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1 MINISTRY OF EDUCATION MINISTRY OF NATIONAL AND TRAINING DEFENCE MEDICAL MILITARY UNIVERSITY  THUY HUYNH THI NGOC EVALUATE THE TREATMENT RESULTS OF SUPPORTING PATIENTS WITH MULTIPLE ORGAN FAILURE BY PRE-AND-POST-DILUTION CONTINUOUS VENO-VENOUS HEMOFILTRATION Speciality: Internal Medicine Code: 972 01 07 ABSTRACT OF MEDICAL DOCTORAL THESIS HA NOI - 2019 THE THESIS WAS COMPLETED AT MEDICAL MILITARY UNIVERSITY The scientific instructors: Ass.Prof. VINH HOANG TRUNG, PhD HUY DO QUOC, PhD Reviewer 1: Prof. TAM VO, PhD Reviewer 2: Ass.Prof. CHI NGUYEN VAN, PhD Reviewer 3: Ass.Prof. MANH BUI VAN, PhD 2 The thesis will be judged by the board of examiners of Medical Military University At: ………… o’clock, … / … / 2019 The thesis can be found at: - National Library of Vietnam - Medical Military University’s Library LIST OF PUBLICATIONS RELATED TO THE THESIS 1. Thuy Huynh Thi Ngoc, Vinh Hoang Trung, Huy Do Quoc (2018), "Khảo sát một số đặc điểm lâm sàng, cận lâm sàng của bệnh nhân suy đa tạng tại Bệnh viện Nhân dân 115", Journal ofMedical Military,43(6): 60-67. 2. Thuy Huynh Thi Ngoc, Vinh Hoang Trung, Huy Do Quoc (2018), "Evaluate the change of some parameters in patients with multiple organ failure supported by continuous renal replacement therapy", Journal ofMedical Military,43(7):130-138. INTRODUCTION OVERVIEW Multiple organ failure (MOF) is the common desease in ICU with complex injured mechanisms and high mortality, from 22% for 1 failured organ, up to 83% for ≥ 4 failured ones. The more number and severity of organ failure, the higher mortality rate, therefore the treatment objective is supporting organ function to reduce the severity of each injured organ and preventing complications until restored organ function. Continuous renal replacement therapy (CRRT) is a blood purification through the outer body circulation on the basis of replacing impaired renal function and removing inflammatory mediators by diffusion, hemofiltration, convection and adsorption. Convection 3 can remove large amounts of solutes if the water flow accross the membrane is strong enough. In CRRT, this quality is optimized by using the replacement fluid infused before the filter(predilution), or after the filter (postdilution). When the replacement fluid infused afterthe filter, solutes concentration are increased within the membrane filter so that the filter efficiency is increased but the filter easily clotted. Pre-dilution reduces the viscosity of the blood as it travels through the filter so it can prolong the life of the filter but the solubility of the solute decreases. As recommended by ADQI (Acute Dialysis Quality Initiative), the two methods can be combined by pre-and-post-dilution. Many domestic and international studies have applied the pre-and-post-dilution hemofiltration in patients with MOF and reported the efficacy in decreasing severity of organ failure and death, however, there were a few topics compared dilution methodsand the efficiency between predilution or postdilution are still controversial. For the above reasons, we do the research "Evaluate the treatment results of supportingpatients with multiple organ failure by pre-and-postdilution continuous veno-venuous hemofiltration". 1. Objectives: The study was conducted in patients diagnosed with multiple organ failure at the ICU, People's Hospital 115, with two objectives: 1.1. Survey the clinical, subclinical characteristics of patients with multiple organ failure having acute kidney injury, indicated CRRT in ICU, People's Hospital 115. 1.2. Evaluate the treatment results of supporting patients with MOF by pre-andpost-dilution compared with post-dilution continuous veno-venous hemofiltration. 2. The urgency of the topic CRRT is a technique that has been used in Vietnam for more than 10 years and is now considered an effective tool to support the patients with multiple organ failure. Continuous veno-venous hemofiltration (CVVH) - one of many methods of CRRT - can eliminate water and inlammatory mediators by using the replacement fluid infused before or after the filter. Any dilution mode brings the benefit to patients, but each mode has advantages and disadvantages. In 4 2002, ADQI (Acute Dialysis Quality Initiative) recommended applying preand-post-dilution in order to get the efficiency as well as to limitdisadvantages of each mode. This method has been applied in many domestic and international studies in supporting the function of organs. However, there are some issues that have not been addressed in many studies, such as how muchthe purifying solutes between post-dilution and pre-and-post-dilution is likely to be? Are there differences in supporting the function of organs? and which mode can extend the filter lifetime? We conducted a prospective, intervention and followup study using two different dilution modes in supporting patients with multiple organ failure to answer the above questions. 3. The contributions of the thesis The thesis contributes further the clinical, subclinical characteristics and the role of pre-and-post-dilution CVVH in supporting patients with MOF.  Data from the research showed that bacterial infection was the leading cause of multiple organ failure (77.9%). Patients had 2-6 injured organs when being admitted to the study, 4 organs accounted for the highest proportion (51.9%). Type of injured organ included: kidney 100%, respiratory 97.4%, cardiovascular 89.6%, and the lowest rate was acute liver failure19.5%.  Showed the common picture of MOF's clinical and subclinical characteristics with 59.8% of oliguria/anuria; used one vasoconstrictor (70.1%); and required mechanical ventilation (70.7%). Almost patients had metabolic acidosis and hypoxia; very high level of inflammatory markers, especially Il-6 > 90 times and TNF- approximately increased 5 times.  Proved the role of continuous veno-venous hemofiltration (CVVH) in patients with MOF: increased MAP from the 24h after intervention (p < 0,05); gradually improved the renal function during treatment (p < 0,001); improved the metabolic acidosis from the 72h after intervention (p < 0,01); improved the respiratory oxygenation after 48h of intervention (p < 0,01);decreased plasma level of cytokins after CVVH (p < 0,01); and decreased the severity of organ failure through the improving of the SOFA score during treatment (p < 0,01). 5  Comparing with post-dilution, the pre-and-post-dilution CVVH had better ability in improving: the renal function (the plasma level of creatinin was lower at 72h after intervention, p < 0,05); the metabolic acidosis (HCO3decreased at 72h after intervention, p < 0,01). It also had higher ability in purifying TNF- (p < 0,01) and prolonging the filter lifetime (33,8 ± 11,8h vs 28,2 ± 11,7h; p < 0,05). 4. The structure of the thesis The thesis consists of 131 pages; excluding the Introduction, Conclusions, and Recommendations, the thesis consists of 4 chapters: chapter 1- Literature review: 34 pages, chapter 2- Subjects and methods: 23 pages, chapter 3: Results: 33 pages, chapter 4- Discussion: 34 pages. The thesis has 53 tables, 2 diagram, 3 pictures, 10 charts. The thesis used 135 references. Chapter 1: LITERATURE REVIEW 1.1. Overview on MOF Multiple organ failure (MOF) is the common desease in ICU with at least two dysfunctional organs. MOF is formed by many causes with complex pathophysiology. The main factors include: immune response, tissue hypoxia, apoptosis, "two-hit" phenomenon; and the system inflammatory response is the best important factor. The MOF clinical manifestations are the combination of many dysfunctional organs, consist of cardiovascular, lung, kidney, liver, coagulation and central nervous system (CNS).There are many testing and diagnostic image need to perform early and repeat many times for diagnosis, follow-up and treatment. Early or late organ failure depends on desease's nature. For the patients having organ failure after the few days of admittinng to hospital, that is usually related to severe infection or surgery. The time to identify MOF is also different in research and patients, but its common point is the longer stay in hospital and the higher mortality rate in patients with late organ failure. Many authors mentioned the diagnostic critiria of MOF, but the Textbook of Critical Care (2011) used SOFA score for evaluating MOF in 6 organs, includingcardiovascular, lung, kidney, liver, coagulation and central nervous system (CNS). In 2004, the nephrologist purposed the RIFLE criteria to discribe 6 three levels of acute renal impairement (Risk, Injury, Failure) and two clinical outcomes (Loss and End-stage kidney desease) for more early diagnosis and treatment the acute kidney injury in order to impove outcome and to decrease mortality rate. The American Association for the Study of Liver Desease (AASLD) accepted definition of the acute liver failure, included an INR ≥ 1,5; and any degree of mental alteration (encephalopathy) in a patient without presisting cirrhosis and with an illness of < 26 weeks duration. 1.2. Therapy methods Although having many progresses in treatment of MOF, but the mortality rate is still very high. That's why need to combine many intensively simultaneous methods; consist of interventing promoted factors and organs dysfunction, as well as supporting organ function by CRRT. This is a method that can replace renal impairement amd eliminate inflammatory mediators by using the replacement fluid infused before or after the filter. According to the dialysis experts - Ronco and Bellomo - postdilution is a completely convection mode. When the replacement fluid infusedafterthe filter, solutes concentration are increased within the membrane filter so that the filter efficiency is increased but the filter easily clotted. Pre-dilution reduces the viscosity of the blood as it travels through the filter so it can prolong the life of the filter but the solubility of the solute decreases. Besides, it requires large amounts ofreplacement fluidas well as the high blood flowrate to get the same efficacy as postdilution. 1.3. Domestic and international studies on MOF In research of Elizabeth in 2001 with 249 patients stayed in ICU, the infection rate was 22%.Zarbock et al in the ELAIN randomized controlled trial publishedin 2016 in 231 patients, reported that earlycomparedwith delayed initiation of renal replacement therapyreduced mortality over the first 90 days. Research ofBoussekey et al, ultrafiltrate flow was delivered prefilterin one-third and postfilter in two-thirds of thepatients, results showed that high volume hemofiltration decreasedvasopressor requirement and tendedto increase urine output in septicshock patients with renal failure.Research ofGuang-Ming Chen also used pre-and-post-dilution hemofiltration, reported that CRRT treatment combined with conventional treatment resulted in ahigher hospital-discharge rate, a greater increase in platelets, a greater decrease in WBC,neutrophils, and 7 greaterimprovement of organ dysfunction thanconventional treatment used alone. In the IVOIRE trial -a prospective,randomized, doubleblined,multicentre clinical trial conducted in 137 patients with septic shock complicated by AKI, applied pre-and-post-dilution hemofiltration. researchers concluded that this method improve haemodynamic profile, respiratory oxygenation and organfunction. The filter lifetime was 45.7h in predilution and 16.1h in postdilution, but creatinin clearance in postdilution was higher (45 ml/minute versus 33 ml/minute) in a study of Van der Voort et al. In Vietnam, there were many trials reported about the clinical, subclinical characterristics of MOF in many groups of age, such as Duyen Le Thi My, Vinh Nguyen Xuan, Tien Nguyen Minh, Tuyet le Thi Diem. Somes studies used preand-post-dilution hemofiltration to evaluate the efficiency of CRRT in patients with MOF: Hai Truong Ngoc (2008), Quang Hoang Van (2009), Thang Vu Dinh (2011). Study was achieved the State Award of Binh Nguyen Gia et al (2013) also used pre-and-post-dilution hemofiltration in 65 patients with MOF and showed that CRRT help to improve haemodynamic profile, metabolic acidosis, respiratory oxygenation and to purify cytokins; howevwe, the mortality was still very high (67.7%) and mean organ failure was 3,12 ± 0,96. In general, although domestic and international studies have not evaluated many clinical and subclinical parameters of organ failure; but almost all of them supported the role of CRRT in patients with MOF. However, dialysis methods differed in lots of parameters such as blood flow rate, total quantity of replacement fluid, dilution mode, and effectiveness between pre-versus-post dilution. Thus, the problem that needs to be answered is: beside the ability to clear for solutes, the pre-and-post-dilutioncan help to extend the filter lifetime when comparing with the post-dilutionway or not? Chapter 2. SUBJECTS AND METHODS 2.1. Subjects A prospective, intervention and follow-up studywith the total of 77patients diagnosed with MOF, admitted toICU - People's Hospital 115, Ho Chi Minh City from February 2014 to February 2016. * The inclusion criteria: patients defined MOF according to SOFA score with 6 organs:cardiovascular, lung, kidney, liver, coagulation and central 8 nervous system (CNS). Organ dysfunction is when SOFA score ≥ 2 or having one of three approaches: a single variable that reflects a physiologic derangement, ora single variable that reflects a therapeutic intervention in response to a physiologic derangement, ora combination of variables that in their own right define a syndrome. And having acute kidney injury (AKI) according to RIFLE criteria: plasma creatinine increases by 2 times the baseline (creatinine concentration in the previous 7 days), or urine volume < 0.5 mL/kg/hr for 12 hours. * The exclusion criteria: MOF without AKI. Death within 24 hours admiited to ICU. Have no enough subclinical data for evaluateing and follow-up the organ function. Have indication for surgical intervention but no effective treatment. Have severe end-stage disease such as decompensated cirrhosis, metastatic cancer. Patients are pregnant. 2.2. Procedures After admitting to ICU, the patients who met the inclusion criteria and the exclusion criteria will be consulted in the study.All patients were only accepted to the study after the patient's legal representative (family) agreed to dialysis and made a commitment in the form of the hospital.Patients will be screened for theantecedent history, laboratory tests for diagnosis and treatment according to the regimens at ICU. The patients will be randomized by blocks, each block involved for 10 with software R.3.3.3. From the first 8 blocks, we collected a total of 77 patients in both groups (03 patients were excluded due to mortality within 24 hours after enrollment in ICU), including 41 patients in the group 1 (pre-and-post-dilution hemofiltration) and 36 patients in group 2 (post-dilution hemofiltration).In addition to initial treatment and resuscitation regimens, patients are supported by CRRT with in two dilution modes. Each patient has been requestedthe following data: * The clinical features of the MOF included: reasons for hospitalization, transfered place, associated diseases, edema, 24-hour urine output, conscious state, heart rate, mean arterial pressure (MAP), vasopressor requirement, respiratory rate, dyspnea, cyanosis,respiratory support, ECG and SpO2. * Examination and folow-up: 9 + Doing laboratory tests to diagnose MOF according to the SOFA score, including parameters: cell blood count, INR, aPTT, ure, creatinin, electrolyte, AST, ALT, total Bilirubin, direct Bilirubin, plasma lactat, CRP, arterial blood gas (ABG). + Right before and after the end of the first CRRT, we collected two blood samples for measuring plasma level of IL-6 and TNF-. These samples will be centrifuged to extract serum and taken to test in Hoa Hao Hospital. +Clinical and subclinical data were collected during treatment and CRRT, with attention given to admission, prior to CRRT (T0), after 24 hours (T24), after 48 hours (T48), after 72 hours (T72) and at the end of the study. * Initial resuscitation and treatment of organ failure: + Solving the resource of infection by drainage abscess focus, surgery, eliminate of necrotic tissue, removal of drainage tube (if necessary). Sterilization and regular check of airway control, bedside lift, sucking. Using intravenous antibiotics in the first hour of recognition of severe infection or septic shock. Insert intravasculardevice and early administration of crystalloids if suspecting the patient has decreased volume. When patient have been in hypotension, vasopressor therapy initially to target a mean arterial pressure (MAP) ≥ 65 mm Hg. + Acute respiratory failure: objectives are SpO2 ≥ 92% or PaO2 ≥ 60mmHg (with ARDS: maintain SpO2 ≥ 88%, PaO2 ≥ 58mmHg) by oxygen therapy or mechanical ventilation. + Cardiovascular dysfunction: objectives are to maintain systolic blood pressure ≥ 90mmHg or MAP ≥ 65mmHg by administration of fluids and vasopressors. + Acute kidney injury: fluid therapy to maintain stable blood pressure and to prevent pre-renal failure. Use blood purification techniques to treat severe acure renal failure. + Red blood cell transfusion occurs only when hemoglobinconcentration decreases to<7.0 g/dL to target a hemoglobin concentration of 7.0–9.0 g/dL in adults. Administer platelets when counts are <10,000/mm3. + Continuous or intermittent sedation be minimized in mechanically ventilated sepsis patients. Neuromuscular blocking agents (NMBAs) be avoided 10 if possible in the septic patient without ARDS due to the risk of prolongedneuromuscular blockade following discontinuation. 2.3 Continuous renal replacement therapy * Follow these steps: insert the catheter into the femoral vein or internal jugular vein. Put the wire system and filter into the machine. Priming filter with Natrichloride 9% together with heparin. Set the cycle between the machine and the patient. Dialysis during the day, when the filter clotted: stop and replace the other filter if the patient still have indicated. * Parameters: CVVH mode, blood flow rate 120-150 mL/minute, replacement flow rate30-40ml/kg/h (study group: pre-and-post-dilution, control group: post-dilution), the ratio of dilution: 50% pre-dilutionand 50%postdilution, change no more 10% in the other dialysis.For patients without high bleeding risk and without contraindications for heparin, systemic heparin was used with a dose of 20-25 UI/kg and followed by 5-15 UI/kg/h. * Follow-up during dialysis: heart rate, blood pressure, temperature, ECG, SpO2 every hour; daily input and output bilan; coagulation (aPTT, INR), blood glucose and electrolyte every 4-6 hours; monitor the alarm on the machine for solving timely; monitor the catheter to prevent slipping or twisting; and monitor the complications that may be encountered during dialysis. 2.4. Data analysis The data were analyzed and processed using SPSS version 22. The qualitative variables were expressed in percentages. Using χ2 test (corrected Fisher 'exact test as appropriate)to compare two ratios. T test was used to compare the mean and paired-samples T test for evaluating changes of parameters between intervals. For non-standard variables, two medians were compared and the Mann-Whitney test assessed the difference between the two groups and the Wilcoxon test assessed the difference between before and after intervention. The statistically significant threshold is p <0.05. 2.5. The ethical aspect of the thesis  The study was approved by the Science Council of People's Hospital 115. 11  All patients were only admitted to the study after the patient's legal representative (family) agreed to CRRT and made a commitment in the form of a hospital.  The legal representative of the patient may request withdrawal from the study at any time and will be unconditionally approved.  PhD student have responsibility to pay for the test sent to other lab center, patients' relatives do not pay extra.  The study will also be stopped immediately if there are any risk relating to the technique and/or therapeutic options associated with dialysis.  The collected data will be only used in the study and in the diagnosis and treatment of the patient, all patient information will be kept confidentially according to current regulations. 12 77 patiets wit MOF iedicatid for CRRT Ask for aeticidiet istory Clieical ixamieatoe Subclieical tists Triatmiet of causis aed orgae dysfuectoe Pri-aed-post dilutoe CVVH (Group 1, e = 41) Post-dilutoe CVVH (Group 2, e = 36) CONCLUSION 1 CONCLUSION 2 cal, subclieical c aractiristcs of patiets T i triatmiet wit MOF risults avieg of supporteg acuti kideiy patiets iejury.wit MOF by pri-aed-post-d RECOMMENDATIONS 13 Chapter 3: RESULTS 3.1. General characteristics of the research subjects Table 3.1. General characteristics of the patients 77 Total number Average age (year) 67,1 ± 17,2 Male/Female 32/45 SOFA score 12,2 ± 2,4 APACHE II score 28,6 ± 5,8 Average number of organ failure 3,96 ± 0,78 Time from diagnosis to CRRT 9,6 ± 10,8 Mortality rate 71,4% The ratio of patients with chronic deseases was 66.2%. Hypertension was the highest (37.7%), chronic liver desease was the lowest (5.2%). The patients diagnosed MOF within 24h after admitting to ICU had the highest rate (84.4%), from 48h to < 72h was the lowest (1.3%). 3.2. Clinical and subclinical characteristics of MOF 3.2.1. The main causes of MOF There was 4 main causes promoted MOF with the different rates: infection had the highest rate (77.9%), hemorrhage shock with the lowest rate (1.3%). In patients with infection, respiratory was the highest (58.3%), and gastrointestical tract was the second one (28.3%). 3.2.2. Number and type of MOF Patients in the study injured from 2 to 6 organs, 4 organs failure had the highest rate (54.5%), impairement of 2 organs and 6 organs was the same with the lowest rate (2.6%). All of patients had acute kidney injury, and then was respiratory failure (97.4%), cardiovascular dysfunction (89,6%). Liver injurryhad the lowest rate (19.5%). 14 3.2.3. Some clinical and subclinical characteristics In patients with AKI, anuria and oliguria were reported in 59.8% of the patients, and 13% had hypertension. All patients with respiratory failure haddyspnea; 45.5% had tachypnea and 70.7% needed mechanical ventilation. Tachycardia occured in 84.62% and 70.1% used a vasopressors in patients with cardiovascular damage. For patients with CNS injury, the lowest Glasgow score was 3 points prior to intervention. Most patients with coagulopathy and aPTT are within the safe range that allowed us to use heparin in CRRT. Most patients hadleukocytosis and anemia pre-dialysis, mean white blood cell count was 18.3 ± 10.9 K/μL and average hemoglobin concentration was 11.3 ± 2.8 g/dL. Patients with metabolic acidosis and hypoxia prior to intervention, with an average pH of 7.27 ± 0.12; HCO3-median concentration was 16.2 ± 5.4 mmol/L and PaO2/FiO2 ratio was 181.7 ± 146.1. Serum creatinine concentration was 3.5 ± 1.9 mg/dL, ure concentration was 106.7 ± 60.7 mg/dL. Inflammatory markers were elevated with mean values of 151.9 ± 106.3 mg/L. The median value of IL-6 was 659.9 pg/mL and that of TNF- was 37.3 pg/mL, it means that the concentration of IL-6 increased >90 times and TNF-increased nearly 5 times by the baseline. 3.3. The treatment results 3.3.1. The patients' number during treatment Table 3.2The patients' number during research Time Gr1 (n=41) Gr2 (n=36) p T0 (n, %) 41 (100) 36 (100) >0.05 T24 (n, %) 41 (100) 36 (100) > 0.05 T48 (n, %) 37 (90.2) 31 (86.1) > 0.05 T72 (n, %) 31 (75.6) 27 (75) > 0.05 15 No patients died in the first 24 hours after intervention. The patients'number started to decrease from the time of T48 (group 1 had 37 patients, group 2 had 31 patients). By the time of T72, Gr1 had 31 patients, Gr2 had 27 patients. 3.3.2.Effects on blood pressure Table 3.3. The change of MAP in research intervals of the 2 groups MAP Gr1 Gr2 n X ± SD p n X ± SD p T24 - T0 41 12.8 ± 30.1 < 0.05 36 13.8 ± 30.5 < 0.05 T48 - T0 37 14.6 ± 28.7 < 0.01 31 17.4 ± 27.1 < 0.01 T72 - T0 31 14.0 ± 34.2 < 0.05 27 16.8 ± 31.8 < 0.05 * Paired-samles T test: at the time ofT48 (GR1 had 37 patients, Gr2 had 31 patients), at the time of T72 (Gr1 had 31 patients, Gr2 had 27 patients), so that the patients' number was the same at T0. MAP in 2 groups improved from the time of T24 after intervention (p < 0.05). 3.3.3. Effects on renal function Table 3.4. The change of serum creatinine concentration at the evaluated times between the 2 group2 Creatinin Gr1 (n=41) PGr2 (n=36) p n X±SD n X± SD T0 41 3.4 ± 2.2 36 3.6 ± 1.7 > 0.05 T24 41 2.1 ± 1.6 36 2.5 ± 1.8 > 0.05 T48 37 1.9 ± 1.2 31 2.0 ± 1.6 > 0.05 T72 31 1.3 ± 0.6 27 1.9 ± 1.2 < 0.05 Creatinine concentration in Gr1 decreased> 50% after 72 hours of CRRT and was significantly lower than in Gr2. 16 Table 3.5. The change of creatinine concentration in research intervals of the 2 groups Gr1 Gr2 Creatinin n X ± SD p n X ± SD p T24 - T0 41 1.2 ± 1.3 < 0.001 36 1.0 ± 1.4 < 0.001 T48 - T0 37 1.5 ± 1.6 < 0.001 31 1.5 ± 1.7 < 0.001 T72 - T0 31 2.3 ± 2.3 < 0.001 27 1.6 ± 1.5 < 0.001 Creatinine concentration in both groups was gradually decreased during treatment, statistically significant from the time of T24 after intervention (p < 0.001). 3.3.4. Effects on metabolic and respiratory oxygenation Table 3.6. The change of HCO3-concentration in research intervals of the 2 groups Gr1 HCO3 Gr2 - n X ± SD p n X ± SD p T24 - T0 41 1.2 ± 5.1 > 0.05 36 0.2 ± 4.4 > 0.05 T48 - T0 37 2.3 ± 7.1 > 0.05 31 2.2 ± 5.4 > 0.05 T72 - T0 31 3.3 ± 6.3 < 0.01 27 2.4 ± 6.4 > 0.05 In group 1, HCO3- concentration statistically improved from the time of T72 after intervention (p < 0.01).However, the improvement of HCO3concentration in Gr2 was not significant during the first 72 hours (p > 0.05). 17 Table 3.7. The change of paO2/FiO2ratioin research intervals of the 2 groups Gr1 Gr2 paO2/FiO2 n X ± SD p n X ± SD p T24 - T0 41 44.3 ± 214.5 > 0.05 36 108.9 ± 233.7 < 0.01 T48 - T0 37 142.7 ± 259.9 < 0.01 31 104.0 ± 208.6 < 0.01 T72 - T0 31 162.4 ± 269.5 < 0.01 27 194.9 ± 269.0 < 0.01 PaO2/FiO2 ratio of patients in Gr1 statistically improved after 48 hours of intervention(p < 0.01), while the improvement in Gr2 happened from 24 hours after intervention (p < 0.01). 3.3.5. Purification of cytokins Table 3.8. The change of serum IL-6 và TNF-α before and after CRRT Chỉ số Gr1 Gr2 n Median n Median Before-After 41 703.3 36 480.8 p 41 < 0.001 36 < 0.001 Before-After 24 6.6 24 (-) 7.3 p 24 < 0.01 24 > 0.05 IL-6 (pg/mL) TNF-α (pg/mL) *Using Wilcoxin test for evaluating the difference between before and after CRRT (Some blood samples were failed while transport, no full enough of TNF-α). SerumIL-6 concentration significantly decreased in both groups, while TNF-αconcentration only statistically decreased in group 1 (p < 0.01). 18 3.3.6. The common results Table 3.9. Mechanical ventilation time, days in ICU and mortality rate of the 2 groups Parameters Total (n = 77) gr1 (n=41) PN2 (n=36) p Mechanical ventilation time (days) 7.4 ± 8.3 5.9 ± 5.3 9.1 ± 10.7 > 0.05 Days in ICU 9.5 ± 8.7 8.2 ± 6.0 10.9 ± 10.9 > 0.05 Mortality rate (n, %) 55 (71.4%) 29 (70.7%) 26 (72.2%) > 0.05 \ There was not different between 2 groups about above parameters. 3.3.7. Evaluate some technical data and side-effects during CRRT Table 3.10. Some technical paremeters related to CRRT Thông số PN1 (n=41) PN2 (n=36) p Time of starting CRRT (hour) 7.7 ± 6.8 11.7 ± 13.8 > 0.05 Numbers of CRRT 1.9 ± 1.3 1.5 ± 0.7 > 0.05 373.78 ± 105.62 408.1 ± 104.7 > 0,05 Transmembrane Pressure-TMP at the end of CRRT (mmHg) 387.9 ± 45.8 379.5 ± 33.1 > 0.05 Average filter lifetime (hour) 33.8 ± 11.8 28.2 ± 11.7 < 0.05 Replacement volume (ml/kg/h) 36.7 ± 4.1 37.9 ± 5.1 > 0.05 Mean dose of heparin (UI/h) Average filter lifetime in group1 was significantly longer than that in group 2 (p < 0.05).The other parameters were similar in the 2 groups. 19 Table 3.11. Some comlications during CRRT Comlications Gr1 (n=41) Gr2 (n=36) p n % n % 1 2.4 0 0 > 0.05 Hemorrhage Hematome due to wrong insert in artery Thrombocytopenia 1 2.4 0 0 > 0.05 15 36.6 8 22.2 > 0.05 Hypokalimia 28 68.3 22 61.1 > 0.05 Glycemia 5 12.2 3 8.3 > 0.05 Hemolysis 0 0 0 0 Membrane rupture 0 0 0 0 Death while CRRT 0 0 0 0 There was not different between 2 groups about above parameters. Chapter 4: DISCUSSION 4.1. The common characteristics of research subjects Patients in the study had a mean age (67.1 ± 17.2 years) and a chronic disease rate of 66.2%. Several studies have shown a link between morbidity and mortality with age; the higher the age are, the greater the death is, especially in patients> 65 years. The increased incidence of chronic disease is costly to individuals and community. When chronic illnesses become an acute severe exacerbation, it may constitute a major cause of death. In our study, the majority of patients manifested MOF within 24 hours of entering the ICU (84.4%) and 58.4% of patients were transferred from other hospitals to our ICU. The basic responsibility of the ICUs is to treat severe patients being transfered from the other departments or hospitals, so the mortality rate of patients who are treated in ICU is usually very high.In addition, the higher the severity as well as the number of organ failure are, the higher the mortality is. Our study found that the mean SOFA score was 12.2 ± 2.4 and the mean APACHE II score was 28.6 ± 5.8. Besides, the mean number of organ failure before intervention was 3.96 ± 0.78. Thus, the patients in our study had severe prognosis and the overall mortality rate is quite high, 71.4%. 20 4.2. Clinical and subclinical characteristics of MOF Clinical andsubclinical characteristics of patients with MOR were very diverse; related to the cause, characteristics and severity of each organ failure. The four most common causes in ICUs were bacterial infection, shock, acute pancreatitis and poisoning. Infection in our study was highest (77.9%) and respiratory infection was also highest (58.3%). In severe patients, any organ can be damaged even if the organ is not the original disease. Our study showed that the patients injured from 2 to 6 organs, 4 simultaneous organs accounted for the highest proportion (51.9%). The higher the number of organ failure, the higher the risk of death. In the study, 100% of patients had AKI with 59.8% of patients presented anuria and oliguria. Respiratory tract infection are common early appears in patients with MOF, the rate of respiratory failure in our study was 97.4%. All patients with respiratory tract injuries exhibited dyspnea and needed oxygen support, with the rate of mechanical ventilation was 70.7%.Cardiovascular system damage can be caused by a variety of causes and depending on the degree of dysfunction in the heart, blood vessels and circulatory volume of the patient, clinical manifestations may be cool-clammy skin, peripheral hypoperfusion, hypotension, arrhythmias.Our results showed that 89.6% of patients had cardiovascular damage with MAP<70 mmHg and tachycardia was 84.62%. Patients with CNS lesions were 63.6% with an average Glawgow score of 8.9 ± 2.9 and Glasgow with a lowest score of 3 points. Thus, the clinical manifestations of patients with MOF in our study are varied. To the subclinical characteristics, our study noted that the majority of patients had leukocytosis with an average white blood cells of 18.3 ± 10.9 K/μL. Leukocytes play an important role in fighting off pathogens, but excessive activation causes tissue damage and aggressive chemicals. In addition, the majority of patients had anemia with a Hb value of 11.3 ± 2.8 g/dL. Anemia plays an important role in the treatment and prognosis. If patients need blood transfusion, they maybe in high risk for sepsis. Biochemical findings suggested that creatinine concentration was 3.5 ± 1.9 mg/dL. Most patients were transferred from other hospitals and other departments to the ICU, so the level of acute kidney failure was worse than
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