Glycerol for Acute Stroke
Brain edema is a major cause of early death after stroke, but no treatment has been shown to be effective, and recommendations in American and European guidelines are based only on expert opinion. A 10% solution of glycerol is a hyperosmolar agent that is claimed to reduce brain edema, and its use has been (and probably still is) rather popular in some countries (Italy, Poland, China).
The objectives of this study were to determine whether intravenous glycerol treatment in acute stroke, either ischemic or hemorrhagic, influences death rates and functional outcome in the short-term or long-term, and whether the treatment is safe.
The Cochrane Stroke Group trials register was searched (January 2003). Some trialists were personally contacted.
All completed, randomized and quasi-randomized, controlled, published, and unpublished comparisons evaluating clinical outcome in which intravenous glycerol treatment was initiated within the first days after stroke onset were used.
Data Collection and Analysis
Two reviewers independently applied the inclusion criteria, assessed the trial quality, and extracted data, and the data were checked with all co-reviewers. Death from all causes, functional outcome, and adverse effects were analyzed.
Eleven completed randomized trials comparing intravenous glycerol and control treatments were considered. Analysis of death during the scheduled treatment period for acute ischemic and/or hemorrhagic stroke was possible in 10 trials in which 482 glycerol-treated patients were compared with 463 control patients. Glycerol was associated with a nonsignificant reduction in the odds of death within the scheduled treatment period (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.58 to 1.06). Among patients with definite or probable ischemic stroke, glycerol was associated with a significant reduction in the odds of death during the scheduled treatment period (OR, 0.65; 95% CI, 0.44 to 0.97) (Figure). However, at the end of the scheduled follow-up period, there was no significant difference in the odds of death (OR, 0.98; 95% CI, 0.73 to 1.31). Functional outcome was reported in only 2 studies, but there were nonsignificantly more patients who had a good outcome at the end of scheduled follow-up (OR, 0.73; 95% CI, 0.37 to 1.42). Hemolysis seems to be the only relevant adverse effect of glycerol treatment.
This systematic review suggests a favorable effect of glycerol treatment on short-term survival in patients with probable or definite ischemic stroke, but the confidence intervals were wide and the magnitude of the treatment effect may be only minimal. Because of the relatively small number of patients, and because some trials were performed in the era before computed tomography, 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. However, this inexpensive and safe treatment should be tested in a large-scale randomized trial, perhaps restricted to patients who have clinical evidence of cerebral edema, in which the long-term effects of glycerol treatment on disability and handicap are reliably assessed.
Note: The full reference of this review is available in the Cochrane Library (for subscribers: www.update-software.com/Cochrane). The full article should be cited as: Righetti E, Celani MG, Cantisani T, Sterzi R, Boysen G, Ricci S. Glycerol for acute stroke (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Cichester, UK: Update Software. 227 Cochrane Library, John Wiley and Sons Ltd.
From the Stroke Service (E.R., M.G.C., S.R.), USL 2 Perugia, Italy; Neurofisiopatologia (T.A.C.), Ospedale Silvestrini, Perugia, Italy; Divisione Neurologia (R.S.), A.O.S. Anna, Como, Italy; Department of Neurology (G.B.), Bispebjerg Hospital, Copenhagen, Denmark.
- Received April 22, 2004.
- Accepted April 26, 2004.