MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENSE THE THESIS WAS DONE AT 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES 108 INSTI TUTE O F CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Scientific instructors: Prof PhD Nguyen Van Thong TRAN THI OANH PhD Nguyen Hong Quan Reviewer 1: STUDYING CLINICAL, SUBCLINICAL CHARACTERISTICS Reviewer 2: AND SOME RELAVANT FACTORS OF PATI ENTS WITH ACUTE CEREBRAL INFARCTIONABOVETHE CEREBELLUM TENT Reviewer 2: REQUIRI NGMECHANICAL VENTI LATION This thesis will be presented at Institute Council at: Speciality: Neurology Code: 62720147 Day Month Year The thesis can be found at: SUMMARY OF MEDICAL DOCTORAL THESIS National library Library of 108 Institute of clinical medical pharmacological sciences HA NOI – 2019 INTRODUCTION THE NEWCONTRIBUTIONOF THE THESIS Stroke is one of the leading causes of death and disability in adults, with about 80-85% of cerebral infarction Patients with severe cerebral infarction often have consciousness disorders, loss of ability to protect the airway, sputum congestion, causing respiratory failure Intubation and mechanical ventilation for these patients is needed to support breathing to protect the airway and ensure adequate oxygen supply to brain cells Although the proportion of patients with right ventilated cerebral infarction is not high (10-16%), the prognosis is very poor All patients have severe The thesis topic has scientific, practical and topical significance to contribute to show some clinical, subclinical and imagingcharacteristics of patients with acute cerebral infarction above the cerebellum tent requiring mechanical ventilation Determining a number of factors related to mechanicalventilation of patients with acute cerebral infarction above thecerebellum tent, some prognostic factors of mortality and prognosis ofgood functional state mRS 0-3 at the time of year This will helpclinicians predict and prescribe timely treatment intervention clinical circumstances, complex evolutions, need many pos itive treatments but high mortality The death rate in the hospital is 35-75% The patients THE S TRUCTURE OF THE THESIS who survived are mostly with severe neurological sequelae and dependent The thesisconsists of130pages: 2pagesof introduction, 36pages of overview, 13pages of subjects and methods, 33pages ofresearchresults, There have been many studies in the world and in the country about patients with cerebral infarction in general but there have not been many studies on patients with mechanical ventilation with cerebral infarction 43pages of discussion, 2pages of conclusionsand page of suggestion, 40 tables,13 charts, images, figures and 148 references about factors related to ventilation indications and prognostic factors in these patients Chapter - OVERVIEW Therefore, we conducted the subject: "Studying clinical, subclinical characteristicand some relevant factors of patients with acute cerebral 1.1 Physiology of cerebral infarction infarction above the cerebellum tent requiring mechanical ventilation" A cerebral infarction occurs when the amount of brain blood falls below 18–20 ml / 100g brain / m inute, the centre of the infarction is the necrotic area with a blood flow of 10-15ml/100g brain/minute, around this area with two objectives as follows: Description of clinical, subclinical characteristics and some factors related to mechanical ventilation of patients with acute cerebral infarction above the cerebellar tent Identify some of prognostic factors of patients with acute cerebral infarction above the cerebellum tent requiring mechanical ventilation (Penumbra area) has a blood flow of 20-25ml/100g brain / minute, although brain cells are still alive but inactive The area cells die over a few hours and are different for every patient This is the window time for reperfusion treatment interventions Treatment measures to save this area 1.2 Edema in cerebral infarction Cerebral edema in a large cerebral infarction causes increased intracranial pressure, which can lead to a brain hernia, aggravate neurological deficiencies and high mortality if left untreated The clinical development of cerebral edema in p atients with massive cerebral infarction can be divided into levels: fulminant (within 24-36 hours), slowly (over several days), or initial acute course then descending (about a week) Cytotoxic Edema: Once clogged, there is a stop of oxygen exchange in the damaged area which leads to the cell losing energy, losing the function of the transport membrane, the ion pump stops working, Na + from outside spills into the cell, dragging water causes the cell to swell causing cytotoxic edema This type of edema does not respond to anti-edematous drugs according to the osmotic mechanism Vasogenic Edema: Occurs to 12 hours after embolization, due to a profound change in the endothelial lining of the capillaries, stagnation of glycogen in stellar cells, causing bulging star cells, breaking the tight bonds between intracellular cells tissue and between endothelial cells and stellar cells leads to blood barrier brain (BBB), the fluid from the lumen of the artery is released causing brain edema Brain edema b ecomes the strongest on the third to fifth day and is reduced after one to two weeks This type of edema responds to anti-edematous drugs according to the osmotic mechanism As recommended by the American Heart Association/American Stroke Association in 2014, the signs predict malignant cerebral edema and poor prognosis on cranial CT include increased mid-cerebral artery photon, dot sign on film within hours, infarction of one-third or more of the midcerebral artery blood supply region, or midline shift push of mm or more on the cranial CT scan in the f irst days is also associated with increased nerve damage and death early in the acute phase The American Heart Association/American Stroke Association (2014) recommends serial CT scans during the first 48 hours of stroke to assess the risk of malignant brain edema 1.3 Indications and role of mechanical ventilation in patients with cerebral stroke The most common causes of hypoxemia in brain stroke patients may be due to partial obstruction of the airways due to sputum stagnation, respiratory depression and hypoventilation, choking pneumonia and collapse In these cases, mechanical ventilation helps improve blood oxygenation, maintain oxygenation to the brain and reduce intracranial pressure, but excessive ventilation should be avoided SpO2 target> 94% and pCO2 35 - 40 mmHg In patients stroke with impaired consciousness, or signs of brain stem dysfunction, decreased oropharyngeal motion and airway reflex loss are at high risk of choking pneumonia Intubation for this patient is necessary to protect the airway and prevent choke complications Some patients have coma, disorders of breathing, have apnea, intubation and mechanical ventilation to ensure respiration, ensure oxygen to the brain and body to prevent brain edema progression The American Heart Association/Stroke Association 2014recommends for mechanical ventilation in the treatment of acute cerebral infarction: Intubation may be considered for patients with decreased levels of consciousness resulting in poor oxygenation or impaired control of secretions 1.4 Hyperventilation and role of pCO2 in treatment intracranial pressure Reducing pCO2 is known as a cerebral artery contraction that reduces cerebral blood flow leading to a reduction in intracranial pressure, mainly due to changes in pH around the blood vessels The effect of reducing cerebral blood flow is temporary, after hours brain blood flow has been restored 90% In addition, a rapid increase in pCO2 causes a decrease in the pH around the blood vessels, causing vasodilation to increase brain blood volume and increase intracranial pressure ("rebound hyperemia") Use hyperventilation should only be used short in cases of life-threatening increase in intracranial pressure, pending surgical intervention pCO2 should be normalized as soon as possible 5 Chapter - SUBJECTS AND METHODS Clinical variables: gender, age, medical history, time of admission, pulse, blood pressure, temperature, level of consciousness at admission on Glasgow scale, NIHSS score, degree of paralysis, language disorder, sensory disorders, urinaryincontinence, pupil abnormalities, light reflexes, head-eye deviation, progression of symptoms, related mechanical ventilation complications Subclinical variables: hematology, biochemistry, coagulation, arterial blood gases Imaging variables: CT, CTA, DSA: parenchymal, artery damage, midline shift Variables of treatment outcome: death, live, mRS at discharge, year 2.2.4 Research contents Patients were divided into groups: MVgroup and non MVgroup The patients were divided into two groups, the MVgroup and the non MV group MVis indicated when at least one of the following criteria: Glasgow ≤ 8, loss of reflexes protects airway causing mucus congestion, patients with consciousness disorders, stimulation must use safety drugs strong spirit causes respiratory depression, patients with respiratory failure, circulatory failure Describe the clinical and paraclinical features with analysis and comparison between two groups of MV and non MV group to highlight c linical and subclinical characteristics of patients requiring MV Identify factors related to MV, factors related to prognosis of death at hospital discharge and mRS 0-3 at year The supposedly relevant variables are included in univariate analysis and logistic multivariate regressions to find meaningful prognostic factors 2.3 Data analysis Data processing using SPSS 16.0 software Description of clinical, subclinical, imaging features: neurological signs on onset, on admission and during hospitalization, intubation designation, subclinical characteristics, imaging, complications during MV, treatments and outcome 2.1 Studying subjects Severe cerebral infarction patients above the cerebellum tent were treated at Strokecenter-Central MilitaryHospital108from 9/2013 – 6/2017 2.1.1 Criteria for selecting a patient The patients was diagnosed as stroke according to the World Health Organization (1989) stroke definition, arriving at the hospital 72 hours prior to the onset of cerebral infarction Images of hemispherical infarction on CT/MRI/ Severe nerve damage with NIHSS≥15 score (if the patient was hospitalized prematurely, the damage on the first CT was unknown, the patient would be diagnosed for a second time on CT Patients were divided into groups: mechanical ventilation group and non mechanical ventilation group 2.1.2 Exclusion criteria History of stroke with mRS score> points, patients with severe medical conditions such as liver failure, severe kidney failure, cancer, COPD,… 2.2 Research methods: 2.2.1 Study design:Progressive, description, follow-up study 2.2.2.Sample size: Sample size is determined by formula: p (1-p) n = Sample size to study 2 n = Z (1-α/2 ) -Z (1-α/2) : At the probability level 95% (Z =1,96) d d: The desired accuracy (d = 0,05) p: Estimated ratio, the rate ofcerebral infarctionpatients requiring mechanical ventilationin previous studies, p= 0,11 → Based on the above formula, the estimated patient sample sizeis 150 In the period of taking data from 9/2013 – 6/2017, we collected 166 patients including 84 ventilated severe cerebral infarction patients and 82 severe cerebral infarction patients without mechanical ventilation 2.2.3 Research variables Analys is of related factors: Chi-square test of qualitative or quantitative variables with clustering Statistically significant variables in Chi-square test were included in univariate regression analys is Variables related to MVand mortality in univariate analysis with significance level p 0,05 Hemiplegia 84 100 82 100 >0,05 Headache 9,5 8,0 >0,05 Dizzy 9,5 9,1 >0,05 Vomiting /nausea 14 16,7 3,7 5mm 3.2 Study some prognostic factors in patients with cerebral infarction in upper cerebellum tent with mechanical ventilation 3.2.1 Clinical outcome 13 Chart3.12 Functional status upon discharge Comment: In the MV group, no patients had a level of mRS 1-2 Mortality (mRS 6) 34,5% In the group with no MV, mRS 4-5 was 68,3% 3.2.2 Some of factors related to prognosis of death in patients with cerebral infarction in the cerebellum tent with MV Table 3.32 Some clinical factors related to clinical outcome at discharge in patients with cerebral infarction abovethe cerebellum tent with MV Clinical outcome at discharge Factors p Dead (n=29) Alive (n=55) Conscious disorders onset 22 (75,9) 45 (81,8) 0,518 Vomiting /nausea onset (17,2) (16,4) 0,918 Urinary incontinenceonset 25 (86,2) 31 (56,4) 0,006 Average Glasgow score 10,31 ±2,12 10,29 ±2,01 0,967 Glasgow point at admission≤10 18 (62,1) 33 (60) 0,854 Average NIHSS score 22,76 ± 5,65 22,84 ± 5,34 0,951 NIHSS point at admission> 20 13 (44,8) 36 (65,5) 0,356 Decreased Glasgow ≥ at intubation 18 (62,1) 25 (45,5) 0,173 Glasgow point ≤8 at intubation 18 (62,1) 28 (50,9) 0,364 Intubation in the first day 17 (58,6) 32 (58,2) 1,000 Aggravation in the first 48 hours 22 (75,9) 41 (75,4) 1,000 Head-eye deviation 13 (44,8) 23 (41,8) 0,791 14 Dilated pupils admission 21 (72,4) 19 (34,5) 0,001 Loss of light reflection 24 (82,8) 10 (18,2) 0,000 Temperature admission>37,5 C 11 (37,9) (10,9) 0,003 AverageSBPadmission 142,79±33,55 145,56 ±21,93 0,65 AverageDBPadmission 85,93 ± 15,47 85,58 ± 14,39 0,918 Averagepulesadmission 89,72 ± 22,22 87,58 ± 19,84 0,653 Pneumonia (24,1) 23 (41,8) 0,108 Comment: Factors with statistical significance: urinary incontinence onset, dilated pupils admission, loss of light refraction, temperature admission >37,5 C Table3.33 Some subclinical factors related to clinical outcome at hospital discharge in patients with cerebral infarction in the cerebellum tent with MV Clinical outcome at discharge Factors p Dead (n=29) Alive(n=55) Leukocytes > 10G/l 18 (62,1) 39 (70,9) 0,409 Blood g lucose >11,1 mmol/l (17,2) (9,1) 0,303 pCO2 on the first MV < 35mmHg 12 (41,4) 17 (30,9) 0,337 Midline shift >5mm 23 (79,3) 30 (54,5) 0,025 Table 3.34 Some factors are associated with mortality prognosis in univariate regression analysis Factors OR 95%CI p Urinary incontinenceonset 4,839 1,483 - 15,784 0,009 Temperature admission>37,5 C 4,991 1,609 - 15,480 0,005 Dilated pupils admission 5,500 1,998 - 15,139 0,001 Loss of light reflection 16,063 5,290 - 48,778 0,000 Midline shift >5mm 3,194 1,125 - 9,070 0,029 Comment: The factors in the table are all related to statistically significant mortality outcomes in univariate analys is 15 16 Table 3.35 Some factors related to mortality prognosis in multivariate logistic regression analysis Chapter – DISCUSSION Factors OR 95%CI p Urinary incontinenceonset 4,326 1,062 - 17,617 0,041 Temperature admission>37,5 C 3,087 0,636 -14,967 0,162 Dilated pupils admission 1,149 0,204 -6,481 0,875 Loss of light reflection 22,426 2,324 - 216,392 0,007 Midline shift >5mm 0,819 0,172 -3,899 0,802 Comment: When analyzing multivariate logistic regression, the factors associated with mortality outcome were statistically significant: urinary incontinenceonset, loss of light reflection 3.2.3.Some factors related to mRS 0-3 good function at year - There are 55 patients discharged At year after discharge, there were patients losing follow-up, 11/48 patients died, 20,3% mRS 0-3 Table 3.39 Some prognostic factors of good functional mRS 0-3 at year in univariate regression analysis Factors OR 95%CI p Ages > 60 0,102 0,024 - 0,438 0,002 Pneumonia 0,229 0,055 - 0,957 0,043 Comment:Factors with a negative predictive effect on good functional mRS 0-3 at year include: ages > 60, pneumonia Table 3.40 Some prognostic factors of good functional mRS 0-3 at year in multivariate regression analysis Significant variables related to the good functional mRS 0-3 at year in univariate analysis were included in the multivariate regression analys is Factors OR 95%CI p Ages > 60 0,091 0,019 - 0,427 0,002 Pneumonia 0,192 0,038 - 0,962 0,045 Comment: When analyzing multivariate logistic regression, the negative predictive factors giving good results of mRS 0-3 recovery at year of statistical significance include: ages > 60, pneumonia 4.1 Clinical, subclinical characteristics and some factors related to MV in patients with cerebral infarction above the cerebellum tent 4.1.1 Clinical characteristics, imagings - Conscious disorders onset The study results showed that 79,8% of patients with MV had consciousness disorder onset compared with 37,8% in the group without MV(p 10G/l are relevant in multivariate analysis (OR = 2,708; p = 0,046) In the study of 21 22 Tran Ngoc Tai (2005), the group of patients with cerebral infarction cerebral death died had a higher leukocyte index than the group of surviving patients (12,2 G/l and 11,3 G/l, there were no statistically significant difference) The proportion of patients with leukocyte>10G /l was higher in the group of mechanical ischemic cerebral infarction (67,9% and 48,8% p 5mm In our study the group of MVpatients were all very severe Signs of intraventricular tamponade and medial compaction indirectly reflect the degree of cerebral edema on cranial computerized tomography Research results, midline shift > 5mm are factors related to MVdesignation in multivariate analysis (OR = 13,511; p = 0,000) 4.2 A number of prognosis factors for patients with cerebral infarction above the cerebellum tent have MV 4.2.1 About a some of prognostic factors of mortality The prognostic factors of mortality in multivariate regression analysis are: urinary incontinence onset, loss of light reflection - Urinary incontinence onset The results of the study showed that the prevalence of urinary incontinence onsetin patients who died was 86,2% compared to 56,4% in patients alived (p = 0,006) Urinary incontinence onsetof stroke were prognostic factors of mortality in univariate analysis (OR = 4,839; p = 0,009) and multivariate (OR = 4,326, p = 0,041) Gupta's (2014) study showed that the rate of urinary incontinence onsetin p atients who died was 96,9% compared to 82,1% of the alived patients (p = 0,088) Li et al (2018) reported that urinary incontinence was more in the mRS 4-6 group than in the mRS 0-3 group (27,9% and 7,1%; p 60 years the recovery rate of mRS 0-3 met 36,4% while the recovery rate inferior to mRS 4-6 was 63,6% (p = 0,036) In Foerch's study (2004), age over 75 years had a negative predictive effect for survival at months after stroke with MV (OR = 0,1; p = 0,004) 23 24 - Pneumonia The study results showed that the rate of pneumonia was 17,6% in the mRS 0-3 recovery group and 48,4% in the 4-6 mRS poor recovery group (p =0,035) Pneumonia had a negative predictive effect with good recovery of mRS 0-3 at year in univariate regression analysis (OR = 0,222; p = 0,043) and multivariate (OR = 0,192; p = 0,045) This result is similar to the result of Li (2018) when studying the factors related to the good outcome of mRS 0-3 in patients with massive cerebral infarction at months recorded the rate of pneumonia seen in the group mRS 0-3 and mRS 4-6 group were 67,1% and 36,3% respectively; (p