In our country today, changes in morphology and kidney function in patients with brain death have not been studied fully and comprehensively.. Therefore, we proceed to the topic “A Study
Trang 11 The necessity of the topic
Use of donated kidneys from patients with brain death is a problem that needs to be developed
However, patients with brain death often have changes
in the pathophysiology that affect the function of organs in the body Changes due to lack of control fromthe brain, a lack of circulating volume, the effects of hormonal disorders, inflammatory factors that lead to organ failure, including kidney function Maintaining the function of organs, including kidneys from brain-dead patients, the best timing for organ removal, is an issue that needs to be studied In our country today, changes in morphology and kidney function in patients with brain death have not been studied fully and
comprehensively Therefore, we proceed to the topic
“A Study on kidney function and morphology in brain dead patients due to traumatic brain
traumatic brain injury.
3 Practical significance and contribution of the thesis
Trang 2The thesis is a research project with scientific significance, clinical practical significance, necessary and practical: there exists a high number of brain death patients due to traumatic brain injury The use ofkidney transplant resources from patients with brain death is a matter of research and development
Maintenance and evaluation of renal function in
patients with cerebral death should be investigated Morphological surveillance on ultrasound,
histopathology and renal function changes in patients with brain death, the proportion of patients with acute kidney damage: 12 hours after brain death,
hemodynamic indicators of renal arteries have
changed kidney damage and tissue accounted for 88.9% Patients are presented with polyuria in the first
24 hours after brain death then the condition subsides.The concentration of NGAL, microalbuminuria
increases, glomerular filtration rate decreases with time of death Renal function is stable in the first 24 hours of brain death and then decreases rapidly
It is possible to find a link between some clinical and laboratory indicators in the diagnosis of AKI Based
on NGAL concentrations, microalbuminuria can be predicted and prognosed for acute renal damage in patients with brain death due to traumatic brain injury
4 Layout of the thesis
The thesis has 126 pages, including the following sections: Introduction (02 pages), literature review (38 pages), research objective and methodology (26
pages), research results (21 pages), discussion (37
Trang 3pages), limitations of the topic (01 page) conclusions (02 pages), recommendations (01 page) The thesis has 50 tables, 24 pictures, 130 references including in Vietnamese, English and French.
CHAPTER 1: LITERATURE REVIEW
1.1 TRAUMATIC BRAIN INJURY AND BRAIN DEATH
Traumatic brain injury is a change in brain function,
or other evidences of brain pathology, caused by an external force Changes in brain function are
determined by periods of loss or impairment of
cognitive ability, memory loss about events that have occurred just before (retrograde amnesia) or after trauma of the nervous system (paralysis, hypoesthesia,dysphasia ) Traumatic brain injury is a common condition Each year in the US there are about 1.5 million cases of traumatic brain injury Traumatic brain injury is a factor that contributes to 30.5% of all injury-related deaths in the United States In Vietnam,
according to the National Traffic Safety Committee, about 10 000 people die from traffic accidents every year Traumatic brain injury is the leading cause of death and disability of all ages One of the main
pathogenetic mechanisms causing severe trauma is cerebral edema and increased intracranial pressure
patients
Trang 4Brain death is a constant cessation of all brain function, including brain stem’s, also known as total brain death This definition is accepted in most
countries throughout the world
Brain death is the clinical syndrome of coma, loss
of brain stem reflexes, and apnea due to known and irreversible causes The most common cause of brain stem death is traumatic brain injury, brain stroke, braintumor, brain damage due to lack of oxygen
Brain death is a condition where the brain is
severely damaged, the brain function stops working and the brain dies cannot be revived (article 3, clause
6, page 7 of Law No 75/2006 / QH11)
Brain death diagnosis is based on:
Degeneration of renal structure: Glomerular
hyperemia, glomerulonephritis and glomerular
inflammation, cellular vacuolization, near and far renal tubular atrophy or necrosis, endothelial hyperplasia and glomerular capillaries hyperplasia
Increased immunogenicity of the kidneys before transplant: an increase in E-selectin, P-selectin, ICAM-1,VCAM-1 in endothelial cells of 44% of kidney from deceased donor compared to 9% from living donor Increased MHC group II (DR) in renal tubular cells
Trang 5Interstitial cell infiltrates such as T cells, macrophages, neutrophils in 53% of kidneys from deceased donors compared with 0% from living donors
The incidence of renal failure and acute tubular necrosis is increased if systolic blood pressure in
patients with brain death fluctuates below 80 - 90 mmHg Experiments in animal models show that in patients with brain death, there is damage to the integrity of renal parenchyma (shown by measuring intracellular Na +: K + ratio) Damage to parenchymal cells can be prevented by using T3, cortisol, insulin andensuring good hemodynamics
Effects of hemodynamics: Changes in hemodynamicfluctuations such as strong vasoconstriction associated with reduced cardiac output, hypotension and lack of circulating volume can all lead to renal damage due to decreased renal perfusion The incidence of renal failureand acute tubular necrosis is increased if systolic blood pressure in patients with cerebral death fluctuates below 80 - 90 mmHg
Effects of endocrine: Impaired function of the
hypothalamus - pituitary system; changes of thyroid hormones
Influence of inflammatory factors: Severe brain damage is fueled by local inflammatory response, whichcan eventually lead to brain death, which then triggers
a "sympathetic storm," releasing large amounts of cytokines into the blood, aggravating inflammation
Trang 61.2.3 Methods for assessing kidney morphology and renal function
Diagnostic imaging methods: Kidney ultrasound, ray diagnostic of the urinary system, computer
X-tomography of the urinary system, magnetic
resonance imaging of the urinary system
Neutrophil gelatinase-associated lipocalin (NGAL): is
a protein with a molecular weight of 25kD, containing
20 amino acids capable of binding free iron in the body, belonging to the lipocalin family NGAL is an important factor in the immune response to infection, manifested
in immune cells, liver cells, renal tubular cells in various medical conditions
NGAL has been shown to be the protein of tubular origin that increases at the earliest when there is acutekidney damage due to anemia, decreased renal
perfusion, often appearing in urine before other
markers When the tubular is damaged, NGAL secretedfrom tubular cells will drain into the urine, partially absorbed into the blood Increased NGAL levels in blood and urine have been shown to be highly
sensitive and specific to predict progression to acute kidney damage
Trang 7Microalbuminuria is a very small amount of albuminexcreted by the kidneys in the urine Urine
microalbumin levels are greater than normal,
indicating kidney damage Urine microalbumin test helps detect kidney disease in early stages
Microalbuminuria has long been shown by
scientists to be associated with the development of chronic kidney disease in patients with diabetes or hypertension However, its value in predicting acute kidney injury has been poorly reported
Trang 8CHAPTER 2: RESEARCH OBJECT AND
METHODOLOGY 2.1 Research object:
Patient diagnosed with brain death due to
traumatic brain injury, treated at Anesthesia and Intensive Care Center - Viet Duc Hospital and
Emergency and Poison Control Center - Military
Hospital 103 from December 2012 to January 2019
Inclusion criteria:
Traumatic brain injury patients
- Be diagnosed with brain death according to the criteria of the Ministry of Health (Decision No
32/2007 / QD-BYT dated August 15, 2007 of the
Ministry of Health on promulgating regulations of clinical standards, subclinical standards and cases where clinical criteria are not applicable for brain deathdetermination):
+ Deep coma, Glasgow Coma Scale: 3 points
+ The pupils are constantly dilated over 4mm.+ Loss of pupils light reflexes
+ Loss of corneal reflexes
+ Loss of pharyngeal reflexes
+ Positive doll’s eyes reflex
+ Loss of vestibulo-ocular reflex
+ Positive apnea test
+ Transcranial doppler ultrasound: Doppler waves are not seen or diastolic blood flow is lost, only the early systolic miniature peaks (Vs < 10cm/s)
+ Criteria for timing: to determine brain death, examine the patient 3 times every 6 hours apart to identify the patient with brain death since the patient
Trang 9has met clinical and irreversible criteria to be declared
as brain dead
The family agreed to participate in the study
Exclusion criteria:
Not qualified to diagnose brain death
Eligible to diagnose brain death but accompanied by:
+ History of kidney disease
+ History of chronic disease: diabetes,
hypertension, cancer,
+ Kidney injury
+ Infectious diseases: HBV, HIV, HCV,
+ Patient's family does not agree to participate
Criteria for removing patients from the study:
The patient was eligible for research but died or his family requested to go home before the study tests were complete
2.2.3.Drugs and means of research
Drugs: Heart failure and vasoconstrictor medications:
adrenaline, noradrenaline, dopamine
Research facilities and equipment:
+ Resuscitation facilities: Drager - Germany
respirator, Phillip multi-parameter monitor, infusion machine, electric injection pump
Trang 10+ Ultrasound machine: 4D E-CUBE 9 Korean color ultrasound machine, which has various features such
as abdominal ultrasound, renal ultrasound, vascular ultrasound and transcranial doppler ultrasound
+ Kidney biopsy kit: A biopsy needle attached to a 16G x15 cm disposable gun, a container containing 10%solution of formol solution
+ Kits for taking and monitoring the amount of urine: urine (Sonde Foley), pouches and urine
measuring devices with measuring lines, test tubes for urine
+ Urine NGAL testing equipment: NGAL ELISA Kit - Sigma - USA
+ Automated biochemical test system meeting ISO
15189 standard - biochemical laboratory - Military Hospital 103
2.2.4.Research content
All patients were informed about their medical history and examined according to a sample of medicalrecords serving the study
2.2.4.1 General characteristics of patients with brain death due to traumatic brain injury
Characteristics of age, gender, height, weight, BMI.Characteristics of injury structure
Cause of injury
Time of injury before brain death
Brain death time
Hemodynamic characteristics of brain-dead
patients
Trang 11Organ dysfunction characteristics are calculated on SOFA scale.
2.2.4.2 Evaluation of some morphological
indicators on ultrasound, histopathological damage and renal function changes within 72 hours in patients with brain death due to traumatic brain injury
Morphological characteristics on renal ultrasound images of patients with brain death due to traumatic brain injury
Characteristics of renal histopathological lesions of patients with brain death due to brain traumatic brain injury
Characteristics of renal function changes in patients with brain death due to traumatic brain injury
2.2.4.3 Understanding the relationship and
predictive value for acute kidney damage of NGAL and microalbuminuria in patients with brain death due to traumatic brain injury
Relationship between some characteristics of brain death due to traumatic brain injury and acute kidney damage
Relationship between some characteristics of brain death due to traumatic brain injury and kidney tissue damage at 12 hours of brain death
Determine the predictive value for acute kidney damage of NGAL, urine microalbumin
2.2.5.Research conduction steps
Patient selection and follow-up interval
T0: When the patient was first diagnosed with brain
death (0 hours after brain death)
Trang 12T1: After 12 hours, when the patient has been
diagnosed with a third brain death (the time of
confirming that the patient was brain dead)
T2: When the patient was diagnosed with brain death
Resuscitation and monitoring of brain death
patients: According to the protocol of the ICU - 103
Military Hospital.
Kidney ultrasound of brain death patients:
Ultrasound is performed under normal kidney
ultrasound and renal artery doppler ultrasound of
Military Hospital 103 by an imaging specialist.
Renal biopsy of brain death patient: The patient is
given a percutaneous renal biopsy, under the guidance
of ultrasound, with a disposable Geotex biopsy gun with 16G x 15 cm size needle The time of biopsy is T1 (12 hours after brain death) Biopsy specimens are fixed in 10% formol solution and casted in paraffin at Department of Histopathology - Military Hospital 103 The specimens are cut with a thickness of 3 - 5Jm, dyed with hematoxylin - eosin (HE), PAS and PAM The
specimen was read under optical microscope and
consulted between the Department of Histopathology ofViet Duc Hospital and the Department of Histopathology
- Military Hospital 103
Trang 132.3 Methods of collecting information and processing data
All data were collected according to research
medical record
Data were collected on Microsoft Excel software and processed by medical statistical method using SPSS software
Hospital 103
Patients after the diagnosis of brain death are unable to communicate and are considered to have died legally However, clinically, patients who maintain vital functions should be considered as other severely ill patients
The study patient's family was thoroughly
explained by the researcher, the purpose, the methodsfor conducting the study and the benefits that the patient is entitled to The families all agreed to conductthe study
All tests are conducted at large centers, fully
equipped with equipment as well as good technical qualifications, ensuring the exact standards of the test
Trang 14The research process is under close supervision by hospital leaders, deans, central and unified research members.
The information on medical records and images is confidential by us and serves only for research
purposes, committing to not having any commercial goals
The cost of equipment and consumables for the patient during the research process is paid by the graduate student, the patient does not have to pay extra
CHAPTER 3: RESEARCH RESULTS
3.1 General characteristics of patients with brain death due to traumatic brain injury
3.1.1.Age and gender characteristics of patients with brain death due to traumatic brain injury
Table 0.1 Distribution of age and gender
Trang 153.1.2.Characteristics of time from traumatic
injury until after brain death and dead time.
brain-Table 3.2 Time from traumatic injury until after
brain death and brain-dead time
0 - 12 (hours) 31 49.2 0.1 – 11.5
>12 - 24
13.25 –23.73
Table 3.3 Time from brain death diagnosis to
cardiac arrest Time after
brain death
Brain death time
n % min - max (hours)
Trang 16Total 63 100 7.00 – 79.75
X ± SD (hours) 27.72 ± 17.83
The mean time after brain death was 27.72 ± 17.83 hours Patients mostly died within 24 hours
3.2 Evaluation of some morphological
indicators on ultrasound, renal histopathological damage at 12 hours and renal function changes within 72 hours in patients after brain death due
to traumatic brain injury
3.2.1.Histopathological lesion characteristics of kidney at 12 hours after brain death due to
traumatic brain injury
Table 3.4 Kidney histopathological lesion 12
hours after brain death Location of lesion No lesions Lesioned
Generalized (n=63) 07 11.1 56 88.9Histopathological lesions at 12 hours after brain death
in glomerular and renal tubules were 52 patients,
accounting for 82.5% Among them, 56 patients had lesions in both the glomeruli and renal tubules
3.2.2.Histopathological lesion classification at
12 hours after brain death according to Karpinski
Trang 17Cầu thận Ống thận Khoảng kẽ Mạch máu
Figure 3.1 Histopathological lesion classification at
12 hours after brain death according to Karpinski
Glomeruli: 63.49% 0 points; 20.63% 1 point;
14.29% 2 points; 1.59% 3 points Tubules 55.56% 0 points; 22.22% 1 point; 19.05% 2 points; 3.17% 3 points
Interstitial space and blood vessels are virtually unscathed and Karpinski score is 0
3.2.3 Changes in renal function in patients with brain death over time
Table 3.5 Progression of the amount of urine by
brain death time Timema
Median (25% - 75%) (mL/hour)
min max (mL/hour )
-T0 63 250 (200 - 400) 60 - 1125T1 63 350 (250 - 410) 100 - 700T2 34 300 (160.5 - 300) 30 - 800