M INISTRY OF EDUCATION AND TRAININGM INISTRY OF DEFENCE 108 IN STITU TE OF C LINI C A L MEDI C A L AN D P HA R MAC EU TI CA L SCI EN C ES - DO THANH HOA STUDYING CLINICAL, SUBCLINICAL CHARACTERISTICS AND EFFECTIVENESS OF PLASMA REPLACEMENT THERAPY IN TREATING ACUTE PANCREATITIS DUE TO HYPERTRIGLYCERIDEMIA Speciality: Anes thesia and Critical Care Code: 62.72.33.01 ABSTRACT OF MEDICAL PHD THESIS Hanoi – 2020 THE THESIS WAS DONE IN:108 INSTITUTE OF CLINICAL MEDICA L AND PHA RMACEUTICAL SCIENCES Supervisor: Ass Prof PhD Le Thi Viet Hoa Prof PhD Nguyen Gia Binh Reviewer: This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: National Library of Vietnam Library of 108 Institute of Clinica l Medica l and Pharmaceutical Sciences BACKGROUND AND OBJECTIVES Acute pancreatitis (AP) is a sudden onset of pancreatic parenchyma with a mild to a severe course of the disease The consequences may be local lesions, which may cause systemic inflammatory response syndrome and multiple organ failure AP is the leading cause of gastrointestinal diseases requiring hospitalization and 21st in the list of diagnoses requiring hospitalization The mechanism of AP due to hypertriglyceridemia is thought to be due to the hydrolysis of triglyceride-rich lipoproteins, releasing large amounts of free fatty acids, thereby damaging vascular endothelium and pancreatic islet cells This damage causes ischemia, cytotoxicity, acidosis due to anaerobic metabolism The treatment of AP due to hypertriglyceridemia, in addition to general procedures, recently, many studies have demonstrated that plasma exchange (PEX) is a more practical option to lower triglyceride (TG) levels rapidly over a short time This therapeutic is also reducing the length of stay in the hospital and improve patient outcomes To add the scientific basis to evaluate the effectiveness of PEX in the treatment of AP due to hypertriglyceridemia, we conducted the subject: “Studying clinical, subclinical characteristics and effectiveness of plasma replacement therapy in treating acute pancreatitis due to hypertriglyceridemia" with the following objectives: Determining clinical features, subclinical, and severity of acute pancreatitis due to hypertriglyceridemia 2 Evaluation of the therapeutic effect and undesirable effects of plasma replacement therapy on patients with acute pancreatitis due to hypertriglyceridemia CHAPTER OVERVIEW 1.1 Hypertriglyceridemic pancreatitis 1.1.1 Metabolic Disorders Hypertriglyceridemia is determined by fasting serum TG level > 150 mg/dL (1.7 mmol/l) TG were classified based on the following level: Mild (serum TG levels of 150 to 199 mg/dL , or 1.7 to 2.2 mmol/l) Moderate (200 to 999 mg/dL, or 2.3 to 11.2 mmol/l) Severe (1000 to 1999 mg/dL, or 11.3 to 2.5 mmol/l) Very severe (≥2000 mg/dL, or > 22.6 mmol/l) 1.1.3 The pathogenesis of acute pancreatitis due to hypertriglyceridemia The pathogenesis of AP with increased TG is not clear Recent studies have found that AP due to elevated TG through free fatty acid (FFA) accumulation, activates an inflammatory response, microcirculation disorders, calcium, oxidative stress Hypertriglyceridemic pancreatitis has two main mechanisms: chylomicrons formation and breakdown of TG into free fatty acid in pancreas 1.1.4 Diagnosis of AP cause by hypertriglyceridemia a Diagnosis of AP AP is diagnosed according to the Atlanta classification, which requires that two or more of the following criteria: (1) abdominal pain suggestive of pancreatitis (i.e., epigastric abdominal pain may spread to the back); (2) serum amylase or lipase level greater than three times the upper normal value; (3) characteristic imaging findings on CT, MRI or ultrasound + Ultrasound: Full or partial enlargement of the pancreas (head, body, or tail), the ambiguous contour of the pancreas, irregular echo density, reduced volume, or mixed echoes may have peritoneal fluid and abdominal cavity + Computerized tomography: Enlarged or normal pancreas, irregular edges, may have necrotic foci, indicating the degree of damage around the pancreas and away from the pancreas b Diagnosis of AP cause by hypertriglyceridemia The diagnosis of AP hypertriglyceridemia is determined when clinical and subclinical manifestations of AP are combined with serum TG concentrations > 1000 mg/dL To diagnose AP due to hypertriglyceridemia, necessary to exclude other AP causes: stones, worms Figure 1.2: Mechanisms involved in the pathophysiology of hypertriglyceridemic pancreatitis (Source: Pretis N et al, United European gastroenterology journal) 1.1.5 Criteria for grading the severity of AP * Revised Atlanta Classification for AP * Clinical signs of severe AP * Prognostic signs on laboratory tests and imaging * The scales to assess prognosis in acute pancreatitis:  Ranson's criteria is one of the first scoring systems used to assess prognosis in AP  Glasgow-Imrie Criteria for Severity of AP  APACHE II score: if ≥ points is severe  The SOFA (Sequential Organ Failure Assessment) score  Balthazar computed tomography severity index 1.2 Hypertriglyceridemia-induced acute pancreatitis treatment 1.2.1 General treatment for acute pancreatitis a Basic resuscitation and medical treatment - Rapid isotonic infusion 1-2 liters in the first 1-2 hours, then maintain 250-300 ml / kg / 24 hours - Respiratory: provide oxygen to SpO2> 95% - Pain relief: NSAIDS or Opi (do not use morphine) - Antibiotics: when there was evidence of infection - Nourishment: intravenously for 24-48 hours, then feed by mouth gradually - Reducing secretion: PPI, sandosatin b Other interventions - Continuous dialysis: when AP was severe, multi-organ failure - Abdominal drainage through the skin: when there was an abdominal fluid in the abdomen c Treatment of the cause 1.2 Treatment for increased triglycerides The recommendations are agreed that the rapid reduction of TG level is key in the treatment Following The American Society for Apheresis (ASFA) guidelines: PEX for severe hypertriglyceridemic pancreatitis as 1C grade recommended, PEX in prophylaxis hypertriglyceridemic pancreatitis as 2C grade recommended 1.3 Therapeutic plasma exchange for hypertriglyceridemia induced acute pancreatitis 1.3.1 Technical principles of plasma exchange Plasma exchange conducted bypassing the blood through an extracellular membrane with a pore size of 0.2 - 0.6 micron (plasma separation filter) - this procedure which allowing plasma proteins to pass through but retain blood cells There are many types of filters: cellulose, polyethylene, polypropylene, and polyvinylchloride 1.3.2 Indication For plasma exchange according to The American Society for Apheresis (2010), the main indications include: - Metabolic disease and kidney disease - Hematological pathology - Neuropathy - Acute pancreatitis due to hypertriglyceridemia - Hypercholesterolemia, Hemolytic uremic syndrome, Druginduced thrombosis (ticlopidine/clopidogrel), systemic lupus erythematosus, multiple myeloma with increased blood viscosity or with acute renal failure 1.3.3 Accidents and unwanted effects - Complications not related to alternative fluids - Complications related to non-plasma replacement fluids - Other complications 1.3.4 Plasma exchange for treatment of AP due to hypertriglyceridemia The beneficial effect of PEX is the rapid elimination of TG and chylomicron from circulation The level of lowering TG after several hours is equivalent to dropping in a few days when using the drug Besides, PEX can improve the prognosis of AP by eliminating pro-inflammatory factors and cytokines The data show that PEX in AP patients with hypertriglyceridemia sooner gives better results Numerous studies show that PEX is an effective treatment to quickly reduce blood TG concentrations in AP patients, especially in patients with severe AP risk of complications PEX should be administered as soon as possible, within 24 - 48 hours after the onset of illness and is applied until the TG concentration is times higher than normal values - Computerized tomography: evidence of acute pancreatitis b TG test ≥ 11.3 mmol/l (1000 mg/dl) - TG is tested once upon admission and retested after 12 hours c AP is diagnosed to exclude due to other causes: gallstones, worms from the bile duct, trauma, alcohol 2.1.2 Exclusion criteria + Patients