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Hypertonic Saline vs. Mannitol in Management of Elevated Intracranial Pressure in Children: A Meta-Analysis

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Abstract

Objective

To compare the efficacy and safety of two hyperosmolar agents (hypertonic saline vs. mannitol) used for the reduction of elevated intracranial pressure (ICP) in children.

Methods

A meta-analysis of randomized controlled trials (RCTs) was conducted and GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) of evidence was applied. Relevant databases were searched till 31st May 2022. Primary outcome was mortality rate.

Results

Of 720 citations retrieved, 4 RCTs were included in the meta-analysis (n = 365, male = 61%). Traumatic and non-traumatic cases of elevated ICP were included. There was no significant difference in the mortality rate between the two groups [relative risk (RR), 1.09; (95% confidence interval (CI), 0.74 to 1.6)]. No significant difference was found for any of the secondary outcomes, except serum osmolality (being significantly higher in mannitol group). Adverse events like shock and dehydration were significantly higher in the mannitol group, and hypernatremia in the hypertonic saline group. The evidence generated for primary outcome was of “low certainty”, and for secondary outcomes, it varied from “very-low to moderate certainty”.

Conclusions

There is no significant difference between hypertonic saline and mannitol used for the reduction of elevated ICP in children. The evidence generated for primary outcome (mortality rate) was of “low certainty”, and for secondary outcomes, it varied from “very-low to moderate certainty”. More data from high-quality RCTs are needed to guide any recommendation.

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References

  1. Melhem S, Shutter L, Kaynar A. A trial of intracranial pressure monitoring in traumatic brain injury. Crit Care. 2014;18:302.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Koenig MA. Cerebral edema and elevated intracranial pressure. Continuum (Minneap Minn). 2018;24:1588–602.

    PubMed  Google Scholar 

  3. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the Brain Trauma Foundation guidelines. Pediatr Crit Care Med. 2019;20:S1-82.

    Article  PubMed  Google Scholar 

  4. Miyoshi Y, Kondo Y, Suzuki H, Fukuda T, Yasuda H, Yokobori S. Japan resuscitation council (JRC) neuroresuscitation task force and the guidelines editorial committee. effects of hypertonic saline versus mannitol in patients with traumatic brain injury in prehospital, emergency department, and intensive care unit settings: a systematic review and meta-analysis. J Intensive Care. 2020;8:61.

  5. Kochanek PM, Adelson PD, Rosario BL, et al. Comparison of intracranial pressure measurements before and after hypertonic saline or mannitol treatment in children with severe traumatic brain injury. JAMA Netw Open. 2022;5:e220891.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fenn NE, Sierra CM. Hyperosmolar therapy for severe traumatic brain injury in pediatrics: a review of the literature. J Pediatr Pharmacol Ther. 2019;24:465–72.

    PubMed  PubMed Central  Google Scholar 

  7. Stopa BM, Dolmans RGF, Broekman MLD, Gormley WB, Mannix R, Izzy S. Hyperosmolar therapy in pediatric severe traumatic brain injury—a systematic review. Crit Care Med. 2019;47:e1022–31.

    Article  PubMed  Google Scholar 

  8. Rameshkumar R, Bansal A, Singhi S, Singhi P, Jayashree M. Randomized clinical trial of 20% mannitol versus 3% hypertonic saline in children with raised intracranial pressure due to acute CNS infections. Pediatr Crit Care Med. 2020;21:1071–80.

    Article  PubMed  Google Scholar 

  9. Kumaraguru D, Varadarajan P, Sangareddi S, Padmanabhan R, Jeyachandran P. Effectiveness of 3% saline versus mannitol in children with cerebral oedema of non-traumatic etiology. J Pediatr Sci. 2012;4:e143.

    CAS  Google Scholar 

  10. Kumar SA, Devi BI, Reddy M, Shukla D. Comparison of equiosmolar dose of hyperosmolar agents in reducing intracranial pressure-a randomized control study in pediatric traumatic brain injury. Childs Nerv Syst. 2019;35:999–1005.

    Article  PubMed  Google Scholar 

  11. Upadhyay P, Tripathi VN, Singh RP, et al. Role of hypertonic saline and mannitol in the management of raised intracranial pressure in children: a randomized comparative study. J Pediatr Neurosci. 2010;5:18–21.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  13. RevMan 5. Cochrane Training. Available at: https://training.cochrane.org/online-learning/core-software/revman. Accessed on 14th May 2022.

  14. Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations. Updated October 2013. The GRADE Working Group, 2013. Available at: https://guidelinedevelopment.org/handbook. Accessed on 1st June 2022.

  15. Schünemann HJ, Schünemann AHJ, Oxman AD, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336:1106–10.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hinson HE, Stein D, Sheth KN. Hypertonic saline and mannitol therapy in critical care neurology. J Intensive Care Med. 2013;28:3–11.

    Article  PubMed  Google Scholar 

  17. Muizelaar JP, Lutz HA, Becker DP. Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head injured patients. J Neurosurg. 1984;61:700–6.

    Article  CAS  PubMed  Google Scholar 

  18. Yildizdas D, Altunbasak S, Celik U, et al. Hypertonic saline treatment in children with cerebral edema. Indian Pediatr. 2006;43:771–9.

    CAS  PubMed  Google Scholar 

  19. Simma B, Burger R, Falk M, et al. A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated ringer’s solution versus hypertonic saline. Crit Care Med. 1998;26:1265–70.

    Article  CAS  PubMed  Google Scholar 

  20. Ding K, Gupta PK, Diaz-Arrastia R. Epilepsy after traumatic brain injury. In: Laskowitz D, Grant G, eds. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Available at: https://www.ncbi.nlm.nih.gov/books/NBK326716/. Accessed on 24th Oct 2022.

  21. Kamel H, Navi BB, Nakagawa K, et al. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011;39:554–9.

    Article  CAS  PubMed  Google Scholar 

  22. Mortazavi MM, Romeo AK, Deep A, et al. Hypertonic saline for treating raised intracranial pressure: literature review with metaanalysis. J Neurosurg. 2012;116:210–21.

    Article  PubMed  Google Scholar 

  23. Gu J, Huang H, Huang Y, Sun H, Xu H. Hypertonic saline or mannitol for treating elevated intracranial pressure in traumatic brain injury: a metaanalysis of randomized controlled trials. Neurosurg Rev. 2019;42:499–509.

    Article  PubMed  Google Scholar 

  24. Schwimmbeck F, Voellger B, Chappell D, Eberhart L. Hypertonic saline versus mannitol for traumatic brain injury: a systematic review and metaanalysis with trial sequential analysis. J Neurosurg Anesthesiol. 2021;33:10–20.

    Article  PubMed  Google Scholar 

  25. Shi J, Tan L, Ye J, Hu L. Hypertonic saline and mannitol in patients with traumatic brain injury: a systematic and meta-analysis. Medicine. 2020;99:e21655.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Li Q, Chen H, Hao JJ, Yin NN, Xu M, Zhou JX. Agreement of measured and calculated serum osmolality during the infusion of mannitol or hypertonic saline in patients after craniotomy: a prospective, double-blinded, randomised controlled trial. BMC Anesthesiol. 2015;15:138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Min L, Tao C, Shu-da C, Jing C, Ying-hong H. Comparison of equimolar doses of mannitol and hypertonic saline for the treatment of elevated intracranial pressure after traumatic brain injury: A systematic review and meta-analysis. Medicine. 2015;94:e668.

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Authors and Affiliations

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Contributions

NRM and RRD contributed to the development of the study protocol; AA and NRM searched the database, reviewed the literature, and generated data extraction forms; RRD and NRM analyzed the data; AA and NRM wrote the first draft; all co-authors critically reviewed the paper and approved the submitted version. RRD will act as guarantor for this manuscript.

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Correspondence to Rashmi Ranjan Das.

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Mishra, N.R., Agrawal, A. & Das, R.R. Hypertonic Saline vs. Mannitol in Management of Elevated Intracranial Pressure in Children: A Meta-Analysis. Indian J Pediatr 90, 899–906 (2023). https://doi.org/10.1007/s12098-023-04532-w

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  • DOI: https://doi.org/10.1007/s12098-023-04532-w

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