Review question: We reviewed evidence on the effectiveness of mannitol and hypertonic saline for brain relaxation in people having surgery (craniotomy) for brain tumour.
Background: People with brain tumour undergo a craniotomy, or opening of the skull bone, for its removal. A relaxed brain allows the surgeon to remove the skull bone easily and to remove the tumour without damaging other brain tissue. Brain relaxation is achieved often by using mannitol, which is a hypertonic fluid. Hypertonic solutions are those that have higher solute concentrations when compared with body fluids and tissue. Some surgeons use hypertonic saline instead of mannitol. We wanted to discover whether using hypertonic saline was better or worse than using mannitol.
Study characteristics: The evidence is current to October 2013. We included studies in children (age > 28 days and < 18 years) and adult patients (age > 18 years) of either gender who received mannitol or hypertonic saline during craniotomy for brain tumour. We reran the search in January 2017 and found five potential studies of interest which have been added to a list of ‘Studies Awaiting Classification' and will be incorporated into the formal review findings during the review update.
Key results: We found six studies with 527 participants.
Three studies reported the level of brain relaxation. Hypertonic saline may provide better brain relaxation than mannitol.
The length of intensive care unit stay and hospital stay was reported by one study.
No study reported on the effects of mannitol and hypertonic saline on mortality, the condition of the patient three months after the operation or patient quality of life. Based on our results, we would expect that of 100 patients who received hypertonic saline during surgery, around 22 patients would fail to have adequate brain relaxation compared with 36 patients given mannitol.
Quality of evidence
The quality of evidence for brain relaxation with use of hypertonic saline is low. Further research is needed to assess more important issues such as long-term mortality, long-term outcomes, adverse events and quality of life with use of the two fluids.
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.
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. This review was conducted to find out which of the two fluids may have a greater impact on brain relaxation.
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.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 10), MEDLINE via Ovid SP (1966 to October 2013) and EMBASE via Ovid SP (1980 to October 2013). We also searched specific websites, such as www.indmed.nic.in, www.cochrane-sadcct.org and www.Clinicaltrials.gov. We reran the search in January 2017 and found five potential studies of interest which have been added to a list of ‘Studies Awaiting Classification' and will be incorporated into the formal review findings during the review update.
We included randomized 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. Primary outcomes were longest follow-up mortality, Glasgow Outcome Scale score at three months and any adverse events related to mannitol or hypertonic saline. Secondary outcomes were intraoperative brain relaxation, intensive care unit (ICU) stay, hospital stay and quality of life.
We used standardized 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.
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 three months or any adverse events related to mannitol or hypertonic saline. Three trials mentioned the secondary outcomes of intraoperative brain relaxation, hospital stay and ICU stay; quality of life was not reported in any of the trials. Brain relaxation was inadequate in 42 of 197 participants in the hypertonic saline group and in 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 (CI) 0.44 to 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 value 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 value 1.00), respectively