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Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study

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Abstract

Purpose

We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI).

Method

We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome.

Results

Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0–11.0)] and initial hypernatremia [0.0 (IQR = 0.0–10.0)], compared to eu-natremia [9.0 (IQR = 4.0–12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0–9.0)] and initial hypernatremia [0.0 (IQR = 0.0–3.0)], compared to eu-natremia [7.0 (IQR = 0.0–11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31–4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01–2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85–12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50–5.98, p = 0.002).

Conclusion

Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Aiyagari V, Deibert E, Diringer MN (2006) Hypernatremia in the neurologic intensive care unit: how high is too high? J Crit Care 21:163–172

    Article  PubMed  Google Scholar 

  2. Albanese A (2001) Personal practice: management of hyponatraemia in patients with acute cerebral insults. Arch Dis Child 85:246–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Alharfi IM, Stewart TC, Kelly SH et al (2013) Hypernatremia is associated with increased risk of mortality in pediatric severe traumatic brain injury. J Neurotrauma 30:361–366

    Article  PubMed  Google Scholar 

  4. Andelic N, Bautz-Holter E, Ronning P et al (2012) Does an early onset and continuous chain of rehabilitation improve the long-term functional outcome of patients with severe traumatic brain injury? J Neurotrauma 29:66–74

    Article  PubMed  Google Scholar 

  5. Asavaaree C, Mao J, Kaur A et al (2019) Malignant middle cerebral artery infarction due to hyponatremia following traumatic brain injury: a case report. Am J Case Rep 20:258–262

    Article  PubMed  PubMed Central  Google Scholar 

  6. Azovskiy D, Lekmanov A, Pilyutik S et al (2010) Hypernatremia in pediatric patients with severe traumatic brain injury. Crit Care 14:P291

    Article  PubMed Central  Google Scholar 

  7. Berkenbosch JW, Lentz CW, Jimenez DF et al (2002) Cerebral salt wasting syndrome following brain injury in three pediatric patients: suggestions for rapid diagnosis and therapy. Pediatr Neurosurg 36:75–79

    Article  PubMed  Google Scholar 

  8. Capatina C, Paluzzi A, Mitchell R et al (2015) Diabetes insipidus after traumatic brain injury. J Clin Med 4:1448–1462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chong S-L, Ong GY-K, Zheng CQ et al (2021) Early coagulopathy in pediatric traumatic brain injury: a pediatric acute and critical care medicine asian network (PACCMAN) retrospective study. Neurosurgery 89:283–290

    Article  PubMed  Google Scholar 

  10. Donati-Genet PC, Dubuis JM, Girardin E et al (2001) Acute symptomatic hyponatremia and cerebral salt wasting after head injury: an important clinical entity. J Pediatr Surg 36:1094–1097

    Article  CAS  PubMed  Google Scholar 

  11. Einaudi S, Bondone C (2007) The effects of head trauma on hypothalamic-pituitary function in children and adolescents. Curr Opin Pediatr 19:465–470

    Article  PubMed  Google Scholar 

  12. Figaji AA (2017) Anatomical and physiological differences between children and adults relevant to traumatic brain injury and the implications for clinical assessment and care. Front Neurol 8:685

    Article  PubMed  PubMed Central  Google Scholar 

  13. Giuliani C, Peri A (2014) Effects of hyponatremia on the brain. J Clin Med 3:1163–1177

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hadjizacharia P, Beale EO, Inaba K et al (2008) Acute diabetes insipidus in severe head injury: a prospective study. J Am Coll Surg 207:477–484

    Article  PubMed  Google Scholar 

  15. Hoffman H, Jalal MS, Chin LS (2018) Effect of hypernatremia on outcomes after severe traumatic brain injury: a nationwide inpatient sample analysis. World Neurosurg 118:e880–e886

    Article  PubMed  Google Scholar 

  16. Kumar N (2016) Evaluation of serum electrolytes in traumatic brain injury patients: prospective randomized observational study. J Anesth Crit Care Open Access 5(3). https://doi.org/10.15406/jaccoa.2016.05.00184

  17. Leonard J, Garrett RE, Salottolo K et al (2015) Cerebral salt wasting after traumatic brain injury: a review of the literature. Scand J Trauma, Resusc Emerg 23:98

    Article  Google Scholar 

  18. Léveillé E, Aljassar M, Beland B et al (2022) Determinants of hyponatremia following a traumatic brain injury. Neurol Sci 43:3775–3782

    Article  PubMed  Google Scholar 

  19. Li M, Hu YH, Chen G (2013) Hypernatremia severity and the risk of death after traumatic brain injury. Injury 44:1213–1218

    Article  CAS  PubMed  Google Scholar 

  20. Lohani S, Devkota UP (2011) Hyponatremia in patients with traumatic brain injury: etiology, incidence, and severity correlation. World Neurosurg 76:355–360

    Article  PubMed  Google Scholar 

  21. Maggiore U, Picetti E, Antonucci E et al (2009) The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury. Crit Care 13:R110

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mai G, Lee JH, Caporal P, Roa GJD, González-Dambrauskas S, Zhu Y et al (2023) Prehospital and emergency management of pediatric traumatic brain injury: a multicenter site survey. J Neurosurg Pediatr:1–9. https://doi.org/10.3171/2023.1.PEDS22456

  23. Meng X, Shi B (2016) Traumatic brain injury patients with a Glasgow coma scale score of ≤8, cerebral edema, and/or a basal skull fracture are more susceptible to developing hyponatremia. J Neurosurg Anesthesiol 28:21–26

    Article  PubMed  Google Scholar 

  24. Mesfin FB, Gupta N, Hays Shapshak A et al (2023) Diffuse axonal injury. In: StatPearls. StatPearls Publishing, Treasure Island (FL)

    Google Scholar 

  25. Moro N, Katayama Y, Igarashi T et al (2007) Hyponatremia in patients with traumatic brain injury: incidence, mechanism, and response to sodium supplementation or retention therapy with hydrocortisone. Surg Neurol 68:387–393

    Article  PubMed  Google Scholar 

  26. Nisticò D, Bossini B, Benvenuto S et al (2022) Pediatric adrenal insufficiency: challenges and solutions. Ther Clin Risk Manag 18:47–60

    Article  PubMed  PubMed Central  Google Scholar 

  27. Paiva WS, Bezerra DAF, Amorim RLO et al (2011) Serum sodium disorders in patients with traumatic brain injury. Ther Clin Risk Manag 7:345–349

    Article  PubMed  PubMed Central  Google Scholar 

  28. Palmer BF (n.d.). Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab 14(4):182–187. https://doi.org/10.1016/s1043-2760(03)00048-1

  29. Poomthavorn P, Zacharin M (2007) Traumatic brain injury-mediated hypopituitarism. Report of four cases. Eur J Pediatr 166:1163–1168

    Article  PubMed  Google Scholar 

  30. Robertson CL, Soane L, Siegel ZT et al (2006) The potential role of mitochondria in pediatric traumatic brain injury. Dev Neurosci 28:432–446

    Article  CAS  PubMed  Google Scholar 

  31. Shanavas C, Basheer N, Alapatt J et al (2016) A prospective study on hyponatremia in traumatic brain injury. Indian J Neurotrauma 13:094–100

    Article  Google Scholar 

  32. Shehata M, Ragab D, Khaled M et al (2010) Impact of hypernatremia on patients with severe traumatic brain injury. Crit Care 14:P355

    Article  PubMed Central  Google Scholar 

  33. Smith M, Baltazar GA, Pate A et al (2017) Hyponatremia on initial presentation correlates with suboptimal outcomes after traumatic brain injury. Am Surg 83:E126–E128

    Article  PubMed  Google Scholar 

  34. Spasovski G, Vanholder R, Allolio B et al (2014) Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 29(Suppl 2):i1–i39

    Article  PubMed  Google Scholar 

  35. Van Beek JGM, Mushkudiani NA, Steyerberg EW et al (2007) Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study. J Neurotrauma 24:315–328

    Article  PubMed  Google Scholar 

  36. Vedantam A, Robertson CS, Gopinath SP (2017) Morbidity and mortality associated with hypernatremia in patients with severe traumatic brain injury. Neurosurg Focus 43:E2

    Article  PubMed  Google Scholar 

  37. Yee AH, Burns JD, Wijdicks EFM (2010) Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am 21:339–352

    Article  PubMed  Google Scholar 

  38. Zafonte RD, Mann NR (1997) Cerebral salt wasting syndrome in brain injury patients: a potential cause of hyponatremia. Arch Phys Med Rehabil 78:540–542

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank the following collaborators from PACCMAN network and LARed network for their contribution to design and data collection: Chin Seng Gan, MPaeds; Rujipat Samransamruajkit, MD; Pei-Chuen Lee, MBBS; Chunfeng Liu, Ph.D.; Tao Zhang, Ph.D.; Meixiu Ming, MD; Hongxing Dang, MD; Hiroshi Kurosawa, Ph.D., MD; Mohannad Antar, MD; Deborah M. Turina, MD; Jesús A Domínguez-Rojas, MD; Francisco J. Pilar-Orive, Ph.D., MD; Willmer E. Diaz Villalobos, MBBS; Ivan J. Ardila, MD; Marisol Fonseca, MD; Gabriela Aparicio, MD; Juan C. Jaramillo-Bustamante, MD; Thelma E. Teran, MD; Nicolas Monteverde-Fernandez, MD; María Miñambres Rodríguez, Ph.D.; Freddy Israel Pantoja Chamorro, MD; Deiby Lasso Noguera, MD; Esteban Cerón, MD; Natalia Gómez Arriola, MD; Ruben Eduardo Lasso Palomino, MD.

Funding

This study was funded by the National Medical Research Council (NMRC) of Singapore (MOH-CSSSP19may-0020).

Author information

Authors and Affiliations

  1. Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

    Gawin Mai

  2. Children’s Intensive Care Unit, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore

    Jan Hau Lee

  3. SingHealth Paediatrics Academic Clinical Programme, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

    Jan Hau Lee

  4. Johns Hopkins International Injury Research Unit, Health Systems Program, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD, 21205, USA

    Paula Caporal

  5. Red Colaborativa Pediátrica de Latinoamérica (LARed Network), Montevideo, Uruguay

    Paula Caporal, Juan D. Roa G & Sebastián González-Dambrauskas

  6. Pediatric Intensive Care Unit, Los Cobos Medical Center, Universidad del Bosque, Ak. 9 #131a-40, Usaquén, Bogotá, Cundinamarca, Colombia

    Juan D. Roa G

  7. Departamento de Pediatría y Unidad de Cuidados Intensivos, de Niños del Centro Hospitalario Pereira Rossell, Facultad de Medicina, Universidad de la República, Bulevar Artigas 1590, Lord Ponsoby 2410, 11600, Montevideo, Uruguay

    Sebastián González-Dambrauskas

  8. Singapore Clinical Research Institute, Consortium for Clinical Research and Innovation, 23 Rochester Park, #06-01, Singapore, 139234, Singapore

    Yanan Zhu

  9. Emergency Department, National Children’s Hospital “Dr. Carlos Saenz Herrera” CCSS, San José, Costa Rica

    Adriana Yock-Corrales

  10. Departments of Pediatrics and Child Health, National Stadium Road, Aga Khan University Hospital, Karachi, Karachi City, Sindh, 74800, Pakistan

    Qalab Abbas

  11. Department of Paediatrics, Ministry of National Guards Health Affairs, Prince Mutib Ibn Abdullah Ibn Abdulaziz Rd, Ar Rimayah, Riyadh, 11426, Saudi Arabia

    Yasser Kazzaz

  12. College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdul Aziz Medical City, Jeddah, 22384, Saudi Arabia

    Yasser Kazzaz

  13. King Abdullah International Medical Research Centre, King Abdul Aziz Medical City, Riyadh, 22384, Saudi Arabia

    Yasser Kazzaz

  14. KK Research Centre, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore

    Dianna Sri Dewi

  15. Department of Emergency Medicine, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore

    Shu-Ling Chong

  16. SingHealth Paediatrics Academic Clinical Programme, Emergency Medicine Academic Clinical Programme, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

    Shu-Ling Chong

Authors
  1. Gawin Mai
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  2. Jan Hau Lee
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  3. Paula Caporal
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  4. Juan D. Roa G
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  6. Yanan Zhu
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Consortia

on behalf of the Pediatric Acute & Critical Care Medicine Asian Network (PACCMAN) and Red Colaborativa Pediátrica de Latinoamérica (LARed Network)

  • Chin Seng Gan
  • , Rujipat Samransamruajkit
  • , Pei-Chuen Lee
  • , Chunfeng Liu
  • , Tao Zhang
  • , Meixiu Ming
  • , Hongxing Dang
  • , Hiroshi Kurosawa
  • , Mohannad Antar
  • , Deborah M. Turina
  • , Jesús A Domínguez-Rojas
  • , Francisco J. Pilar-Orive
  • , Willmer E. Diaz Villalobos
  • , Ivan J. Ardila
  • , Marisol Fonseca
  • , Gabriela Aparicio
  • , Juan C. Jaramillo-Bustamante
  • , Thelma E. Teran
  • , Nicolas Monteverde-Fernandez
  • , María Miñambres Rodríguez
  • , Freddy Israel Pantoja Chamorro
  • , Deiby Lasso Noguera
  • , Esteban Cerón
  • , Natalia Gómez Arriola
  •  & Ruben Eduardo Lasso Palomino

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Shu-Ling Chong and Gawin Mai. The first draft of the manuscript was written by Shu-Ling Chong and Gawin Mai, and all authors performed critical revisions on previous versions of the manuscript. Jan Hau Lee and Sebastián González-Dambrauskas provided supervision on the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shu-Ling Chong.

Ethics declarations

Ethics approval

The study was approved in the coordinating center in Singapore (SingHealth Centralised Institutional Review Board CIRB 2018/2457), and each site followed local prevailing ethics requirements, requiring documented informed consents from all participants. All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

Informed consent was obtained from all individual participants included in the study. Informed consent was obtained from legal guardians for minor participants.

Consent for publication

Consents to publish were obtained from all participants.

Competing interests

The authors declare no competing interests.

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Mai, G., Lee, J.H., Caporal, P. et al. Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study. Acta Neurochir 166, 82 (2024). https://doi.org/10.1007/s00701-024-05919-0

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