Mannitol versus hypertonic saline for brain relaxation in patients undergoing craniotomy – A Cochrane Systematic Review
Authors: Prabhakar Hemanshu , Singh Gyaninder , Kalaivani Mani , Anand Vidhu 
Published: January 2019

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.