Glycerol for acute stroke: a Cochrane systematic review

Brain oedema is a major cause of early death after stroke. Glycerol is a hyperosmolar agent that is claimed to reduce brain oedema. We sought to determine whether I. V. glycerol treatment in acute stroke, either ischaemic or haemorrhagic, influences death rates and functional outcome in the short or long term and whether the treatment is safe. The Cochrane Stroke Group Trials Register was searched, conference proceedings were screened and some trialists were personally contacted. We considered all completed, controlled, published and unpublished comparisons, evaluating clinical outcome, in which intravenous glycerol treatment was initiated within the first days after stroke onset. Death from all causes, functional outcome and adverse effects were analysed. Analysis of short term death for acute ischaemic and/or haemorrhagic stroke was possible in ten trials where 482 glycerol treated patients were compared with 463 control patients. Glycerol was associated with a non-significant reduction in the odds of death within the scheduled treatment period (OR 0.78, 95% Confidence Intervals 0.58-1.06). Among patients with definite or probable ischaemic stroke, glycerol was associated with a significant reduction in the odds of death during the scheduled treatment period (odds ratio 0.65, 95% CI 0.44-0.97). However, at the end of the scheduled follow up period there was no significant difference in the odds of death (odds ratio 0.98, 95% CI 0.73-1.31). Functional outcome was reported in only two studies and there was a non-significant positive effect on outcome at the end of scheduled follow up (odds ratio 0.73, 95% CI 0.37-1.42). Haemolysis seems to be the only relevant adverse effect of glycerol treatment. This systematic review suggests a favourable effect of glycerol treatment on short term survival in probable or definite ischaemic stroke, but the magnitude of the treatment effect may be minimal (as low as a 3% reduction in odds). Because of the relatively small number of patients and because the trials have been performed in the pre-CT era, the results must be interpreted cautiously. The lack of evidence of benefit in long term survival does not support the routine or selective use of glycerol treatment in patients with acute stroke.