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Comparison of equiosmolar hypertonic saline and mannitol for brain relaxation during craniotomies: A meta-analysis of randomized controlled trials

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Abstract

There is a controversy about the effects of hypertonic saline (HS) used for brain relaxation in patients requiring craniotomies. We conducted a meta-analysis to compare the efficacy of equiosmolar hypertonic saline with mannitol on intraoperative brain relaxation in patients undergoing craniotomies. We searched PubMed, EMBASE, Cochrane Library databases, and Web of Science for randomized controlled trials (RCTs). The outcome indicators included brain relaxation, hemodynamic status, fluid volume, and blood chemistry. A total of nine RCTs involving 665 patients were identified and included. There was a greater increase in the odds of good intraoperative brain relaxation in the HS group (odds ratio (OR) 2.05, 95% confidence interval (CI) 1.40~3.01; P = 0.0002) compared with mannitol. In comparison with HS, mannitol slightly reduced the central venous pressure (CVP) (mean difference (MD) 1.03, 95% CI 0.03~2.03; P = 0.04) as well as significantly increasing the diuretic effect regardless of the dosage of HS (standardized mean difference (SMD) −0.86, 95% CI −1.35~−0.37; P = 0.0006). HS increased the plasma sodium level significantly (MD 7.86, 95% CI 2.78 ~ 12.95, P = 0.002) but reduced the intraoperative fluid intake (SMD −0.56, 95% CI −0.98~−0.15, P = 0.008). However, there were no significant differences in plasma osmolality and mean arterial pressure (MAP). Our results suggest that there appears to be better brain relaxation without a significant increase in urine volume in the HS group compared with mannitol in patients requiring craniotomies. High-quality RCTs with larger sample sizes will be required in the future to confirm the conclusions.

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References

  1. Hans P, Bonhomme V (2006) Why we still use intravenous drugs as the basic regimen for neurosurgical anaesthesia. Curr Opin Anaesthesiol 19:498–503

    Article  PubMed  Google Scholar 

  2. Quentin C, Charbonneau S, Moumdjian R, Lallo A, Bouthilier A, Fournier-Gosselin MP, Bojanowski M, Ruel M, Sylvestre MP, Girard F (2013) A comparison of two doses of mannitol on brain relaxation during supratentorial brain tumor craniotomy: a randomized trial. Anesth Analg 116:862–868

    Article  PubMed  CAS  Google Scholar 

  3. Hernández-Palazón J, Fuentes-García D, Doménech-Asensi P, Piqueras-Pérez C, Falcón-Araña L, Burguillos-López S (2016) A comparison of equivolume, equiosmolar solutions of hypertonic saline and mannitol for brain relaxation during elective supratentorial craniotomy. Br J Neurosurg 30:70–75

    Article  PubMed  Google Scholar 

  4. Diringer MN, Zazulia AR (2004) Osmotic therapy: fact and fiction. Neurocrit Care 1:219–233

    Article  PubMed  CAS  Google Scholar 

  5. Bentsen G, Breivik H, Lundar T, Stubhaug A (2006) Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamics in a placebo-controlled study involving stable patients with subarachnoid hemorrhage. Crit Care Med 34:2912–2917

    Article  PubMed  CAS  Google Scholar 

  6. Forsyth LL, Liu-DeRyke X, Parker D Jr, Rhoney DH (2008) Role of hypertonic saline for the management of intracranial hypertension after stroke and traumatic brain injury. Pharmacotherapy 28:469–484

    Article  PubMed  CAS  Google Scholar 

  7. Jagannatha AT, Sriganesh K, Devi BI, Rao GS (2016) An equiosmolar study on early intracranial physiology and long term outcome in severe traumatic brain injury comparing mannitol and hypertonic saline. J Clin Neurosci 27:68–73

    Article  PubMed  Google Scholar 

  8. Upadhyay P, Tripathi VN, Singh RP, Sachan D (2010) Role of hypertonic saline and mannitol in the management of raised intracranial pressure in children: a randomized comparative study. J Pediatr Neurosci 5:18–21

    Article  PubMed  PubMed Central  Google Scholar 

  9. Huang XC, Yang LL (2015) Comparison clinical efficacy of 3% hypertonic saline solution with 20% mannitol in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage. Zhejiang Da Xue Xue Bao Yi Xue Ban 44:389–395

    PubMed  CAS  Google Scholar 

  10. Dostal P, Dostalova V, Schreiberova J, Tyll T, Habalova J, Cerny V, Rehak S, Cesak T (2015a) A comparison of equivolume, equiosmolar solutions of hypertonic saline and mannitol for brain relaxation in patients undergoing elective intracranial tumor surgery: a randomized clinical trial. J Neurosurg Anesthesiol 27:51–56

    Article  PubMed  Google Scholar 

  11. De Vivo P, Del Gaudio A, Ciritella P, Puopolo M, Chiarotti F, Mastronardi E (2001) Hypertonic saline solution: a safe alternative to mannitol 18% in neurosurgery. Minerva Anestesiol 67:603–611

    PubMed  CAS  Google Scholar 

  12. Wu CT, Chen LC, Kuo CP, Ju DT, Borel CO, Cherng CH, Wong CS (2010) A comparison of 3% hypertonic saline and mannitol for brain relaxation during elective supratentorial brain tumor surgery. Anesth Analg 110:903–907

    Article  PubMed  CAS  Google Scholar 

  13. Harutjunyan L, Holz C, Rieger A, Menzel M, Grond S, Soukup J (2005) Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients—a randomized clinical trial. Crit Care 9:R530–R540

    Article  PubMed  PubMed Central  Google Scholar 

  14. Dostal P, Schreiberova J, Dostalova V, Dostalova V Jr, Tyll T, Paral J, Abdo I, Cihlo M, Astapenko D, Turek Z (2015b) Effects of hypertonic saline and mannitol on cortical cerebral microcirculation in a rabbit craniotomy model. BMC Anesthesiol 15:88

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Kamel H, Navi BB, Nakagawa K, Hemphill JC 3rd, Ko NU (2011) Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med 39:554–559

    Article  PubMed  CAS  Google Scholar 

  16. Fenstermacher JD, Johnson JA (1966) Filtration and reflection coefficients of the rabbit blood-brain barrier. Am J Phys 211:341–346

    CAS  Google Scholar 

  17. Zornow MH (1996) Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesthesiol 8:175–177

    Article  PubMed  CAS  Google Scholar 

  18. McAlister V, Burns KE, Znajda T, Church B (2010) Hypertonic saline for peri-operative fluid management. Cochrane Database Syst Rev :CD005576

  19. Shao L, Hong F, Zou Y, Hao X, Hou H, Tian M (2015) Hypertonic saline for brain relaxation and intracranial pressure in patients undergoing neurosurgical procedures: a meta-analysis of randomized controlled trials. PLoS One 10:e0117314

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Prabhakar H, Singh GP, Anand V, Kalaivani M (2014) Mannitol versus hypertonic saline for brain relaxation in patients undergoing craniotomy. Cochrane Database Syst Rev :CD010026

  21. Raghava A, Bidkar PU, Prakash MV, Hemavathy B (2015) Comparison of equiosmolar concentrations of hypertonic saline and mannitol for intraoperative lax brain in patients undergoing craniotomy. Surg Neurol Int 6:73

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Malik ZA, Mir SA, Naqash IA, Sofi KP, Wani AA (2014) A prospective, randomized, double blind study to compare the effects of equiosmolar solutions of 3% hypertonic saline and 20% mannitol on reduction of brain-bulk during elective craniotomy for supratentorial brain tumor resection. Anesth Essays Res 8:388–392

    Article  PubMed  PubMed Central  Google Scholar 

  23. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535

    Article  PubMed  PubMed Central  Google Scholar 

  24. Higgins JPT, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 updated March 2011. The Cochrane Collaboration: http://www.cochrane-handbook.org. Accessed 28 July 2016

  25. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, Norris S, Falck-Ytter Y, Glasziou P, DeBeer H, Jaeschke R, Rind D, Meerpohl J, Dahm P, Schünemann HJ (2011) GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 64:383–394

    Article  PubMed  Google Scholar 

  26. Attari MA, Abyaneh HRK (2012) Comparison of the effects of hypertonic saline 3.2% and mannitol 20% on brain relaxation during brain tumor surgery. Journal of Isfahan Medical School 30:1386–1392

    Google Scholar 

  27. Vilas Boas WW, Marques MB, Alves A (2011) Hydroelectrolytic balance and cerebral relaxation with hypertonic isoncotic saline versus mannitol (20%) during elective neuroanesthesia. Rev Bras Anestesiol 61:456–468

    Article  PubMed  Google Scholar 

  28. Rozet I, Tontisirin N, Muangman S, Vavilala MS, Souter MJ, Lee LA, Kincaid MS, Britz GW, Lam AM (2007) Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. Anesthesiology 107:689–691

    Article  Google Scholar 

  29. Todd MM, Warner DS, Sokoll MD, Maktabi MA, Hindman BJ, Scamman FL, Kirschner J (1993) A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy: propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology 178:1005–1020

    Article  Google Scholar 

  30. Citerio G, Pesenti A, Latini R, Masson S, Barlera S, Gaspari F, Franzosi MG, NeuroMorfeo Study Group (2012) A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy. Eur J Anaesthesiol 29:371–379

    Article  PubMed  CAS  Google Scholar 

  31. Weed LH, McKibben PS (1919) Experimental alteration of brain bulk. Am J Phys 48:512–530

    Google Scholar 

  32. Wang LC, Papangelou A, Lin C, Mirski MA, Gottschalk A, Toung TJ (2013) Comparison of equivolume, equiosmolar solutions of mannitol and hypertonic saline with or without furosemide on brain water content in normal rats. Anesthesiology 118:903–913

    Article  PubMed  CAS  Google Scholar 

  33. Wakai A, Roberts I, Schierhout G (2007) Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev :CD001049

  34. Kheirbek T, Pascual JL (2014) Hypertonic saline for the treatment of intracranial hypertension. Curr Neurol Neurosci Rep 14:482

    Article  PubMed  Google Scholar 

  35. Hijiya N, Horiuchi K, Asakura T (1991) Morphology of sickle cells produced in solutions of varying osmolarities. J Lab Clin Med 117:60–66

    PubMed  CAS  Google Scholar 

  36. Badaut J, Ashwal S, Obenaus A (2011) Aquaporins in cerebrovascular disease: a target for treatment of brain edema? Cerebrovasc Dis 31:521–531

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Chatterjee N, Koshy T, Misra S, Suparna B (2012) Changes in left ventricular preload, afterload, and cardiac output in response to a single dose of mannitol in neurosurgical patients undergoing craniotomy: a transesophageal echocardiographic study. J Neurosurg Anesthesiol 24:25–29

    Article  PubMed  Google Scholar 

  38. Gemma M, Cozzi S, Tommasino C, Mungo M, Calvi MR, Cipriani A, Garancini MP (1997) 7.5% hypertonic saline versus 20% mannitol during elective neurosurgical supratentorial procedures. J Neurosurg Anesthesiol 9:329–334

    Article  PubMed  CAS  Google Scholar 

  39. Li J, Wang B, Wang S, Mu F (2014) Effects of hypertonic saline - hydroxyethyl starch and mannitol on serum osmolality, dural tension and hemodynamics in patients undergoing elective neurosurgical procedures. Int J Clin Exp Med 7:2266–2272

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge Dr. David Jack for his assistance with language editing.

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Correspondence to Gang Cheng.

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Fang, J., Yang, Y., Wang, W. et al. Comparison of equiosmolar hypertonic saline and mannitol for brain relaxation during craniotomies: A meta-analysis of randomized controlled trials. Neurosurg Rev 41, 945–956 (2018). https://doi.org/10.1007/s10143-017-0838-8

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