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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE SCIENCE RESEARCH INSTITUTE OF CLINICAL MEDICINE AND PHARMACY 108 ============ NGUYEN DINH DUNG STUDYING CLINICAL, SUBCLINICAL

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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE

SCIENCE RESEARCH INSTITUTE OF CLINICAL MEDICINE AND

PHARMACY 108

============

NGUYEN DINH DUNG

STUDYING CLINICAL, SUBCLINICAL

CHARACTERISTICS, ASSOCITATED FACTORS

AND TREATMENT RESULTS OF HYPONATREMIA

IN PATIENTS WITH CEREBRAL HEMORRHAGE

Major : Anesthesia - Resusciation Major code : 62.72.01.22

SUMMARY OF MEDICAL DOCTORAL THESIS

HA NOI– 2019

The thesis has beeb successfully completed at :

SCIENCE RESEARCH INSTITUTE OF CLINICAL MEDICINE AND

PHARMACY 108

Science Instructor :

PGS.TS Nguyen Phuong Dong

Opponent 1:

Opponent 2:

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

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LIST OF ABRREVIATION

CSWS cerebral salt wasting syndrome

SIADH of inappropriate anti-diuretic hormone secretion

CNS 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

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

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because they differ in their nature and treatment

SIADH syndrome is an unreasonable secretion of ADH, leading to

hyponatremia due to dil ution (excess fluid volume) so treatment should li mit

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

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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 non-hyponatremiainclude: 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

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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 contrai ndications, 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:

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2.3 Analyzing data

- Enteri ng 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

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

Figure 3.1 Status - The hyponatremia

moment

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

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Intracerebral (n=283)

Subarachnoid (n=126)

41%(11 6))

50,8%(6 4)

53%(15 0)

46%(58)

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

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

Figure 3.5 The level of

hyponatremia

Figure 3.4 Causes of 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

0

10

20

30

40

50

19

31

24

5 17 2

15

16

15 40

7

22

0

16

42

4 23

17 5 13

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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

Causes

symptoms

CSWS (n=44)

SIADH (n=60)

Unknow cause

Headache 17(38,64%) 35(58,33%) 52(43,9%) <0.01

Dehydrated dry

Dysphagia 29(65.9%) 23(38,3%) 19(25,0%) <0.01

24-hour urine (ml) 3547.95± 1161.45 2463.52 ± 974.98 2629.93 ±1086.42 <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)

Clinic

Hyponatre mia

due to CSWS

(n=44)

Hyponatre mia due to SIADH (n=60)

Unknow cause (n=76)

p

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

(n=31)

SIADH

NT-proBNP (pg/ml) 420,1± 285,5 107,1 ± 133,1 <0,005

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

hemorrhage

3.3.3 Relationship between hyponatremia and medical history Table 3.22 Relationship between hyponatremia and medical history

(n=180)

Normal (n=208)

OR

(1,1 – 5,9) 0,018

No 161 (44,7%) 199 (55,3%)

Hypertension with regular treatment

Yes 31 (77,5%) 9 (22,5%)

4,6 (2,1- 9,9) < ,001

No 149 (42,8%) 199 (57,2%)

(1 – 3,1) 0,032

No 142 (44%) 181 (56%)

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

( n=180)

Normal (n=208)

OR

Frontal lobe (12)

Yes 22(66.7%) 11(33.3%) 2,5(1,2-5,3)

< 0,01

No 158(44.5%) 197(55.5%) 1

Central gray (94)

Yes 30 (31,9%) 64 (68,1%) 1

< 0,01

No 150 (51%) 144 (49%) 2,2 (1,4 – 3,6)

Ventricle (81)

Yes 52 (64,2%) 29 (35,8%) 2,5 (1,5 – 4,2)

< 0,001

No 128 (41,7%) 179 (58,3%) 1

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 non-hemorrhagic ventricular patients (p <0.001)

Relationship between hyponatremia and lesion size

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Table 3.24.Relationship between hyponatre mia and lesion size

Volume of

injury (cm3)

Hyponatre mia

<0,05

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

(n=180)

Normal (n=208)

OR

Non- intervention

< 0,05

Drain, open the

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

>8 139 (42,9%) 185 (57,1%)

No 35(32.1%) 74(67.9%) 1

No 81(42.4%) 110(57.6%) 1

With oxygen

respirator

Yes 54 (65,1%) 29 (34,9%)

2,6 (1,6 – 4,4) <0,001

No 126 (41,3%) 179 (58,7%)

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

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)

Number of patients (n)

Percentage (%)

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

Na

CSWS (n=29)

SIADH (n=34)

Others (n=20)

All causes (n=83)

Na before treatment (mmol/l) 128.83± 3.66 129.02± 3.25 129.10 ±2.96 128.97±3.30

Na after treatment (mmol/l) 137.13± 6.70 137.5 ±4.01 137.52±5.85 137.37±5.47

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%

Complications Number of patients

(n=83)

Percentage (%)

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

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withNaCl3% solution

Cognitive changes (Glasgow) before and after treatment with NaCl 3% solution

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

(n=180)

Normal (n=205)

p

<0,05 Living without complications 51 (28,3%) 73 (35,6%)

Living with complications 116 (64,4%) 127 (62,0%) Mild disability (mRs=0,1,2) 71(39.4%) 125(60.1%)

<0,05 Moderate disability (mRs=3,4) 77(42.8%) 61(29.3%)

Serious disability, TV (mRs=5,6) 32(17.8%) 22(10.6%) Average mRs 2.95±1.65 2.19 ±1.513 <0,05

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

0 5 10 15 20

19 (63.3%)

16(47%)

10(52.6)%

6(20%)

16(47%)

8(42.1%) 5(16.6%)

Better (45/83) Unchanged (30/83) Worse (8/83)

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

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

0

5

10

15

14 (7,8%)

5 (2,78%)

4 (1,92%)

Trang 10

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

4.2.6 Clinical characteristics of hyponatremia in the groups of causes:

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

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