Hypomagnesemia as a possible marker of disability in patients with severe traumatic brain injury.

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Claudia Yaneth Rodriguez-Triviño, Zulma Dueñas This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6256509/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: To find association between hydroelectrolyte disbalance and disability in patients with severe traumatic brain injury using the Glasgow Outcome Scale (GOS) for classification. Method: This is a retrospective cohort study based on 83 clinical charts of inpatients with severe traumatic brain injury (TBI) and a Glasgow Coma Scale score lower than 8, covering a three-year period. Data from the clinical charts aim to establish a relationship between GOS results and electrolyte levels analysis six months after initial trauma. Bivariate analysis and chi square 95% reliability rate, were applied to categorical variables. One-way ANOVA, for independent groups, was used to determine association between different levels of individual electrolytes (Na+, K+, Ca++, Mg++ and Cl-) and disability. The statistical analysis for continuous variables comparison was made by chi square test. Multivariate Logistic Regression analysis was useful to determine association. Results: Disability was statistically associated with the increment of age (p=<0,01), higher APACHE II score, (Acute Physiology and Chronic Health Evaluation) prolonged mechanic ventilation use, hypomagnesemia and hyperkalemia. Conclusions: Hypomagnesemia and hyperkalemia could be associated with higher disability according to measurement of GOS. Neurosurgery Neurology Critical Care & Emergency Medicine Brain Injuries Traumatic electrolytes disability hypomagnesemia Glasgow Outcome Scale Introduction Traumatic brain injury (TBI) is a frequent health problem (proportion for all ages was 295 per 100,000) ( 16 ), with a very important impact on life expectancy and years of potential life lost in young people worldwide. Not to mention its high cost for the health system ( 13 ), ( 6 ), ( 18 ), ( 2 ), ( 19 ). It is associated to certain types of occupations and social risks in Latin America. The incidence and mortality (18%) by TBI are very high; 31% deceased and 54% of disability with neurological sequel ( 22 ), ( 15 ), ( 23 ), ( 21 ), ( 31 ). TBI is responsible for years of life lost due to disability in young people. Alvis et al., ( 1 ) found 28,8 years of life lost for each patient who die for trauma. Electrolyte equilibrium is one of the cornerstones of treatment in patients with TBI at the emergency wards and Intensive Care Units ( 10 ). However, the efforts for keeping electrolyte balance and the liquid replacement could be associated with polyuria and worsening ion levels. The study of Vedantam A., et., al. show increased risk to develop hypomagnesemia, hypophosphatemia, and hypokalemia in patients with severe TBI and also hyponatremia related with the treatment or specific conditions such the salt losing brain and the inappropriate secretion of antidiuretic hormone. Different investigations have shown the same electrolyte abnormalities and correlation in patients with chronic renal failure and bad outcomes related with functionality ( 11 ), ( 26 ). There are different pathways to explain how electrolyte changes disturb the neuron and muscular membranes stability. And also, an increment of apoptosis aggravating secondary lesions in patients with TBI ( 24 ), ( 29 ), ( 27 ). The main purpose of this study was to stablish a possible relationship between electrolytes disturbances and disability in patients with TBI based on the results of the Glasgow Outcome Scale (GOS) six months after the initial trauma. Methods A cohort retrospective study was made with follow up of 400 clinical charts of inpatients with diagnosis of severe TBI covering a three-year period. Inclusion criteria were applied such as: age: older than 18 years old, diagnosis of severe TBI with Glasgow score ≤ 8, Marshall classification of traumatic brain injury level III or higher, the brain Abbreviated Injury Scale (AIS) ≥ 3, The Injury Severity Score (ISS) ≤ 3, and Sequential Organ Failure Assessment (SOFA) > 2 not related to The Glasgow scale. The exclusion criteria were comorbidities such as: COPD, Diabetes Mellitus, Hypertension, Chronic Kidney Failure, Adrenal Insufficiency and Chronic Liver Disease. Other exclusion criteria were the use of diuretics, corticosteroids and digitalis and multiple organ failure or damage on more than two vital organs. A total of 317 clinical charts were excluded as follow: 125 due to ISS > 3, 72 for AIS < 3, 62 because its Marshall classification was lower than III, 12 patients were younger than 18 years old, 12 had chronic illnesses and 34 patients with multiple organ failure. Only 83 clinical charts of patients completed the inclusion criteria and were included in the cohort. Even though GOS is a scale to measure disability after trauma, based in the original article by Jennett and Bond ( 9 ), in this study a modified version was used in the clinical environment to classify the cohort of patients ( 5 ). Demographic data was collected and added to variables. Electrolyte values ​​were followed from day one to day 10 of hospitalization and the follow up of electrolyte corrections was made (83% of patients). Electrolyte alteration was considered when deviations from the normal values ​​were sustained more than three days spite corrections. The intervals of normal values were adjusted to the standards of lab and literature values such as: Potassium (3,5 a 4,5mEq/l), Calcium (8,5mEq/l- 9,5 mEq/l), Ionic calcium (1,0 mmol/l-1,5mmol/l), Magnesium (2,0 a 2,5mEq/l), Sodium (135 a 145mEq/l) and Chlorine (101 mEq/l-110 mEq/l). There was follow-up of patients for six months after TBI and the score of GOS was always evaluated by neurologist and specialists physical medicine. According to GOS at six months, patients were classified in three groups for univariate analysis: Group 1 GOS between 1 and 2 (n = 31 patients), group 2 GOS between 3 and 4 (n = 19 patients) and group 3 GOS with a value of 5 (n = 33 patients). In order to perform the multivariate analysis, The GOS score was classified as high between 4 to 5 and low between 1 and 3. The Universidad Nacional de Colombia´s and Hospital Simón bolivar ethic committees gave the approval to the present research work. Data Analysis Data were collected and variables classified as continues in order to be evaluated with central tendency, dispersion measurements. The categorical variables were evaluated with frequency distribution and proportions. The behaviour of numerical variables was proved by Kolmogorov-Smirnoff test and those without values in a normal range were analyzed with a non-parametric measurement. A bi varied analysis, for categorical variables, were made by chi square test with 95% of reliability. Yate´s correction was applied for variables frequency lower than five. One-way ANOVA for independent groups and multiple comparison Chi square with 95% of reliability, were used to determine relationship between hydro electrolyte alterations and disability. Bi variate analysis a multivariate logistic regression was used for statistically different variables. There was not interaction between variables and the confusion variables were added to a regression model. Results 400 clinical charts of patients with TBI, from the Hospital Simón Bolivar, were analyzed. Four years charts, from January 2012 to December 2015 were chosen. 317 clinical charts did no make de inclusion criteria and were excluded (Fig. 1). 83 clinical charts were included for the study and data were collected. Table 1 describe data of socio demographic, clinical electrolyte levels and disability of patients. According to results three groups were instituted. Group 1 with the worst clinical outcome (n = 31), only 4 patients survived and the end point was a persistent Vegetative State ( 22 ). Groups 2 and 3 had better clinical outcome, but disability. Table 1 Factors associated with disability in patients with TBI (n = 83) Dates GOS (1 y 2) N = 31 GOS (3 y 4) N = 19 GOS 5 N = 33 P Age Mean (Standard Deviation) 49,5 ( 18 , 8 ) 32,5 ( 13 , 9 ) 40,7 ( 18 , 3 ) < 0,01 * Sex Male Female 28 (90,3) 3 ( 9 , 7 ) 17 (89,5) 2 ( 10 , 5 ) 31 (93,9) 2 ( 6 , 1 ) 0,80 Hospital stays Mean (Standard Deviation) 9 ( 12 , 6 ) 17,3 ( 14 , 7 ) 11,6 ( 10 , 6 ) 0,07 APACHE II Income Mean (Standard Deviation) 17,8 (5,0) 13,9 ( 3 , 8 ) 13,4 ( 5 , 1 ) < 0,01 * Days of mechanical ventilation Mean (Standard Deviation) 4,3 ( 4 , 2 ) 7,3 ( 4 , 2 ) 4,9 ( 3 , 4 ) 0,03 * Hydro electrolytic Alteration Yes 31 (100) 19 (100) 27 (81,8) < 0,01 ** Potassium Hypokalemia Hyperkalemia 14 (45,2) 7 ( 22 , 6 ) 6 ( 31 , 6 ) 0 (0) 17 (51,5) 0 (0) 0,37 < 0,01 ** Calcium Hypocalcemia Hypercalcemia 6 ( 19 , 4 ) 0 (0) 0 (0) 2 ( 10 , 5 ) 9 ( 27 , 3 ) 0 (0) 0,04 ** 0,04 ** Magnesium Hypomagnesemia Hypermagnesemia 13 (41,9) 2 ( 6 , 5 ) 15 (78,9) 0 (0) 5 ( 15 , 2 ) 0 (0) < 0,01 ** 0,17 Sodium Hyponatremia Hypernatremia 14 (45,2) 6 ( 19 , 4 ) 10 (52,6) 2 ( 10 , 5 ) 18 (54,5) 5 ( 15 , 2 ) 0,73 0,70 Chlorine Hypochloremia Hyperchloremia 7 ( 22 , 6 ) 2 ( 6 , 5 ) 2 ( 10 , 5 ) 2 ( 10 , 5 ) 1 ( 3 ) 4 ( 12 , 1 ) 0,05 ** 0,73 One-way ANOVA test for independent groups with significance p < 0.05. ** Chi square test with multiple comparisons with significance p < 0.05. There was statistically significant association between age, APACHE II, length of mechanical ventilation (S.D. 4,2 days) and disability measured by GOS. GOS between 1 and 2 was more frequent in older patients (ẋ=49,5 ± 18,8 years old) and in those higher with APACHE II score on the initial medical attention. Patients with electrolyte disturbances showed more disability according to the scale applied and the results were statistically significant (p = < 0,01). 14 patients (45.2% of the group) with GOS between 1 and 2 (group 1) had hypercalcemia, this finding was absent in patients from groups 2 and 3. Hypomagnesemia was found in 13 patients from group 1 (41%), 15 patients from group 2 (78%) and 5 patients from group 3(15%); those results were statistically significant (p = < 0,01). In addition, hypochloremia was found in 5 patients from group 1 (6%), 2 patients from group 2 (10,5%) and 1 patient from group 3 (3%) and the results were statistically significant (p = 0,04). A negative significant relationship between plasma osmolarity and disability (r = -02,8 p = < 0,01) was an important finding. Potassium and magnesium disturbances were statistically different in all the three groups; being the first one more prominent in group 1 (67,7% p = 0,04) and the second one in group 2 (78,9% p < 0,01). Patients with hyperkalemia and hypomagnesemia had the worst statistically significant disability outcome (p < 0,01) (Table 2 ). Table 2 Proportion of Patients with Hydro-Electrolyte Alterations According to Disability Level in Patients with Severe Traumatic Brain Injury (n = 83) Hydro-Electrolyte Alteration GOS (1 and 2) N = 31 GOS (3 and 4) N = 19 GOS 5 N = 33 P Potassium Calcium Magnesium Sodium Chloride 21 (67,7) 6 ( 19 , 4 ) 15 (48,4) 20 (64,5) 9 (29,0) 6 ( 31 , 6 ) 2 ( 10 , 5 ) 15 (78,9) 12 (63,2) 4 ( 21 , 1 ) 17 (51,5) 9 ( 27 , 3 ) 5 ( 15 , 2 ) 23 (69,7) 5 ( 15 , 2 ) 0,04 * 0,32 < 0,01 * 0,86 0,40 * Chi-square test significance p < 0.05 The multivariate logistic regression showed that patients who had hypomagnesemia were 10 times prone to disability measured by GOS than those without this electrolyte alteration. Adjusted to the other variables this relationship was statically significant (p = 0.001). Hypochloremia was identified as a confounding variable and was included in the model, those patients with hypochloremia had 36 times higher risk of bad outcome, measured by GOS, than those who did not have this condition. This relationship was statistically significant (p = 0.004). Hypoosmolarity was a variable with a negative correlation. The possibility of low GOS was seven times lower in those patients with hypoosmolarity compared with those with normal plasmatic osmolarity being statistically significant (p = 0,01). Age also showed a negative correlationship, however there was not statically significance when adjusted with other variables (Table 3 ). Table 3 Multivariate Logistic Regression analysis for GOS GOS Dependent variable OR Ajustado P IC Age 0.98 0.21 0.9446703–1.01279 GCS 0.79 0.05* 0.6529311–0.965047 Hypomagnesemia 11.53 0.001* 2.785023–47.74559 Hypochloremia 37.9 0.004* 5.951983–1693.215 Hyposmolarity (less than 290 mOsmol / l) 0.1482221 0.01* 0.0350202–0.6273468 GOS: Glasgow Outcome Scale; GCS: Glasgow Coma Scale; CI: Confidence interval. Multivariate Logistic Regression analysis Prob > chi2 = 0.0000 Pseudo R2 = 0.3152 Discussion Patients with electrolyte alterations (hypomagnesemia and hypochloremia) showed more disability than those without it, this was statistically significant. Ion Magnesium participate in cell´s energy metabolism, vascular tone and ion transportation on cell membrane ( 12 ). Furthermore, Mg + + plays an important role on the elimination of oxygen reactive species and preventing reperfusion lesions; factors related with bad outcome on rehabilitation. In the other hand Mg + + intracellular flow could help to stabilize cell membrane, improve energy balance and to ease calcium overload effects ( 14 ). Hypomagnesemia could contribute to secondary lesions in TBI patients by increasing apoptosis, worsening the final outcome. The flow of magnesium and its non-competitive blockage of NMDA (N-methyl-D Aspartate) receptors ( 14 ), generate a protective action over the hippocampus, and the brain´s white substance avoiding the necrotic effect of glutamate over excitation and ischemia. Increasing levels of extracellular Mg + + improves hippocampal high energy neuronal phosphates levels and also accelerates blood flow on the injury area so Mg + + is unspecific antagonist of every subtype of calcium channel voltage sensible. Bareyre FM et al. ( 3 ), showed that free Mg + + intracellular concentration decreases after lateral fluid-percussion brain injury is related to depletion of intracellular levels of high energy phosphate depending of the lesion severity. Polderman et al. ( 20 ), reported in its study hypomagnesemia as the worst prognostic factor on the rehabilitation of critically ill patients. Hypomagnesemia have been also related to metabolic disbalance such as insulin resistance, as Noronha and Matuschak showed on invitro studies ( 17 ). This resistance is associated to Mg + + capacity of chelates formation; specially with ATP (adenosine triphosphate), also competition with Calcium for membrane unions sites and promoting calcium sequestration by the sarcoplasmic reticulum ( 28 ). It is important to mention that hypomagnesemia was caused by multiple factors, like polyureic effect of osmotic diuretics and hyperglycemia both associated to plasmatic hyperosmolarity and increasing paracellular transport and Mg + + excretion. ( 20 ), ( 28 ). In this study hyperglycemia was the main cause of hyperosmolarity, 42,1% of patients, and associated with bad prognosis; in fact, this result is concordant with literature findings. Hyperkalemia was statistically associated with disability and prognosis worsening; however, this finding was less frequent than hypokalemia, being the last one more common in trauma patients due to catecholamines increase by the effect of intracellular K + reabsorption ( 4 ). There was association between hypochloremia and disability and it was a confusion variable included in the logistic regression model. Low levels of Chlorine in adult neurons is related with GABA (Gamma-Aminobutyric Acid) hyperpolarization action. In opposition immature neurons express chlorine transporters so GABA produces post-synaptic depolarizing potentials important to stabilize developing synapsis. Hypochloremia could be an awareness signal of bad prognosis for trauma patients ( 7 ). There is a possible association between Claudins-2 expression drop and hypochloremia due to secondary hypoperfusion in patients with trauma ( 22 ), ( 32 ). Huang Y. et al., y Baldwin MR. et al. ( 2 ), ( 8 ), showed higher mortality when correlated APACHE II and GOS worst results in patients with TBI, a similar finding was made in this study. Longer hospitalization and mechanical ventilation (S.D. 4,2 days) were variables of bad outcome for rehabilitation. Similar results were found in Silva PE et al., where muscle atrophy was the result of electrophysiologic neuromuscular changes associated to TBI and prolonged mechanical ventilation, similar in this study ( 25 ). Patients in this study were very similar, so comparison among them was accurate, being this aspect a strength. A novelty in this study was the analysis of disability degree six month after trauma, important data to measure final outcomes and cost for the health system. The use of GOS scale, related in clinical charts, was a limitation of this study, since DRS (Disability Rating Scale) and GOSE (Extended Glasgow Outcome Scale) scale have more sensitivity to evaluate disability ( 32 ). 7,2% of patients did not have any electrolyte alteration even thought the similarity of characteristics. Furthermore, the type of study (retrospective), the sample size and the fact that most of patients were males could be a limitation for its reliability. Conclusions Mostly patients were males (91,5%), media of 45 years old without co-morbidities. There was association between hypomagnesemia and hypochloremia with worst outcomes measured with GOS. It is necessary to replay this study increasing the number of patients and including more females to improve its strength. A proper Mg + + therapy in trauma patients could contribute to improve cognitive and physical rehabilitation results ( 24 ). Declarations Compliance with ethical standards Conflict of interest : All authors declare that they have no conflict of interest. Ethical approval: Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the Universidad Nacional de Colombia´s and Hospital Simón Bolivar ethic committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. This article does not contain any studies with human participants performed by any of the authors. No funding was received for this research. Financing: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. References Alvis N, Valenzuela MT (2010) Los QALYs y DALYs como indicadores sintéticos de salud. Rev Médica Chile 138:83–87 Baldwin MR, Reid MC, Westlake AA, Rowe JW, Granieri EC, Wunsch H et al (2014) The feasibility of measuring frailty to predict disability and mortality in older medical intensive care unit survivors. J Crit Care 29(3):401–408 Bareyre FM, Saatman KE, Raghupathi R, McIntosh TK (2000) Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma 17(11):1029–1039 Beal AL, Deuser WE, Beilman GJ (2007) A role for epinephrine in post-traumatic hypokalemia. Shock Augusta Ga 27(4):358–363 Brooks DN, Hosie J, Bond MR, Jennett B, Aughton M (1986) Cognitive sequelae of severe head injury in relation to the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry 49(5):549–553 Dang B, Chen W, He W, Chen G (2017) Rehabilitation Treatment and Progress of Traumatic Brain Injury Dysfunction. Neural Plast 2017:1582182 Duran C, Thompson CH, Xiao Q, Hartzell HC (2010) Chloride channels: often enigmatic, rarely predictable. Annu Rev Physiol 72:95–121 Huang Y, Chen J, Zhong S, Yuan J (2016) Role of APACHE II scoring system in the prediction of severity and outcome of acute intracerebral hemorrhage. Int J Neurosci 126(11):1020–1024 Jennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet Lond Engl 1(7905):480–484 Khalili H, Niakan A, Ghaffarpasand F, Kiani A, Behjat R (2017) Outcome Determinants of Decompressive Craniectomy in Patients with Traumatic Brain Injury; A Single Center Experience from Southern Iran. Bull Emerg Trauma 5(3):190–196 Kovesdy CP, Lott EH, Lu JL, Malakauskas SM, Ma JZ, Molnar MZ et al (2012) Hyponatremia, hypernatremia, and mortality in patients with chronic kidney disease with and without congestive heart failure. Circulation 125(5):677–684 Li W, Bai Y-A, Li Y-J, Liu K-G, Wang M-D, Xu G-Z et al (2015) Magnesium sulfate for acute traumatic brain injury. J Craniofac Surg 26(2):393–398 Ma VY, Chan L, Carruthers KJ (2014) Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil 95(5):986–995e1 McDonald JW, Silverstein FS, Johnston MV (1990) Magnesium reduces N-methyl-D-aspartate (NMDA)-mediated brain injury in perinatal rats. Neurosci Lett 109(1–2):234–238 Natalie P, Holz M, Hermes Pereira A, Bresolin AP, Zimmermann N, Paz Fonseca R (2016) FREQUENCY OF NEUROLOPSYCHOLOGICAL DEFICITS AFTER TRAUMATIC BRAIN INJURY. Acta Colomb Psicol 19(2):127–137 Nguyen R, Fiest KM, McChesney J, Kwon C-S, Jette N, Frolkis AD et al (2016) The International Incidence of Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Can J Neurol Sci J Can Sci Neurol 43(6):774–785 Noronha JL, Matuschak GM (2002) Magnesium in critical illness: metabolism, assessment, and treatment. Intensive Care Med 28(6):667–679 Palmer CS, Gabbe BJ, Cameron PA (2016) Defining major trauma using the 2008 Abbreviated Injury Scale. Injury 47(1):109–115 Petgrave-Pérez A, Padilla JI, Díaz J, Chacón R, Chaves C, Torres H et al (2016) [Epidemiological profile of traumatic brain injury at the Dr. Rafael A. Calderón Guardia Hospital, Neurosurgery Department, during the period from 2007 to 2012]. Neurocir Astur Spain 27(3):112–120 Polderman KH, Bloemers FW, Peerdeman SM, Girbes AR (2000) Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury. Crit Care Med 28(6):2022–2025 Puvanachandra P, Hyder AA (2008) Traumatic brain injury in Latin America and the Caribbean: a call for research. Salud Publica Mex 50(Suppl 1):S3–5 Rodríguez-Triviño CY, Castro IT, Dueñas Z (2019) Hypochloremia in Patients with Severe Traumatic Brain Injury: A Possible Risk Factor for Increased Mortality. World Neurosurg 124:e783–e788 Roozenbeek B, Maas AI, Menon DK (2013) Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 9(4):231 Silva PE, Maldaner V, Vieira L, de Carvalho KL, Gomes H, Melo P et al (2017) Neuromuscular electrophysiological disorders and muscle atrophy in mechanically-ventilated traumatic brain injury patients: New insights from a prospective observational study. J Crit Care 44:87–94 Silva PE, Maldaner V, Vieira L, de Carvalho KL, Gomes H, Melo P et al (2017) Neuromuscular electrophysiological disorders and muscle atrophy in mechanically-ventilated traumatic brain injury patients: New insights from a prospective observational study. J Crit Care 44:87–94 Stein DM, Feather CB, Napolitano LM (2017) Traumatic Brain Injury Advances. Crit Care Clin 33(1):1–13 Stys PK, Ransom BR, Waxman SG (1990) Effects of polyvalent cations and dihydropyridine calcium channel blockers on recovery of CNS white matter from anoxia. Neurosci Lett 115(2–3):293–299 Temkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J et al (2007) Magnesium sulfate for neuroprotection after traumatic brain injury: a randoised controlled trial. Lancet Neurol 6(1):29–38 Vedantam A, Robertson CS, Gopinath SP (2017) Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus 43(5):E2 Wilson JT, Pettigrew LE, Teasdale GM (1998) Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 15(8):573–585 Yoon S-Y, Choi Y-J, Park S-H, Hwang J-H, Hwang SK (2017) Traumatic Brain Injury in Children under Age 24 Months: Analysis of Demographic Data, Risk Factors, and Outcomes of Post-traumatic Seizure. J Korean Neurosurg Soc 60(5):584–590 Zhang L, Li Z-H, Deng X, Yin Y (2014) [Expression of tight junction protein claudin-2 in renal tissues and its significance in children with acute kidney injury]. Zhongguo Dang Dai Er Ke Za Zhi Chin J Contemp Pediatr 16(4):361–365 Figure 1 Figure 1 is not available with this version. Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6256509","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":430722222,"identity":"428d9aab-4bd5-41e1-b5f8-33c653a67e0d","order_by":0,"name":"Claudia Yaneth Rodriguez-Triviño","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-6884-3931","institution":"Universidad del Valle","correspondingAuthor":true,"prefix":"","firstName":"Claudia","middleName":"Yaneth","lastName":"Rodriguez-Triviño","suffix":""},{"id":430722223,"identity":"528bac7b-007f-4902-8a09-fd191495e6f6","order_by":1,"name":"Zulma Dueñas","email":"","orcid":"https://orcid.org/0000-0001-6068-4174","institution":"Universidad Nacional de Colombia","correspondingAuthor":false,"prefix":"","firstName":"Zulma","middleName":"","lastName":"Dueñas","suffix":""}],"badges":[],"createdAt":"2025-03-18 22:53:23","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-6256509/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6256509/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79065228,"identity":"e1827df2-d742-45e2-bbc8-0d352ce25ec6","added_by":"auto","created_at":"2025-03-24 04:05:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":585358,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6256509/v1/b2ba21c7-e4f8-485e-9ff2-6f0047f2817d.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eHypomagnesemia as a possible marker of disability in patients with severe traumatic brain injury.\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTraumatic brain injury (TBI) is a frequent health problem (proportion for all ages was 295 per 100,000) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), with a very important impact on life expectancy and years of potential life lost in young people worldwide. Not to mention its high cost for the health system (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). It is associated to certain types of occupations and social risks in Latin America. The incidence and mortality (18%) by TBI are very high; 31% deceased and 54% of disability with neurological sequel (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). TBI is responsible for years of life lost due to disability in young people. Alvis et al., (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) found 28,8 years of life lost for each patient who die for trauma.\u003c/p\u003e \u003cp\u003eElectrolyte equilibrium is one of the cornerstones of treatment in patients with TBI at the emergency wards and Intensive Care Units (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, the efforts for keeping electrolyte balance and the liquid replacement could be associated with polyuria and worsening ion levels. The study of Vedantam A., et., al. show increased risk to develop hypomagnesemia, hypophosphatemia, and hypokalemia in patients with severe TBI and also hyponatremia related with the treatment or specific conditions such the salt losing brain and the inappropriate secretion of antidiuretic hormone. Different investigations have shown the same electrolyte abnormalities and correlation in patients with chronic renal failure and bad outcomes related with functionality (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). There are different pathways to explain how electrolyte changes disturb the neuron and muscular membranes stability. And also, an increment of apoptosis aggravating secondary lesions in patients with TBI (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e), (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). The main purpose of this study was to stablish a possible relationship between electrolytes disturbances and disability in patients with TBI based on the results of the Glasgow Outcome Scale (GOS) six months after the initial trauma.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA cohort retrospective study was made with follow up of 400 clinical charts of inpatients with diagnosis of severe TBI covering a three-year period. Inclusion criteria were applied such as: age: older than 18 years old, diagnosis of severe TBI with Glasgow score\u0026thinsp;\u0026le;\u0026thinsp;8, Marshall classification of traumatic brain injury level III or higher, the brain Abbreviated Injury Scale (AIS)\u0026thinsp;\u0026ge;\u0026thinsp;3, The Injury Severity Score (ISS)\u0026thinsp;\u0026le;\u0026thinsp;3, and Sequential Organ Failure Assessment (SOFA)\u0026thinsp;\u0026gt;\u0026thinsp;2 not related to The Glasgow scale. The exclusion criteria were comorbidities such as: COPD, Diabetes Mellitus, Hypertension, Chronic Kidney Failure, Adrenal Insufficiency and Chronic Liver Disease. Other exclusion criteria were the use of diuretics, corticosteroids and digitalis and multiple organ failure or damage on more than two vital organs.\u003c/p\u003e \u003cp\u003eA total of 317 clinical charts were excluded as follow: 125 due to ISS\u0026thinsp;\u0026gt;\u0026thinsp;3, 72 for AIS\u0026thinsp;\u0026lt;\u0026thinsp;3, 62 because its Marshall classification was lower than III, 12 patients were younger than 18 years old, 12 had chronic illnesses and 34 patients with multiple organ failure. Only 83 clinical charts of patients completed the inclusion criteria and were included in the cohort.\u003c/p\u003e \u003cp\u003eEven though GOS is a scale to measure disability after trauma, based in the original article by Jennett and Bond (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), in this study a modified version was used in the clinical environment to classify the cohort of patients (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDemographic data was collected and added to variables. Electrolyte values ​​were followed from day one to day 10 of hospitalization and the follow up of electrolyte corrections was made (83% of patients). Electrolyte alteration was considered when deviations from the normal values ​​were sustained more than three days spite corrections. The intervals of normal values were adjusted to the standards of lab and literature values such as: Potassium (3,5 a 4,5mEq/l), Calcium (8,5mEq/l- 9,5 mEq/l), Ionic calcium (1,0 mmol/l-1,5mmol/l), Magnesium (2,0 a 2,5mEq/l), Sodium (135 a 145mEq/l) and Chlorine (101 mEq/l-110 mEq/l).\u003c/p\u003e \u003cp\u003eThere was follow-up of patients for six months after TBI and the score of GOS was always evaluated by neurologist and specialists physical medicine. According to GOS at six months, patients were classified in three groups for univariate analysis: Group 1 GOS between 1 and 2 (n\u0026thinsp;=\u0026thinsp;31 patients), group 2 GOS between 3 and 4 (n\u0026thinsp;=\u0026thinsp;19 patients) and group 3 GOS with a value of 5 (n\u0026thinsp;=\u0026thinsp;33 patients). In order to perform the multivariate analysis, The GOS score was classified as high between 4 to 5 and low between 1 and 3.\u003c/p\u003e \u003cp\u003e The Universidad Nacional de Colombia\u0026acute;s and Hospital Sim\u0026oacute;n bolivar ethic committees gave the approval to the present research work.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eData were collected and variables classified as continues in order to be evaluated with central tendency, dispersion measurements. The categorical variables were evaluated with frequency distribution and proportions. The behaviour of numerical variables was proved by Kolmogorov-Smirnoff test and those without values in a normal range were analyzed with a non-parametric measurement. A bi varied analysis, for categorical variables, were made by chi square test with 95% of reliability. Yate\u0026acute;s correction was applied for variables frequency lower than five.\u003c/p\u003e \u003cp\u003eOne-way ANOVA for independent groups and multiple comparison Chi square with 95% of reliability, were used to determine relationship between hydro electrolyte alterations and disability. Bi variate analysis a multivariate logistic regression was used for statistically different variables. There was not interaction between variables and the confusion variables were added to a regression model.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e400 clinical charts of patients with TBI, from the Hospital Sim\u0026oacute;n Bolivar, were analyzed. Four years charts, from January 2012 to December 2015 were chosen. 317 clinical charts did no make de inclusion criteria and were excluded (Fig. 1). 83 clinical charts were included for the study and data were collected. Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e describe data of socio demographic, clinical electrolyte levels and disability of patients. According to results three groups were instituted. Group 1 with the worst clinical outcome (n\u0026thinsp;=\u0026thinsp;31), only 4 patients survived and the end point was a persistent Vegetative State (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e). Groups 2 and 3 had better clinical outcome, but disability.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u0026nbsp;\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFactors associated with disability in patients with TBI (n\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDates\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS (1 y 2)\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS (3 y 4)\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS 5\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (Standard Deviation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e49,5 (\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e32,5 (\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e40,7 (\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0,01\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e28 (90,3)\u003c/p\u003e\n \u003cp\u003e3 (\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e17 (89,5)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e31 (93,9)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHospital stays\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (Standard Deviation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e9 (\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e17,3 (\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e11,6 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPACHE II Income\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (Standard Deviation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e17,8 (5,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e13,9 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e13,4 (\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0,01\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDays of mechanical ventilation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (Standard Deviation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e4,3 (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e7,3 (\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e4,9 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,03\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHydro electrolytic Alteration\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e31 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e19 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e27 (81,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0,01\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePotassium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHypokalemia\u003c/p\u003e\n \u003cp\u003eHyperkalemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e14 (45,2)\u003c/p\u003e\n \u003cp\u003e7 (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e17 (51,5)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,37\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0,01\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCalcium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHypocalcemia\u003c/p\u003e\n \u003cp\u003eHypercalcemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e9 (\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,04\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0,04\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMagnesium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHypomagnesemia\u003c/p\u003e\n \u003cp\u003eHypermagnesemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e13 (41,9)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e15 (78,9)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e5 (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0,01\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0,17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSodium\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHyponatremia\u003c/p\u003e\n \u003cp\u003eHypernatremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e14 (45,2)\u003c/p\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e10 (52,6)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e18 (54,5)\u003c/p\u003e\n \u003cp\u003e5 (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,73\u003c/p\u003e\n \u003cp\u003e0,70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChlorine\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHypochloremia\u003c/p\u003e\n \u003cp\u003eHyperchloremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e7 (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e1 (\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e4 (\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e0,05\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0,73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eOne-way ANOVA test for independent groups with significance p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. ** Chi square test with multiple comparisons with significance p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n\u003cp\u003eThere was statistically significant association between age, APACHE II, length of mechanical ventilation (S.D. 4,2 days) and disability measured by GOS. GOS between 1 and 2 was more frequent in older patients (ẋ=49,5\u0026thinsp;\u0026plusmn;\u0026thinsp;18,8 years old) and in those higher with APACHE II score on the initial medical attention. Patients with electrolyte disturbances showed more disability according to the scale applied and the results were statistically significant (p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0,01). 14 patients (45.2% of the group) with GOS between 1 and 2 (group 1) had hypercalcemia, this finding was absent in patients from groups 2 and 3. Hypomagnesemia was found in 13 patients from group 1 (41%), 15 patients from group 2 (78%) and 5 patients from group 3(15%); those results were statistically significant (p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0,01). In addition, hypochloremia was found in 5 patients from group 1 (6%), 2 patients from group 2 (10,5%) and 1 patient from group 3 (3%) and the results were statistically significant (p\u0026thinsp;=\u0026thinsp;0,04). A negative significant relationship between plasma osmolarity and disability (r = -02,8 p\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0,01) was an important finding.\u003c/p\u003e\n\u003cp\u003ePotassium and magnesium disturbances were statistically different in all the three groups; being the first one more prominent in group 1 (67,7% p\u0026thinsp;=\u0026thinsp;0,04) and the second one in group 2 (78,9% p\u0026thinsp;\u0026lt;\u0026thinsp;0,01). Patients with hyperkalemia and hypomagnesemia had the worst statistically significant disability outcome (p\u0026thinsp;\u0026lt;\u0026thinsp;0,01) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eProportion of Patients with Hydro-Electrolyte Alterations According to Disability Level in Patients with Severe Traumatic Brain Injury (n\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHydro-Electrolyte Alteration\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS (1 and 2)\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS (3 and 4)\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;19\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS 5\u003c/p\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;33\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003csup\u003eP\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePotassium\u003c/p\u003e\n \u003cp\u003eCalcium\u003c/p\u003e\n \u003cp\u003eMagnesium\u003c/p\u003e\n \u003cp\u003eSodium\u003c/p\u003e\n \u003cp\u003eChloride\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (67,7)\u003c/p\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e15 (48,4)\u003c/p\u003e\n \u003cp\u003e20 (64,5)\u003c/p\u003e\n \u003cp\u003e9 (29,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e2 (\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e15 (78,9)\u003c/p\u003e\n \u003cp\u003e12 (63,2)\u003c/p\u003e\n \u003cp\u003e4 (\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17 (51,5)\u003c/p\u003e\n \u003cp\u003e9 (\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e5 (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003e23 (69,7)\u003c/p\u003e\n \u003cp\u003e5 (\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0,04\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0,32\u003c/p\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0,01\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e0,86\u003c/p\u003e\n \u003cp\u003e0,40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e* Chi-square test significance p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe multivariate logistic regression showed that patients who had hypomagnesemia were 10 times prone to disability measured by GOS than those without this electrolyte alteration. Adjusted to the other variables this relationship was statically significant (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\n\u003cp\u003eHypochloremia was identified as a confounding variable and was included in the model, those patients with hypochloremia had 36 times higher risk of bad outcome, measured by GOS, than those who did not have this condition. This relationship was statistically significant (p\u0026thinsp;=\u0026thinsp;0.004).\u003c/p\u003e\n\u003cp\u003eHypoosmolarity was a variable with a negative correlation. The possibility of low GOS was seven times lower in those patients with hypoosmolarity compared with those with normal plasmatic osmolarity being statistically significant (p\u0026thinsp;=\u0026thinsp;0,01). Age also showed a negative correlationship, however there was not statically significance when adjusted with other variables (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMultivariate Logistic Regression analysis for GOS\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOS Dependent variable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR Ajustado\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIC\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9446703\u0026ndash;1.01279\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.6529311\u0026ndash;0.965047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypomagnesemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.785023\u0026ndash;47.74559\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypochloremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.951983\u0026ndash;1693.215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyposmolarity (less than 290 mOsmol / l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.1482221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.0350202\u0026ndash;0.6273468\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eGOS: Glasgow Outcome Scale; GCS: Glasgow Coma Scale; CI: Confidence interval.\u003c/p\u003e\n\u003cp\u003eMultivariate Logistic Regression analysis Prob\u0026thinsp;\u0026gt;\u0026thinsp;chi2\u0026thinsp;=\u0026thinsp;0.0000 Pseudo R2\u0026thinsp;=\u0026thinsp;0.3152\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePatients with electrolyte alterations (hypomagnesemia and hypochloremia) showed more disability than those without it, this was statistically significant. Ion Magnesium participate in cell\u0026acute;s energy metabolism, vascular tone and ion transportation on cell membrane (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Furthermore, Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;plays an important role on the elimination of oxygen reactive species and preventing reperfusion lesions; factors related with bad outcome on rehabilitation. In the other hand Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;intracellular flow could help to stabilize cell membrane, improve energy balance and to ease calcium overload effects (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Hypomagnesemia could contribute to secondary lesions in TBI patients by increasing apoptosis, worsening the final outcome.\u003c/p\u003e \u003cp\u003eThe flow of magnesium and its non-competitive blockage of NMDA (N-methyl-D Aspartate) receptors (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), generate a protective action over the hippocampus, and the brain\u0026acute;s white substance avoiding the necrotic effect of glutamate over excitation and ischemia. Increasing levels of extracellular Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;improves hippocampal high energy neuronal phosphates levels and also accelerates blood flow on the injury area so Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;is unspecific antagonist of every subtype of calcium channel voltage sensible. Bareyre FM et al. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), showed that free Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;intracellular concentration decreases after lateral fluid-percussion brain injury is related to depletion of intracellular levels of high energy phosphate depending of the lesion severity. Polderman et al. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), reported in its study hypomagnesemia as the worst prognostic factor on the rehabilitation of critically ill patients. Hypomagnesemia have been also related to metabolic disbalance such as insulin resistance, as Noronha and Matuschak showed on invitro studies (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This resistance is associated to Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;capacity of chelates formation; specially with ATP (adenosine triphosphate), also competition with Calcium for membrane unions sites and promoting calcium sequestration by the sarcoplasmic reticulum (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). It is important to mention that hypomagnesemia was caused by multiple factors, like polyureic effect of osmotic diuretics and hyperglycemia both associated to plasmatic hyperosmolarity and increasing paracellular transport and Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;excretion. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). In this study hyperglycemia was the main cause of hyperosmolarity, 42,1% of patients, and associated with bad prognosis; in fact, this result is concordant with literature findings.\u003c/p\u003e \u003cp\u003eHyperkalemia was statistically associated with disability and prognosis worsening; however, this finding was less frequent than hypokalemia, being the last one more common in trauma patients due to catecholamines increase by the effect of intracellular K\u0026thinsp;+\u0026thinsp;reabsorption (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). There was association between hypochloremia and disability and it was a confusion variable included in the logistic regression model. Low levels of Chlorine in adult neurons is related with GABA (Gamma-Aminobutyric Acid) hyperpolarization action. In opposition immature neurons express chlorine transporters so GABA produces post-synaptic depolarizing potentials important to stabilize developing synapsis. Hypochloremia could be an awareness signal of bad prognosis for trauma patients (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). There is a possible association between Claudins-2 expression drop and hypochloremia due to secondary hypoperfusion in patients with trauma (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHuang Y. et al., y Baldwin MR. et al. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), showed higher mortality when correlated APACHE II and GOS worst results in patients with TBI, a similar finding was made in this study. Longer hospitalization and mechanical ventilation (S.D. 4,2 days) were variables of bad outcome for rehabilitation. Similar results were found in Silva PE et al., where muscle atrophy was the result of electrophysiologic neuromuscular changes associated to TBI and prolonged mechanical ventilation, similar in this study (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatients in this study were very similar, so comparison among them was accurate, being this aspect a strength. A novelty in this study was the analysis of disability degree six month after trauma, important data to measure final outcomes and cost for the health system. The use of GOS scale, related in clinical charts, was a limitation of this study, since DRS (Disability Rating Scale) and GOSE (Extended Glasgow Outcome Scale) scale have more sensitivity to evaluate disability (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). 7,2% of patients did not have any electrolyte alteration even thought the similarity of characteristics. Furthermore, the type of study (retrospective), the sample size and the fact that most of patients were males could be a limitation for its reliability.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eMostly patients were males (91,5%), media of 45 years old without co-morbidities. There was association between hypomagnesemia and hypochloremia with worst outcomes measured with GOS. It is necessary to replay this study increasing the number of patients and including more females to improve its strength. A proper Mg\u0026thinsp;+\u0026thinsp;+\u0026thinsp;therapy in trauma patients could contribute to improve cognitive and physical rehabilitation results (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompliance with ethical standards\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e: All authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthical approval: \u0026nbsp;Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the Universidad Nacional de Colombia´s and Hospital Simón Bolivar ethic committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required. This article does not contain any studies with human participants performed by any of the authors. No funding was received for this research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFinancing: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlvis N, Valenzuela MT (2010) Los QALYs y DALYs como indicadores sint\u0026eacute;ticos de salud. Rev M\u0026eacute;dica Chile 138:83\u0026ndash;87\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaldwin MR, Reid MC, Westlake AA, Rowe JW, Granieri EC, Wunsch H et al (2014) The feasibility of measuring frailty to predict disability and mortality in older medical intensive care unit survivors. J Crit Care 29(3):401\u0026ndash;408\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBareyre FM, Saatman KE, Raghupathi R, McIntosh TK (2000) Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma 17(11):1029\u0026ndash;1039\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeal AL, Deuser WE, Beilman GJ (2007) A role for epinephrine in post-traumatic hypokalemia. Shock Augusta Ga 27(4):358\u0026ndash;363\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrooks DN, Hosie J, Bond MR, Jennett B, Aughton M (1986) Cognitive sequelae of severe head injury in relation to the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry 49(5):549\u0026ndash;553\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDang B, Chen W, He W, Chen G (2017) Rehabilitation Treatment and Progress of Traumatic Brain Injury Dysfunction. Neural Plast 2017:1582182\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuran C, Thompson CH, Xiao Q, Hartzell HC (2010) Chloride channels: often enigmatic, rarely predictable. Annu Rev Physiol 72:95\u0026ndash;121\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang Y, Chen J, Zhong S, Yuan J (2016) Role of APACHE II scoring system in the prediction of severity and outcome of acute intracerebral hemorrhage. Int J Neurosci 126(11):1020\u0026ndash;1024\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJennett B, Bond M (1975) Assessment of outcome after severe brain damage. Lancet Lond Engl 1(7905):480\u0026ndash;484\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhalili H, Niakan A, Ghaffarpasand F, Kiani A, Behjat R (2017) Outcome Determinants of Decompressive Craniectomy in Patients with Traumatic Brain Injury; A Single Center Experience from Southern Iran. Bull Emerg Trauma 5(3):190\u0026ndash;196\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovesdy CP, Lott EH, Lu JL, Malakauskas SM, Ma JZ, Molnar MZ et al (2012) Hyponatremia, hypernatremia, and mortality in patients with chronic kidney disease with and without congestive heart failure. Circulation 125(5):677\u0026ndash;684\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi W, Bai Y-A, Li Y-J, Liu K-G, Wang M-D, Xu G-Z et al (2015) Magnesium sulfate for acute traumatic brain injury. J Craniofac Surg 26(2):393\u0026ndash;398\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa VY, Chan L, Carruthers KJ (2014) Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil 95(5):986\u0026ndash;995e1\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcDonald JW, Silverstein FS, Johnston MV (1990) Magnesium reduces N-methyl-D-aspartate (NMDA)-mediated brain injury in perinatal rats. Neurosci Lett 109(1\u0026ndash;2):234\u0026ndash;238\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNatalie P, Holz M, Hermes Pereira A, Bresolin AP, Zimmermann N, Paz Fonseca R (2016) FREQUENCY OF NEUROLOPSYCHOLOGICAL DEFICITS AFTER TRAUMATIC BRAIN INJURY. Acta Colomb Psicol 19(2):127\u0026ndash;137\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen R, Fiest KM, McChesney J, Kwon C-S, Jette N, Frolkis AD et al (2016) The International Incidence of Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Can J Neurol Sci J Can Sci Neurol 43(6):774\u0026ndash;785\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNoronha JL, Matuschak GM (2002) Magnesium in critical illness: metabolism, assessment, and treatment. Intensive Care Med 28(6):667\u0026ndash;679\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalmer CS, Gabbe BJ, Cameron PA (2016) Defining major trauma using the 2008 Abbreviated Injury Scale. Injury 47(1):109\u0026ndash;115\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePetgrave-P\u0026eacute;rez A, Padilla JI, D\u0026iacute;az J, Chac\u0026oacute;n R, Chaves C, Torres H et al (2016) [Epidemiological profile of traumatic brain injury at the Dr. Rafael A. Calder\u0026oacute;n Guardia Hospital, Neurosurgery Department, during the period from 2007 to 2012]. Neurocir Astur Spain 27(3):112\u0026ndash;120\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePolderman KH, Bloemers FW, Peerdeman SM, Girbes AR (2000) Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury. Crit Care Med 28(6):2022\u0026ndash;2025\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuvanachandra P, Hyder AA (2008) Traumatic brain injury in Latin America and the Caribbean: a call for research. Salud Publica Mex 50(Suppl 1):S3\u0026ndash;5\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodr\u0026iacute;guez-Trivi\u0026ntilde;o CY, Castro IT, Due\u0026ntilde;as Z (2019) Hypochloremia in Patients with Severe Traumatic Brain Injury: A Possible Risk Factor for Increased Mortality. World Neurosurg 124:e783\u0026ndash;e788\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoozenbeek B, Maas AI, Menon DK (2013) Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 9(4):231\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva PE, Maldaner V, Vieira L, de Carvalho KL, Gomes H, Melo P et al (2017) Neuromuscular electrophysiological disorders and muscle atrophy in mechanically-ventilated traumatic brain injury patients: New insights from a prospective observational study. J Crit Care 44:87\u0026ndash;94\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva PE, Maldaner V, Vieira L, de Carvalho KL, Gomes H, Melo P et al (2017) Neuromuscular electrophysiological disorders and muscle atrophy in mechanically-ventilated traumatic brain injury patients: New insights from a prospective observational study. J Crit Care 44:87\u0026ndash;94\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStein DM, Feather CB, Napolitano LM (2017) Traumatic Brain Injury Advances. Crit Care Clin 33(1):1\u0026ndash;13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStys PK, Ransom BR, Waxman SG (1990) Effects of polyvalent cations and dihydropyridine calcium channel blockers on recovery of CNS white matter from anoxia. Neurosci Lett 115(2\u0026ndash;3):293\u0026ndash;299\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTemkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J et al (2007) Magnesium sulfate for neuroprotection after traumatic brain injury: a randoised controlled trial. Lancet Neurol 6(1):29\u0026ndash;38\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVedantam A, Robertson CS, Gopinath SP (2017) Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus 43(5):E2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilson JT, Pettigrew LE, Teasdale GM (1998) Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 15(8):573\u0026ndash;585\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoon S-Y, Choi Y-J, Park S-H, Hwang J-H, Hwang SK (2017) Traumatic Brain Injury in Children under Age 24 Months: Analysis of Demographic Data, Risk Factors, and Outcomes of Post-traumatic Seizure. J Korean Neurosurg Soc 60(5):584\u0026ndash;590\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Li Z-H, Deng X, Yin Y (2014) [Expression of tight junction protein claudin-2 in renal tissues and its significance in children with acute kidney injury]. Zhongguo Dang Dai Er Ke Za Zhi Chin J Contemp Pediatr 16(4):361\u0026ndash;365\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Figure 1","content":"\u003cp\u003eFigure 1 is not available with this version. \u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Universidad del Valle","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Brain Injuries, Traumatic, electrolytes, disability, hypomagnesemia, Glasgow Outcome Scale","lastPublishedDoi":"10.21203/rs.3.rs-6256509/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6256509/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTo find association between hydroelectrolyte disbalance and disability in patients with severe traumatic brain injury using the Glasgow Outcome Scale (GOS) for classification.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e This is a retrospective cohort study based on 83 clinical charts of inpatients with severe traumatic brain injury (TBI) and a Glasgow Coma Scale score lower than 8, covering a three-year period. Data from the clinical charts aim to establish a relationship between GOS results and electrolyte levels analysis six months after initial trauma. Bivariate analysis and chi square 95% reliability rate, were applied to categorical variables. One-way ANOVA, for independent groups, was used to determine association between different levels of individual electrolytes (Na+, K+, Ca++, Mg++ and Cl-) and disability. The statistical analysis for continuous variables comparison was made by chi square test. Multivariate Logistic Regression analysis was useful to determine association.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Disability was statistically associated with the increment of age (p=\u0026lt;0,01), higher APACHE II score, (Acute Physiology and Chronic Health Evaluation) prolonged mechanic ventilation use, hypomagnesemia and hyperkalemia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Hypomagnesemia and hyperkalemia could be associated with higher disability according to measurement of GOS.\u003c/p\u003e","manuscriptTitle":"Hypomagnesemia as a possible marker of disability in patients with severe traumatic brain injury.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-24 03:49:03","doi":"10.21203/rs.3.rs-6256509/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3aedbea5-57f9-4603-9291-0efb6ce54ec1","owner":[],"postedDate":"March 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":45874922,"name":"Neurosurgery"},{"id":45874923,"name":"Neurology"},{"id":45874924,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2025-03-24T03:49:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-24 03:49:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6256509","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6256509","identity":"rs-6256509","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}