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MINISTRY OF EDUCATION AND TRAINING
MINISTRY OF DEFENSE
SCIENCE RESEARCH INSTITUTE OF CLINICAL MEDICINE AND PHARMACY 108
The thesis has beeb successfully completed at : SCIENCE RESEARCH INSTITUTE OF CLINICAL MEDICINE AND PHARMACY 108
Science Instructor : PGS.TS. Nguyen Phuong Dong
NGUYEN DINH DUNG
Opponent 1: Opponent 2:
STUDYING CLINICAL, SUBCLINICAL CHARACTERISTICS, ASSOCITATED FACTORS AND TREATMENT RESULTS OF HYPONATREMIA IN PATIENTS WITH CEREBRAL HEMORRHAGE Major
: Anesthesia - Resusciation
Opponent 3: Thesis has been defended at Institite- level Thesis Evaluation Council held in Science Research Institute Of Clinical Medicine And Pharmacy 108 At (hour), / / 2019 This thesis may be found at: 1. National library 2. Library of Science Research Institute Of Clinical Medicine And Pharmacy 108
SUMMARY OF MEDICAL DOCTORAL THESIS
HA NOI– 2019
CSWS SIADH CNS
LIST OF ABRREVIATION
Clinical symptoms:Patients with mild hyponatremia only exhibit anorexia, insensitive drowsiness, nausea, vomiting. Consciousness disorders, coma, convulsions, hypothermia, acute circulatory failure, breathing disorders, decreased tendon reflexes may occur in patients with severe hyponatremia. Patients with acute severe hyponatremia may have a very high risk of neurological complications: confusion, coma, convulsions, apnea. Some nonspecific signs, such as loss of appetite, vomiting, apathy, nausea and fatigue, can be detected through clinical manifestations of hypotension, delayed pinches, sunken eyes, dry mucous membranes, lack of armpits sweat, tachycardia and orthostatic hypotension. Subclinical: + Serum sodium concentration ✓ Normal: 135 - 145 mmol/l ✓ Mild: 130 - 134 mmol/l ✓ Moderate: 125 - 129 mmol/l ✓ Servere: < 125 mmol/l + Serum osmolality: Sodium is the main ingredient that determines the serum osmotic pressure (90%). + Urinary sodium concentration: ✓ Urinary sodium concentration<20 mmol/l: Cause of hyponatremia is due to extra-renal salt loss. ✓Urinary sodium concentration> 20 mmol/l:Cause ofhyponatremia is due to renal salt loss. 1.2. The role and significance of sodium - osmostic pressure in the treatment of cerebral hemorrhage Hypotonic hyponatremia causes water to enter brain cells, leading to cerebral edema. Because the skull surrounds the brain, the brain is limited in dilation increasing intracranial pressure occurs, thereby aggravating the brain damage inherent in patients with cerebral hemorrhage. Hypovolemic hyponatremia may cause a decrease in cerebral perfusion flow, thereby aggravating the brain lesions in patients with cerebral hemorrhage. Hypernatremia is always accompanied by hypertonicity, so hypernatremia causes water to be pulled out from the brain cells, leading to brain cell atrophy. 1.3. Causes of hyponatremia in patients with cerebral bleeding Hyponatremia in patients with cerebral stroke and CNS lesions has begun to be studied much in the 70s of the twentieth century. Hyponatremia in patients with brain damage is mainly attributed to two syndromes: SIADH, CSWS, in addition to many causes such as the use of mannitol diuretics, furosemide, multiple fluids or possibly a combination of many causes. The differential diagnosis of these two syndromes is important
cerebral salt wasting syndrome of inappropriate anti-diuretic hormone secretion central nervous system
INTRODUCTION Hyponatremia is a common electrolyte disorder in patients with cerebral hemorrhage, accounting for 30-60%.Hyponatremia in patients with cerebral hemorrhage increases the rate of complications, mortalityand prolongsthe duration of treatment. Clinical symptoms of hyponatremia are poor, especially in patients with cerebral hemorrhage, they easily confused with symptoms of central nervous system (CNS)damage caused by cerebral hemorrhage such as confusion, seizure, coma…The reasons of hyponatremia and associatedfactors have not been clearly defined, but the results of many studies often suggest that the causes of hyponatremia are two syndromes: syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSWS). Clinically, these two syndromes have many similar and easily confused symptoms, but the pathogenesis mechanisms are completely different and treatment principles are also different. Some studies suggest that it is possible to determine causes of hyponatremia based on BNP, NT - ProBNP concentrations. Treatment of hyponatremia in patients with cerebral hemorrhage to ensure efficiency and safety is based not only on sodium levels even as mild but also on clinicalcharateristics , associated factors, and causes of hyponatremia. Currently, the consented recommendations is that3% NaCl solution is appropriate concentration, ensure treatment goals, minimize complications. Therefore we conducted the research:"Studying clinical and subclinical characteristics, asociated factors and treatment results of hyponatremia in patients with cerebral hemorrhage" with twoobjectives: 1. Comment on clinical, subclinical characteristics and factors associated with hyponatremia in patients with cerebral hemorrhage. 2. Evaluation of the treatment results of hyponatremia in patients with cerebral hemorrhage. Chapter 1 LITERATURE OVERVIEW 1.1. Definition of hyponatre mia Hyponatremia is defined as a serum sodium concentrationof less than 135 mEq/L. While hypernatremia is always associated with increasedserum osmolality, hyponatremia may be associated with low, normal or high blood osmolality.
because they differ in their nature and treatment. SIADH syndrome is an unreasonable secretion of ADH, leading to hyponatremia due to dilution (excess fluid volume) so treatment should limit infusion. CSWS syndrome is hyponatremia due to an increase in loss of sodium and water through the kidneys, so treatment needs to compensate for sodium and water. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) includes: ✓ Serum sodiumconcentration ≤ 135mmol/l ✓ Urinary sodiumconcentration> 20 mEq/l ✓ CVP> 6cmH2O ✓ Blood osmotic pressure <280mmol / kg ✓Urine osmotic pressure >Blood osmotic pressure ✓ Decreased A. uric, albumin, protein, Hb, Hct... ✓ Kidney function, thyroid, adrenal gland normal ✓There are no signs of peripheral edema, no signs of dehydration Principles of treatment Treat underlying disease. Restrict fluid - fluid restriction is the main treatment in most SIADH patients, with a proposed goal of less than 800 - 1000 ml /day. Fluid restriction may promote cerebral vasoconstriction in patients with subarachnoid hemorrhage because it is usually treated with an increase in circulating volume. As well as related to blood pressure, intracranial pressure is a very important factor in monitoring the treatment of patients with cerebral or subarachnoid hemorrhage. Therefore, hyponatremia in patients with cerebral or subarachnoid hemorrhageshould be treated with hypertonic saline (3%) to preserve cerebrospinal fluid and prevent cerebral edema complications of hyponatremia. Cerebral salt wasting syndrome (CSWS) includes: ✓ Serum sodium concentration ≤ 135mmol / l ✓ Urinary sodium concentration> 20 mEq / l ✓ CVP <6cmH2O ✓ Dehydration of the body: dry skin, tachycardia, increasedhematocrite, increased blood uric acid, increased blood albumin concentration. ✓ No renal failure, hypothyroidism, hypopituitarism Principles of treatment Restoring circulating volume with isotonic saline is the recommended therapy in CSWS, as it may prevent the release of ADH, thus allowing the elimination of excess water and correction of hyponatremia. Patients can continue to maintain 3% NaCl, depending on clinical manifestation.
1.4. Treatment of hyponatremia in patients with cerebral he morrhage The principle of treatment of hyponatremia is based on: ➢The condition of the extracellular fluid volume ➢The occurrence of clinical symptoms ➢The length of osmotic pressure reduction ➢ Risk of neurological complications Adjusting too quickly hyponatremia to normal values may cause myelin loss in the pons. Target of sodium adjustment: ➢Serum sodium concentration increase < 0.5 mmol / h, the total increase<10 mmol / 24h. ➢If the patient has seizures or other neurological symptoms, adjust the serum sodium concentration by 2-4 mmol / h within 2-4 hours to bring the patient out of danger. Chapter 2 SUBJECTS AND RESEARCH METHODOLOGY 2.1. Study subjects These patients diagnosed and treated for cerebral hemorrhage(intracerebralhemorrhage, subarachnoid hemorrhage) at Stroke Center 108 from 9/2016 to 9/2018. 2.1.1. Inclusion criteria Diagnostic criteria for cerebral hemorrhage: According the defination about stroke of WHO in 1989 Subclinical symptoms: brain CT image scan ... Diagnostic criteria for hyponatremia: serumsodium concentration <135 mmol/ l. 2.1.2. Exclusion criteria Patients with a history of heart failure, chronic renal failure, adrenal insufficiency, hypothyroidism, pituitary disease. Patients with brain tumors, tuberculous meningitis, cerebral infarction... Patients did not agree to participate in the study. 2.1.3.Standards to remove from the study The patient died within 24 hours during treatment. 2.1.4. Time and place of research Time: September 2016 - September 2018 Place: Brain Stroke Center - Central Military Hospital 108 2.2. Study methods A prospective descriptive study, longitudinal monitoring from admission to discharge or death - return home.
2.3. Research content and research criteria 2.3.1. General characteristics of the subject group in the study Age, gender Reasons for admission to the hospital Characteristics of the disease onset: gradual, exertion, sudden Time from onset of illness to admission (days) The previous treatment Medical history: hypertension, diabetes, stroke, hyperlipidemia, smoking, alcoholism ... Signs of onset: headache, vomiting, nausea, hemiplegia, coma in 2 groups of normal and low serum sodium concentration patients and finding differences. 2.3.2. Clinical, subclinical characteristics and related factors Describe clinical and subclinical characteristics • Clinical characteristics of cerebral hemorrhage patients with hyponatremia compared toa group with normal serum sodiumconcentrationat admission: + Headache, nausea, vomiting, dizziness, stiff neck, meningeal syndrome, sensory disorders, swallowing disorders. + Cognitive disorders: calculated on a scale of Glassgow divided into 3 levels of cognitive disorders: the severe level when Glassgow ≤8, the moderate level when Glasgow from 9 to12, the mild level when Glassgow from 13 to15 points. + Evaluation of muscle strength: right and left hemiplegia. + Evaluation of vital signs:an average of 2 groups through indicators: pulse, temperature, blood pressure, breathing rate. + Evaluation of stroke status on NISSH scale is divided into 5 levels: 0 points, 1-4 points, 5-15 points, 16-20 points, and 21 to 41 points. • Subclinical characteristics of cerebral hemorrhage patients with hyponatremia compared to a group with normal serum sodium concentration: + The average values of the indicators: erythrocytes, leukocytes, hemoglobin, hematocrit, platelets, APTT, PT, fibrinogen, glucose, urea, creatinine, cholesterol, triglycerides, enzymes AST, ALT, GGT, and bilirubin ... • Clinical characteristics in patients with cerebral hemorrhage with hyponatremia at the time of hyponatremia + Clinical changes when hyponatremia. + Classifyhyponatremia by three levels: <125 mmol / l, 125-129 mmol/l and 130- <135 mmol/l. Causes of hyponatremia + Classify clinical symptoms at the time of hyponatremia by causes: CSWS, SIADH, and other groups, and compare the differences among the groups of the causes + Assess the subclinical characteristics of patients at the time of hyponatremia according to 3 cause groups and compare the differences among them. + Blood osmotic pressure, assess blood osmotic pressure according to three
groups of causes and find differences. + Urinary osmotic pressure, assess the urinary osmotic pressure according to three groups of causes and find differences. + Urinary sodium concentration of the patients, surveyurinary sodium concentrationin 3 groups of causes and find differences. + Average Pro-BNP concentration by gender, age and correlation with NISSH stroke scale + Average ProBNP concentration according to 3 causes groups and find differences among these groups. Relationships • Relationship between hyponatremia and medical history. • Relationship between the site of brain lesions and hyponatremia. • Relationship between the size of brain damage and hyponatremia. • Relationship between vascular intervention and hyponatremia. • Relationship between treatment measures and hyponatremia. 2.3.3. Evaluate the results of treating hyponatremia in patients with cerebral hemorrhage • Treatment results in two patient groups with hyponatremia and nonhyponatremiainclude: living without sequel, living with sequeles and death according to mRs Score from admission to discharge, then find difference between two groups. • Treatment results for three causes of hyponatremia: CSWS, SIADH and other causes. Compare the difference among them. • Change of clinical and subclinical indicators after treatment compared to before treatment. • Average hospitalization duration of hyponatremia patients in 3 groups. • Duration of treatment with 3% NaCl. • Complications of both hyponatremia and non-hyponatremia groups during a period of hospitalization: pneumonia, sepsis, convulsions and acute renal failure... • Results of hyponatremia treatment with NaCl3%: changes in blood osmotic pressure, urinary osmotic pressure, urinary sodium concentration, serum sodium concentration,and complications during treatment. • Cognitive changes when treating withNaCl3% in three groups of causes according to three levels: better, unchanged, worse. • Post-treatment change in patients with hyponatremia. • Effect of hyponatremia on the outcome of treatment. • Changes in muscle strength after treatment • Change NISSH scale after treatment. • Rankin from admission upon discharge. 2.4. Research process
All patients admitted and diagnosed with cerebral hemorrhage were tested for plasma electrolyte tests; asked about the disease; exam on clinic and subclinical according to sample medical record of 108 Central Military Hospital. Electrolyte test was repeated at least once during treatment of patients with cerebral hemorrhage, normally serum sodium concentration was checked every 2 -3 days; in severe cases, hyponatremia patients were checked for serum sodium concentration every 24 - 48 hours. Hyponatremia patients (Na + <135 mmol/l) were tested for urinary electrolyte tests(urinarysodium concentration at a moment and/or urinary sodium concentration in the next morning), urine osmotic pressure, blood osmotic pressure. Hyponatremia patients with urinary sodium concentration> 20mmol/l (renal sodium loss) were clinically monitored, placeda central venous catheter to measure central venous pressure, tested urea, creatinine, a.uric, albumin, protein, Hb, Hct ... to diagnose and determine the causes of hyponatremia. The NT-proBNP test was performed on apatient at the time of hyponatremia detection. Patients with hyponatremia are classified, assessed for risk, and treated: +Patients with mild hyponatremia (131 ≤ Na ≤134 mmol / l), mild clinical manifestations, no clinical adverse events and diabetes with poor blood sugar control, hypertension or fluctuating blood pressure,did not treat hyponatremia and continued to be monitored and corrected based on clinical status and subsequent blood sodium. + Patients with mild hyponatremia, without symptoms, risk of complications such as worse cognitive, worse paralysis, increased headache, vomiting, nausea ... and stable blood pressure control, were guided to increase serum sodium concentration by a rise in solute intake with 10g of salt in the daily diet. + Patients with profound hyponatremia (Na + <125mmol / l), moderate hyponatremia (125 ≤ Na + ≤ 129 mmol / l) and mild hyponatremia (130 ≤ Na + ≤134 mmol / l) accompanied by symptoms , risk of complications such as worse cognition, worse paralysis, more or not reduced headache, vomiting, nausea, convulsion - epilepsy..., were used NaCl3% solution in hyponatremia treatment. These patients were tested for blood sodium monitoring every 24 -48 hours during hypertonic salt treatment and checked every 6 hours for the progression and severity of the disease. Patients were monitored during treatment until thedisease stabilized or death. The procedure of intravenously infused maintenance of NaCl 3% solution in the treatment of hyponatremia according to Carolyn W et al: + Patients with profound and moderate hyponatremia: starting with
intravenously infusion of 450ml ofNaCl3% solution and maintaining for 24 hours. + Patients with mild hyponatremia: starting with intravenously infusion of 225ml ofNaCl3% solution and maintaining for 24 hours. Serum sodium concentration test is repeated every 24 - 48 hours and the dose of NaCl 3% solution is adjusted [Na +] below 130mmol/l: increase the volume of NaCl 3% solution to 650ml/24h; if currently not infused, the volume is 450ml / 24h. [Na +] in the range of 130 - 134 mmol / l: maintaining the volume ofNaCl 3% solution; if currently not infused, the volume is 225ml/24h. [Na +] in the range of 135 - 150mmol / l: stop the infusion, check the sodium concentration and adjust according to the reference scale. * In case of severe, acute and complicated hyponatremia: quickly remove serum sodium concentration from the danger zone before sustaining intravenous infusion. * When identifying the cause of hyponatremia, hyponatremia treatment is adjusted according to the specific cause: + Treatment of hyponatremia in patients with cerebral bleeding when the cause is SIADH: NaCl 3% solution should be continued to maintain (recommended to use in hyponatremia due to SIADH in patients with cerebral hemorrhage). NaCl 0.9% solution is indicated for about 1000ml/24 hours with no limit of lower fluid because of the risk of other complications such as cerebral vasospasm, cerebral infarction ...; consider using furosemide if there are no contraindications, the doses of furosemide and NaCl 3% solution are based on the level of fluid excess, the level of hyponatremia. + Treatment of hyponatremia in patients with cerebral hemorrhage when the cause is CSWS: Circulating volume compensation with isotonic saline solution (NaCl 0.9%) is the recommended therapy in CSWS, as it may prevent the release of ADH, thus allowing the elimination of excess water and adjusting hyponatremia. The volume of NaCl 0.9% depends on the patient's lack of fluid and is adjusted according to the course of the disease, the amount of fluid is usually supplemented at 2000 - 3000ml / 24 hours, NaCl 3% solution is considered further whether maintained or not, depending on the degree of hyponatremia and clinical manifestations of the patient. Treatment of brain bleeding according to the algorithm:
hyponatremia from day 1 to day 4, from day 5 to day 8, and between day 9 and from day 14 are 42.23%, 32.72% and 16.67%, respectively. 3.2.3.Clinical changes at the time of hyponatremia
2.3. Analyzing data - Entering data and cleaning data with EpiData software 3.1 - The data after cleaning will be transferred to STATA 12.0 software to analyze the results.
1 2 01
3 0 20 0 0 01 00 12
32 23 15
Figure 3.3. Clinical changes when hyponatremia Comme nt: There were 87 patients with hyponatremia from the second day after admission in which: 40/59 patients still had headache at the moment of hyponatremia, 1 patient had just appeareda headache and 5 patients had increased headache. 17/87 patients (19.50%) worsened with perception, 42/87 patients (48.27%) had no improvement in perception. 13 /51 patients (25.49%) increased paralysis. 3.2.4. Causes - The degree of hyponatremia
Chapter 3 RESULTS 3.1. General informations of the research subjects We followed 409 patients with cerebral hemorrhage between 2016 and 2018, among them there were 180 hyponatremia patients (44%), 21 hypernatremia patients (5.1%) and 208 patients with normal serum sodium concentration. The average age of the study group was 58.9 years old. The proportion of male patients (64.3%) was higher than female patients (35.7%). 3.2.Clinical and subclinical characte ristics of cere bral he morrhage patie nts with hyponatre mia 3.2.1. Status - The hyponatremia moment 6% (17) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
41%(11 6)) Intracerebral (n=283)
Subarachnoid (n=126) Normal
Figure 3.1. Status - The hyponatremia moment
Figure 3.5. The level of Figure 3.4. Causes of hyponatremia hyponatremia Comme nt: Among 180 cerebral hemorrhage patients with hyponatremia, 14 patients (8%) had severe hyponatremia(<125 mmol / l), 59 ones (33%) had moderate level (125-129 mmol / l) and 107 patients (59%) had mild hyponatremia (130 - 134mmol / l). Hyponatremia caused by CSWS, SIADH and unexplained causes accounted for 24.4%, 33.3%, and 42.3%, respectively.
Figure 3.2.The rate of hyponatremia over time
Comme nt: 180/409 patients with hyponatremia accounted for 44%, ones with hypernatremia accounted for 5.1%, 50.9% of total patients had normal serum sodium concentration. The rate of hyponatremia patients with subarachnoid hemorrhage (50.8%) was higher than hyponatremia patients with intracerebral hemorrhage, whereas hypernatremia was more common in patients with intracerebral hemorrhage (6% - 3.2%). Occurrence of hyponatremia is most prevalent in the first day of the disease, accounting for 15%, the percentages ofpatients with occurrence of
3.2.6. Clinical characteristics of hyponatremia in the groups of causes: CSWS, SIADH and unknown causes Table 3.8. Clinical characteristics of the groups of hyponatremia causes CSWS SIADH Unknow cause Causes (n=44) (n=60) (76) symptoms Headache 17(38,64%) 35(58,33%) 52(43,9%) Dehydrated dry 12(27,27%) 0 0 skin Dysphagia 29(65.9%) 23(38,3%) 19(25,0%) 24-hour urine (ml) 3547.95± 1161.45 2463.52 ± 974.98 2629.93 ±1086.42
107,1 ± 133,1
OR 95% CI
2,6 (1,1 – 5,9)
4,6 (2,1- 9,9)
1,8 (1 – 3,1)
Medical history Diabetes
0.00 <0.01 <0.01
Comme nt: Dehydrated dry skin was only seen in patients with hyponatremia due to CSWS (p <0.05). Dysphagia were more common in hyponatremia owning to CSWS (p <0.05). The amount of urine of patients with hyponatremia due to CSWS was higher than that of patients with hyponatremia due to SIADH and other causes. Table 3.9. Clinical symptoms of patients with hyponatremia according to etiology groups(continued) Hyponatre mia Hyponatre mia Unknow Clinic due to CSWS due to SIADH cause p (n=44) (n=60) (n=76) Glasgow 10.02 ±3.63 11.46 ±3.40 13± 2.75 <0.001 NISSH 21.21± 1.36 14.12 ±10.66 10.19 ±10.85 <0.001 Comme nt: The Glasgow score of patients with CSWS hyponatremia was the lowest, there was a difference in Glasgow score of 3 etiology groups (p <0.05). There was a difference in NISSH score at admission in the 3 groups of hyponatremia causes. The NISSH score was the highest in CSWS patients. 3.2.12. NT-proBNP concentration in causes of hyponatremia Table 3.18. NT-proBNP concentration in causes of hyponatremia Cause of CSWS SIADH hyponatremia p (n=31) (n=47) NT-proBNP (pg/ml)
hemorrhage 3.3.3. Relationship between hyponatremia and medical history Table 3.22. Relationship between hyponatremia and medical history
Comme nt:NT-proBNP concentration in patients with hyponatremia due to CSWS (420.1 ± 285.5 pg / ml) was higher than in patients with hyponatremia due to SIADH (107.1 ± 133.1pg / ml) with statistical significance p <0.05. 3.3. Several factors associated with hyponatremia in patients with cerebral
Hypertension with regular treatment Smoke
Comme nt: Patients with diabetes had a 2.6 times higher risk of hyponatremia (p <0.05). Patients with regularly treated hypertension had 4.6 times higher risk of hyponatremia (p <0.001). Smoking patients had 1.8 times higher risk of hyponatremia than non-smoking patients (p <0.05). 3.3.4. Relationship between hyponatremia and brain damage Relationship between hyponatremia and location of the injury Table 3.23. Relationship between hyponatremia and location of the injury Location of injury
Hyponatremia ( n=180)
OR (95% CI)
Frontal lobe (12)
Central gray (94)
2,2 (1,4 – 3,6)
2,5 (1,5 – 4,2)
Comme nt: Patients with frontal lobe lesions had 2.5 times higher risk of hyponatremia than patients without frontal lobe lesions (p <0.01). Patients without lesions in central gray were 2.2 times higher at risk hyponatremia than patients with central gray lesions (p <0.01). Patients with ventricular hemorrhage were 2.5 times more likely to have hyponatremia than nonhemorrhagic ventricular patients (p <0.001). Relationship between hyponatremia and lesion size
Table 3.24.Relationship between hyponatre mia and lesion size
times higher than those without mechanical ventilation (p <0.001). Patients with Glasgow ≤ 8 had 2.4 times higher risk of hyponatremia than Glasgow patients with Glasgow score > 8 (p <0.01). 3.4. Treatment results 3.4.2. Change of serum sodium concentration, blood osmotic pressure before and after treatment Percentage of patients reaching the target of treating hyponatremia with NaCl 3% infusion (135mmol/l ≤ Na < 150mmol/l) Table 3.28.Percentage of patients reaching the goal of treating hyponatremia with NaCl 3% infusion(135mmol/l ≤ Na < 150mmol/l)
Volume of Hyponatre mia Normal (122) p injury (cm3) (91) <30 52(35,9%) 93(64,1%) 30-60 24(54,5%) 20(45,5%) <0,05 >60 15(57,7%) 11(42,3%) Comme nt:There was a statistically significant relationship (p <0.05) between hyponatremia and brain lesion size, the greater the volume of lesions, the higher the rate of hyponatremia. 3.3.5. Relationship between vascular intervention and hyponatremia Relationship between vascular intervention and hyponatremia Table 3.25.Relationship between vascular intervention and hyponatremia Vascular intervention Non- intervention (257) Coil embolization (79) Drain, open the skull(52)
OR (95% CI)
Comme nt:Patients with opened or drained skulls had 2.7 times higher risk of hyponatremia than non-intervention patients and the difference was statistically significant with p <0.05. 3.3.6. Relationship between hyponatremia and perception, the internal treatment Table 3.26. Relationship between hyponatremia and perception and treatment Method Glasgow Mannitol 20% Furosemid With oxygen respirator
Commme nt: The rate of patients infused 20% mannitol and having hyponatremia (51.8%) was 2.3 times higher than patients with normal serum sodium concentration. Patients with oxygen respirator had a risk of hyponatremia 2.6
135mmol/l ≤ Na < 150mmol/l Na < 135 mmol/l Na ≥ 150 mmol/l
Number of patients (n) 69 12 2
Percentage (%) 83.13% 14.46% 2.41%
Commets:69/83 patients (83.13%) reached the goal of treating hyponatremia (135mmol/l ≤ Na < 150mmol/l), 12 patientshad hyponatremia (14.46%), 2 patients had hypernatremia (2.41%). Modification of serum sodium concentration before and after treatment with NaCl 3% solution Table 3.30.Modification of sodium before and after treatment withNaCl 3% solution Causes CSWS Na (n=29) Na before treatment 128.83± 3.66 (mmol/l) Na after treatment 137.13± 6.70 (mmol/l) Delta Na per day (mmol/l)
All causes (n=83)
137.37±5.47 2.95 ± 3.45
Comme nt:The average serum sodium concentration was 128.97±3.30 mmol/l at the start of using NaCl 3% the infusion and 137.25±5.53 mmol/l when stopping infusion, the average correction of serum sodium concentrationwas 2.95 ± 3.45 mmol per day. Increased blood sodium concentration and blood osmotic pressure during treatment with 3% NaCl solution Table 3.32.Complications during treatment withNaCl 3% Number of patients Percentage Complications (n=83) (%) Hypertonic 2 2,4% Hypernatremia 2 2,4% Comme nt: 2/83 patients (2,4%) had hypernatremia, 2 patients had blood hypertonic during treatment of NaCl 3% infusion. 3.4.4. Clinical changes before and after hyponatremia treatment
withNaCl3% solution Cognitive changes (Glasgow) before and after treatment with NaCl 3% solution 19 (63.3%)
10 4 (1,92%) 2 (0,96%)
20 5 (2,78%) 3 (1,4%)
Chapter 4 DISCUSSION 4.1. General characteristics of the research group 4.1.1. Distribution of patients with cerebral hemorrhage by gender and age Age and gender From 2016 to 2018, we monitored 409 patients with cerebral hemorrhage, including 126 patients with subarachnoid hemorrhage, 283 patients with bleeding in the brain parenchyma,accounting for 30.8%, 69.2% respectively. The average age of the study group was 58.9 ± 15.2. The common age is 41 - 60 years old (45.5%) and 61 - 80 years old (39.1%). The proportion of men (64.3%) was more than women (35.7%), this was also characteristic of the stroke group. Males were more common than females in both subarachnoid hemorrhage and bleeding in brain parenchyma. 4.2. Clinical and subclinical characteristics of cerebral he morrhage patients with hyponatre mia 4.2.1. Blood sodium concentration status 180/409 patients with hyponatremia accounted for 44% and hypernatremia patients made up 5.1%.50.9% of total patients had normal blood sodium concentration. The rate of hyponatremia in patients with subarachnoid bleeding (50.8%) was higher than in patients with cerebral hemorrhage (41%), whereas hypernatremia was more common in patients with intracerebral bleeding (6% - 3.2%). 4.2.2. The moment of hyponatremia occurence
Convulsions Acute renal failure
Figure 3.13.Complications during hospitalization Comme nt:7.8% of total hyponatremia patientshad pneumonia complications, while this rate in patients with normal blood sodium concentration was .9%, this difference was statistically significant. Sepsis complication - severe infections and seizures in hyponatremia and normal groups was 4.4%, 1%, respectivelyand this difference was statistically significant with p <0.05.Acute renal failure in the hyponatremia group was also more common.
Better (45/83) Unchanged (30/83)
Figure 3.9. Perception change before and after treatment with NaCl 3% solution in the groups of hyponatremia causes Comme nt: 42/79 patients were better about cognitionafter treatment, accounting for 53.16%, the cognition of 31/79 patients(39.24%) was unchanged. 6 patients (7.59%) were worse aboutcognition after treatment. The average Glasgow score was 12,84 ± 2,89 point at the starting of treatment and 13,01 ± 2,86 point when finishing treatment 3.4.8. The general results of the research group Table 3.35.The general results of the research group Results
Living without complications
Living with complications
Mild disability (mRs=0,1,2)
Moderate disability (mRs=3,4)
Serious disability, TV (mRs=5,6)
Comme nt: The rate of dead(7,3%) và complicated(64,4%)hyponatremia patients was higher than patients having normal serum sodium concentration ,with 2,4%; 62,0% (p <0,05), respectively.The rate of having a moderate and serious disability in the hyponatremia cerebral hemorrhagic patientswas higher than those in patients with normal serum sodium concentration. The average ranking score of hyponatremia group (2.95±1.65) was higher than that of the group without hyponatremia (2.19 ±1.513). 3.4.12. Complications during hospitalization
Occurrence of hyponatremia is most prevalent in the first day of the disease, accounting for 15%, the percentages of patients with the occurrence of hyponatremia from day 1 to day 4, from day 5 to day 8, and between day 9 and after day 14 are 42.23%, 32.72% and 16.67% , respectively (Figure. 3.3).These results indicate that monitoring of hyponatremia should be considered at the time of admission and continue for approximately 14 days of illness. This result is also consistent with studies of Dang Hoc Lam (2010), Saleem S (2014), Alimohamadi M et al. (2016): hyponatremia on the first day of 15.1%. 4.2.3. Clinical changes at the time of hyponatremia Among 180 cerebral hemorrhage patients with hyponatremia, 87 patients had hyponatremia from the second day after admission, we compared some clinical symptoms at the time of hyponatremia occurrence: Headache: 40/59 patients (67.79%) still had a headache at the time of hyponatremia, 5/41 patients (12.19%) had an increase in head level. Perceptual status (Glasgow): 17/87 patients (19.50%) had the cognitive deterioration, 42/87 patients (48.27%) had the unchanged perception status; thus worsening perception is a hyponatremia symptom in patients with cerebral hemorrhage, especially when these patients have no change in brain lesion on CT or MRI of the brain. Nguyen Viet Quang (2013) researched on patients with traumatic brain injury and showed a positive correlation between Glasgow score and blood sodium concentration. Paralysis: 13/51 patients (25.49%) had increased paralysis, 23/51 patients (45.09%) had unchanged paralysis. The high rate of increased paralysis may be due to the progression of cerebral bleeding, but it is also possible that hyponatremia may contribute to this increase. 4.2.4. Causes of hyponatremia Hyponatremia caused by CSWS, SIADH and unknown causeaccounted for 24.4%, 33.3%, and 42.2%, respectively. Our rate is similar to that of Kao L et al (23% - 34.5%). The rate of CSWS is very diverse, not consistent according to each author and it is often described in cases of meningeal tuberculosis, neurosurgery and CNS lesions. According to Natarajan K et al (2016), the rates of hyponatremia due to CSWS, SIADH and unexplained causes were 31%, 46%, 23%, respectively. 4.2.5. Levels of hyponatremia Among 180 cerebral hemorrhage patients with hyponatremia, 14 patients (8%) had severe hyponatremia (<125 mmol / l), 59 ones (33%) had moderate level (125-129 mmol / l) and 107 patients (59%) had mild hyponatremia, thus patients mainly hadmild hyponatremia (130 - 134 mmol / l). According to Ha QuangBinh (2012), these percentages are 16,7%,23,8%, and 59,5%, respectively.
CSWS, SIADH and unknown causes Dry skin (100%), dysphagia (45.4%) were more common in patients with hyponatremia due to CSWS (<0.05). This result is consistent with the pathogenetic mechanism of CSWS. Hyponatremia associated with dehydration, swallowing disorders can be confused because compared to SIADH and other causes CSWS often occurs in more severe patients. Glasgow score of patients with CSWS hyponatremia was the lowest, there was a difference of Glasgow score in 3 cause groups (p <0.05). The rate of patients having Glasgow score ≤ 8 pointsis higher than one in 2 rest causes. There was a difference in NISSH score at admission in the three groups of hyponatremia causes, the NISSH score was the highest in CSWS patients, and CSWS patientshavingNISSH scores> 21 pointsaccounted for a much higher proportion than those in the rest two causes. This result confirms our finding above: CSWS is more common in patients with severe clinical manifestations. The urine indices had a statistically significant difference (p <0.01) in 3 groups of causes, in which hyponatremia due to CSWS was much higher. Thus, polyuria is the symptom suggesting a diagnosis of hyponatremia due to CSWS. According to Allen IArieff et al (2017), the amount of urine in CSWS patients is more than that of SIADH patients. Symptoms such as low urination, oliguria were not clear because a large number of patients with cerebral hemorrhage were treated with mannitol and/ or furosemide. There were no signs of dehydration, thus we did not monitor weight gain due to fluid retention in study patients. 4.2.7. NT-proBNP concentrations in the groups of hyponatremia causes The concentration of NT-proBNP in CSWS patients (420.1 ± 285.5 pg / ml) was higher than in SIADH patients (107.1 ± 133.1pg / ml), the difference was statistically significant with p <0.05. Our results were similar to those of Spatenkova V et al. in 2008: NT-proBNP concentration was significantly higher in patients with CSWS (430.4 ± 706.4 pg / ml) compared to not only the reference range (125 pg / ml, P = 0.001) but also the control group (268.3 ± 203.9, P <0.001). According to George Tobin et al (2018), NT-proBNP> 125 pg / ml could diagnose CSWS with 87.50% sensitivity and 93.33% specificity (P <0.001). Positive predictive value is 93, 33% and the negative predictive value is 87.50%. 4.3. Some factors associated with hyponatremia in patients with cerebral hemorrhage 4.3.1. Relationship between hyponatremia and medical history Patients with diabetes are 2.6 times more likely to suffer from hyponatremia than those without diabetes (p <0.05). Huang WY et al. (2012) studied 925 patients with cerebral infarction. Diabetes was significantly 4.08
4.2.6. Clinical characteristics of hyponatremia in the groups of causes:
times higher in patients with hyponatremia (p <0.001). Patients with hypertension who were regularly treated had 4.6 times higher risk of hyponatremia and the difference was statistically significant (p <0.001). Smoking patients had a 1.8 times higher risk of hyponatremia than nonsmokers and the difference was statistically significant (p < 0.05). We do not understand the causes and pathogenetic mechanisms of these factors. According to Kuramatsu JB et al (2014), a 464- patient study showed that medical histories of hypertension, smoking, and thiazide diuretics were seen in hyponatremia patients more than patients with normal blood sodium concentration. 4.3.2. Relationship between hyponatremia and brain lesions Relationship between hyponatremia and site of lesions Patients with brain lesions in the frontal lobe were 2.5 times more likely to have hyponatremia than patients without brain lesions in the frontal lobe and the difference was statistically significant (p <0.01). The percentage hyponatremia at this position was 66.7%. The rate of hyponatremia in the brain lesion group in the periaqueductal gray was 31.9%. Patients without damage of the central gray were 2.2 times more likely to have hyponatremia and the difference was statistically significant (p <0.01 ) Patients with ventricular hemorrhage were 2.5 times more likely to have hyponatremia and this is statistically significant difference (p <0.001). The rate of hyponatremia in this position is 64.2%. Research by Natarajan K et al. (2016) shows that hyponatremia is more common in patients with right brain lesions. Relationship between hyponatremia and size of the lesions The patients with lesion size less than 30cm3 had a lower rate of hyponatremia (35.9%), while the large size group above 60cm3 had a significantly higher rate of hyponatremia (57.7%). There was a statistically significant relationship (p <0.05) between hyponatremia and size of brain lesions, the larger the volume of lesions, the higher the rate of hyponatremia. According to Kuramatsu JB et al. (2014), patients with hyponatremia have a larger lesion size compared to the group without hyponatremia (23.4cm3 compared to 17.7cm3). 4.3.3.Relationship between hyponatremia and cognition , treatment methods Relationship between vascular intervention and hyponatremia Vascular interventions are related to hyponatremia in patients with cerebral hemorrhage. In 52 patients with opening cranial interventions and having an external drain, more than half (67.3%) of patients had hyponatremia. Among patients with coil embolizations, 43% of them hadhyponatremia, 43.2% of patients without interventionhad hyponatremia. Patients with opening cranial and drainage interventions were 2.7 times more likely to have hyponatremia, and the difference was statistically significant with p <0.05. Relationship between hyponatremia and cognitition, treatment methods
In cerebral hemorrhage patients infusedmannitol 20% solution, the proportion of patients with hyponatremia (51.8%) was 2.3 times higher than patients with normal blood sodium concentration. Osmotic diuretics cause water distribution disorders, leading to hyponatremia. A study of Carole I et al. (2009) mannitol 20% reduced serum sodium and chloride concentration to 97.7% and 98.5%, respectively. Patients with mechanical ventilation had a risk of hyponatremia 2.6 times higher than those without mechanical ventilation and the difference was statistically significant (p <0.001). According to Truong Thi Mai Hong (2012), the rate of intubation and mechanical ventilation in patients with hyponatremia 105/339 (31%) is significantly higher compared to patients with normal blood sodium concentration 40/470 (8.5%). Patients with Glasgow ≤ 8 points were 2.4 times more at risk of hyponatremia than patients with Glasgow > 8 point and the difference was statistically significant (p <0.01). According to Ha QuangBinh (2012): the rate of hyponatremia in Glasgow ≤ 8 group is 90.5% and higher than that of Glasgow> 8 point group (9.5%). 4.4. Results of treatment 4.4.1.Change of serum sodium concentration, blood osmotic pressure before and after treatment with NaCl 3% solution Rate of the patients reaching the goal of treatment 69 / 82 patients (83.13%) achieved the goal of treating hyponatremia(135mmol / l ≤ Na <150mmol / l). 12 patients have low blood sodium concentration because these patients were discharged or determined the cause and blood sodium> 130mmol / l, we stoppedto infuse NaCl 3% solution. 2 patients had hypernatremia. In the group of patients supplemented with table salt, 12 / 20 patients (60%) reached the goal of treating hyponatremia (135mmol / l ≤ Na <150mmol / l), 8 patients had low blood sodium concentration in the range 130 - 134 mmol / l, accounting for 40% , no patients had hypernatremia. Carolyn Woo et al. (2009) studied 176 hyponatremia patients treated with 3% NaCl solution (Na ≤ 133 mmol / l or a rapid reduction of 6mmol / 24h) and in 49 patients who weresustantively infused NaCl3% solution 83.8% of them reachedthe goal of treatment. Change of serum sodium concentration before and after treatment with NaCl 3% solution The average blood sodium concentration at the beginning of infusingNaCl 3% solution was 128.97 ± 3.30 mmol / l, and 137.37 ± 5.47 mmol / l when stopping infusion. The rate of blood sodium correction is 2.95 ± 3.45 mmol /day. Our blood sodium correction rate is lower than that of the study of Carolyn Woo (0.44 ± 0.36mmol / hour). This result may be due to that in Carolyn Woo's study, the 3% NaCl infusion rate was adjusted more frequently
every 6 hours, whereas in our study every 24 to 48 hours. Change of Blood osmotic pressure before anđ after treatment with NaCl 3% solution Blood osmotic pressure increased after treatment with the most changes in SIADH group. All SIADH patients increased osmotic pressure, while the remaining 2 groups had some patients with decreased blood osmotic pressureafter treatment. Hypernatremia, blood osmotic pressure during treatment with NaCl 3% solution 2/83 patients (2.4%) had hypernatremia (Na> 150mmol), 2 patients increased blood osmotic pressure,at the time of hyponatremia and after treatment: 334mosmol / kg, 342 mosmol / kg, respectively) . The reason is that at the beginning of treatment, we did not have the result of blood osmotic pressure, and patients with diabetes. During treatment with NaCl 3% solution, no clinical manifestations of complications were noted. Blood sodium concentration also quickly returned to normal when stopped using NaCl 3% solution. 1 patient increased blood osmotic pressure due to hypernatremia (Na = 163mmol / l), this patient also stopped infusion, adjusted to normal and the patient was discharged from hospital with good status (Glasgow: 15 points), our complication rate was similar to Carolyn Woo and much lower according to Froelich M et al. This is due to that infusion NaCl3% did not have a suitable reference and adjustment process. 4.4.2. Change of cognition before and after treating hyponatremia with NaCl 3% solution 42/79 patients had a good improvement in perception after treatment accounted for 53.16%, 31/79 patients (39.24%) did not have any change in perception after treatment. Post-treatment perceptions of 6 patients (7.59%) worsened. The average value of Glasgow at the beginning of treatment was 12.84 ± 2.89 point and 13.01 ± 2.86 point in the end . Among them, CSWS patients have the most obvious improvement in perception Figure 3.10. In addition to treating hyponatremia, NaCl 3% solutionhas antiedematous effect and is the most effective in hyponatremia patients in the acute phase of brain bleeding (<7 days). According to Nguyen Anh Tuan (2014), Le Hong Trung (2017), Kamel H et al. (2012) NaCl 3% solution is effective in the treatment of increased intracranial pressure. The time of control intracranial pressure of this solution is longer than mannitol. This may also be the cause of clinical change, especially headache manifestation when infusingNaCl 3% to treat hyponatremia.
4.4.3. The general results of the research group The mortality rate of the hyponatremia group was 7.3%, 69.5% of the surviving patients had complications at some levels: living without complications at 28.3% while in the group having normal blood sodium concentration, these rates were 2.4%, 62% and 35.6%, respectively There was a statistically significant difference with p <0.05 of these rates. The mortality rate in patients with hyponatremia was higher than in patients with normal blood sodium complications while the rate of unsequeled survival was lower. Evaluation of treatment results on 1195 patients with cerebral hemorrhage due to hypertension at 108 Hospital Brain Stroke Center from 2003 to 2011: the death rate was 11.3%, 68.2%. ofthe survival lived with complication. Evaluation of the degree of disability of the patients on a Rankin scale when discharge showed that patients with CMN had hyponatremia, the rate of cerebral hemorrhage patients with mild disability (39.4%) was lower than that of patients without hyponatremia(60.1%). However, the prevalence of moderate and severe disability was higher (42.8% - 17.8% compared to 29.3% - 10.6%). The average Rankin score of the group with hyponatremia (2.95 ± 1.65) was higher than the group without hyponatremia (2.19 ± 1,513), these differences were statistically significant with p <0.05. According to Ha QuangBinh( 2012) the mortality rate in the hyponatremia group was much higher than the group with normal blood sodium concentration, univariate analysis showed a significant association with OR = 0.273, 95% CI 0.08 - 0.88 , p = 0.029.Corona et al. (2013): hyponatremia even mildly was associated with a significant increase in mortality in the ICU department (RR: 2.60; 95% CI: 2 , 31 - 2.93, p <0.0001). 4.4.4. Complications during hospitalization The rate of pneumonia in cerebral hemorrhagic and hyponatremia patients (7.8%) was higher than that of patients with normal blood sodium concentration (1.9%). According to Huang WY et al. (2012) , in 925 patients with cerebral infarction, pneumonia found in the hyponatremia group was 2.15 times higher than the group with normal blood sodium concentration (p <0.05). Sepsis complication - severe infections and seizures in the hyponatremia group was 4.4% while in the normal sodium group,this rate was 1%. This difference was statistically significant with p <0.05. Acute renal failure was also found morein the hyponatremia group (2.78% compared to 1.4%). According to Do Mai Huyen and Nguyen Van Thong ‘s (2012) retrospective study on 6213 patients with acute brain stroke pneumonia rate was 4.8%, convulsive complication rate was 0.94%, secondary brain bleeding was 0.3% while in our study, two patients (1.1%) were diagnosed with secondary brain bleeding in the hyponatremia group and nobody in the normal blood sodium concentration group.
CONCLUSIONS Through a study of 409 patients with cerebral hemorrhage, including 180 patients with hyponatremia at Military Central Hospital 108 from 2016 to 2018, we draw some conclusions 1, Clinical, subclinical characteristics, factors associated with hyponatremia in patients with cerebral hemorrhage: Hyponatremia was a common electrolyte disorder in patients with cerebral hemorrhage at 44%; the rate of hyponatremia in patients with intracerebral hemorrhage was 41% and in subarachnoid bleeding was 50.8%. The most common occurrence of hyponatremia is in the first day of the disease, accounting for 15%, hyponatremia from day 1 to 4 accounted for (42.23%); Severe hyponatremia (blood sodium <125mmol / l) accounted for 8%, moderate and mild hyponatremia made up 33% and 59% respectively. Cerebral hemorrhagic patients with hyponatremia have lower Glasgow points and higher NISSH scores than those with normal sodium concentration; the frequency of symptoms of nausea, stiff neck, meningeal syndrome, swallowing disorders in patients with hyponatremia is higher. 25.49% of patients showed signs of worsening perception had little improvement in headaches and more significant paralysis. Hyponatremia caused by CSWS accounted for 24.4%, by SIADH accounted for 33.3%, by the unknown causes made up 42.2%; CSWS patients are older than SIADH. Signs of dry skin and dehydration were seen only in CSWS patients, swallowing disorders were higher in CSWSgroup , and a headache was more common in SIADH patients (p <0.05). Hyponatremia due to CSWS has a lower Glasgow score and a higher NISSH score than SIADH patients and other causes (p <0.05). There was a statistically significant difference in the amount of urine of patients in 3 cause groups (p <0.01) The amount of urine of CSWS patients (3547.95 ± 1161.45ml) was much higher than that of SIADH and other groups. The blood osmotic pressure group (>295mosmol/kg) in CSWS patients accounted for and was more than that in SIADH patients (15.6%), with p <0.05. NT-proBNP in CSWS patients (420.1 ± 285.5pg / ml) was higher than in SIADH patients (107.1 ± 133.1pg / ml) with p <0.05. Patients with medical histories of diabetes, hypertension, smoking had a higher risk of hyponatremia than the group without these diseases (p <0.05). Patients with brain lesions in the frontal lobe, ventricular hemorrhage were at higher risk of hyponatremia, whereas lesions of central gray had a low risk of hyponatremia with OR respectively: 2.5-2.2-2.5.\ (p <0.05).The larger the
volume of lesions is, the higher the rate of hyponatremia is. Patients with 20% mannitol use, mechanical ventilation, Glasgow score ≤ 8 point, cranial opening and cranial drainage have a higher risk of hyponatremia with OR: 2,3-2,6-2,4-2,7, respectively. 2. Evaluation of results of hyponatremia treatment in patients with cerebral he morrhage: 83 patientswith cerebral hemorrhage (46.11%) were selected to treat hyponatremia with infusing NaCl 3% 63 / 83 patients (83.13%) achieved the goal of treatment (135mmol / l ≤ Na <150mmol / l); blood sodium correction rate is 2.95 ± 3.45 mmol / day. Treatment of hyponatremia with NaCl3% solution improves headaches, nausea, perception, ... The rate of hypernatremia and an increase in blood osmotic pressure during the treatment of hyponatremia with NaCl 3% infusion was very low (2.4%, 2.4%). There was a statistically significant improvement of hyponatremia group in Glasgow points, muscle strength, and NISSH scores when discharge. The group of patients with hyponatremia had a longer average hospitalization, a longer duration of treatment at the lower health facilities and a statistically significant difference (p <0.01). CSWS patients had a longer hospital stay than SIADH patients (p <0.05). The mortality rate of patients with hyponatremia was 7.3%, 69.5% of all patients lived with complications at some levels . The mortality rate of patients with hyponatremia (7.3%) was higher than that of patients with normal blood sodium concentration (2.4%) with p <0.05. CSWS patients had a higher mortality rate and complicated rate (15.91% - 83.8%) than SIADH patients (1.67% - 74.57%). Hyponatremia patients with cerebral hemorrhage had higher rates of pneumonia, sepsis, convulsions, acute renal failure, and secondary bleeding than patients with normal blood sodium concentration. RECOMMENDATIONS Through this study we recommend: 1. Particular attention should be paid to monitor treatment of hyponatremia in patients with cerebral hemorrhage, especially patients with changes in perception, swallowing disorders, severe headache, increased headache, nausea, vomiting, slowly improving paralysis, mechanical ventilation, deep coma, open-skull surgery, using 20% mannitol, brain lessionsin the frontal lobe, ventricular hemorrhage. Time of monitoring is in 14 days. 2. Conduct in-depth research with large sample sizes to determine the diagnostic criteria for the causes of hyponatremia (NT-ProBNP values), as well as the effeciency of hyponatremia treatment according to the pathogenetic mechanisms.
LIST OF ANNOUNCED RESEARCH PROJECTS RELATED TO THESIS TOPIC
characteristics and treatment of hyponatremia in patients with cerebral hemorrhage. Journal of Practical Medicine, 1047-2017, page 10-13. 2.
Nguyen Dinh Dung (2018).Study on NT-proBNP values in patients with cerebral hemorrhage, Vietnam Medical Journal, 2(471), page 99-103.
Nguyen Dinh Dungvà Nguyen Phuong Dong (2019). Study on clinical, subclinical characteristics, associated factors and results of treatment of hyponatremia in patients with cerebral hemorrhage. Journal of Practical Medicine, 8(1106), page 32-36.
Nguyen Dinh Dungvà Nguyen Phuong Dong (2019). Comment on NT-proBNP value in the diagnosis of hyponatremia in patients with cerebral hemorrhage. Journal of Clinical Medicine and Pharmacy 108, 14(4), page 24-29.