Glycerol for acute stroke: a Cochrane systematic review

Abstract

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 We considered all completed, controlled, published and unpublished comparisons, evaluating clinical outcome, in which intravenous glycerol treatment was initiated within the first days after stroke onset.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.

Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008

“…If ICP monitoring is available, cerebral perfusion pressure should be kept above 70 mm Hg [438]. Intravenous glycerol (4 × 250 ml of 10% glycerol over 30–60 min) or mannitol (25–50 g every 3–6 h) is first line medical treatment if clinical or radiological signs of space-occupying oedema occur [439, 440]. Intravenous hypertonic saline solutions are probably similarly effective [441].…”

European Stroke Initiative Recommendations for Stroke Management – Update 2003

“…If ICP monitoring is available, cerebral perfusion pressure should be kept 170 mm Hg [Unterberg et al, 1997]. Although strong evidence is lacking [Righetti et al, 2002;Bereczki et al, 2001], osmotherapy with 10% glycerol usually given intravenously (4 250 ml of 10% glycerol over 30-60 min) or intravenous mannitol 25-50 g every 3-6 h is the first medical treatment to be used if clinical and/or radiological signs of space-occupying oedema occur. Hypertonic saline solutions given intravenously (5!…”

Empfehlungen der European Stroke Initiative (EUSI) zur Behandlung des ischämischen Schlaganfalls — Aktualisierung 2003

“…Das Basismanagement des erhöhten intrakraniellen Druckes beinhaltet die 30°-Oberkörperhochlagerung, das Vermeiden schmerzhafter Stimuli,suffiziente Analgesie,ausreichende Oxygenierung und Normalisierung der Körpertemperatur.Wenn ein ICP-Monitoring verfügbar ist,sollte der zerebrale Perfusionsdruck mehr als 70 mmHg betragen [121].Auch wenn es keine eindeutige Evidenz hierfür gibt [10,95], ist die Osmotherapie mit 10%igem Glycerol i.v. (4×20 ml über 30-60 min) oder intravenösem Mannitol (25-40 g alle 3-6 h) oftmals die erste medikamentöse Maßnah-me,wenn klinische und/oder neuroradiologische Zeichen eines raumfordernden Ödems auftreten.Hypertone NaCl-Lösung (5×100 ml 3%ig i.v.)…”