Abstract
BACKGROUND:
Electrolyte imbalance is common following traumatic brain injury (TBI) and can significantly impact patient outcomes. We aimed to explore the occurrence, patterns, and consequences of electrolyte imbalance in adult patients with TBI.
METHODS:
A retrospective study was conducted from 2016 to 2021 at a level 1 trauma center among hospitalized TBI patients. On admission, the levels of serum electrolytes, including sodium, potassium, calcium, magnesium, and phosphate, were analyzed. Demographics, injury characteristics, and interventions were assessed. The primary outcome was the in-hospital mortality. Multivariate logistic regression analysis was performed to identify independent predictors of mortality in TBI patients.
RESULTS:
A total of 922 TBI patients were included in the analysis, of whom 902 (98%) had electrolyte imbalance. The mean age of patients with electrolyte imbalance was 32.0±15.0 years. Most patients were males (94%). The most common electrolyte abnormalities were hypocalcemia, hypophosphatemia, and hypokalemia. The overall in-hospital mortality rate was 22% in the entire cohort. In multivariate logistic analysis, the predictors of mortality included age (odds ratio [OR]=1.029, 95% confidence intervals [CI]: 1.013-1.046, P<0.001), low GCS (OR=0.883, 95%CI: 0.816-0.956, P=0.002), high Injury Severity Score (ISS) scale (OR=1.051, 95%CI: 1.026-1.078, P<0.001), hypernatremia (OR=2.175, 95%CI: 1.196-3.955, P=0.011), hyperkalemia (OR=4.862, 95%CI: 1.222-19.347; P=0.025), low serum bicarbonate levels (OR=0.926, 95%CI: 0.868-0.988, P=0.020), high serum lactate levels (OR=1.128, 95%CI: 1.022-1.244, P=0.017), high glucose levels (OR=1.072, 95%CI: 1.014-1.133, P=0.015), a longer activated partial thromboplastin time (OR=1.054, 95%CI: 1.024-1.084, P<0.001) and higer international normalized ratio (INR) (OR=3.825, 95%CI: 1.592-9.188, P=0.003).
CONCLUSION:
Electrolyte imbalance is common in TBI patients, with the significant prevalence of hypocalcemia, hypophosphatemia, and hypokalemia. However, hypernatremia and hyperkalemia were associated with the risk of mortality, emphasizing the need for further research to comprehend electrolyte dynamics in TBI patients.
Keywords: Electrolyte imbalance, Traumatic brain injury, Mortality
INTRODUCTION
Traumatic brain injury (TBI), refers to the disruption of normal brain function following head trauma.[1] This remains a global public health challenge due to its overwhelming incidence rate and substantial burden on healthcare systems. According to prior reports, there are more than 27 million cases of TBI worldwide, with an increasing trend in both incidence and prevalence. These injuries, which primarily result from falls and road accidents, contribute to patients lived with disability. [2]
Among the various complications associated with TBI, electrolyte imbalances are of concern and require appropriate management to prevent further neurological complications and adverse outcomes.[3-8] Sodium level imbalances, including hyponatremia and hypernatremia, are commonly reported in several studies.[6,9-12] Furthermore, TBI patients also exhibit disturbances in serum levels of potassium, magnesium, calcium, and phosphate.[3-13] Potassium plays a pivotal role in muscle contraction and nerve transmission. Changes in serum potassium levels have clinical implications, such as cardiac arrhythmias and muscle weakness, including the respiratory muscles. Hypokalemia also contributes to rhabdomyolysis, renal failure, and hyperglycemia.[14]
Notably, hypocalcemia was added as a part of the lethal triad of trauma, along with hypothermia, acidosis, and coagulopathy, highlighting its substantial impact on patients with polytrauma.[15] Phosphate is an essential component of normal muscle function. Hypophosphatemia is associated with muscle weakness, including respiratory muscles weakness, increased vulnerability to respiratory infections, and challenges in weaning critically ill patients from mechanical ventilation. Hypophosphatemia can also decrease cardiac output and increase the risk of ventricular tachycardia following a heart attack. [5,16,17]
Effectively managing these electrolyte disturbances becomes integral to the appropriate care of TBI patients, as they are associated with implications for neurological recovery and overall patient well-being. This study aims to describe the prevalence and outcomes of serum electrolyte imbalances in hospitalized TBI patients in a level 1 trauma center. In addition, this study investigated the role of initial serum electrolyte imbalance as predictors of mortality in TBI patients.
METHODS
Study design
A retrospective study was conducted at Hamad Trauma Center (HTC) which is a governmental not-profit tertiary hospital that admits and treats moderate to severe traumatic injuries. The study included all TBI patients admitted to the trauma intensive care unit (TICU) between June 1, 2016, and May 30, 2021. Data for the study were obtained from the Hamad General Hospital Trauma Registry (QTR) and the electronic medical records (CERNER).
TBI was defined using the ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes from the QTR database, which includes S02.0, S02.1, S02.8, S02.9, S04.02, S04.03, S04.04, S06, S07.1, and S09.90 codes. These codes include cases involving skull fractures, facial bone fractures, optic nerve and pathway injuries, visual cortex injuries, intracranial injuries, skull-crushing injuries, and unspecified head injuries.
Study population and serum electrolyte measurements
The study included all TBI-diagnosed and hospitalized patients, regardless of age or gender, and their serum electrolytes were measured upon admission. Patients with penetrating injuries and transfers from other hospitals were excluded. The median time from injury to admission at the trauma center was 70 min (interquartile range 55-91 min). Patients admitted to the trauma center received treatment as per Advanced Trauma Life Support (ATLS) guidelines.[18] In addition, we use our hospital’s TBI management protocol, which includes specific guidelines for managing TBI patients.[19] We also have an electrolyte management protocol to address any imbalances identified during patient care. Initial serum electrolyte levels (sodium, potassium, calcium, magnesium, and phosphate) were measured from the first blood samples taken upon the patient’s admission to the trauma center. These measurements represent the initial readings recorded in the hospital. However, the exact timing of sample collection was not documented; the analysis relies on the first available reading within the first 24 h post-admission and usually within the first blood sampling. Serum electrolyte levels were categorized in accordance with institutional standards (Supplementary Table 1).
Data collection and defination
The collected data included patient demographics, injury mechanisms, TBI categories, injury scores, admission serum electrolyte levels, other serum biomarkers, interventions, massive transfusion activation protocols (MTPs), complications, and in-hospital outcomes. Assessment of consciousness after a head trauma was conducted using the Glasgow Coma Scale (GCS), which ranges from 3 to 15, with a severity scale ranging from 3 to 8 indicating major, 9 to 12 moderate, and 13 to 15 minor head injuries.[20] The Abbreviated Injury Scale (AIS) assesses injury severity on a scale of 1 to 6 (1=minor, 2=moderate, 3=serious, 4=severe, 5=critical, and 6=non-survivable) injuries to various body parts.[21] The Injury Severity Score (ISS) was calculated as an overall score for polytrauma by squaring the AIS ratings of the three most severely injured body regions and summing them. The ISS scores ranged from 0 to 75, with categories including minor (ISS 1-8), moderate (ISS 9-15), severe (ISS 16-24), and critical (ISS>24).[22] The shock index (SI) was defined the pulse rate at admission divided by simultaneous systolic blood pressure.[23]
The study provided the baseline characteristics of the patients included in the study, the distribution of patients by serum electrolyte levels, and information about the severity of electrolyte abnormalities and their proportionate mortality. In addition, a comparison of demographics, clinical characteristics, and outcomes was performed between survivors and non-survivors. Furthermore, independent predictors of mortality were investigated. Ethical approval with a waiver of consent for the study was obtained from the Institutional Review Board of Hamad Medical Corporation (MRC#01-21-501), as there was no direct contact with the patients, and the data were collected anonymously.
Statistical analysis
Descriptive analyses, including means with standard deviations or medians with interquartile ranges, were performed to summarize continuous variables such as age, vital signs, injury scores and serum biomarker levels. Distribution normality was assessed using the Shapiro-Wilk and Kolmogorov-Smirnov tests. Comparative analyses employed the Student’s t-test to compare normally distributed continuous data and the Mann-Whitney U-tests to compare non-normally distributed data. Categorical data were analyzed using Chi-square tests. A multivariate logistic regression model (Enter method) was constructed to identify independent predictors of mortality in TBI patients. Variables were chosen based on their clinical importance and statistical significance in the univariate analysis. Key factors, such as demographics, ISS, and initial serum electrolyte levels, are relevant to TBI outcomes. The model fit was evaluated using the Hosmer-Lemeshow test, and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported for each predictor. A significance level of two-tailed P< 0.05 was applied for all statistical tests performed in the study. SPSS version 21 (IBM, USA) was used for statistical analyses.
RESULTS
Among the 922 hospitalized TBI patients included in the present study, 902 (98%) had abnormal serum levels of at least one electrolyte at admission. Figure 1 shows the flowchart of the study design for electrolyte imbalances in TBI patients. Associated injuries included chest injuries in 55% of patients, abdominal injuries in 27%, pelvic injuries in 19%, cervical spine injuries in 15%, thoracic spine injuries in 13%, and lumbar spine injuries in 14%. The most prevalent serum electrolyte imbalances were related to calcium and phosphate levels, affecting 764 (83%) and 725 (80%) individuals, respectively. Specifically, 757 (82%) patients exhibited hypocalcemia, and 607 (66%) patients had hypophosphatemia. All five electrolyte imbalances were reported in 21 (2.27%) patients. Supplementary Figure 1 shows the results of the distribution normality tests for all the electrolyte levels in the study cohort.
Figure 1. Study flowchart for electrolyte imbalances in TBI patients. TBI: traumatic brain injury; ICU: intensive care unit.
The mean age of patients with electrolyte imbalance (n=902) was 32.0 ±15.0 years. Most patients were males (94%). The primary mechanisms of injury included road traffic injuries (60%) and falls (24%). The most common types of head injury included subarachnoid hemorrhage (SAH) (42%), subdural hematoma (SDH) (35%), and epidural hematoma (EDH) (22%). Figure 2 shows the TBI types in patients with electrolyte abnormalities. The mean head AIS was 3.9, and most patients had severe (AIS=3) or critical (AIS ≥5) injuries. The median ISS was 27, and most patients presented with a GCS score less than 9, indicating severe head injury (76%). Serum lactate and glucose levels were above normal in the overall patient population. Common interventions included intubation (90%) and blood transfusion (52%). MTP was activated in 15% of patients. Craniotomy or craniectomy was performed in 21% of the patients. The median durations of mechanical ventilation, ICU stay, and hospital stay were 4, 8, and 16 d, respectively. The overall in-hospital mortality rate was 22% in the entire cohort. The crude unadjusted in-hospital mortality among TBI patients based on the electrolyte imbalance categories is shown in Supplementary Figure 2.
Figure 2. Traumatic brain injury (TBI) types in patients with electrolyte abnormality. Single injuries accounts for 35% and combination of injuries 65%. Most prevalent single injury is SAH followed by SDH and EDH. There were 49 combinations of TBI types. SAH: subarachnoid hemorrhage; SDH: subdural hematoma; EDH: epidural hematoma.
Initial serum electrolyte levels
Most patients had normal sodium levels; however, hypernatremia was more prevalent in the severe TBI group (16%). A substantial proportion of patients exhibited normal potassium levels, with varying degrees of hypokalemia. Hyperkalemia was less common but was present in 3% of the severe TBI group. Calcium imbalance showed a high prevalence of hypocalcemia, especially in the severe TBI group (88%), while hypercalcemia was rare. Regarding magnesium, normal values were dominant, while hypomagnesemia was observed in a notable proportion, particularly in the moderate to severe TBI group (32%). Hypermagnesemia was infrequent. Phosphate imbalance in terms of hypophosphatemia was observed mainly in patients with severe TBI (63%-69%). However, hyperphosphatemia was present less frequently (14% of the severe TBI group) (Table 1).
Table 1.
Distribution of patients by serum electrolyte levels and Glasgow Coma Scale (GCS) (n=893)*
| Variables | Mild TBI (GCS 13-15) n=84 |
Moderate TBI (GCS 9-12) n=134 |
Severe TBI (GCS 3-8) n=675 |
|---|---|---|---|
| Age, years, mean ± SD | 37.8 ±17.5 | 34.0±17.7 | 31.3±13.7 |
| Males, n (%) | 80 (95.2) | 123 (91.8) | 635 (94.1) |
| Sodium level, n (%) | |||
| Normal | 75 (89.3) | 116 (86.6) | 550 (81.5) |
| Hyponatremia | 6 (7.1) | 11 (8.2) | 19 (2.8) |
| Hypernatremia | 3 (3.6) | 7 (5.2) | 106 (15.7) |
| Potassium level, n (%) | |||
| Normal | 45 (53.6) | 81 (60.4) | 421 (62.4) |
| Hypokalemia | 37 (44.0) | 51 (38.1) | 231 (34.2) |
| Hyperkalemia | 2 (2.4) | 2 (1.5) | 23 (3.4) |
| Calcium level, n (%) | |||
| Normal | 25 (29.8) | 39 (29.1) | 73 (10.8) |
| Hypocalcemia | 59 (70.2) | 94 (70.1) | 596 (88.3) |
| Hypercalcemia | 0 (0.0) | 1 (0.7) | 6 (0.9) |
| Magnesium levela, n (%) | |||
| Normal | 60 (71.4) | 88 (65.7) | 444 (66.7) |
| Hypomagnesemia | 24 (28.6) | 45 (33.6) | 211 (31.7) |
| Hypermagnesemia | 0 (0.0) | 1 (0.7) | 11 (1.7) |
| Phosphate levelb, n (%) | |||
| Normal | 24 (28.6) | 25 (18.7) | 116 (17.4) |
| Hypophosphatemia | 53 (63.1) | 92 (68.7) | 457 (68.7) |
| Hyperphosphatemia | 7 (8.3) | 17 (12.7) | 92 (13.8) |
*GCS data available for 893 patients; SD: standard deviation; GCS: Glasgow Coma Score; amagnesium level, n=913; bphosphate level, n=912.
Severity of electrolyte imbalance and outcome
Table 2 presents a comprehensive overview of the severity of electrolyte abnormalities and their proportionate mortality rates in TBI patients. Notably, mild hypernatremia (n=110) was the most predominant sodium imbalance. Among patients with mild hypernatremia, the mortality rate was 48%, which increased progressively with severity. However, fewer patients were in the moderate and severe categories than in the mild category.
Table 2.
Severity of electrolyte imbalances and outcomes in traumatic brain injury (TBI) patients (n=902)
| Electrolyte imbalances | Severity | Number (%) | Mortality n (%) |
Shock Index, Mean ±SD | Glasgow Coma Score, Mean ±SD |
Injury Severity Score, Mean ±SD |
|---|---|---|---|---|---|---|
| Hypernatremia (n=118; 13.1%) | Severe | 4 (3.4) | 3 (75.0) | 1.24 ±0.60 | 3.0±0.0 | 34.8±13.6 |
| Moderate | 4 (3.4) | 3 (75.0) | 0.88±0.50 | 4.0±2.0 | 35.0±6.0 | |
| Mild | 110 (93.2) | 53 (48.2) | 1.17±0.50 | 3.9±2.4 | 31.1±10.3 | |
| Hyponatremia (n=38; 4.2%) | Severe | 0 | 0 | |||
| Moderate | 2 (5.3) | 1 (50.0) | 0.73±0.20 | 8.5±4.9 | 17.5±12.0 | |
| Mild | 36 (94.7) | 8 (22.2) | 0.68±0.20 | 7.6±4.7 | 23.7±9.8 | |
| Hyperkalemia (n=27; 3.0%) | Severe | 3 (11.1) | 3 (100) | 1.43±0.30 | 3.3±0.6 | 36.7±14.0 |
| Moderate | 4 (14.8) | 3 (75.0) | 1.21±0.69 | 5.0±4.0 | 41.8±18.1 | |
| Mild | 20 (74.1) | 15 (55.6) | 1.13±0.67 | 4.6±3.9 | 36.3±10.8 | |
| Hypokalemia (n=323; 35.8%) | Severe | 5 (1.5) | 1 (20.0) | 0.80±0.43 | 5.8±4.0 | 26.2±8.2 |
| Moderate | 44 (13.6) | 7 (15.9) | 0.78±0.34 | 6.9±4.6 | 27.2±10.6 | |
| Mild | 274 (84.8) | 55 (20.1) | 0.88±0.35 | 5.8±4.1 | 26.4±9.4 | |
| Hypercalcemia (n=7; 0.8%) | Severe | 1 (14.3) | 1 (100) | 1.38 | 3 | 34 |
| Moderate | 2 (28.6) | 1 (50.0) | 1.84±0.32 | 3.0±0.0 | 44.0±8.5 | |
| Mild | 4 (57.1) | 3 (75.0) | 1.61±0.70 | 4.5±3.0 | 44.0±4.9 | |
| Hypocalcemia (n=757; 83.9%) | Severe | 310 (41.0) | 103 (33.2) | 1.10±0.52 | 4.3±3.2 | 30.8±10.1 |
| Moderate | 200 (26.4) | 42 (21.0) | 0.91±0.44 | 5.1±3.6 | 26.8±10.1 | |
| Mild | 247 (32.6) | 35 (14.2) | 0.82±0.33 | 6.3±4.2 | 25.0±9.5 | |
| Hypermagnesemia (n=12; 1.3%) | Severe | 0 | 0 | |||
| Moderate | 0 | 0 | ||||
| Mild | 12 (100) | 7 (58.3) | 0.99±0.49 | 4.0±2.3 | 29.3±11.4 | |
| Hypomagnesemia (n=283; 31.4%) | Severe | 1 (0.4) | 0 | 0.76 | 3 | 13 |
| Moderate | 12 (4.2) | 5 (41.7) | 1.06±0.29 | 2.9±0.3 | 27.1±9.2 | |
| Mild | 270 (95.4) | 39 (14.4) | 0.92±0.41 | 5.5±3.9 | 28.2±10.5 | |
| Hyperphosphatemia (n=118; 13.1%) | Severe | 30 (26.5) | 26 (86.7) | 1.61±1.05 | 3.9±2.7 | 38.4±10.6 |
| Moderate | 20 (17.7) | 10 (50.0) | 1.48±0.46 | 4.5±2.9 | 35.2±13.0 | |
| Mild | 68 (60.2) | 19 (27.9) | 1.11±0.53 | 5.7±4.1 | 27.3±11.3 | |
| Hypophosphatemia (n=607; 67.3%) | Severe | 14 (2.3) | 4 (28.6) | 0.84±0.27 | 5.1±3.6 | 21.4±8.2 |
| Moderate | 144 (16.0) | 37 (25.7) | 0.89±0.36 | 5.0±3.4 | 25.9±9.5 | |
| Mild | 449 (73.9) | 65 (14.5) | 0.86±0.47 | 5.7±4.0 | 26.3±10.4 |
Mild hypokalemia was the most common potassium imbalance (n=274); however, moderate and severe hyperkalemia was associated with high mortality rate. For calcium imbalance, hypocalcemia was reported in 757 patients, but mortality was high among patients with hypercalcemia (50%-100%). Among magnesium imbalances, hypomagnesemia was more common (n=283). Neither moderate or severe hypermagnesemia was reported. In phosphate imbalances, hypophosphatemia was more common, and mortality increased with severity, reaching up to 29% in severe hypophosphatemia. Notably, a high mortality rate of 87% was observed in the severe hyperphosphatemia group.
Survival outcomes and risk factors
Table 3 compares survivors (n=718) and non-survivors (n=204) of TBI. Serum biomarker levels significantly differed between the two groups, and coagulation parameters significantly differed between survivors and non-survivors. Table 4 presents a multivariate logistic regression analysis for mortality risk in TBI patients. The significance of the crude odds of mortality associated with magnesium, phosphate and calcium imbalance disappeared on multivariable regression analysis after adjustment for covariates. For sodium imbalance, hypernatremia was associated with a 2.2-fold increase of mortality (adjust OR 2.175, 95%CI:1.196-3.955, P=0.011). Hyperkalemia showed higher adjust OR 4.862 (95%CI:1.222-19.347, P=0.025), while the substantial wide confidence interval negatively impacted its robustness. Notably, the INR was associated with almost four times the odds of mortality (OR=3.825, 95%CI: 1.592-9.188, P=0.003). For each higher one-point on the ISS scale, the odds of mortality increased by approximately 5.1% (OR=1.051, 95%CI: 1.026-1.078, P<0.001). Every less point on the GCS scale corresponded to a 11.7% reduction in the odds of mortality (OR= 0.883, 95% CI: 0.816-0.956, P=0.002).In addition, age (OR=1.029, 95%CI: 1.013-1.046, P<0.001), low serum bicarbonate levels (OR=0.926, 95%CI: 0.868-0.988, P=0.020), high serum lactate levels (OR=1.128, 95%CI: 1.022-1.244, P=0.017), high glucose levels (OR=1.072, 95%CI: 1.014-1.133, P=0.015), a longer aPTT (OR =1.054, 95%CI: 1.024-1.084, P<0.001) were associated with increased mortality risk.
Table 3.
Comparative analysis between survivors and non-survivors in traumatic brain injury (TBI) patients
| Variables | Survivors (n=718) | Non-survivors (n=204) | P-value |
|---|---|---|---|
| Age, years, mean ± SD | 31.4±14.4 | 35.8±16.8 | 0.001 |
| Males, n (%) | 671 (93.5) | 192 (94.1) | 0.730 |
| Injury Severity Score, mean ± SD | 25±10 | 34±9 | 0.001 |
| Shock index, mean ± SD | 0.87±0.35 | 1.15±0.64 | 0.001 |
| Glasgow Coma Scale, mean ± SD | 6±4 | 4±2 | 0.001 |
| Serum sodium, mmol/L, mean ± SD | 140.5± 3.9 | 143.2±6.6 | 0.001 |
| Serum potassium, mmol/L, mean ± SD | 3.8±0.6 | 4.1±0.9 | 0.001 |
| Serum calcium, mmol/L, mean ± SD | 2.0±0.2 | 1.9±0.4 | 0.001 |
| Serum magnesium, mmol/L, mean ± SD | 0.6±0.1 | 0.7±0.1 | 0.001 |
| Serum phosphate, mmol/L, mean ± SD | 0.9±0.4 | 1.2±0.8 | 0.001 |
| Serum bicarbonate, mmol/L, mean ± SD | 20.1±3.9 | 17.2±5.2 | 0.001 |
| Serum lactate, mmol/L, median (IQR) | 2.7 (1.9-3.8) | 4.6 (2.8-7.4) | 0.001 |
| Hemoglobin, g/dL, mean ± SD | 12.9±2.3 | 11.7±2.5 | 0.001 |
| Serum glucose, mmol/L, mean ± SD | 8.5±3.8 | 11.5±4.9 | 0.001 |
| Prothrombin time, s, median (IQR) | 11.9 (11.0-12.9) | 14.7 (12.1-17.3) | 0.001 |
| Activated partial thromboplastin time, s, median (IQR) | 25.7 (23.7-28.2) | 36.9 (28.0-52.3) | 0.001 |
| International normalized ratio (INR), median (IQR) | 1.1 (1.1-1.2) | 1.4 (1.2-1.7) | 0.001 |
| Craniectomy/craniotomy, n (%) | 163 (22.8) | 29 (14.4) | 0.010 |
| MTP activation, n (%) | 66 (9.2) | 66 (32.5) | 0.001 |
Statistical comparisons used the Student t-test or Mann-Whitney U test for continuous variables and the Chi-square test for categorical variables. MTP: massive transfusion protocol. SD: standard deviation; IQR: interquartile range.
Table 4.
Multivariate logistic regression analysis of risk factors for mortality in traumatic brain injury (TBI) patients
| Factors | OR | 95% CI | P-value |
|---|---|---|---|
| Age | 1.029 | 1.013-1.046 | <0.001 |
| ED Glasgow Coma Scale | 0.883 | 0.816-0.956 | 0.002 |
| Injury Severity Score | 1.051 | 1.026-1.078 | <0.001 |
| Serum sodium category | |||
| Normal sodium level | Reference | ||
| Hypernatremia vs. hyponatremia | 2.175 | 1.196-3.955 | 0.011 |
| Serum potassium category | |||
| Normal potassium level | Reference | ||
| Hyperkalemia vs. hypokalemia | 4.862 | 1.222-19.347 | 0.025 |
| Serum calcium category | |||
| Normal calcium level | Reference | ||
| Hypercalcemia vs. hypocalcemia | 3.471 | 0.386-31.255 | 0.267 |
| Serum phosphate category | |||
| Normal phosphate level | Reference | ||
| Hyperphosphatemia vs. hypophosphatemia | 1.672 | 0.736-3.802 | 0.220 |
| Serum magnesium category | |||
| Normal magnesium level | Reference | ||
| Hypermagnesemia vs. hypomagnesemia | 0.817 | 0.102-6.520 | 0.849 |
| Serum bicarbonate | 0.926 | 0.868-0.988 | 0.020 |
| Serum lactate | 1.128 | 1.022-1.244 | 0.017 |
| Serum glucose | 1.072 | 1.014-1.133 | 0.015 |
| Activated partial thromboplastin time | 1.054 | 1.024-1.084 | <0.001 |
| International normalized ratio | 3.825 | 1.592-9.188 | 0.003 |
| Craniectomy/craniotomy | 0.569 | 0.320-1.010 | 0.054 |
| MTP activated | 0.524 | 0.265-1.037 | 0.064 |
OR: odds ratio; CI: confidence interval; ED: emergency department; MTP: massive transfusion protocol.
DISCUSSION
This study examined 902 hospitalized patients who had TBI and serum electrolyte disturbances. Electrolyte imbalances included serum sodium, potassium, calcium, magnesium, or phosphate levels on admission. Most patients who sustained severe TBI were young males who were injured in road traffic accidents or falls. The most typical electrolyte imbalance was hypocalcemia, followed by hypophosphatemia and hypokalemia. This study showed that the head injury severity scores were significantly correlated with the initial serum electrolytes levels.
The multivariate logistic regression analysis showed that elevated sodium levels, in addition to other variables such as age, INR, higher ISS, lower GCS, reduced bicarbonate levels, increased lactate levels, higher glucose levels, and prolonged aPTT, were associated with increased mortality. Additionally, the study demonstrated a significant relationship between magnesium levels and various laboratory parameters. Hyperkalemia was also a predictor of mortality; however, it had a large confidence interval affecting its reliability in this study.
In our cohort, sodium imbalances are common in TBI patients, with hyponatremia being more prevalent. Previous studies have reported varying rates of hyponatremia, up to 82% among TBI patients, with fluid intake and cranial fractures identified as risk factors.[3] Hypernatremia is also reported in TBI patients, and severe hypernatremia is associated with high mortality.[24] Hyponatremia can lead to a range of neurological symptoms often attributed to causes such as cerebral salt wasting (CSW), syndrome of inappropriate antidiuretic hormone secretion (SIADH), low albumin levels, and certain medications (such as antipsychotics, antidepressants, anticonvulsants, and thiazide diuretics).[25] Hypopituitarism after TBI may occur in 27.5% of patients[26] and can contribute to hyponatremia, so monitoring hormonal levels, especially in TBI patients, is important. Central diabetes insipidus may occur in 3%-51% of patients after trauma and is a common cause of hypernatremia in TBI patients, often resulting from damage to the hypothalamus-pituitary axis.[27] Treatment options for these electrolyte imbalances include fluid restriction, hormone replacement therapy, and other interventions depending on the patient’s underlying cause and volume status. Hypernatremia can be iatrogenic in post-TBI patients as an overcorrection of hyponatremia.
A previous study has shown associations between hypokalemia and increased mortality, especially in severe TBI patients.[16] On the other hand, hyperkalemia is less common and is often related to specific treatments or associated conditions.[5,13] Management of these imbalances depends on their severity. Treatment for hypokalemia includes oral or intravenous potassium supplementation. Hyperkalemia management includes monitoring for cardiac arrhythmia, dietary adjustments, and medications. The most frequent potassium abnormality in our study was hypokalemia.
Hypocalcemia can be caused by multiple transfusions, hemorrhagic shock, tissue injury, and acidosis. Studies have shown that persisting hypocalcemia in TBI patients is associated with increased mortality and other adverse outcomes.[3,7,8,28,29] The “calcium hypothesis” suggests that excessive calcium influx into brain cells after TBI contributes to cell death.[30] Various mechanisms, including membrane pore formation, glutamate release, and ATP depletion, increase intracellular calcium levels and activate enzymes that cause cell damage. Management of hypocalcemia involves monitoring and maintaining calcium levels within normal limits during massive transfusions.[31] In our study, hypocalcemia was the most predominant electrolyte imbalance, with a prevalence of 82%. However, more significant mortality was reported in the hypercalcemia group. Hypercalcemia treatment depends on the severity, ranging from discontinuation and avoidance of causative agents and hydration for mild cases to a combination of therapies, including intravenous saline and medications for moderate to severe cases.
Magnesium plays a crucial role in brain function and synaptic transmission, and its disruption can affect neuronal health. Varied prevalence of hypomagnesemia in TBI patients have been reported, ranging up to 63%.[7] For instance, Stippler et al [32] reported a hypomagnesemia prevalence of 55% in severe TBI patients, and it was associated with poor outcomes. However, Pin-on et al[4] did not find a significant impact of hypomagnesemia on mortality, although it had a prevalence of 43% among TBI patients. Dhandapani et al [33] found that severe TBI patients had significantly lower serum magnesium levels than health controls. The exact mechanism behind magnesium depletion in head injury patients remains largely unknown. However, one plausible explanation is that the stress-induced surge in catecholamines may trigger increased lipolysis, leading to elevated levels of free fatty acids that bind to magnesium ions, subsequently increasing their excretion in the urine.[34] Hypomagnesemia is linked to increased calcium influx into brain cells, contributing to neuronal degeneration and cell death, even beyond the initial injury. However, evidence on the therapeutic effects of magnesium supplementation in TBI remains inconclusive. Hypermagnesemia treatment involves fluid and renal replacement therapy, along with symptomatic management, including intravenous calcium administration to counteract its effects on neuromuscular and cardiac functions.
Phosphate imbalances can lead to muscle weakness, respiratory issues, and infections. Hypophosphatemia poses challenges for ventilator weaning in critical patients. On the other hand, hyperphosphatemia can reduce cardiac output and trigger ventricular tachycardia. In previous studies, hyperphosphatemia was reported in up to 87% of patients with TBI, whereas hypophosphatemia was up to 56% of patients.[5] In our study, hypophosphatemia was more common than hyperphosphatemia. Mortality rates increased with increasing severity of hypophosphatemia. However, a high mortality rate was observed in the severe hyperphosphatemia group in our study. Hypophosphatemia treatment includes intravenous administration of phosphate. Management of hyperphosphatemia involves the use of phosphate binders such as calcium carbonate, sevelamer hydrochloride, or calcium acetate. Dialysis should be considered if renal impairment presents.
Wu et al [16] highlighted the significant concern about concomitant electrolyte imbalances in TBI patients. In their prospective study involving 375 TBI patients with hypokalemia upon admission, they observed higher mortality rates among patients who also had other electrolyte imbalances along with hypokalemia. Severe hypokalemia patients with hypernatremia and hypophosphatemia had an 80% mortality rate, compared with 56% for those with moderate hypokalemia and 9% for those with mild hypokalemia.[17] Outcomes of combinations of electrolytes need to be studied further, which is limited in our study by the inadequate sample size of some groups of patients in our study.
Electrolyte disturbances in TBI patients can be influenced by pre-existing comorbidities and chronic treatments, even though detailed data on such factors were not available in this study. Common conditions like chronic kidney disease, diabetes mellitus, and endocrine disorders (e.g., hypothyroidism, adrenal insufficiency) are known to affect electrolyte homeostasis.[35] Additionally, medications such as diuretics, corticosteroids, antiepileptics, and certain antihypertensives may predispose patients to imbalances in sodium, potassium, calcium, magnesium, or phosphate levels. For instance, diuretic use can cause hypokalemia and hyponatremia,[36] whereas corticosteroids and antiepileptic drugs can alter calcium and magnesium metabolism.[37] Moreover, patients with chronic illnesses often experience baseline disturbances in hydration status, acid-base balance, and nutritional deficiencies, which can exacerbate electrolyte changes during acute injuries like TBI. These factors highlight the importance of evaluating and managing comorbidities in TBI patients to mitigate potential contributions to poor outcomes from electrolyte disturbances.[35]
While severe electrolyte imbalances had higher mortality rates, they were much less common compared to mild imbalances in our study. The mortality among patients with mild electrolyte disturbances could be explained by the severity of injury in terms of high SI and ISS and low GCS in some cases. This may highlight the importance of addressing even the mild degrees of electrolyte imbalances in TBI.
To improve the care of trauma patients from the perspective of electrolytes, our HTC established a TICU Multidisciplinary Electrolyte Replacement Order Set (Supplementary file 1). This protocol was approved by the corporate critical care committee in 2019 and is currently being implemented in the TICU.
Limitations
This study has several limitations. First, its retrospective design and small sample sizes in certain patient subgroups may limit the generalizability of these findings. There were no missing data for sodium, potassium, or calcium levels; however, phosphate levels were missing for 10 patients, and magnesium levels were missing for 9 patients. For the remaining relevant variables analyzed, the proportion of missing data was minimal, typically around 1%-2%. Valid percentages were used in all analyses to account for these small amounts of missing data. Second, while we collected data on diabetes mellitus and hypertension as comorbidities, only a small number of patients had these conditions (58 had diabetes mellitus and 61 had hypertension), as most patients were young. Third, detailed information on other comorbidities or chronic drug therapies that could explain the high percentage of electrolyte imbalances was not available. We relied on the initial electrolyte readings, but the exact timing and treatment received prior to testing were not documented. These factors could influence the interpretation of electrolyte levels at admission. Fourth, we did not perform priori sample size calculation or power analysis as we intended to include all patients with TBI admitted to the TICU during the study period and who underwent on-admission serum electrolyte testing. Given the retrospective nature of the study and the multiple comparative sub-analyses conducted on various electrolyte abnormalities, a post hoc power analysis was not feasible. Despite these limitations, this study offers valuable insights into the complex relationship between serum electrolytes and outcomes in TBI patients. Future research with larger sample sizes, prospective designs, and longer follow-up periods is needed to confirm and expand upon these findings.
CONCLUSIONS
This study highlights the significant prevalence of hypocalcemia, hypophosphatemia, and hypokalemia in TBI patients, emphasizing the importance of addressing these electrolyte imbalances in clinical management. Hypernatremia and hyperkalemia were associated with the mortality risk after adjusting covariates. Further research is required to understand electrolyte dynamics in TBI patients appropriately.
Funding: This study did not receive external funding.
Ethical approval: Ethical approval with a waiver of consent for the study was obtained from the Institutional Review Board of Hamad Medical Corporation, Qatar (MRC#01-21-501), as there was no direct contact with the patients, and data were collected anonymously.
Conflicts of interest: The authors declare no conflicts of interest.
Author contributions: conceptualization, AE, TC, and HA; methodology, AE, AM; formal analysis, AM; data curation, AM; writing—original draft preparation, AE, and AM; writing—review and editing, HA, AE, AA, ANA, TC, AS, and AB. All authors have read and agreed to the published version of the manuscript.
All the supplementary files in this paper are available at http://wjem.com.cn.
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