Management of Acute, Severe Pancreatitis Lisa Ferrigno, MD, MPH

Management of Acute, Severe Pancreatitis Lisa Ferrigno, MD, MPH

Management of Acute Pancreatitis: Outline Epidemiology Spectrum of Disease Early management controversies: Nutrition Role of ERCP Antibiotics Surgical management New techniques Prognostication SFGH experience

Emergency surgery for severe pancreatitis Pre 80-Hour Work Week Eat when you can Sleep when you can Don t t operate on the pancreas Post 80-Hour Work Week Eat three square meals a day, high fiber, low fat Sleep 7.5 to 9 hours a night When you can, operate on the pancreas

Age Standardized Incidence rates of the 3 principal types of pancreatitis,, 1994-2001. Frey CF, Zhou H, Harvey DJ, White RH. 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 first-time time acute biliary,, alcoholic, or idiopathic pancreatitis in year 2000 by age. Frey. The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994 2001. Pancreas 2006; 33: 336 44.

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

Percentage of patients with acute biliary,, alcoholic, or idiopathic pancreatitis that died 0 to 91 days after admission. Frey CF, Zhou H, Harvey DJ, White RH. The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994 2001. Pancreas 2006; 33: 336 44.

Multivariate Logistic Analysis of Predictors of Death Within 14 or 91 Days of Hospitalization for First-time time Acute Biliary, Alcoholic, or Idiopathic Pancreatitis Frey CF, Zhou H, Harvey DJ, White RH. The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994 2001. Pancreas 2006; 33: 336 44.

Spectrum of Disease Pancreatitis Interstitial / Edematous 80% Mortality=1% Necrosis 20% Non-infected Mortality=10% Infected necrosis (1-3 weeks) Mortality > 25% Pancreatic abscess (4-8 weeks) Resolving (1-16 weeks) Non-resolving sequestrum, symptomatic (4-12 weeks) Phlegmon = resolving necrosis Hemorrhagic = ischemic Pancreatitis---- specify Necrotizing ----includes peripancreatic necrosis

Sequelae / Complications Pseudocyst Pancreatic ascites Duct disruption Fistula Bleeding

Initial / Early Therapy Fluid resuscitation Monitoring: prognostic criteria helpful, but early course most informative Assess and reassess for ICU admission, transfer NPO** +/- NGT: emesis, nausea, distension Stress ulcer and DVT prophylaxis Glycemic control

Initial / Early Therapy: Special Considerations Nutrition Gallstone pancreatitis: : role of ERCP Surgery: any role early? Use of prophylactic antibiotics

Early Therapy: Nutrition Enteral feeds preferential over parenteral Jejunal feeds do not stimulate pancreas exocrine function (Nathens( Nathens AB. Crit Care Med 2004;32(12):2524 36 36) Facts Early nutrition prudent TPN is not poison, but not as good as enteric feeds Early NJ feeds

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 SchmetaAnalysis: Random effects ects model of risk of infections associated with enteral versus parenteral nutrition 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 Considerations Gastric ileus?? Nausea, emesis, large, fluid filled stomach on XR, CT. Abdominal distension? Abdominal compartment syndrome / htn? Respiratory insufficiency? Fluid overload? Degree of SIRS?

Heyland, Crit Care Med 1998 PN vs Nothing

PN versus nothing Sandstrom et al: randomized TPN vs glucose post-op; op; continued until po intake tolerated Mortality rate threefold higher (p < 0.15) in glucose-treated patients versus TPN-treated patients (n=2 and 6) No differences in other outcomes, including infectious complications Sandstrom. Ann Surg, 1993.

ERCP in Acute Pancreatitis: : CBD Obstruction CBD obstruction: urgent ERC (Nathens( Nathens; Uhl) Neoptolemos: : n=11 with cholangitis complication rate was significantly lower after ERC (15% versus 60%, P 0.003) CBD exploration versus ERCP

ERCP in Non Obstructing Severe Gallstone Pancreatitis Fan et al found a reduction in biliary sepsis in patients with severe biliary AP Meta-analysis analysis by Sharma and Howden,, N=4 randomized trials demonstrated significantly lower morbidity (38.5% versus 25%; P 0.001) and mortality (9.1% versus 5.2%; P 0.05) rates following early ERC compared with interval ERC. Nonobstructing: : controversial, but data supportive of early ERCP in severe AP Diagnosis in question: EUS potentially helpful

ERCP Induced Pancreatitis Increased risk in SOD, if pancreatic duct cannulated (pre-existent existent duct htn), small duct or recurrent attempts at cannulation Overall=5.4%; 30-45% asymptomatic hyperamylasemia

Cholecystectomy after ERC ERC ES versus ERC ES followed by LC in patients with ASA scores I to III If LC was performed within 6 weeks after ES, recurrent biliary symptoms occurred less often within 2 years (47% versus 2%, P 0.0001) Conversion from lap to open chole higher in wait and see group (55% vs 23%) Boerma Lancet 2002

Antibiotic Prophylaxis: Study Designs & Outcomes Heinrich. Ann Surg 2006

Antibiotic Prophylaxis: Meta- Analysis Heinrich. Ann Surg 2006

Antibiotic Prophylaxis: Conclusions Antibiotic prophylaxis for infected necrosis may reduce sepsis and mortality Imipenem may reduce infection of necrosis Use of imipenem for pancreatic necrosis appropriate and recommended

Outcomes for Pancreatitis by Type: Rates of Organ Failure 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). Buchler: Ann Surg, Volume 232(5).November 2000.619-626

Necrotizing Pancreatitis

Surgical management of severe pancreatitis including sterile necrosis Hartwig W.J Hepatobiliary Pancreat Surg 2002:9:429-35 Due to improved intensive care treatment, including prophylactic antibiotics, surgical intervention is usually not indicated in the t early course of severe acute pancreatitis. Surgery is clearly indicated in patients with proven infected necrosis. Patients with sterile necrosis should undergo surgery when there is no clinical improvement within 4 weeks of intensive care treatment. In the majority of patients a single intervention is sufficient. Re-operation is rare even in patients with abscess formation because these can easily be drained interventionally

Necrotizing Pancreatitis: : operative therapy? Bradley (1991): nonsurgical management of sterile necrosis n=11; mortality=0% Alexandre: : 60% mortality with necrosectomy (World J Surg 1981; 5:369-77.) Teerenhovi,, n=84 and Smadja failed to show benefit for necrosis (Br J Surg 1986; 73: 408-10 & Br J Surg 1988; 75: 793-5)

Timing of Surgical Intervention: Mortality by Presence of Organ Failure Timing of Surgical Intervention in Necrotizing Pancreatitis Besselink ARCH SURG/VOL 142 (NO. 12), DEC 2007

Timing of Surgical Intervention Randomization to either early (within 48 72 hours, n =25) or late necrosectomy (more than 12 days, n =15) Indication = MOF with clinical deterioration despite maximal intensive care (NOT proof infection) Late: 3/15 recovered Terminated as OR death = 3.4 for early group Mortality: Early: 56% Late: 27% Mier J Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg. 1997;173:71 75.

Timing and Indications for Operative Intervention Operate only for infected necrosis confirmed by FNA Do not operate right away Exceptions: Compartment syndrome Prolonged course pancreatic necrosis without evidence of infection or improvement

Abdominal Compartment Syndrome: Definition Sustained intra-abdominal abdominal hypertension leading to Local & remote organ failure Hemodynamic compromise Inability to ventilate Oliguria Usually 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: Grading IAP 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

Pancreatitis may require 8-108 liters of resuscitative fluid (or more) in the first 24 hours! Where does all the fluid go?

Right Here!!

Pancreatic Compartment Syndrome

Technique of Debridement Closed cavity Lavage Open abdomen Surgical drainage Pancreatic resection

Initial Operative Approach Midline incision (maintain lateral abd wall for drains, stoma) Full exposure pancreas Check the gallbladder Cholecystectomy / CBD exploration if necessary Drains Extensive necrosectomy CT is roadmap Paracolic gutters Suprapancreatic space Base of mesentery

Operative management of pancreatic necrosis Past Bilateral subcostal incision Wide mobilization of pancreas in lesser sac Cholecystectomy Cholangiogram T-Tube Tube Placement Feeding jejunostomy Marsupialization or wide drainage of pancreatic bed Present Midline incision Necrosectomy though transverse mesocolon to left of middle colic vessels Closed suction drainage of pancreatic bed

Surgical Approach Single necrosectomy with primary abdominal wall closure versus 1-21 takebacks and sump drains probably preferable Cater to patient and expertise of surgeons

SFGH: 94-02 N=21 to OR for necrosis Indications: 1) evidence of pancreatic infection or sepsis (24%), 2) clinical instability (33%) or 3) clinical intransigence, +/- of infected necrosis (43%) Necrotizing pancreatitis: a surgical approach independent of documented infection. HPB 2004,6 (3):161-8

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

SFGH Experience Midline approach Flank laparostomy with large Penrose drains: used as subsequent access Mortality = 14% Necrotizing pancreatitis: a surgical approach independent of documented infection. HPB 2004,6 (3):161-8

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

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

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

Minimally Invasive Approaches Laparoscopic assisted Peroral / endoscopic

A technique for laparoscopic-assisted assisted percutaneous drainage of infected pancreatic necrosis and pancreatic abscess Horvath. Surg Endosc 2001;15:1221-5 Infection documented by fine needle aspiration Percutaneous drains placed If further drainage needed retroperitoneoscopic debridement of necrosectum is performed under direct visualization

A technique for laparoscopic-assisted assisted percutaneous drainage of infected pancreatic necrosis and pancreatic abscess Horvath. Surg Endosc 2001;15:1221-5 Using combination of percutanious drains and post-drain CT scan, ports are placed and retroperitoneoscopic debridement of the necrosectum is performed under direct visualization. A postoperative lavage system is created.

A technique for laparoscopic-assisted assisted percutaneous drainage of infected pancreatic necrosis and pancreatic abscess Horvath. Surg Endosc 2001;15:1221-5 6 patients, worked in 4 No deaths One fistula, self-limited limited One flank hernia Feasible

Case-matched comparison of the retroperitoneal approach with laparotomy for necrotizing pancreatitis. Dutch Acute Pancreatitis Study Group. World J Surg.. 2007;31:1635-42 Case-controlled cohort study of 15 patients Reintervention in 6 patients in both groups MOF in 10 in lap group and 2 in MIS p=.008 6 deaths in lap vs. 1 in MIS p=.080

PANTER Trial Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy.

Peroral / Endoscopic Assisted Necrosectomy

Peroral Endoscopic Drainage/Debridement Debridement of Walled-off Pancreatic Necrosis N=53 Sterile=51%, nonresponders Intervention performed a median of 49 days (range, 20 300 days) after onset median of 3 endoscopic procedures/ patient (range, 1 12) 1 12) Twenty-one patients (40%) required concurrent radiologic-guided guided catheter drainage of associated or subsequent areas of peripancreatic fluid and/or WOPN. Twelve patients (23%) required open operative intervention a median of 47 days (range, 5 540) 5 540) after initial endoscopic drainage/ debridement (persistence of WOPN (n 3), recurrence of a fluid collection (n 2), cutaneous fistula formation (n 2), or technical failure, persistence of pancreatic p pain, colonic obstruction, perforation, and flank abscess (n 1 each)) Successful endoscopic therapy in 43 (81%) and persistence of WOPN in 10 (19%). (median, 178 days) Papachristou. Ann Surg 2007 Jun;245(6):943-51

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

Prognosis Scales: Comparison of Baseline Evaluations Papachristou. Gastroenterol Clin N Am, 2004.

Prognosis Scales: Comparison of Evaluations at 48 Hours Papachristou. Gastroenterol Clin N Am, 2004.

Ongoing 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 pancreatitis in relation to the peak APACHE II score recorded Wilson. Br J Surg, 1990.

Frey, Lancet

Edemetous versus Necrotizing Predictors Buchler: Ann Surg, Volume 232(5).November 2000.619-626

Sterile versus Infected Necrosis Predictors Buchler: Ann Surg, Volume 232(5).November 2000.619-626

Prognostication based on CT findings Maximum Extent of Necrosis According to CT Findings Buchler: Ann Surg, Volume 232(5).November 2000.619-626

Multidisciplinary Approach The repeat CT: coordinated care

Field Surgery in Total War Douglas W. Jolly, 1939 The recovery rate in abdominal injuries depends less on the individual ability of the surgeon than on any other single factor in the forward system. In fact, young, comparatively inexperienced surgeons working well within the five-hour period can usually show far better figures than more practiced surgeons who are condemned to operate on similar injuries further back. An all important factor is the system, not the surgeon.