AbstractObjectiveThe present study aimed to investigate the clinical characteristics of electrolyte imbalance in patients with moderate to severe traumatic brain injury (TBI) who underwent craniotomy and its influence on prognosis.
MethodsA total of 156 patients with moderate to severe TBI were prospectively collected from June 2019 to June 2021. All patients underwent craniotomy and intracranial pressure (ICP) monitoring. We aimed to explore the clinical characteristics of electrolyte disturbance and to analyze the influence of electrolyte disturbance on prognosis.
ResultsA total of 156 patients with moderate and severe TBI were included. There were 57 cases of hypernatremia, accounting for 36.538%, with the average level of 155.788±7.686 mmol/L, which occurred 2.2±0.3 days after injury. There were 25 cases of hyponatremia, accounting for 16.026%, with the average level of 131.204±3.708 mmol/L, which occurred 10.2±3.3 days after injury. There were three cases of hyperkalemia, accounting for 1.923%, with the average level of 7.140±1.297 mmol/L, which occurred 5.3±0.2 days after injury. There were 75 cases of hypokalemia, accounting for 48.077%, with the average level of 3.071±0.302 mmol/L, which occurred 1.8±0.6 days after injury. There were 105 cases of hypocalcemia, accounting for 67.308%, with the average level of 1.846±0.104 mmol/L, which occurred 1.6±0.2 days after injury. There were 17 cases of hypermagnesemia, accounting for 10.897%, with the average level of 1.213±0.426 mmol/L, which occurred 1.8±0.5 days after injury. There were 99 cases of hypomagnesemia, accounting for 63.462%, with the average level of 0.652±0.061 mmol/L, which occurred 1.3±0.4 days after injury. Univariate regression analysis revealed that age, Glasgow coma scale (GCS) score at admission, pupil changes, ICP, hypernatremia, hypocalcemia, hypernatremia combined with hypocalcemia, epilepsy, cerebral infarction, severe hypoproteinemia were statistically abnormal (p<0.05), while gender, hyponatremia, potassium, magnesium, intracranial infection, pneumonia, allogeneic blood transfusion, hypertension, diabetes, abnormal liver function, and abnormal renal function were not statistically significant (p>0.05). After adjusting gender, age, GCS, pupil changes, ICP, epilepsy, cerebral infarction, severe hypoproteinemia, multivariate logistic regression analysis revealed that hypernatremia or hypocalcemia was not statistically significant, while hypernatremia combined with hypocalcemia was statistically significant (p<0.05).
ConclusionThe incidence of hypocalcemia was the highest, followed by hypomagnesemia, hypokalemia, hypernatremia, hyponatremia and hypermagnesemia. Hypocalcemia, hypomagnesemia, and hypokalemia generally occurred in the early post-TBI period, hypernatremia occurred in the peak period of ICP, and hyponatremia mostly occurred in the late period after decreased ICP. Hypernatremia combined with hypocalcemia was associated with prognosis.
INTRODUCTIONTraumatic brain injury (TBI) has been the leading cause of death or disability in young people [10]. Although the therapeutic level of TBI has been greatly improved due to the development of medical technology, the treatment of severe TBI is still difficult, with multiple types of complications, causing high disability rate and death rate [8]. Electrolyte disturbance, including hypernatremia, hypokalemia and hypocalcemia, are common in moderate and severe TBI, which will affect the prognosis of patients if not timely corrected. Most of the existing literature only focuses on the disturbance of single ions, such as sodium, potassium and calcium. Although a small number of studies focus on the overall electrolyte disturbance of patients with TBI [34], the rules of occurrence and development of various electrolyte disturbance and the influence on prognosis are still unclear. In this article, we investigated various electrolyte disturbance and the influence on clinical outcome of patient with TBI.
MATERIALS AND METHODSThis study was approved by the Ethics Committee of our hospital, and all patients or their family members signed written informed consent.
Study subjectTBI patients were prospectively selected from June 2019 to June 2021, who were admitted to The Second Affiliated Hospital of Jiaxing University (IRB No. JXEY-2022SW011). The inclusion criteria were as follows : 1) patients with moderate to severe TBI (Glasgow coma scale [GCS] ≤13 points); 2) aged 18 to 75 years; 3) no severe underlying disease; 4) undergoing craniotomy and intracranial pressure (ICP) monitoring; and 5) survival ≥1 week. The exclusion criteria were as follows : 1) patients with a history of adrenal glands, thyroid, etc. that may cause electrolyte disturbance and 2) patients with severe damage to other organs (injuries to other organs affect the lives of patients or require emergency surgery), or TBI patients who have received cardiopulmonary resuscitation.
Therapeutic approachesAll patients were treated with neurosurgery intensive treatment plan according to the individual study protocols, but largely based on the guidelines for treatment of severe TBI at the time. All patients underwent craniotomy and ICP monitoring within 24 hours after injury. None of the patients were treated with hypertonic saline to decrease ICP.
Observational indicatorsThe following parameters of patients were recorded, including age, gender, GCS score at admission, pupil changes, ICP, intracranial infection, pneumonia, epilepsy, cerebral infarction, allogeneic blood transfusion, severe hypoproteinemia, hypertension, diabetes, abnormal liver function, and abnormal renal function. Electrolytes were monitored at least once a day during the first week and then at least once every 2 days from 1 week to 2 weeks. Patients were followed up for 0.5 years to investigate the clinical characteristics of electrolyte disturbance and its influence on prognosis in TBI patients. Several definitions were as follows : hyponatremia, serum sodium level <135 mmol/L; hypernatremia, serum sodium level >145 mmol/L; hypokalemia, serum potassium level <3.5 mmol/L; hyperkalemia, serum potassium level >5.5 mmol/L; hypocalcemia, serum calcium level <2.0 mmol/L ; hypomagnesemia, serum magnesium level <0.75 mmol/L; hypermagnesemia, serum magnesium level >1.02 mmol/L; severe hypoproteinemia, serum protein <25 g/L; high ICP, ICP ≥20 mmHg; good prognosis, Glasgow outcome scale (GOS) score >3; poor prognosis, GOS score ≤3.
Statistical analysisSPSS ver. 17.0 software (IBM Corporation, Armonk, NY, USA) was used for statistical analysis. Measurement data with normal distribution were shown as mean±standard deviation, and t-test was used for comparison. Counting data were shown as the number of cases (percentage), and chi-squared test was used for comparison. Logistic regression analysis was used to adjust for other possible influencing factors to assess the correlation between electrolyte disturbance and prognosis. p<0.05 was considered as statistically significant.
RESULTSGeneral informationA total of 156 eligible TBI patients were enrolled, including 118 males and 38 females, with the age ranging from 18 to 75 years (average age, 57.9±15.3 years). There were 21 cases of open injuries and 135 cases of closed injuries. For GCS score at admission, there were 63 cases with 9-13 points, 36 cases with 6-8 points, and 57 cases with ≤5 points. There were 79 cases with pupil changes, including 56 cases with dilated pupils on one side, and 23 cases with dilated pupils on both sides. All patients underwent craniotomy, including 111 cases undergoing unilateral craniectomy decompression, 25 cases undergoing bilateral craniectomy decompression and 20 cases undergoing skull reintroduction.
The clinical characteristics of electrolyte disturbanceOf the 156 patients with severe TBI, there were 57 cases of hypernatremia, accounting for 36.538%, with the average level of 155.79±7.69 mmol/L, which occurred 2.2±0.3 days after injury. There were 25 cases of hyponatremia, accounting for 16.03%, with the average level of 131.20±3.71 mmol/L, which occurred 10.2±3.3 days after injury. There were three cases of hyperkalemia, accounting for 1.92%, with the average level of 7.14±1.30 mmol/L, which occurred 5.3±0.2 days after injury. There were 75 cases of hypokalemia, accounting for 48.08%, with the average level of 3.07±0.30 mmol/L, which occurred 1.8±0.6 days after injury. There were 105 cases of hypocalcemia, accounting for 67.31%, with the average level of 1.85±0.10 mmol/L, which occurred 1.6±0.2 days after injury. There were 17 cases of hypermagnesemia, accounting for 10.90%, with the average level of 1.21±0.43 mmol/L, which occurred 1.8±0.5 days after injury. There were 99 cases of hypomagnesemia, accounting for 63.46%, with the average level of 0.65±0.06 mmol/L, which occurred 1.3±0.4 days after injury. The detailed results were shown in Table 1.
Univariate regression analysis of the influence of electrolyte disturbance on prognosisUnivariate regression analysis revealed that age, GCS score at admission, pupil changes, ICP, hypernatremia, hypocalcemia, hypernatremia combined with hypocalcemia, epilepsy, cerebral infarction, severe hypoproteinemia were statistically abnormal (p<0.05), while gender, hyponatremia, potassium, magnesium, intracranial infection, pneumonia, allogeneic blood transfusion, hypertension, diabetes, abnormal liver function, and abnormal renal function were not statistically significant (p>0.05). The detailed results were shown in Table 2.
Multivariate analysis of the influence of electrolyte imbalance on prognosisAfter Adjusting gender, age, GCS score, pupil changes, ICP, epilepsy, cerebral infarction and severe hypoproteinemia, multivariate Logistic regression analysis showed that hypernatremia combined with hypocalcemia was statistically abnormal (p<0.05), while simple hypernatremia or hypocalcemia was not statistically significant. The detailed results were shown in Table 3.
DISCUSSIONThe incidence of electrolyte disturbance in TBI patients is high. It has been reported that the most common electrolyte disturbance in TBI patients is serum sodium among all types of serum electrolytes [1,30,34,36]. Among them, hyponatremia accounts for 4% to 51% [34,35,48]. Hyponatremia occurs from 2 days to 2 months after injury [4,39], mostly from 1 week to 2 weeks after injury [48]. The incidence of hyponatremia was low in our study, and the occurrence time of hyponatremia was 10.2±3.3 days. It is currently believed that central hyponatremia is common in cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) [6], but the specific causes of CSWS and SIADH are still unclear [19], no cause has been found to be the only cause at present [19]. Hyponatremia can induce cerebral edema, leading to seizures and aggravating the condition. If it is not treated timely or properly, it can even endanger the life of the patients [19], which is an independent predictor of poor prognosis in TBI patients [37]. However, we failed to reveal any correlation between hyponatremia and poor prognosis in this group of cases.
Rafiq et al. [34] reported that the most common electrolyte disturbance in TBI was hypernatremia, accounting for 65.1%, followed by hyponatremia and hypokalemia. Pin-On et al. [31] also revealed that hypernatremia was more common than hyponatremia, and 86.3% of patients with severe TBI had hypernatremia. In our group, hypernatremia accounted for 37.2%, which was higher than hyponatremia. The average time of occurrence of hypernatremia was 2.2±0.3 days after injury, which was significantly earlier than that of hyponatremia. Pin-On et al. [31] found that patients with hypernatremia were older, which was consistent with our study. In our study, the average age of hypernatremia was 62.7±11.7 years, which was significantly older than the overall average age (57.9±15.3 years). It may be due to the decreased total water content in the body of elderly patients and women, who are, therefore, more susceptible to hypernatremia [17]. Hoffman et al. [14] and Wilcox [46] considered that hypernatremia was mainly caused by negative water balance, generally due to the water loss of kidney or gastrointestinal tract and sweating, occasionally accompanied by insufficient fluid intake or improper electrolyte solution treatment. Our cases have shown that hypernatremia is associated with intracranial hypertension, especially in patients with severe hypernatremia, which is often accompanied by severe intracranial hypertension. The average ICP in hypernatremia patients was 31.246±22.836 mmHg in our study. It remains controversially whether hypernatremia worsens the prognosis alone or is only a surrogate indicator of disease severity. On the one hand, the increased concentration of serum sodium can not only attenuate brain edema, but also regulate neuroinflammatory pathways, restore neuronal membrane potential as well as decrease blood viscosity [27,28]. On the other hand, hypernatremia can disrupt the balance of the body and may be detrimental to the body [21]. Hypernatremia can cause decreased glomerular filtration rate, leading to increased levels of creatinine and blood urea nitrogen [12,13,46]. Hypernatremia had also been confirmed to be associated with rhabdomyolysis [18], which had a negative effect on cardiac contraction [16] and can cause myelin lysis and cell necrosis. Additionally, rapid correction of hypernatremia may lead to ICP rebound, cerebral edema and seizures [9]. Many scholars have reported that hypernatremia after severe TBI is independently associated with poor prognosis and death [14,20,23,42,43]. Univariate analysis of this group revealed that hypernatremia was a risk factor for poor prognosis, while multivariate analysis showed that hypernatremia was not an independent risk factor for poor prognosis.
It has been reported that patients with TBI are more likely to develop hypokalemia than patients with other types of trauma [3,33]. Wu et al. [47] has revealed that the incidence of hypokalemia was 32.4%, and the peak of severe hypokalemia occurred in the first 24-96 hours. Pin-On et al. [31] has found that hypokalemia is the most common electrolyte disturbance in TBI patients, accounting for 65.5%. The incidence of hypokalemia in this group was 48.077%, which occurred 1.8±0.6 days after injury. Hypokalemia after TBI is caused by the massive release of catecholamines after TBI, which leads to the transfer of potassium ions from extracellular space to intracellular space [7,11,33]. The application of diuretics such as furosemide can cause hypokalemia, and mannitol can also increase urinary potassium excretion and cause hypokalemia [5]. Wu et al. [47] demonstrates poor prognosis in severe hypokalemia group, which is considered as an independent risk factor for death in TBI patients. However, our study failed to show any correlation between hypokalemia and poor prognosis.
Hypocalcemia after TBI is very common, with an incidence of 33-62.3% [34,44]. Our study showed that the incidence of hypocalcemia was 67.308%, which is the most common type of electrolyte disturbance in moderate to severe TBI. After TBI, due to the sudden influx of calcium ion into the cells, the level of extracellular calcium ions is decreased, resulting in hypocalcemia [24]. Traumatic deformation of the cell membrane [22], hyperphenylalanineemia [32], decreased serum magnesium concentration and hyperventilation to control the increased ICP [8] might all promote the entrance of calcium ions into cells, resulting in hypocalcemia. Extensive use of furosemide and mannitol increases calcium excretion, and colloid-induced hemodilution is also an important cause of hypocalcemia in severe trauma patients [45]. The increased content of intracellular calcium inhibits mitochondrial enzymes and activates lipase, playing a role in apoptosis [2]. Vinas-Rios et al. [44] considers that the rapid increase of intracellular calcium ions after TBI can trigger the cellular mechanism causing neuronal dysfunction and death. Manuel et al. [24] considers that hypocalcemia is a risk factor for poor prognosis. In our study, univariate analysis suggested that hypocalcemia was associated with poor prognosis, but multivariate analysis failed to reveal that hypocalcemia was associated with poor prognosis.
The incidence of hypomagnesemia in TBI patients is 5.6-58% [29,34,41]. Our data showed that hypomagnesemia was 63.462%, second only to hypocalcemia. The incidence of hypermagnesemia is relatively low, which is reported to be 2.8% by Rafiq et al. [34]. Our study demonstrated that hypermagnesemia was 10.897%. The mechanism of magnesium depletion in TBI patients remains unclear. The possible explanation is that stress induces sharply increased catecholamines to trigger an increase in lipolysis, leading increased free fatty acids bound to Mg2+, thereby increasing the urine excretion of Mg2+ [25,38]. Some scholars have also observed that the content of magnesium in the cerebrospinal fluid (CSF) was increased after TBI, but decreased in the serum [15,26,41]. Stippler M considers that blood brain barrier destruction can cause the penetration of serum Mg2+ into CSF, and Mg2+ of CSF may also originate from damaged brain cells secondary to hypoxia [41]. Stippler et al. [41] and Nayak et al. [29] believe that hypomagnesemia is associated with poor prognosis after TBI. In particular, when high magnesium of CSF and low magnesium of serum coexist after TBI, the prognosis will be significantly worse [15,41]. Our data show that abnormal magnesium ion is not associated with prognosis.
Univariate analysis of this group showed that the prognosis of patients with hypernatremia and hypocalcemia was poor. However, after adjusting for gender, age, GCS score, pupil changes, ICP, epilepsy, cerebral infarction, severe hypoproteinemia, hypernatronemia and hypocalcemia were not independent risk factors for poor prognosis of severe TBI, while hypernatremia combined with hypocalcemia, age, GCS score at admission and pupil changes were independent risk factors of prognosis in patients with severe TBI.
CONCLUSIONElectrolyte disturbances are common in patients with moderate and severe TBI. The incidence of hypocalcemia is the highest, followed by hypomagnesemia, hypokalemia, hypernatremia, hyponatremia and hypermagnesemia. Hypocalcemia, hypomagnesemia and hypokalemia generally occur in the early post-injury period, hypernatremia occurs in the peak period of ICP, and hyponatremia mostly occurs in the late period after decreased ICP. Hypernatremia combined with hypocalcemia is associated with poor prognosis. We suggest that dehydrating agents should not be used excessively, blood volume should be kept stable, and colloids should be used as little as possible. It is reasonable to regularly measure calcium concentrations and treat hypocalcemia [40].
NotesInformed consent Informed consent was obtained from all individual participants included in this study. AcknowledgementsThis study was supported by Zhejiang provincial medical science and technology program (2022KY1257). The authors would like to thank Jiaxing Key Scientific and Technological Innovation Team--Targeted Drug Research and Tumor Nanotargeting and TCM Technology Innovation Team.
Table 1.Table 2.Table 3.References1. Askar A, Tarif N : Cerebral salt wasting in a patient with head trauma: management with saline hydration and fludrocortisone. Saudi J Kidney Dis Transpl 18 : 95-99, 2007
2. Balbino M, Capone Neto A, Prist R, Ferreira AT, Poli-de-Figueiredo LF : Fluid resuscitation with isotonic or hypertonic saline solution avoids intraneural calcium influx after traumatic brain injury associated with hemorrhagic shock. J Trauma 68 : 859-864, 2010
3. Beal AL, Scheltema KE, Beilman GJ, Deuser WE : Hypokalemia following trauma. Shock 18 : 107-110, 2002
4. Berkenbosch JW, Lentz CW, Jimenez DF, Tobias JD : Cerebral salt wasting syndrome following brain injury in three pediatric patients: suggestions for rapid diagnosis and therapy. Pediatr Neurosurg 36 : 75-79, 2002
5. Bilotta F, Giovannini F, Aghilone F, Stazi E, Titi L, Zeppa IO, et al : Potassium sparing diuretics as adjunct to mannitol therapy in neurocritical care patients with cerebral edema: effects on potassium homeostasis and cardiac arrhythmias. Neurocrit Care 16 : 280-285, 2012
6. Brimioulle S, Orellana-Jimenez C, Aminian A, Vincent JL : Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate antidiuretic hormone secretion. Intensive Care Med 34 : 125-131, 2008
7. Brown MJ, Brown DC, Murphy MB : Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med 309 : 1414-1419, 1983
8. Carney N, Totten AM, O’Reilly C, Ullman JS, Hawryluk GW, Bell MJ, et al : Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 80 : 6-15, 2017
9. De Petris L, Luchetti A, Emma F : Cell volume regulation and transport mechanisms across the blood-brain barrier: implications for the management of hypernatraemic states. Eur J Pediatr 160 : 71-77, 2001
10. Deveduthras N, Balakrishna Y, Muckart D, Harrichandparsad R, Hardcastle T : The prevalence of sodium abnormalities in moderate to severe traumatic brain injury patients in a level 1 trauma unit in Durban. S Afr J Surg 57 : 62, 2019
12. Froelich M, Ni Q, Wess C, Ougorets I, Härtl R : Continuous hypertonic saline therapy and the occurrence of complications in neurocritically ill patients. Crit Care Med 37 : 1433-1441, 2009
13. Gerber JG, Branch RA, Nies AS, Hollifield JW, Gerkens JF : Influence of hypertonic saline on canine renal blood flow and renin release. Am J Physiol 237 : F441-F446, 1979
14. Hoffman H, Jalal MS, Chin LS : Effect of hypernatremia on outcomes after severe traumatic brain injury: a nationwide inpatient sample analysis. World Neurosurg 118 : e880-e886, 2018
15. Kafadar AM, Sanus GZ, Is M, Coskun A, Tanriverdi T, Hanimoglu H, et al : Prolonged elevation of magnesium in the cerebrospinal fluid of patients with severe head injury. Neurol Res 29 : 824-829, 2007
16. Kozeny GA, Murdock DK, Euler DE, Hano JE, Scanlon PJ, Bansal VK, et al : In vivo effects of acute changes in osmolality and sodium concentration on myocardial contractility. Am Heart J 109 : 290-296, 1985
17. Kugler JP, Hustead T : Hyponatremia and hypernatremia in the elderly. Am Fam Physician 61 : 3623-3630, 2000
18. Kung AW, Pun KK, Lam KS, Yeung RT : Rhabdomyolysis associated with cranial diabetes insipidus. Postgrad Med J 67 : 912-913, 1991
19. Leonard J, Garrett RE, Salottolo K, Slone DS, Mains CW, Carrick MM, et al : Cerebral salt wasting after traumatic brain injury: a review of the literature. Scand J Trauma Resusc Emerg Med 23 : 98, 2015
20. Li M, Hu YH, Chen G : Hypernatremia severity and the risk of death after traumatic brain injury. Injury 44 : 1213-1218, 2013
21. Lindner G, Funk GC : Hypernatremia in critically ill patients. J Crit Care 28 : 216.e11-e20, 2013
22. Lucas SM, Rothwell NJ, Gibson RM : The role of inflammation in CNS injury and disease. Br J Pharmacol 147 : S232-S240, 2006
23. Maggiore U, Picetti E, Antonucci E, Parenti E, Regolisti G, Mergoni M, et al : The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury. Crit Care 13 : R110, 2009
24. Manuel VR, Martin SA, Juan SR, Fernando MA, Frerk M, Thomas K, et al : Hypocalcemia as a prognostic factor in mortality and morbidity in moderate and severe traumatic brain injury. Asian J Neurosurg 10 : 190-194, 2015
25. McKee JA, Brewer RP, Macy GE, Borel CO, Reynolds JD, Warner DS : Magnesium neuroprotection is limited in humans with acute brain injury. Neurocrit Care 2 : 342-351, 2005
26. McKee JA, Brewer RP, Macy GE, Phillips-Bute B, Campbell KA, Borel CO, et al : Analysis of the brain bioavailability of peripherally administered magnesium sulfate: a study in humans with acute brain injury undergoing prolonged induced hypermagnesemia. Crit Care Med 33 : 661-666, 2005
27. Muizelaar JP, Wei EP, Kontos HA, Becker DP : Cerebral blood flow is regulated by changes in blood pressure and in blood viscosity alike. Stroke 17 : 44-48, 1986
28. Murphy N, Auzinger G, Bernel W, Wendon J : The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure. Hepatology 39 : 464-470, 2004
29. Nayak R, Attry S, Ghosh SN : Serum magnesium as a marker of neurological outcome in severe traumatic brain injury patients. Asian J Neurosurg 13 : 685-688, 2018
30. Paiva WS, Bezerra DA, Amorim RL, Figueiredo EG, Tavares WM, De Andrade AF, et al : Serum sodium disorders in patients with traumatic brain injury. Ther Clin Risk Manag 7 : 345-349, 2011
31. Pin-On P, Saringkarinkul A, Punjasawadwong Y, Kacha S, Wilairat D : Serum electrolyte imbalance and prognostic factors of postoperative death in adult traumatic brain injury patients: a prospective cohort study. Medicine (Baltimore) 97 : e13081, 2018
32. Plöchl E, Thalhammer O, Weissenbacher G : Brain damage of acute course in an infant with hyperphenylalaninemia and hypercalcemia. Helv Paediatr Acta 23 : 292-304, 1968
33. Pomeranz S, Constantini S, Rappaport ZH : Hypokalaemia in severe head trauma. Acta Neurochir (Wien) 97 : 62-66, 1989
34. Rafiq MF, Ahmed N, Khan AA : Serum electrolyte derangements in patients with traumatic brain injury. J Ayub Med Coll Abbottabad 25 : 162-164, 2013
35. Rajagopal R, Swaminathan G, Nair S, Joseph M : Hyponatremia in traumatic brain injury: a practical management protocol. World Neurosurg 108 : 529-533, 2017
36. Rhoney DH, Parker D Jr : Considerations in fluids and electrolytes after traumatic brain injury. Nutr Clin Pract 21 : 462-478, 2006
37. Sajadieh A, Binici Z, Mouridsen MR, Nielsen OW, Hansen JF, Haugaard SB : Mild hyponatremia carries a poor prognosis in community subjects. Am J Med 122 : 679-686, 2009
38. Sakamoto T, Takasu A, Saitoh D, Kaneko N, Yanagawa Y, Okada Y : Ionized magnesium in the cerebrospinal fluid of patients with head injuries. J Trauma 58 : 1103-1109, 2005
39. Simsek E, Dilli D, Yasitli U, Ozlem N, Bostanci I, Dallar Y : Cerebral salt wasting in a child with cervicothoracic hematoma. J Pediatr Endocrinol Metab 21 : 695-700, 2008
40. Spahn DR : Hypocalcemia in trauma: frequent but frequently undetected and underestimated. Crit Care Med 33 : 2124-2125, 2005
41. Stippler M, Fischer MR, Puccio AM, Wisniewski SR, Carson-Walter EB, Dixon CE, et al : Serum and cerebrospinal fluid magnesium in severe traumatic brain injury outcome. J Neurotrauma 24 : 1347-1354, 2007
42. Van Beek JG, Mushkudiani NA, Steyerberg EW, Butcher I, McHugh GS, Lu J, et al : Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study. J Neurotrauma 24 : 315-328, 2007
43. Vedantam A, Robertson CS, Gopinath SP : Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus 43 : E2, 2017
44. Vinas-Rios JM, Sanchez-Aguilar M, Sanchez-Rodriguez JJ, GonzalezAguirre D, Heinen C, Meyer F, et al : Hypocalcaemia as a prognostic factor of early mortality in moderate and severe traumatic brain injury. Neurol Res 36 : 102-106, 2014
45. Vivien B, Langeron O, Morell E, Devilliers C, Carli PA, Coriat P, et al : Early hypocalcemia in severe trauma. Crit Care Med 33 : 1946-1952, 2005
|
|