Prognostic Value of Sodium Imbalance in Patients by

Traumatic Brain Injury

Hanan Anwar Rusidi *1, Hanis Setyono2, Ferry Wijanarko2, Geizar Arsika Ramadhana2,
Kharisma Ridho Husodo3

1
Surakarta Central General Hospital, Surakarta, Indonesia
2
Department of Neurosurgery, Faculty of Medicine, Sebelas Maret University/Dr. Moewardi
General Public Hospital, Surakarta, Indonesia
3
Wonosari General Hospital, Gunungkidul, Yogyakarta, Indonesia

ABSTRACT
Background: Traumatic Brain Injury (TBI) is a global health issue that
disproportionately affects the economically productive age group. This study focuses on
the prognostic significance of sodium imbalances in TBI patients.
Objective: This study aims to assess the impact of sodium imbalance (hyponatremia
and hypernatremia) on the prognosis of TBI patients.
Methods: A systematic review adhering to PRISMA guidelines was conducted,
searching databases from 2016 to 2023 for TBI and sodium imbalance studies. Inclusion
criteria included randomized controlled trials (RCT), cohort studies, and case-control
designs discussing hyponatremia in TBI.
Findings: The review included ten studies that met the inclusion criteria. Sodium
imbalance, particularly hypernatremia, was found to be associated with increased
morbidity and mortality among TBI patients. There was a significant relationship
between sodium levels and patient outcomes, including Glasgow Coma Scale (GCS)
scores Glasgow Outcome Scale (GOS) scores and mortality rates.
Discussion: Sodium imbalances play a critical role in the prognosis of TBI, both
hypernatremia and hyponatremia demonstrating a notable correlation with worse
outcomes with hypernatremia more frequently. The severity of the TBI, pre-existing
conditions, age, and initial treatments influence the development of sodium imbalances.
Conclusion: The management of sodium imbalance in TBI patients is important.
Timely and appropiate correction of sodium imbalances, regardless of the treatment
method, can significantly reduce morbidity and mortality.
Keywords: Traumatic Brain Injury, Sodium Imbalance, Hyponatremia, Hypernatremia,
Prognosis.

1. Introduction
TBI continues to plague millions of individuals around the world on an annual basis.
The most common causes of TBI include falls and road traffic accidents (RTA).[1], [2]
RTA, which accounts for approximately 60% of TBI, affects not only the highest
intellectually and economically productive age group of 15-29 years but also results in a
1-3% reduction in the country’s Gross Domestic Product.[3]
TBI comprises a spectrum of brain injuries that arise as a consequence of
traumatic events affecting the brain. In the most profound manifestation of TBI, the
entire brain is afflicted by a diffuse pattern of injury and subsequent swelling.[4] These
injuries can be categorized into primary and secondary categories. Primary injury
happens at the time of the initial trauma. Secondary injury, on the other hand, progresses
over time and involves a diverse array of cellular processes.[5] It can manifest as an
outcome of the primary injury or occur autonomously.[6] One of the secondary
damages that can arise in TBI is an electrolyte imbalance, particularly involving
sodium.[3]
Electrolyte imbalance in cases of TBI can be ascribed to the brain’s pathological
changes or is allowed to have an iatrogenic origin.[7] This is a commonly encountered
problem and is considered one of some preventable secondary injuries. The probability
of developing electrolyte imbalances in TBI patients relies on various factors, including
the severity of the head injury, pre-existing medical situations, age, and primary
therapeutic interventions such as the selection of resuscitation fluids, the administration
of mannitol or diuretics, and hyperventilation.[7], [8]Among all the serum electrolytes,
serum sodium is the most frequently impacted in TBI patients.[9] The presence of
sodium imbalance will affect the outcome of TBI patients, so it requires special
attention and appropriate management. This systematic review aims to evaluate the
prognostic importance of sodium imbalance in individuals by TBI.

2. Methods
Search strategy and data extraction
This systematic review is based on Preferred Reporting Items for Systematic
Review and Meta-Analyses (PRISMA). A thorough search was utilized in the following
databases, spanning 2016 to 2023: PubMed, the National Library of Medicine (NLM),
and Google Scholar. The search strategy consisted of keywords connected to “traumatic
brain injury”, “sodium imbalance”, and “prognosis”. We also included other types of
keywords such as “skull fracture”, “diffuse axonal injury”, “epidural hematoma”,
“subdural hematoma”, “subarachnoid hemorrhage”, “intracerebral hematoma”, “natrium
imbalance”, “salt imbalance”, “hyponatremia”, “hypernatremia”, “prognostic factor”
and “prognostic value”.
These studies’ objectives are to explore the relationship between sodium
imbalance and traumatic brain injury, as well as investigate any potential prognostic
value connected by this relationship. Studies that met the inclusion criteria were
included in this review: (1) studies with RCT, cohort, and case-control designs, (2) The
study discusses hyponatremia in TBI and patient outcomes. The categories of studies
that were excluded: (1) animal studies, (2) non-English articles, (3) non-original
investigations such as protocols, assessments, posters, abstracts, and (4) case reports and
case series involving fewer than five patients. All full-text studies meeting our inclusion
criteria underwent a screening process utilized by reviewers.
 Articles figured out utilizing PubMed,
National Library of Medicine (NLM) and
Google Scholar
(n=17.696)

Articles screened
(n=5799)
Articles excluded
(n=5710)

Articles assessed for

eligibility Articles excluded, by reason
(n=132) (n=122)

 Only abstract (n=76)

 Not utilizing sodium
Articles consisted imbalance (n=13)
(n=10)  Not including outcome
(n=33)

Figure 1. Flow of studies through the Assessment

Risk of bias
The threat of bias in the included studies was evaluated by two reviewers using
the Quality in Prognostic Studies (QUIPS) tool. Through deliberation, any discrepancies
that arose among the reviewers were resolved.[10]
Data analysis
The reviewers conducted the data extraction process using a specialized data
extraction form developed to meet the particular requirements of this systematic review.
The extracted data consisted of research characteristics, baseline characteristics of
participants, and clinical characteristics. Research characteristics include author name,
year of research, count, research design, time frame, sample size, inclusion and
exclusion criteria, and severity measurement/grade. Baseline characteristics include age
(years), length of hospital admission (days), gender (male), and type of injury. Data
collection and analysis were also utilized regarding sodium imbalance stages, including
statistical significance and whether multivariate analysis was used in consisted studies.

3. Outcome
Search outcome
An overview of data grouping and searching is shown in Figure 1. The initial
articles were screened using these data according to the inclusion and exclusion criteria
mentioned. After that, the articles were assessed for eligibility, and 122 articles were
excluded, by details of 76 articles only, including abstracts, 13 articles that did not
mention sodium imbalance, and 33 articles that did not mention prognosis or outcome.
According to the screening, 10 studies were considered the source of this study.

Characteristics of the included studies and patients

The characteristics of the included studies and patients in each article are all
mentioned in Table 1. The oldest article included in this study was from 2017, and the
latest was from 2022. The research involved studies from diverse countries like Nepal,
Thailand, China, Iran, the United States, Saudi Arabia, and South Korea, conducted
between 2016 and 2021. These studies varied in design, including non-randomized and
retrospective research, focusing on observational and cohort analysis. Sample sizes
ranged from 80 to 775 patients, employing different severity measurements like the
Glasgow Coma Scale, Glasgow Outcome Scale, and various injury severity scores.
Most of the studies were in the Asian continent, and 1 study was in the Americas. Based
on the study design, 3 studies by Khambu 2020, Pin-on 2018, and Vedantam 2017 were
found using a prospective design, and 3 other studies, namely by Wang 2022, Behzadnia
2022, and Liu 2021, using a retrospective design. One study by Vedantam 2017 has an
extensive timeframe, namely from 1986 to 2012. There were 1272 samples from all
studies, with 100 patients from Nepal, 145 patients from Thailand, 338 from China, 101
from Iran, and 588 from the United States. Table I mentions the inclusion and exclusion
criteria for each study. The severity measurements used included the Glasgow Outcome
Scale (GOS), the Glasgow Coma Scale (GCS), mortality, and the Glasgow Outcome
Scale Extended (GOSE).
Based on patient characteristics, it was found that the youngest mean age was in
Behzandia's study, namely 34.78 years, and the oldest average age was 51.47 years by
Wang. Only 2 studies mentioned the average length of stay, namely Khambu (2020) and
Vedantam (2017). Based on gender, all studies had the same characteristics; namely, the
number of patients with TBI was more male than female. The type of injury and GCS at
arrival are shown in Table I. This survival rate is based on all TBI patients and is not
specific to TBI patients with sodium imbalance except in a study by Vedantam (2017).
The baseline characteristics of participants in these studies showed a wide age range,
with some studies reporting average ages (like 51.7 years in Wang's study) and others
specifying ranges (like 15 to 65 years in Selim's study). The length of hospital
admission varied significantly, from an average of 11 days in Khambu's study to 22.53 ±
1.89 days in Kiaei's research. The gender distribution also varied across studies, with
some, like Liu's study, having a higher male proportion.
Regarding the type of injury and admission status, many studies did not specify
details like the type of skull fracture or hematoma. The Glasgow Coma Scale scores on
admission were noted in some studies, indicating the severity of the injuries. Survival
rates were mentioned in a few studies, ranging from 23% in Kiaei's study to higher
percentages like 82.8% in Pin-on's research.
 Table 1. The baseline characteristic of each consisted of studies and sample
Research and Khambu, 2020[6] Pin-on, 2018[7] Wang, 2022[11] Behzadnia, Vedantam, Liu, 2021[14]
baseline 2022[12] 2017[13]
characteristics
Research
characteristics
Country Nepal Thailand China Iran US China
Research design Non-randomized Prospective cohort Retrospective cohort Retrospective Prospective Retrospective
prospective, research cross-sectional database TBI research
observational research research
hospital-according
to research
Time frame 1st Baisakh 1st April January 2016 to June 2019 to June 2019 – 2020 1986 – 2012 April 2018 and
2017) February 2017 2021 December 2019
April 2018)
Sample size 100 patients 145 patients 156 patients 101 patients 588 patients 182 patients
Severity measurement Glasgow Outcome Glasgow Coma Scale GOS GCS Mortality Glasgow Outcome
Scale (GOS) (GCS) Scale Extended
(GOSE)
The baseline
characteristic
consisted of
participants
Age, years 45 years (1-95 42 years 51,7 years 34,78 years 39,4 years 50,41 years
years)
Length of hospital 11 days NA NA NA 18 days NA
admission, days
Gender
Male 83 129 118 88 489 135
Female 17 16 38 13 98 47
Type of injury
Skull fracture NA NA NA NA NA 109
Diffusion axonal NA 5 NA NA 335 NA
injury NA 52 NA NA NA 69
Epidural hematoma NA 73 NA NA NA 111
Subdural hematoma NA 5 NA NA NA 125
Subarachnoid NA 10 NA NA NA 76
 hemorrhage
Intracerebral
hematoma
GCS on admission NA 10,1 5,4 11,68
≤8 101 93
9 – 12 25 63
13 – 15 19 NA
Survival NA 82,8% NA NA 74,9% 73,6%

Research and Kiaei, 2018[15] Selim, 2019[16] Jung, 2022[17] Chandrasekar,

baseline 2020[18]
characteristics
Research
characteristics
Country Iran Saudi Arabia South Korea United States
Research design Observational, Retrospective analysis Retrospective study Retrospective
prospective, data analysis.
descriptive-analytic
Time frame 2015-2016 February 2017 to January 2018 to January 2016 to
November 2018 December 2019. December 2018
Sample size 100 patients 80 patients 775 patients 310 patients
Severity measurement Mortality Glasgow Coma Scale Abbreviated Injury Injury Severity
(GCS) score ≤ 13 Scale (AIS) and New Score (ISS) and
Injury Severity the Abbreviated
Score (NISS). Injury Score for
the head region
(AIS-H)
The baseline
characteristic
consisted of
participants
Age, years 38-80 years (Mean 15 to 65 years old 2 groups ( 18-64 Cerebral Salt
69.1 ± 10.64 years) years and 65 years or Wasting (CSW)
older) was 61.5 years,
compared to 53.6
years for those
 without CSW
Length of hospital 22 days (Mean NA NA CSW group (14.1
admission, days 22.53 ± 1.89 days) days) compared
to those without
CSW (3.5 days)
Gender
Male 52 53 530 NA
Female 48 27 244 NA
Type of injury
Skull fracture NA 12 NA NA
Diffusion axonal NA 2 NA NA
injury NA NA NA
Epidural hematoma NA 5 NA NA
Subdural hematoma NA 8 NA NA
Subarachnoid NA 5 NA NA
hemorrhage 13
Intracerebral
hematoma
GCS on admission NA NA
≤8 30 (37.5%) 32
9 – 12 50 (62.5%) 78
13 – 15 NA 664
Survival 23% NA NA CSW group
(88%) compared
to those without
CSW (99%).
 Quality assessment of consisted studies.
QUIPS quality scores for risk of bias are presented in Table 2In general,
the methodology employed in the included studies was deemed adequate. There
was a low to moderate risk of bias in each study's prognostic factor and outcome
measurements. Additionally, each study was considered acceptable, as there was a
negligible potential for bias in the statistical analysis and reporting.
QUIPS quality score Khambu, 2020[6] Pin-on, 2018[7] Wang, 2022[11]
Study participation: Yes Yes Yes
The study sample
represents population of
interest on key
characteristics?
Study attrition: Yes Yes Yes
The proportion of study
sample providing outcome
data is adequate?
Prognostic factor Yes Yes Yes
measurement:
The prognostic factor of
interest is adequately
measured in study subjects?
Outcome measurement: Yes Yes Yes
The outcome of interest is
adequately measured in
study subjects?
Study confounding: No Yes Yes
Important potential
confounders are accounted
for?
Statistical analysis: Yes Yes Yes
The statistical analysis is
appropriate for answering?
Behzadnia, Vedantam, 2017[13] Liu, 2021[14]
2022[12]
Study participation: Yes Yes Yes
The study sample
represents population of
interest on key
characteristics?
Study attrition: Yes Yes Yes
The proportion of study
sample providing outcome
 data is adequate?
Prognostic factor No No Yes
measurement:
The prognostic factor of
interest is adequately
measured in study subjects?
Outcome measurement: No No Yes
The outcome of interest is
adequately measured in
study subjects?

Study confounding: Yes Yes Yes

Important potential
confounders are accounted
for?
Statistical analysis: No No Yes
The statistical analysis is
appropriate for answering?
Kiaei, 2018[15] Selim, 2019[16] Jung, 2022[17]
Study participation: Yes Yes Yes
The study sample represents
population of interest on key
characteristics?
Study attrition: Yes Yes Yes
The proportion of study sample
providing outcome data is
adequate?
Prognostic factor measurement: Yes Yes Yes
The prognostic factor of interest
is adequately measured in study
subjects?
Outcome measurement: Yes No Yes
The outcome of interest is
adequately measured in study
subjects?

Study confounding: Yes No No

Important potential confounders
are accounted for?
Statistical analysis: Yes Yes Yes
The statistical analysis is
appropriate for answering?
 Chandrasekar,
2020[18]
Study participation: Yes
The study sample represents
population of interest on key
characteristics?
Study attrition: No
The proportion of study sample
providing outcome data is
adequate?
Prognostic factor measurement: Yes
The prognostic factor of interest
is adequately measured in study
subjects?
Outcome measurement: Yes
The outcome of interest is
adequately measured in study
subjects?

Study confounding: No
Important potential confounders
are accounted for?
Statistical analysis: Yes
The statistical analysis is
appropriate for answering?

Table 2. Risk of bias in consisted studies

Sodium imbalance and prognostic in TBI

Sodium imbalance and prognosis are shown in Table 3. In a study by
Khambu (2020) using sodium imbalance in general, including hyponatremia and
hypernatremia. This study found a significant difference between favorable (GOS
3-5) and unfavorable (GOS 1 and 2). This study found 12 patients with GOS 1
and 1 with GOS 2.[6] In a study by Pin-on in 2018, it was found that patients with
hyponatremia and hypernatremia died more, but this was not proven statistically.
This research also mentions unfavorable outcomes related to preoperative
hematocrit, blood loss, PRC transfusion, FFP transfusion, blood glucose, PaO2,
and PaCO2.[7]
Wang (2022) found that patients with hypernatremia showed a GOS ≤3
More than GOS > 3. This is also statistically significant (p=<0.001). In his study,
multivariate analysis was also carried out, and hypernatremia was found when
combined with hypokalemia, indicating a worse prognosis of up to 3.63 times.
[11]Research by Behzadnia in 2022 found no significant difference in the
prognosis between GCS and TBI with sodium imbalance and not with sodium
imbalance. two studies focused on hypernatremia.[12]In a study by Vedantam
(2022), it was reported that severe hypernatremia (>160) had a hazard ration of
7.9.[13] Liu (2021) found that hypernatremia (> 145 mmol/L) had a worse GOSE
and proved statistically significant.[14]
 Kiaei's 2018 study focused on the impact of sodium imbalances like
hypernatremia and hyponatremia on mortality. The research found a significantly
higher mortality rate associated with hypernatremia compared to hyponatremia or
no electrolyte disorders. This trend was particularly notable in the second week of
observation. The study quantitatively demonstrated the significance of these
imbalances, with notable differences in mortality rates (8 vs. 4, p=0.04) and
multivariate outcomes (15 vs. 10, p=0.029).[15]
Selim's 2019 research focused on the Glasgow Coma Scale (GCS) scores
in patients with hypernatremia. The study revealed a significant difference in
serum sodium levels between the surviving and deceased groups in both the first
and second weeks. The outcomes showed clear distinctions between the groups
(142 vs. 146, p=0.001; 144 vs. 147, p=0.001), highlighting the prognostic
significance of serum sodium levels in these cases.[16]
Jung's 2022 study and Chandrasekar's 2020 research explored the
association of hyponatremia with injury severity and mortality. Jung's study
indicated that hyponatremia was not significantly linked with increased mortality
risk at hospital discharge but suggested a trend toward higher mortality at 6
months. Chandrasekar's study, focusing on a hyponatremia (CSW) , found
significant correlations with the severity of outcomes and survival to discharge
implications (21.8 vs 14.2, p< 0.0001 ; 88% vs 99%, p < 0.0001).
 Table 3. Prognostic outcome and sodium imbalance
Included studies Outcome Sodium imbalance Multivariate outcome analysis Notes
Favorable/ Unfavorable Significance Measurement Value Significance
alive
Khambu, 2020 GOS 12 13 <0,0001 NA NA NA 12 patients with GOS
Sodium imbalance 1 and 1 patient with
GOS 2
Pin-on, 2018 GCS NA NA NA Preoperative
Hyponatremia 1 2 NA hematocrit, blood loss,
Hypernatremia 0 6 NA PRC transfusion, FFP
transfusion, blood
glucose, PaO2, PaCO2
related to an
unfavorable outcome
Wang, 2022 GOS Odd Ratio 3,630 0,029 Hypernatremia
Hyponatremia 18 7 0,594 (OR) (1,141-11,551) combined with
Hypernatremia 18 39 <0,001 hypocalcemia
Behzadnia, 2022 GCS NA NA 0,555 NA NA NA GCS difference
Sodium imbalance between TBI with
sodium imbalance and
without sodium
imbalance
Vedantam, 2022 Mortality 440 148 HR 7,9; NA NA NA Severe hypernatremia
Hypernatremia p<0,001 (>160) had the lowest
survival rates, and
patients with mild-to-
moderate
hypernatremia had an
intermediate survival
rate.
Liu, 2021 GOSE 10 12 <0,05 NA NA NA Blood Na+
Hypernatremia concentration was
141.08 ± 3.57
(mmol/L), and high
Na+ concentration (>
145 mmol/L)
Kiaei, 2018 Mortality 8 4 0.04 15 10 0.029 There was a higher
Hypernatremia mortality rate
Hyponatremia associated with
No Electrolyte hypernatremia than
impairment with hyponatremia or
no electrolyte
disorders, particularly
in the second week.
Selim, 2019 Glasgow 142 146 0.001 144 147 0.001 There was a
Hypernatremia Coma Scale significant difference
(GCS) score in serum sodium levels
≤ 13 between the survived
group and the non-
survival group in both
the first and second
weeks
Jung,2022 Abbreviated 672 68 0.001 102 8 0.001 hyponatremia was not
Hyponatremia Injury Scale significantly
(AIS) and associated with an
New Injury increased risk of
Severity mortality at hospital
Score discharge but did show
(NISS). a tendency towards
higher mortality at 6
months
Chandrasekar, 2020 Injury 310 125 0.0028 53 14 0.001 The outcomes in
Hyponatremia Severity relation to CSW in the
(CSW) Score (ISS) patient population
and the studied, indicating the
Abbreviated severity of the
Injury Score outcomes and the
for the head significance of the
region (AIS- CSW in their
H) prognoses.
4. Discussion
TBI remains a problem because it causes high mortality in the productive
age group and economic losses. TBI encompasses a range of brain injuries that
occur as a result of traumatic events. The most severe form of TBI involves
diffuse brain injury and brain edema. These injuries can be classified into primary
and secondary injuries, with secondary injuries occurring over time due to various
cellular processes.
Patients with TBI frequently exhibit electrolyte imbalance conditions and
the most common is sodium imbalance. Sodium imbalance is one of the
conditions included in secondary injury. Manifestations of sodium imbalance may
include hyponatremia or hypernatremia. This imbalance can be attributed to
pathological changes in the brain or be iatrogenic in origin. It is considered a
preventable secondary injury and can significantly impact the prognosis of TBI
patients. The likelihood of developing electrolyte imbalances in TBI patients
depends on several factors, including the severity of the head injury, pre-existing
medical conditions, age, and primary therapeutic interventions.[7]
The search outcome reveals that 10 studies meet the inclusion criteria and
are considered for this systematic review. These articles provide valuable insights
into the relationship between sodium imbalance and TBI prognosis. The quality
assessment of the included studies, based on QUIPS quality scores for risk of bias
(Table 2), generally indicates a methodology with a low to moderate risk of bias in
prognostic factor and outcome measurements. Prognostic factors were mainly
adequately measured, although there were exceptions in Behzadnia, Vedantam,
and Liu's studies. Similarly, outcome measurement was generally adequate, but
there were exceptions in Behzadnia, Vedantam, Liu, and Jung's studies. Most
studies accounted for potential confounders, but some did not, such as Khambu,
Behzadnia, Vedantam, Liu, Selim, and Chandrasekar's studies. The statistical
analysis was generally appropriate, except for Behzadnia, Vedantam, and Liu's
studies. Overall, the studies demonstrated a consistent level of quality, with some
variations in certain aspects across different studies.
TBI can affect the stability of water and sodium haemostasis, which is
controlled by the central nervous system. Sodium plays a role in cell size and
plays a role in the interaction between the brain and kidneys in maintaining
osmolarity.[19] In hypernatremia, the criteria used is when the serum sodium level
is >145 mEq/L.[19] In patients with TBI, the complex mechanism of
hypernatremia involves central diabetes insipidus, osmotic diuretic treatment,
fluid restriction or fluid loss leading to dehydration, or iatrogenic causes, which
will cause cell dehydration.[13], [19] Symptoms that can appear in hypernatremia
conditions are muscle weakness, confusion, drowsiness, fatigue, dysphoria,
seizures, and up to coma.[19]–[21]
Hyponaatremia is defined as sodium levels < 135 mmol, with a relative
excess of extracellular water to extracellular sodium with body sodium levels that
can be normal, reduced, or increased.[19] In TBI, hyponatremia is most
commonly caused by syndrome of inappropriate secretion of antidiuretic hormone
(SIADH) and cerebral salt wasting (CSW), and insufficient intake from the diet.
[16],[22]
The stress response in TBI will stimulate antidiuretic hormones which then
causes an increase in sodium reabsorption in the renal tubules and leads to
conditions that decrease sodium levels. In addition, the use of therapeutic drugs in
TBI can lead to dehydration and sodium depletion. (7, 8) [23] Hyponatremia
aggravates cerebral edema and can lead to conditions such as ensefalopaty,
irritability, confusion, weakness, headache, disorientation, nausea, and vomiting,
lethargy, seizure, hingga koma (24, 25)[19],[23],[24]
The relationship between sodium imbalance and prognosis in TBI is
highlighted in several studies. Khambu (2020) and Pin-on (2018) examined the
effects of sodium imbalance, including hyponatremia and hypernatremia, on the
Glasgow Outcome Scale (GOS) and mortality rates.[6], [7] Khambu found a
significant difference in GOS scores between patients with favorable and
unfavorable outcomes.[6] In contrast, Pin-on noted higher mortality in patients
with sodium imbalances, but the findings were not statistically significant.[7]
Wang (2022) observed that hypernatremic patients had worse GOS scores, and
reported the findings to be statistically significant.[11] Behzadnia (2022) found no
significant difference in prognosis between patients with and without sodium
imbalances when considering the Glasgow Coma Scale (GCS) scores.[12]
Further studies by Vedantam (2022) and Liu (2021) focused on
hypernatremia, finding significant correlations with worse outcomes. Vedantam
reported a high hazard ratio for severe hypernatremia, while Liu found that
hypernatremia (>145 mmol/L) led to poorer Extended Glasgow Outcome Scale
(GOSE) scores.[13], [14] Kiaei's (2018) study concentrated on the mortality
impact of sodium imbalances, discovering a notably higher mortality rate in
hypernatremia patients, especially in the second week of observation.[15] Selim
(2019) explored the prognostic significance of serum sodium levels in TBI
patients, finding significant differences in GCS scores concerning sodium levels
between survivors and non-survivors.[16]
Lastly, Jung (2022) and Chandrasekar (2020) investigated the association
between sodium imbalances and injury severity and mortality. Jung's study
indicated no significant link between hyponatremia and increased mortality at
hospital discharge, but a trend toward higher mortality at 6 months was observed.
[17] Chandrasekar's study highlights the significant correlation between CSW and
patients with TBI, and underscores the worse outcome in TBI patients with CSW.
[18]
These studies collectively emphasize hyponatremia critical role in TBI
patients' prognosis, with varying impacts based on the type and severity of the
imbalance. Sodium imbalance, both hypernatremia and hyponatremia all
contribute to increased mortality and morbidity of TBI patients. Based on reports
of various studies in this systematic review, hypernatremia is more prevalent than
hyponatremia in TBI. Hypernatremia also appears earlier after injury and is more
susceptible in patients with older age. In addition, the mortality rate of
hypernatremia is higher when compared to hyponatremia.
Further understanding of sodium imbalance in TBI is reported by the
Harrois (2021). They investigated the impact of serum sodium variability in
severe TBI cases. The researchers focused on daily serum sodium standard
deviation (dNaSD), which serves as a measure of variability, to understand its
relationship with mortality rates over 28 days. The study reported a mortality rate
due to sodium imbalance of 28%, with hypernatremia (64%) and hyponatremia
(24%).[25]
 These imbalances, which can occur as secondary damages post-TBI due to
pathological changes or iatrogenic causes, significantly influence patient
prognosis. Various studies have explored the impact of sodium imbalances on TBI
outcomes, highlighting the prognostic significance of serum sodium levels. These
studies, following rigorous methodologies and systematic reviews, consistently
demonstrate the critical role of sodium balance in TBI prognosis.
The research reveals that factors such as the severity of the head injury,
pre-existing conditions, age, and initial treatments play a crucial role in the
likelihood of developing sodium imbalances. These findings emphasize the
importance of monitoring and managing sodium levels in TBI patients to improve
outcomes, as imbalances are indicators of TBI severity and potentially modifiable
factors influencing patient recovery.

5. Conclusion
Sodium imbalances, such as hyponatremia and hypernatremia, carry the
potential to worsen organ system dysfunctions, thereby influencing morbidity and
mortality rates in TBI patients. Hypernatremia is more common than
hyponatremia and has a worse prognosis. Timely and appropriate correction of
sodium concentration in patients with TBI is essential to reduce patient morbidity
and mortality.

FUNDING
No institutions or organizations financially supported this research.

CONFLICT OF INTEREST
The authors assert that the research was utilized without any commercial
or financial associations that could be construed as potential conflicts of interest.

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