Mannitol versus hypertonic saline for brain relaxation in patients undergoing craniotomy – A Cochrane Systematic Review

Abstract

Background: Patients with brain tumour usually suffer from increased pressure in the skull due to swelling of brain tissue. A swollen brain renders surgical removal of the brain tumour difficult. To ease surgical tumour removal, measures are taken to reduce brain swelling, often referred to as brain relaxation. Brain relaxation can be achieved with intravenous fluids such as mannitol or hypertonic saline. The objective of this review was to compare the effects of mannitol versus those of hypertonic saline on intraoperative brain relaxation in patients undergoing craniotomy. Methods: We searched the Cochrane Central Register of Controlled Trials (2013, Issue 10), MEDLINE through OvidSP (1966 to October 2013) and EMBASE through OvidSP (1980 to October 2013). We also searched specific websites, such as www.indmed.nic.in, www.cochrane-sadcct.org and www.clinicaltrials.gov. We included randomised controlled trials (RCTs) that compared the use of hypertonic saline versus mannitol for brain relaxation. We also included studies in which any other method used for intraoperative brain relaxation was compared with mannitol or hypertonic saline. The primary outcomes were longest follow-up mortality, Glasgow outcome scale score at 3 months and any adverse event related to mannitol or hypertonic saline. The secondary outcomes were intraoperative brain relaxation, Intensive Care Unit (ICU) stay, hospital stay and quality of life. We used standardised methods for conducting a systematic review as described by the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. All analyses were made on an intention-to-treat basis. We used a fixed-effect model when no evidence was found of significant heterogeneity between studies and a random-effects model when heterogeneity was likely. Results: We included six RCTs with 527 participants. Only one RCT was judged to be at low risk of bias. The remaining five RCTs were at unclear or high risk of bias. No trial mentioned the primary outcomes of longest follow-up mortality, Glasgow outcome scale score at 3 months or any adverse event related to mannitol or hypertonic saline. Three trials mentioned that the secondary outcomes of intraoperative brain relaxation, hospital stay, ICU stay and quality of life were not reported in any of the trials. Brain relaxation was inadequate in 42 of 197 participants in the hypertonic saline group and 68 of 190 participants in the mannitol group. The risk ratio for brain bulge or tense brain in the hypertonic saline group was 0.60 (95% confidence interval 0.44–0.83, low-quality evidence). One trial reported ICU and hospital stay. The mean (standard deviation [SD]) duration of ICU stay in the mannitol and hypertonic saline groups was 1.28 (0.5) and 1.25 (0.5) days (P - 0.64), respectively; the mean (SD) duration of hospital stay in the mannitol and hypertonic saline groups was 5.7 (0.7) and 5.7 (0.8) days (P - 1.00), respectively. Conclusions: From the limited data available on the use of mannitol and hypertonic saline for brain relaxation during craniotomy, it is suggested that hypertonic saline significantly reduces the risk of tense brain during craniotomy. A single trial suggests that ICU stay and hospital stay are comparable with the use of mannitol or hypertonic saline. However, focus on other related important issues such as long-term mortality, long-term outcome, adverse events and quality of life is needed.

Keywords

Brain relaxation - craniotomy - hypertonic saline - mannitol

• REFERENCES

• 1 Battison C, Andrews PJ, Graham C, Petty T. Randomized, controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury. Crit Care Med 2005; 33: 196-202
• 2 Schwarz S, Georgiadis D, Aschoff A, Schwab S. Effects of hypertonic (10%) saline in patients with raised intracranial pressure after stroke. Stroke 2002; 33: 136-40
• 3 Vialet R, Albanèse J, Thomachot L, Antonini F, Bourgouin A, Alliez B. et al. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med 2003; 31: 1683-7
• 4 De Vivo P, Del Gaudio A, Ciritella P, Puopolo M, Chiarotti F, Mastronardi E. Hypertonic saline solution: A safe alternative to mannitol 18% in neurosurgery. Minerva Anestesiol 2001; 67: 603-11
• 5 Gemma M, Cozzi S, Tommasino C, Mungo M, Calvi MR, Cipriani A. et al. 7.5% hypertonic saline versus 20% mannitol during elective neurosurgical supratentorial procedures. J Neurosurg Anesthesiol 1997; 9: 329-34
• 6 White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury. Anesth Analg 2006; 102: 1836-46
• 7 Lefebvre C, Manheimer E, Glanville J. Searching for studies. In: Higgins JP, Green S. editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. Ch. 6. The Cochrane Collaboration; 2011. Available from: http://www.cochrane-handbook.org [Last updated on 2011 Mar].
• 8 Higgins JP, Altman DG, Sterne JA. Assessing risk of bias in included studies. In: Higgins JPT, Green S. editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. Ch. 8. The Cochrane Collaboration; 2011. Available from: http://www.cochrane-handbook.org [Last updated on 2011 Mar].
• 9 Review Manager (RevMan) 5.2. Copenhagen [Computer Program]. Version 5.2. Copenhagen: The Nordic Cochrane Centre; The Cochrane Collaboration; 2013
• 10 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-88
• 11 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-58
• 12 Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ. GRADE Working Group. What is “quality of evidence” and why is it important to clinicians?. BMJ 2008; 336: 995-8
• 13 Demneri M, Hoxha A, Pilika K, Saraci M. Comparison of 20% mannitol and 7.5% hypertonic saline for supratentorial craniotomy. Eur J Anaesthesiol 2011; 28: 106-7
• 14 Rozet I, Tontisirin N, Muangman S, Vavilala MS, Souter MJ, Lee LA. et al. Effect of equiosmolar solutions of mannitol versus hypertonic saline on intraoperative brain relaxation and electrolyte balance. Anesthesiology 2007; 107: 697-704
• 15 Vilas Boas WW, Marques MB, Alves A. Hydroelectrolytic balance and cerebral relaxation with hypertonic isoncotic saline versus mannitol (20%) during elective neuroanesthesia. Rev Bras Anestesiol 2011; 61: 456-68
• 16 Wu CT, Chen LC, Kuo CP, Ju DT, Borel CO, Cherng CH. et al. A comparison of 3% hypertonic saline and mannitol for brain relaxation during elective supratentorial brain tumor surgery. Anesth Analg 2010; 110: 903-7
• 17 Levin AB, Duff TA, Javid MJ. Treatment of increased intracranial pressure: A comparison of different hyperosmotic agents and the use of thiopental. Neurosurgery 1979; 5: 570-5
• 18 Smedema RJ, Gaab MR, Heissler HE. A comparison study between mannitol and glycerol therapy in reducing intracranial pressure. Intracranial Pressure 1993; VIII: 605-8
• 19 Eldahab HA, Awad W, Wagh O. Should hypertonic saline 3% replace mannitol 20% for reduction of intracranial pressure in craniotomy for supratentorial tumors? A comparative study. Egypt J Anaesth 2009; 25: 413-28
• 20 Erard A, Bracco D, Walder B, Ravussin P. Effect of mannitol, NaCl 7.5% and NaCl 0.9% on osmolality and osmolarity: A randomized controlled study in neurosurgical patients [abstract]. Br J Anaesth 1999; 82 Suppl (Suppl. 01) 87(A287)
• 21 Pausawasdi S, Bunyaratavej S. Furosemide and mannitol – Induced changes in intracranial pressure during the removal of intracranial tumours. J Med Assoc Thai 1982; 65: 413-9
• 22 Muangman S, Rozet I, Vavilala MS, Lee LA, Lam AM. Iso-osmolar solutions of mannitol vs. hypertonic saline for intraoperative brain relaxation. Anesthesiology 2005; 103: A76
• 23 Harutjunyan L, Holz C, Rieger A, Menzel M, Grond S, Soukup J. 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 [ISRCTN62699180]. Crit Care 2005; 9: R530-40