of early ERCP in severe APearly ERCP in severe APDiagnosis in question: EUS potentially helpfulDiagnosis in question: EUS potentially helpful

ERCP Induced ERCP Induced PancreatitisPancreatitis

Increased risk in SOD, if Increased risk in SOD, if pancreatic duct pancreatic duct cannulatedcannulated (pre(pre--existent existent duct duct htnhtn), small duct or ), small duct or recurrent attempts at recurrent attempts at cannulationcannulationOverall=5.4%; 30Overall=5.4%; 30--45% 45% asymptomatic asymptomatic hyperamylasemiahyperamylasemia

CholecystectomyCholecystectomy

after ERCafter ERC

ERC ES versus ERC ES followed by LC in ERC ES versus ERC ES followed by LC in patients with ASA scores I to III patients with ASA scores I to III If LC was performed within 6 weeks after ES, If LC was performed within 6 weeks after ES, recurrent recurrent biliarybiliary symptoms occurred less often symptoms occurred less often within 2 years (47% versus 2%, within 2 years (47% versus 2%, P P 0.0001)0.0001)Conversion from lap to open Conversion from lap to open cholechole higher in higher in wait and see group (55% wait and see group (55% vsvs 23%)23%)

•Boerma Lancet 2002

Antibiotic Prophylaxis: Study Antibiotic Prophylaxis: Study Designs & OutcomesDesigns & Outcomes

Heinrich. Ann Surg 2006

Antibiotic Prophylaxis: MetaAntibiotic Prophylaxis: Meta-- AnalysisAnalysis

Heinrich. Ann Surg 2006

Antibiotic Prophylaxis: ConclusionsAntibiotic Prophylaxis: Conclusions

Antibiotic prophylaxis for infected necrosis may Antibiotic prophylaxis for infected necrosis may reduce sepsis and mortalityreduce sepsis and mortalityImipenemImipenem may reduce infection of necrosismay reduce infection of necrosisUse of Use of imipenemimipenem for pancreatic necrosis for pancreatic necrosis appropriate and recommendedappropriate and recommended

Outcomes for Outcomes for PancreatitisPancreatitis

by Type: by Type: Rates of Organ FailureRates of Organ Failure

Buchler: Ann Surg, Volume 232(5).November 2000.619-626

death rate was 1.8% (1/56) in patients with sterile necrosis managed without surgery versus 24% (7/29) in patients with infected necrosis (P <.01).

Necrotizing Necrotizing PancreatitisPancreatitis

Surgical management of severe Surgical management of severe pancreatitispancreatitis

including sterile necrosisincluding sterile necrosis

HartwigHartwig

W.J W.J HepatobiliaryHepatobiliary

PancreatPancreat

SurgSurg

2002:9:4292002:9:429--3535

Due to improved intensive care treatment, including prophylacticDue to improved intensive care treatment, including prophylactic antibiotics, surgical intervention is usually not indicated in tantibiotics, surgical intervention is usually not indicated in the he

early course of severe acute early course of severe acute pancreatitispancreatitis..Surgery is clearly indicated in patients with proven infected neSurgery is clearly indicated in patients with proven infected necrosis.crosis.Patients with sterile necrosis should undergo surgery when therePatients with sterile necrosis should undergo surgery when there

is is

no clinical improvement within 4 weeks of intensive care no clinical improvement within 4 weeks of intensive care treatment.treatment.

In the majority of patients a single intervention is sufficient.In the majority of patients a single intervention is sufficient.ReRe--operation is rare even in patients with abscess formation operation is rare even in patients with abscess formation

because these can easily be drained because these can easily be drained interventionallyinterventionally

Necrotizing Necrotizing PancreatitisPancreatitis: operative : operative therapy?therapy?

Bradley (1991): Bradley (1991): nonsurgicalnonsurgical management of management of sterile necrosissterile necrosis

n=11; mortality=0%n=11; mortality=0%

AlexandreAlexandre: 60% mortality with : 60% mortality with necrosectomynecrosectomy(World J (World J SurgSurg 1981; 5:3691981; 5:369--77.)77.)TeerenhoviTeerenhovi, n=84 and , n=84 and SmadjaSmadja failed to show failed to show benefit for necrosis (Br J benefit for necrosis (Br J SurgSurg 1986; 73: 4081986; 73: 408--10 10 & Br J & Br J SurgSurg 1988; 75: 7931988; 75: 793--5)5)

Timing of Surgical Intervention in Necrotizing PancreatitisBesselink ARCH SURG/VOL 142 (NO. 12), DEC 2007

Timing of Surgical Intervention: Timing of Surgical Intervention: Mortality by Presence of Organ Mortality by Presence of Organ

FailureFailure

Timing of Surgical InterventionTiming of Surgical Intervention

Randomization to either early (within 48Randomization to either early (within 48––72 hours, n 72 hours, n =25) or late =25) or late necrosectomynecrosectomy (more than 12 days, n =15)(more than 12 days, n =15)Indication = MOF with clinical deterioration despite Indication = MOF with clinical deterioration despite maximal intensive care (NOT proof infection)maximal intensive care (NOT proof infection)Late: 3/15 recoveredLate: 3/15 recoveredTerminated as OR death = 3.4 for early groupTerminated as OR death = 3.4 for early groupMortality: Mortality:

Early: 56%Early: 56%Late: 27%Late: 27%

Mier J Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg. 1997;173:71–75.

Timing and Indications for Timing and Indications for Operative InterventionOperative Intervention

Operate only for infected necrosis confirmed by Operate only for infected necrosis confirmed by FNAFNADo not operate right awayDo not operate right awayExceptions:Exceptions:

Compartment syndromeCompartment syndromeProlonged course pancreatic necrosis without Prolonged course pancreatic necrosis without evidence of infection or improvementevidence of infection or improvement

Abdominal Compartment Syndrome:Abdominal Compartment Syndrome: DefinitionDefinition

Sustained intraSustained intra--abdominal hypertension leading abdominal hypertension leading to to

Local & remote organ failureLocal & remote organ failureHemodynamicHemodynamic compromisecompromiseInability to ventilateInability to ventilateOliguriaOliguriaUsually requires operative decompressionUsually requires operative decompression

Wittmann DH, Iskander GA. The compartment syndrome of the abdominal cavity: a state of the art review. J Intensive Care Med 2000;15:201-220

Abdominal Compartment Syndrome:Abdominal Compartment Syndrome: Grading IAPGrading IAP

Wittmann DH, Iskander GA. The compartment syndrome of the abdominal cavity: astate of the art review. J Intensive Care Med 2000;15:201-220

PancreatitisPancreatitis

may require 8may require 8--10 liters 10 liters of resuscitative fluid (or more) in of resuscitative fluid (or more) in

the first 24 hours!the first 24 hours!

Where does all the Where does all the fluid go?fluid go?

Right Here!!

Pancreatic Compartment SyndromePancreatic Compartment Syndrome

Technique of DebridementTechnique of Debridement

Closed cavity LavageClosed cavity LavageOpen abdomenOpen abdomenSurgical drainageSurgical drainagePancreatic resectionPancreatic resection

Initial Operative ApproachInitial Operative Approach

Midline incision (maintain lateral Midline incision (maintain lateral abdabd wall for drains, wall for drains, stoma)stoma)Full exposure pancreasFull exposure pancreasCheck the gallbladderCheck the gallbladderCholecystectomyCholecystectomy / CBD exploration if necessary/ CBD exploration if necessaryDrainsDrainsExtensive Extensive necrosectomynecrosectomy–– CT is roadmapCT is roadmap

ParacolicParacolic guttersguttersSuprapancreaticSuprapancreatic spacespaceBase of mesenteryBase of mesentery

Operative management of pancreatic Operative management of pancreatic necrosisnecrosis

PastPast

Bilateral Bilateral subcostalsubcostal incisionincisionWide mobilization of Wide mobilization of pancreas in lesser sacpancreas in lesser sacCholecystectomyCholecystectomyCholangiogramCholangiogramTT--Tube PlacementTube PlacementFeeding Feeding jejunostomyjejunostomyMarsupializationMarsupialization or wide or wide drainage of pancreatic beddrainage of pancreatic bed

PresentPresentMidline incisionMidline incisionNecrosectomyNecrosectomy though though transverse transverse mesocolonmesocolon to left to left of middle colic vesselsof middle colic vesselsClosed suction drainage of Closed suction drainage of pancreatic bedpancreatic bed

Surgical ApproachSurgical Approach

Single Single necrosectomynecrosectomy with primary abdominal with primary abdominal wall closure versus 1wall closure versus 1--2 2 takebackstakebacks and sump and sump drains probably preferabledrains probably preferableCater to patient and expertise of surgeonsCater to patient and expertise of surgeons

SFGH: 94SFGH: 94--0202

N=21 to OR for necrosisN=21 to OR for necrosisIndications: 1) evidence of pancreatic infection Indications: 1) evidence of pancreatic infection or sepsis (24%), 2) clinical instability (33%) or 3) or sepsis (24%), 2) clinical instability (33%) or 3) clinical intransigence, +/clinical intransigence, +/-- of infected necrosis of infected necrosis (43%)(43%)

Necrotizing pancreatitis: a surgical approach independent of documented infection. HPB 2004,6 (3):161 -8

SFGH ExperienceSFGH Experience


SFGH ExperienceSFGH Experience

Midline approachMidline approachFlank Flank laparostomylaparostomy with large Penrose drains: with large Penrose drains: used as subsequent accessused as subsequent accessMortality = 14%Mortality = 14%


SFGH Experience: ComplicationsSFGH Experience: Complications


SFGH Experience: ComparisonSFGH Experience: Comparison


Minimally Invasive ApproachesMinimally Invasive Approaches

Laparoscopic assistedLaparoscopic assistedPeroralPeroral / / endoscopicendoscopic

A technique for laparoscopicA technique for laparoscopic--assisted assisted percutaneouspercutaneous drainage of infected pancreatic necrosis and drainage of infected pancreatic necrosis and

pancreatic abscesspancreatic abscess Horvath. Horvath. SurgSurg

EndoscEndosc

2001;15:12212001;15:1221--55

Infection documented by fine needle aspirationInfection documented by fine needle aspirationPercutaneousPercutaneous drains placeddrains placedIf further drainage needed If further drainage needed retroperitoneoscopicretroperitoneoscopicdebridementdebridement of of necrosectumnecrosectum is performed under is performed under direct visualizationdirect visualization



EndoscEndosc

2001;15:12212001;15:1221--55

Using combination of Using combination of percutaniouspercutanious drains and drains and postpost--drain CT scan, ports are placed and drain CT scan, ports are placed and retroperitoneoscopicretroperitoneoscopic debridementdebridement of the of the necrosectumnecrosectum is performed under direct is performed under direct visualization.visualization.A postoperative A postoperative lavagelavage system is created.system is created.



EndoscEndosc

2001;15:12212001;15:1221--55

6 patients, worked in 46 patients, worked in 4No deathsNo deathsOne fistula, selfOne fistula, self--limitedlimitedOne flank herniaOne flank herniaFeasible Feasible

CaseCase--matched comparison of the retroperitoneal matched comparison of the retroperitoneal approach with approach with laparotomylaparotomy

for necrotizing for necrotizing

pancreatitispancreatitis.. Dutch Acute Dutch Acute PancreatitisPancreatitis

Study Group.Study Group. World J World J SurgSurg. 2007;31:1635. 2007;31:1635--4242

CaseCase--controlled cohort study of 15 patientscontrolled cohort study of 15 patientsReinterventionReintervention in 6 patients in both groupsin 6 patients in both groupsMOF in 10 in lap group and 2 in MIS p=.008MOF in 10 in lap group and 2 in MIS p=.0086 deaths in lap vs. 1 in MIS p=.0806 deaths in lap vs. 1 in MIS p=.080

PANTER TrialPANTER Trial

Minimally invasive 'stepMinimally invasive 'step--up approach' up approach' versus maximal versus maximal necrosectomynecrosectomy in patients in patients with acute with acute necrotisingnecrotising pancreatitispancreatitis

group A) minimally invasive 'stepgroup A) minimally invasive 'step--up approach' up approach' starting with drainage followed, if necessary, by starting with drainage followed, if necessary, by videoscopicvideoscopic assisted retroperitoneal assisted retroperitoneal debridementdebridement(VARD) or group B) maximal (VARD) or group B) maximal necrosectomynecrosectomy by by laparotomylaparotomy. .

PeroralPeroral

/ / EndoscopicEndoscopic

Assisted Assisted NecrosectomyNecrosectomy

PeroralPeroral

EndoscopicEndoscopic

Drainage/Drainage/DebridementDebridement

of of WalledWalled--off Pancreatic Necrosisoff Pancreatic Necrosis

N=53 N=53 Sterile=51%, Sterile=51%, nonrespondersnonrespondersIntervention performed a median of 49 days (range, 20Intervention performed a median of 49 days (range, 20––300 days) after onset 300 days) after onset median of 3 median of 3 endoscopicendoscopic procedures/ patient (range, 1procedures/ patient (range, 1––12) 12) TwentyTwenty--one patients (40%) required concurrent one patients (40%) required concurrent radiologicradiologic--guided catheter guided catheter drainage of associated or subsequent areas of drainage of associated or subsequent areas of peripancreaticperipancreatic fluid and/or fluid and/or WOPN.WOPN.Twelve patients (23%) required open operative intervention a medTwelve patients (23%) required open operative intervention a median of 47 ian of 47 days (range, 5days (range, 5––540) after initial 540) after initial endoscopicendoscopic drainage/ drainage/ debridementdebridement(persistence of WOPN (n 3), recurrence of a fluid collection (n(persistence of WOPN (n 3), recurrence of a fluid collection (n 2), 2), cutaneouscutaneousfistula formation (n 2), or technical failure, persistence of pfistula formation (n 2), or technical failure, persistence of pancreatic pain, ancreatic pain, colonic obstruction, perforation, and flank abscess (n 1 each))colonic obstruction, perforation, and flank abscess (n 1 each))Successful Successful endoscopicendoscopic therapy in 43 (81%) and persistence of WOPN in 10 therapy in 43 (81%) and persistence of WOPN in 10 (19%). (median, 178 days) (19%). (median, 178 days)

Papachristou. Ann Surg 2007 Jun;245(6):943-51

PrognosticationPrognostication

APACHE-O: additional point for BMI between 25-30; 2 points if >30

Prognosis Scales: Comparison of Prognosis Scales: Comparison of Baseline EvaluationsBaseline Evaluations

Papachristou. Gastroenterol Clin N Am, 2004.

Prognosis Scales: Comparison of Prognosis Scales: Comparison of Evaluations at 48 HoursEvaluations at 48 Hours

Papachristou. Gastroenterol Clin N Am, 2004.

Ongoing APACHE AssessmentOngoing APACHE Assessment

Mean daily APACHE II scores by outcome in 119 patients with an uncomplicated course (- . - . -), 26 patients with a complicated course (----) and 12 patients with a fatal outcome (-).

Wilson. Br J Surg, 1990.

Incidence of death and morbidity from acute Incidence of death and morbidity from acute pancreatitispancreatitis

in relation to the peak APACHE II in relation to the peak APACHE II

score recordedscore recorded

Wilson. Br J Surg, 1990.

Frey, Lancet

EdemetousEdemetous

versus Necrotizing versus Necrotizing PredictorsPredictors


Sterile versus Infected Necrosis Sterile versus Infected Necrosis PredictorsPredictors


Prognostication based on CT Prognostication based on CT findingsfindings


Maximum Extent of Necrosis According to CT Findings

Multidisciplinary ApproachMultidisciplinary Approach The repeat CT: coordinated careThe repeat CT: coordinated care

Field Surgery in Total WarField Surgery in Total War Douglas W. Jolly, 1939Douglas W. Jolly, 1939

The recovery rate in abdominal injuries depends less The recovery rate in abdominal injuries depends less on the individual ability of the surgeon than on any on the individual ability of the surgeon than on any other single factor in the forward system. In fact, other single factor in the forward system. In fact, young, comparatively inexperienced surgeons young, comparatively inexperienced surgeons working well within the fiveworking well within the five--hour period can usually hour period can usually show far better figures than more practiced show far better figures than more practiced surgeons who are condemned to operate on similar surgeons who are condemned to operate on similar injuries further back. injuries further back. An all important factor is An all important factor is the system, not the surgeon.the system, not the surgeon.

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