Pancreatitis. Leigh Ann Mike, Pharm.D., BCPS, CGP Clinical Assistant Professor UW School of Pharmacy. Spring 2014

Transcription

1 Pancreatitis Leigh Ann Mike, Pharm.D., BCPS, CGP Clinical Assistant Professor UW School of Pharmacy Spring 2014

2 Case Study Tina is a 42 year old woman who presents to the Emergency Department with severe epigastric abdominal pain x 24 hours. HPI: The pain started 24 hours before presentation. She describes it as severe, steady, and radiating to her back. She also had several episodes of vomiting. She has experienced similar painful episodes in the past, usually following a heavy meal in the evening, but those episodes usually respond spontaneously within a couple of hours. There was not improvement with this episode, so she sought medical attention. PHM none Medications none Allergies - NKDA

3 Social History 3 children No alcohol No tobacco Vitals Afebrile; BP 115/74 mmhg; HR 104 bpm; RR 22 bpm, shallow breaths PE: Moving uncomfortably on stretcher; skin is warm and diaphoretic; scleral icterus Abdomen soft, mildly distended, marked upper right quadrant and epigastric tenderness to palpation, no masses or organomegaly Stool negative for occult blood Pertinent labs: WBC 16.5 Tbili/dbili 9.2/4.4 mg/dl AST/ALT 78/92 U/L Amylase 1249 IU/L Studies: Plain film abdomen: nonspecific gas pattern; no pneumoperitoneum

4

5 Pancreatic Function Endocrine pancreas Islets of Langerhans Secretion of insulin, glucagon, somatostatin, other polypeptide hormones Exocrine pancreas Water, electrolytes Bicarbonate Digestive enzymes

6

7 Exocrine Pancreatic Function Acinar cells secrete fluid containing water, electrolytes, pancreatic enzymes Ductular cells secrete aqueous bicarbonate solution

8

9 Exocrine Pancreatic Enzymes Proteolytic Trypsinogen Chymotripsinogen Procarboxypeptidase Proelastase Amylolytic Amylase Other Trypsin inhibitor Lipolytic Lipase Procolypase Prophospholipase A2 Carboxylesterase lipase Nucleolytic Ribonuclease Deoxyribonuclease

10 Control of Enzyme Secretion Pancreas under neural and endocrine control Vagus nerve Enteric endocrine system Cholecystokinin Secretin Gastrin

11 Pancreatitis Inflammatory process involving the pancreas Marked by severe abdominal pain Involvement of regional tissues and other organs variable Subtypes Acute Chronic

12 Acute Pancreatitis

13 Epidemiology cases per 100,000 people years 2% patients admitted to hospital 25% will require intensive care ICU length of stay: 9 days Hospital length of stay: 39 days Mortality Mild disease: <1% Severe disease: 20-40% 20% have multi-organ system failure

14 Risk Factors Obstruction Gallstones Tumor Toxins and medications Alcohol Scorpion venom, medications Trauma Abdominal trauma, post-ercp Metabolic Derangements Hypercalcemia, hypertriglyceridemia Infection Vascular Idiopathic

15 Medication-Associated Pancreatitis Many medications implicated Causal association difficult to confirm Exact mechanism unknown

16 Classification Systems Definite, Probable, Possible association Five categories: Ia Ib III II IV Refer to: Badalov N, et al. Clinic Gastroenterol Hepatol 2007;5:648-61

17 Drug-Associated Pancreatitis Classification System Badalov N, et al. Clinic Gastroenterol Hepatol 2007;5:648-61

18 Medications Definitely Associated with Pancreatitis Ksiadzyna D. Eur J Intern Med 22:20-25.

19 Proposed Mechanisms Pancreatic duct constriction Direct cellular toxicity Metabolic effects Accumulation of toxic metabolite or intermediary Arteriolar thrombosis Hypersensitivity reaction

20 More recent agents implicated Boceprevir Incretin-based therapies GLP-1 analogs DPP-4 inhibitors Herbal products Devil s claw (Harpagophytum) Valerian radix

21 Pancreatitis-Related Medications on the Top 200 Drug List* Statins ACE-Inhibitors Oral contraceptives and HRT Diuretics HAART Valproic Acid *2007

22 Medications and Acute Pancreatitis: Summary Rare 0.3 up to 2%; may be higher No distinguishing features Time course highly variable Need high index of suspicion Requires thorough medication history Proving association is difficult Rechallenge indicated? Must search current literature If medication is suspected, it is prudent to discontinue the medication in question

23 Pathogenesis Events that initiate injury Secondary events that establish and perpetuate injury Premature activation of zymogens Ischemia Pancreatic duct obstruction

24 Presentation Abdominal pain Radiation of pain to back Abdominal distension Nausea and vomiting Low-grade fever Hypotension Mental status changes Jaundice

25 Making the Diagnosis Surgical examination Clinical Presentation Signs and symptoms Markers of pancreatic injury Amylase/Lipase Other laboratory changes Imaging studies CT Ultrasound MRI ERCP

26 Predicting Severity Mild vs. severe disease Ranson s criteria 11 variables Monitor at admission and at 48 hours APACHE II More sensitive and specific than Ranson s 14 indicators of physiologic biochemical function Calculate on admission to ICU BISAP 5 variables Use within first 24 hours of admission Atlanta Criteria and others

27 Ranson s Criteria < 3 criteria mortality < 1% 6 criteria mortality 100%

28 BMI normal >30 2

29 BISAP Anand N, et al. Gastroenterol Clin N Am 2012;41:1-8.

30 SIRS Criteria Anand N, et al. Gastroenterol Clin N Am 2012;41:1-8.

31 Severe Acute Pancreatitis Presence of at least 1 organ failure 3 Ranson s criteria 8 APACHE II score criteria Local complications Necrosis Pseudocyst Abscess

32 Pancreatic pseudocyst

33 Management Overview Remove offending agent, if possible Aggressive fluid and electrolyte repletion Management of nausea and vomiting Aggressive pain management Nutrition support Antimicrobials Probiotics Octreotide

34 Gallstone Pancreatitis

35 ERCP

36

37 Fluid Management Aggressive fluid resuscitation Golden hours Monitor hemodynamics, urine output, electrolytes Inadequate resuscitation results in: Hypotension hypoperfusion end organ dysfunction Acute tubular necrosis Pancreatic necrosis

38 Choice of Fluid? Crystalloid or colloid? Which crystalloid? How much? How fast? What/how do you monitor?

39 Pain Relief Meperidine vs. other opioid? Select agent based on safety, efficacy

40 Nutrition Support Bowel rest or feeding? Enteral or parenteral nutrition? Gastric or jejunal feeding? Initiate enteral nutrition after initial resuscitation Use parenteral nutrition when: Attempts at enteral nutrition fail Otherwise contraindicated

41

42 Infection Usually occurs ~10 days after onset of pancreatitis Most common pathogens E. coli Klebsiella Pseudomonas S. aureus

43 Prophylactic Antibiotics Ann Pharmacother Sep;43(9):

44 Prophylactic Antibiotics Routine use of prophylactic antibiotics not recommended Selective decontamination of the GI tract is not recommended If infection is confirmed, antimicrobial therapy should be based on Presentation Culture and sensitivity

45 Prophylactic Probiotics Dutch Acute Pancreatitis Study Group RCT, severe acute pancreatitis Combination of 6 viable bacteria per feeding tube twice daily Lactobacillus spp. Bifidobacterium spp. No difference in infectious complications Bowel ischemia associated with probiotics Lancet Feb 23;371(9613):651-9.

46 Complications of Acute Severe Pancreatitis Local complications Fluid collection Pancreatic necrosis Abscess formation Pseudocyst formation Multi-system organ failure Impaired exocrine and endocrine function Resolves over variable period of time

47 Chronic Pancreatitis

48 Chronic Pancreatitis Syndrome of destructive and inflammatory conditions Exocrine and endocrine insufficiency Related to sequelae of long-standing pancreatic injury Irreversible Fibrosis Increased risk of developing pancreatic cancer

49 Natural Course Progression and endocrine and exocrine insufficiency varies based on etiology Alcoholic CP Exocrine insufficiency develops: ~5 years Severe insufficiency ( burnout ): 10 years Hereditary CP Exocrine insufficiency occurs more frequently and at a younger age than endocrine insufficiency Idiopathic early-onset CP Delay in progression to exocrine insufficiency in compared to alcoholic or late-onset CP Nutr Clin Prac. 2014;29:

50 Etiology Toxic metabolic Ethanol Smoking Chronic hypercalcemia Chronic hypertriglyceridemia Autoimmune Genetic mutations PRSS1 CFTR CTRC SPINK1 Obstructive Pancreas divisum Pancreatic cancer Idiopathic Nutr Clin Prac. 2014;29:

51 Presentation Abdominal pain Exocrine insufficiency Fat maldigestion Steatorrhea Carbohydrate and protein maldigestion Endocrine insufficiency Diabetes Weight loss Jaundice Pseudocysts Pleural effusions Ascites

52 Abdominal Pain Constant or episodic Dull, epigastric, radiating to back Deep-seated Associated with oral intake Positional Unresponsive to medication Accompanied by nausea, vomiting

53 Diagnosis No universally accepted gold standard Based on combination of clinical symptoms and confirmed by morphologic, funtional, and/or histological criteria History of heavy ethanol use and attacks of recurrent upper abdominal pain Classic triad Calcification Steatorrhea Diabetes Imaging Ultrasound CT ERCP Pancreatic Exocrine function testing

54

55 Approach to Management Abstinence from alcohol Relief from pain Analgesics Tramadol Narcotic analgesics Adjuvant therapy Pancreatic enzyme supplements Antioxidants Other strategies Management of malabsorption Pancreatic enzyme replacement Assessment and correction of nutrition deficiencies Maintenance of adequate dietary intake Exogenous insulin

56 Pancreatic Enzyme Replacement Standard of treatment for exocrine insufficiency Aid digestion Alleviate diarrhea and maldigestion Maintain normal nutrition Exogenous pancreatic enzymes Enteric- vs. non-enteric coated preparations Derived from porcine sources Goal: deliver at least 1000 units lipase/kg with each meal 2000 units lipase needed to digest 1 g fat 25K 75K units lipase needed per meal 25K units lipase needed per snack

57 Examples of Pancreatic Enzyme Preparations Enzyme Content (USP) Preparation Dosage Form Lipase Protease Amylase Uncoated Viokace Tablet 10,440 39,150 39,150 20,880 78,300 78,300 Coated Pancreaze DR EC microtablets 4,200 10,000 17,500 10,500 25,000 43,750 Creon DR EC spheres 6,000 19,000 30,000 12,000 38,000 60,000 24,000 76, ,000 Zenpep DR EC beads 5,000 17,000 27,000 10,000 34,000 55,000 15,000 51,000 82,000 20,000 68, ,000 *Not a complete listing of available products*

58 More on Pancreatic Enzymes Products not interchangeable Take with meals or snacks with sufficient liquid Take during and after meals Dose is variable and patient-specific Range: 500-2,500 lipase units/kg/meal Max: 10,000 lipase units/kg/day Alternative regimens: 25K-80K lipase units per meal 20K-40K lipase units per snack lipase units per gram of fat Do not chew or crush EC products Non-EC product must be taken with PPI

59 Adverse Effects of Pancreatic Enzyme Replacements GI complaints Stricture, obstruction Fibrosing colonopathy Allergic-type reactions Hyperuricemia Mucosal irritation

60 Uses for Pancreatic Enzyme Replacements Cystic fibrosis Chronic pancreatitis Pancreatic cancer Chronic exocrine pancreatic insufficiency Full or partial pancreatectomy Unclogging of feeding tube

61 Nutritional Deficiencies Macronutrient deficiencies Micronutrient deficiencies Fat soluble vitamins Vitamin B12, folate Calcium, zinc, copper, magnesium Dietary considerations High calorie diet Reduced fiber intake 6-8 small meals daily g fat per day 1-2 g/kg protein MCTs

62 Prognosis Mortality 50% within years 15-20% die of complications associated with acute attacks Most deaths occur as consequence of Malnutrition Infection Ethanol, narcotic, and tobacco use

63 Concluding Comments Acute pancreatitis Remove offending agent Aggressively manage fluids and electrolytes Treat nausea and vomiting Treat acute pain Provide nutrition support Use antibiotics judiciously Chronic pancreatitis Discontinue alcohol and tobacco use Manage pain Treat malabsorption

64 Case Study 2 PV is a 33 y/o woman transferred to HMC from OSH with shock, severe acute pancreatitis, and acute kidney injury. HPI She had experienced abdominal pain and vomiting x few days which caused her to present to an OSH. She was diagnosed with pancreatitis, was admitted and treated conservatively x 3 days and was discharged. After discharge home, her abdominal pain continued to worsen and she began to vomit again. She was readmitted to OSH ICU. Pertinent findings were elevated blood glucose at 512 mg/dl, elevated lipase at 2444 units/l, CT abdomen showed severe inflammation. In the ICU she received aggressive fluid resuscitation, empiric antibiotics, and was placed on bowel rest. The next day she developed acute respiratory failure and was intubated and placed on mechanical ventilation. Later that day, she developed anuric acute renal failure. At this point she was transferred to HMC ICU for further workup and management.

65 PMH/PSH Hypertriglyceridemia h/o pancreatitis in prior month Hypercholesterolemia DM2, on insulin Obesity Obstructive sleep apnea s/p cholecystectomy Allergies NKDA Meds PTA (doses unknown) Prevacid Metformin Insulin Citalopram Gabapentin Vicodin

66 FH + paternal hypertriglyceridemia, pancreatitis, DM2 SH Former 911 dispatcher, currently unemployed Lives with partner and 7 children Smokes ½ ppd No EtOH x 4 months No recreational drugs

67 Vitals: T 39.4, BP 85/45, HR 150, RR 22, 91% on FiO2 1.0 PE: Sedated, unresponsive. Abd obese, absent bowel tones. Extremities warm, edematous ABG: 7.13/44/ Ca Mg 1.7 PO4 5.4 Amylase/lipase 711/199 Triglyceride 2100 AST 115 ALT 13 AP 76 Bili 2.0 Prot 5.0 Alb 1.9 Ranson s score 6 APACHE II 30