MINISTRY OF EDUCATION MINISTRY OF NATIONALMEDICAL MILITARY UNIVERSITY THUY HUYNH THI NGOC EVALUATE THE TREATMENT RESULTS OF SUPPORTING PATIENTS WITH MULTIPLE ORGAN FAILURE BY PRE-AN
Trang 1MINISTRY OF EDUCATION MINISTRY OF NATIONAL
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
Trang 2The 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 withcomplex injured mechanisms and high mortality, from 22% for 1 failuredorgan, up to 83% for ≥ 4 failured ones The more number and severity oforgan failure, the higher mortality rate, therefore the treatment objective issupporting organ function to reduce the severity of each injured organ andpreventing complications until restored organ function Continuous renalreplacement therapy (CRRT) is a blood purification through the outer bodycirculation on the basis of replacing impaired renal function and removinginflammatory mediators by diffusion, hemofiltration, convection andadsorption Convection can remove large amounts of solutes if the water
Trang 3flow accross the membrane is strong enough In CRRT, this quality isoptimized by using the replacement fluid infused before thefilter(predilution), or after the filter (postdilution).
When the replacement fluid infused afterthe filter, solutes concentrationare increased within the membrane filter so that the filter efficiency isincreased but the filter easily clotted Pre-dilution reduces the viscosity ofthe blood as it travels through the filter so it can prolong the life of the filterbut the solubility of the solute decreases As recommended by ADQI (AcuteDialysis 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 theefficacy in decreasing severity of organ failure and death, however, therewere a few topics compared dilution methodsand the efficiency betweenpredilution 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-post-dilution continuous veno-venuous hemofiltration".
1.2 Evaluate the treatment results of supporting patients with MOF by and-post-dilution compared with post-dilution continuous veno-venous hemofiltration.
pre-2. The urgency of the topic
CRRT is a technique that has been used in Vietnam for more than 10years and is now considered an effective tool to support the patients withmultiple organ failure Continuous veno-venous hemofiltration (CVVH) -one of many methods of CRRT - can eliminate water and inlammatorymediators by using the replacement fluid infused before or after the filter
Trang 4Any dilution mode brings the benefit to patients, but each mode hasadvantages and disadvantages In 2002, ADQI (Acute Dialysis QualityInitiative) recommended applying pre-and-post-dilution in order to get theefficiency as well as to limitdisadvantages of each mode This method hasbeen applied in many domestic and international studies in supporting thefunction of organs However, there are some issues that have not beenaddressed in many studies, such as how muchthe purifying solutes betweenpost-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 filterlifetime? We conducted a prospective, intervention and follow-up studyusing two different dilution modes in supporting patients with multipleorgan failure to answer the above questions
3. The contributions of the thesis
The thesis contributes further the clinical, subclinical characteristicsand the role of pre-and-post-dilution CVVH in supporting patients withMOF
− Data from the research showed that bacterial infection was the leadingcause of multiple organ failure (77.9%) Patients had 2-6 injured organswhen being admitted to the study, 4 organs accounted for the highestproportion (51.9%) Type of injured organ included: kidney 100%,respiratory 97.4%, cardiovascular 89.6%, and the lowest rate was acuteliver failure19.5%
− Showed the common picture of MOF's clinical and subclinicalcharacteristics with 59.8% of oliguria/anuria; used one vasoconstrictor(70.1%); and required mechanical ventilation (70.7%) Almost patientshad metabolic acidosis and hypoxia; very high level of inflammatorymarkers, especially Il-6 > 90 times and TNF-α approximately increased
5 times
− Proved the role of continuous veno-venous hemofiltration (CVVH) inpatients with MOF: increased MAP from the 24h after intervention (p <0,05); gradually improved the renal function during treatment (p <
Trang 50,001); improved the metabolic acidosis from the 72h after intervention(p < 0,01); improved the respiratory oxygenation after 48h ofintervention (p < 0,01);decreased plasma level of cytokins after CVVH(p < 0,01); and decreased the severity of organ failure through theimproving of the SOFA score during treatment (p < 0,01).
− Comparing with post-dilution, the pre-and-post-dilution CVVH hadbetter ability in improving: the renal function (the plasma level ofcreatinin was lower at 72h after intervention, p < 0,05); the metabolicacidosis (HCO3-decreased at 72h after intervention, p < 0,01) It also hadhigher ability in purifying TNF-α (p < 0,01) and prolonging the filterlifetime (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: 23pages, chapter 3: Results: 33 pages, chapter 4- Discussion: 34 pages Thethesis has 53 tables, 2 diagram, 3 pictures, 10 charts The thesis used 135references
Chapter 1: LITERATURE REVIEW
1.1 Overview on MOF
Multiple organ failure (MOF) is the common desease in ICU with atleast two dysfunctional organs MOF is formed by many causes withcomplex pathophysiology The main factors include: immune response,tissue hypoxia, apoptosis, "two-hit" phenomenon; and the systeminflammatory response is the best important factor The MOF clinicalmanifestations are the combination of many dysfunctional organs, consist ofcardiovascular, lung, kidney, liver, coagulation and central nervous system(CNS).There are many testing and diagnostic image need to perform earlyand repeat many times for diagnosis, follow-up and treatment Early or lateorgan failure depends on desease's nature For the patients having organfailure after the few days of admittinng to hospital, that is usually related tosevere infection or surgery The time to identify MOF is also different in
Trang 6research and patients, but its common point is the longer stay in hospital andthe higher mortality rate in patients with late organ failure.
Many authors mentioned the diagnostic critiria of MOF, but theTextbook of Critical Care (2011) used SOFA score for evaluating MOF in 6organs, includingcardiovascular, lung, kidney, liver, coagulation and centralnervous system (CNS) In 2004, the nephrologist purposed the RIFLEcriteria to discribe three levels of acute renal impairement (Risk, Injury,Failure) and two clinical outcomes (Loss and End-stage kidney desease) formore early diagnosis and treatment the acute kidney injury in order toimpove outcome and to decrease mortality rate The American Associationfor the Study of Liver Desease (AASLD) accepted definition of the acuteliver 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 themortality rate is still very high That's why need to combine manyintensively simultaneous methods; consist of interventing promoted factorsand organs dysfunction, as well as supporting organ function by CRRT This
is a method that can replace renal impairement amd eliminate inflammatorymediators by using the replacement fluid infused before or after the filter.According to the dialysis experts - Ronco and Bellomo - postdilution is acompletely convection mode When the replacement fluid infusedafterthefilter, solutes concentration are increased within the membrane filter so thatthe filter efficiency is increased but the filter easily clotted Pre-dilutionreduces the viscosity of the blood as it travels through the filter so it canprolong the life of the filter but the solubility of the solute decreases.Besides, it requires large amounts ofreplacement fluidas well as the highblood 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, theinfection rate was 22%.Zarbock et al in the ELAIN randomized controlledtrial publishedin 2016 in 231 patients, reported that earlycomparedwith
Trang 7delayed initiation of renal replacement therapyreduced mortality over thefirst 90 days Research ofBoussekey et al, ultrafiltrate flow was deliveredprefilterin one-third and postfilter in two-thirds of thepatients, resultsshowed that high volume hemofiltration decreasedvasopressor requirementand tendedto increase urine output in septicshock patients with renalfailure.Research ofGuang-Ming Chen also used pre-and-post-dilutionhemofiltration, reported that CRRT treatment combined with conventionaltreatment resulted in ahigher hospital-discharge rate, a greater increase inplatelets, a greater decrease in WBC,neutrophils, and greaterimprovement oforgan dysfunction thanconventional treatment used alone In the IVOIREtrial -a prospective,randomized, doubleblined,multicentre clinical trialconducted in 137 patients with septic shock complicated by AKI, appliedpre-and-post-dilution hemofiltration researchers concluded that this methodimprove haemodynamic profile, respiratory oxygenation and organfunction.The filter lifetime was 45.7h in predilution and 16.1h in postdilution, butcreatinin clearance in postdilution was higher (45 ml/minute versus 33ml/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 pre-and-post-dilution hemofiltration to evaluate theefficiency of CRRT in patients with MOF: Hai Truong Ngoc (2008), QuangHoang Van (2009), Thang Vu Dinh (2011) Study was achieved the StateAward of Binh Nguyen Gia et al (2013) also used pre-and-post-dilutionhemofiltration in 65 patients with MOF and showed that CRRT help toimprove haemodynamic profile, metabolic acidosis, respiratory oxygenationand 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 notevaluated many clinical and subclinical parameters of organ failure; butalmost all of them supported the role of CRRT in patients with MOF.However, dialysis methods differed in lots of parameters such as blood flowrate, total quantity of replacement fluid, dilution mode, and effectiveness
Trang 8between pre-versus-post dilution Thus, the problem that needs to beanswered 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 of77patients 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 SOFAscore with 6 organs:cardiovascular, lung, kidney, liver, coagulation andcentral nervous system (CNS) Organ dysfunction is when SOFA score ≥ 2
or having one of three approaches: a single variable that reflects aphysiologic derangement, ora single variable that reflects a therapeuticintervention in response to a physiologic derangement, ora combination ofvariables that in their own right define a syndrome And having acute kidneyinjury (AKI) according to RIFLE criteria: plasma creatinine increases by 2times the baseline (creatinine concentration in the previous 7 days), or urinevolume < 0.5 mL/kg/hr for 12 hours
* The exclusion criteria: MOF without AKI Death within 24 hoursadmiited to ICU Have no enough subclinical data for evaluateing andfollow-up the organ function Have indication for surgical intervention but
no effective treatment Have severe end-stage disease such asdecompensated cirrhosis, metastatic cancer Patients are pregnant
2.2 Procedures
After admitting to ICU, the patients who met the inclusion criteria andthe exclusion criteria will be consulted in the study.All patients were onlyaccepted 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 andtreatment according to the regimens at ICU
The patients will be randomized by blocks, each block involved for 10with software R.3.3.3 From the first 8 blocks, we collected a total of 77
Trang 9patients in both groups (03 patients were excluded due to mortality within
24 hours after enrollment in ICU), including 41 patients in the group 1 and-post-dilution hemofiltration) and 36 patients in group 2 (post-dilutionhemofiltration).In addition to initial treatment and resuscitation regimens,patients are supported by CRRT with in two dilution modes
(pre-Each patient has been requestedthe following data:
* The clinical features of the MOF included: reasons forhospitalization, transfered place, associated diseases, edema, 24-hour urineoutput, conscious state, heart rate, mean arterial pressure (MAP),vasopressor requirement, respiratory rate, dyspnea, cyanosis,respiratorysupport, ECG and SpO2
* Examination and folow-up:
+ Doing laboratory tests to diagnose MOF according to the SOFAscore, 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 twoblood samples for measuring plasma level of IL-6 and TNF-α Thesesamples will be centrifuged to extract serum and taken to test in Hoa HaoHospital
+Clinical and subclinical data were collected during treatment andCRRT, 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 severeinfection or septic shock Insert intravasculardevice and early administration
of crystalloids if suspecting the patient has decreased volume When patienthave been in hypotension, vasopressor therapy initially to target a meanarterial pressure (MAP) ≥ 65 mm Hg
Trang 10+ Acute respiratory failure: objectives are SpO2 ≥ 92% or PaO2 ≥60mmHg (with ARDS: maintain SpO2 ≥ 88%, PaO2 ≥ 58mmHg) by oxygentherapy or mechanical ventilation.
+ Cardiovascular dysfunction: objectives are to maintain systolic bloodpressure ≥ 90mmHg or MAP ≥ 65mmHg by administration of fluids andvasopressors
+ Acute kidney injury: fluid therapy to maintain stable blood pressureand to prevent pre-renal failure Use blood purification techniques to treatsevere acure renal failure
+ Red blood cell transfusion occurs only whenhemoglobinconcentration decreases to<7.0 g/dL to target a hemoglobinconcentration of 7.0–9.0 g/dL in adults Administer platelets when countsare <10,000/mm3
+ Continuous or intermittent sedation be minimized in mechanicallyventilated sepsis patients Neuromuscular blocking agents (NMBAs) beavoided if possible in the septic patient without ARDS due to the risk ofprolongedneuromuscular blockade following discontinuation
2.3 Continuous renal replacement therapy
* Follow these steps: insert the catheter into the femoral vein orinternal jugular vein Put the wire system and filter into the machine.Priming filter with Natrichloride 9% together with heparin Set the cyclebetween the machine and the patient Dialysis during the day, when the filterclotted: 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-dilutionand50%post-dilution, change no more 10% in the other dialysis.For patientswithout high bleeding risk and without contraindications for heparin,systemic heparin was used with a dose of 20-25 UI/kg and followed by 5-15UI/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
Trang 11the machine for solving timely; monitor the catheter to prevent slipping ortwisting; and monitor the complications that may be encountered duringdialysis.
2.4 Data analysis
The data were analyzed and processed using SPSS version 22 Thequalitative variables were expressed in percentages Using χ2 test (correctedFisher 'exact test as appropriate)to compare two ratios T test was used tocompare the mean and paired-samples T test for evaluating changes ofparameters between intervals For non-standard variables, two medians werecompared and the Mann-Whitney test assessed the difference between thetwo groups and the Wilcoxon test assessed the difference between beforeand 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 Hospital115
− All patients were only admitted to the study after the patient's legalrepresentative (family) agreed to CRRT and made a commitment in theform of a hospital
− The legal representative of the patient may request withdrawal from thestudy at any time and will be unconditionally approved
− PhD student have responsibility to pay for the test sent to other labcenter, 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 andtreatment of the patient, all patient information will be keptconfidentially according to current regulations
Trang 1277 patients with MOF indicated for CRRT
Ask for antecedent historyClinical examinationSubclinical tests
Pre-and-post dilution CVVH(Group 1, n = 41)
Post-dilution CVVH(Group 2, n = 36)
CONCLUSION 2
The treatment results of supporting patients with MOF by pre-and-post-dilution CVVHTreatment of causes and organ dysfunction
RECOMMENDATIONS CONCLUSION 1
Clinical, subclinical characteristics of patients with MOF having acute kidney injury
Trang 133.1 General characteristics of the research subjects
Table 3.1 General characteristics of the patients
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 lowestrate (1.3%)
In patients with infection, respiratory was the highest (58.3%), andgastrointestical 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 hadthe highest rate (54.5%), impairement of 2 organs and 6 organs was the samewith 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 lowestrate (19.5%)
Trang 143.2.3 Some clinical and subclinical characteristics
In patients with AKI, anuria and oliguria were reported in 59.8% of thepatients, and 13% had hypertension All patients with respiratory failurehaddyspnea; 45.5% had tachypnea and 70.7% needed mechanicalventilation Tachycardia occured in 84.62% and 70.1% used a vasopressors
in patients with cardiovascular damage For patients with CNS injury, thelowest Glasgow score was 3 points prior to intervention Most patients withcoagulopathy and aPTT are within the safe range that allowed us to useheparin in CRRT
Most patients hadleukocytosis and anemia pre-dialysis, mean whiteblood cell count was 18.3 ± 10.9 K/μL and average hemoglobinconcentration 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 ± 5.4mmol/L and PaO2/FiO2 ratio was 181.7 ± 146.1
Serum creatinine concentration was 3.5 ± 1.9 mg/dL, ure concentrationwas 106.7 ± 60.7 mg/dL Inflammatory markers were elevated with meanvalues of 151.9 ± 106.3 mg/L The median value of IL-6 was 659.9 pg/mLand that of TNF-α was 37.3 pg/mL, it means that the concentration of IL-6increased >90 times and TNF-αincreased 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