Double-blind randomised trial of intravenous glycerol in acute stroke. Double-blind trial of glycerol therapy in early stroke. [Treatment with 10% glycerin in acute ischemic cerebral infarct. Doubleblind study]. Glycerol and dextran combined in the therapy of acute stroke. A placebo-controlled, double-blind trial with a planned interim analysis. Investigation of intravascular haemolysis during treatment of acute stroke with intravenous glycerol. The effect of glycerol infusion in acute cerebral infarction. Intravenous glycerol in cerebral infarction: a controlled 4-month trial. Association of glycerol to dexamethasone in treatment of stroke patients. Treatment in a combined acute and rehabilitation stroke unit: which aspects are most important?
The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind randomised controlled trial. 173 patients received either 500 ml of a 10% solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days. The number of deaths within the first week was 10 (12%) in the glycerol group versus 26 (30%) in the controls. Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment (p less than 0.02). The neurological and functional recovery of survivors, their length of hospital stay, and the proportion able to return to live in their own home were similar in the two groups. The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability. The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke. Administration continued for up to 6 days. A standard scoring system was used for neurological evaluation. There was no difference in mortality or in improvement in neurological score between the two groups. 56 patients with acute ischemic cerebral infarction were randomly allocated to intravenous treatment for 6 days with either 500 ml of a 10% glycerol solution or 500 ml of a 5% dextrose solution (placebo). The neurological status of the patients was evaluated by a blinded investigator before the beginning of the treatment, after 2 weeks and again after 6 months. According to the initial degree of neurological deficit, patients were stratified into a mild, intermediate and severe group (using a scoring system). After 2 weeks there was significantly less neurological deficit in the total glycerol-treated group than in the placebo group (2p less than 0.02). This favourable effect of glycerol was even greater in the patients with an initially intermediate degree of neurological deficity (2p less than 0.01). After 6 months there was no difference between the total glycerol-treated and the placebo group. A beneficial effect of glycerol treatment, however, was still demonstrable in the intermediate group (2p less than 0.05). Mortality was not influenced by glycerol treatment. No side effects of the glycerol treatment could be detected. Intravenous administration of 10% glycerol can thus be recommended in patients with acute cerebral infarction. The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent. The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind, placebo-controlled study. Repeated neurologic examinations (Day 0, Weeks 1, 6, 12, and 24) according to a modified Mathew score were performed on 62 patients. Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke. A retrospective estimation of the Type II error of the study yielded approximately p = 0.25. A major side effect was hemolysis in 98% of patients treated with glycerol. 1. In patients with acute strokes entering a large ongoing randomised double-blind controlled trial of intravenous glycerol therapy, the extent and pathogenesis of any ensuing haemolysis were evaluated using standard clinical investigations and in vitro techniques. 2. Twenty patients received 10% glycerol in saline (500 ml over 4 h on 6 consecutive days) and 15 received corresponding control treatment with saline. 3. Intravascular haemolysis was evident after the first infusion; compared with the controls the glycerol group had i) a greater mean reduction in serum haptoglobin concentration (P less than .05), and ii) a greater proportion exhibiting haemoglobinaemia (P = 0.03). 4. After 6 days of glycerol treatment, the mean reduction in haemoglobin concentration was only 0.8 g more than in controls; this difference being neither clinically nor statistically significant. 5. Glycerol therapy was not associated with haemoglobinuria, renal insufficiency or disseminated intravascular coagulation. 6. Exposure of red blood cells to 1-10% glycerol in vitro did not induce haemolysis per se; on re-exposure to lower concentrations lysis ensued provided a minimum osmotic gradient was present. 7. Whilst taking standard dosage regimes of glycerol, the stroke patients we studied manifested a degree of intravascular haemolysis but its consequences were not clinically significant; lysis probably ensued after venous blood acquiring high glycerol concentrations mixed with blood containing little or no glycerol. Intravenous administration of glycerol has been used in an effort to improve the prognosis for patients with acute cerebral infarction. Fifty patients were treated actively and 56 served as a control group. The neurological status before, during and after treatment for six days was assessed by a score system. The patients were grouped according to the initial score. Those with the highest and lowest scores did not improve from glycerol infusion. However, the treated patients with intermediate scores, where the prognosis is known to be dubious, showed a significant improvement compared to the controls. The mortality was not influenced. No undesirable side-effects from glycerol were registered. A double-blind, randomized trial was performed with 51 patients suffering from focal ischemic lesions in the territory of the middle cerebral artery. Intravenous infusions of 10% glycerol in 0.9% NaCl--5% glucose solutions were administered twice daily for 6 days to 26 patients, and the same amount of NaCl--glucose solutions to 25 controls. Glycerol did not reduce mortality (9 deaths in each group). The functional recovery was assessed by repeated neurological examinations during the 4 month trial. Glycerol significantly improved global performances and motor and sensory functions in patients with moderate disability, but its effect on global performances was transient. The patients with severe disability were not improved at all. A prospective study of 93 acute stroke patients randomly selected by type of antiedema treatment given (hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke. We have previously shown that treatment of acute stroke patients in our stroke unit (SU) compared with treatment in general ward (GWs) improves short- and long-term survival and functional outcome and increases the possibility of earlier discharge to home. The aim of the present study was to identify the differences in treatment between the SU and the GW and to assess which aspects of the SU care which were most responsible for the better outcome.
                Of the 220 patients included in our trial, only 206 were actually treated (SU, 102 patients; GW, 104 patients). For these patients, we identified the differences in the treatment and the consequences of the treatment. We analyzed the factors that we were able to measure and their association with the outcome, discharge to home within 6 weeks.
                Characteristic features in our SU were teamwork, staff education, functional training, and integrated physiotherapy and nursing. Other treatment factors significantly different in the SU from the GW were shorter time to start of the systematic mobilization/training and increased use of oxygen, heparin, intravenous saline solutions, and antipyretics. Consequences of the treatment seem to be less variation in diastolic and systolic blood pressure (BP), avoiding the lowest diastolic BP, and lowering the levels of glucose and temperature in the SU group compared with the GW group. Univariate analyses showed that all these factors except the level of glucose were significantly associated with discharge to home within 6 weeks. In the final multivariate Cox regression model, shorter time to start of the mobilization/training and stabilized diastolic BP were independent factors significantly associated with discharge to home within 6 weeks.
                Shorter time to start of mobilization/training was the most important factor associated with discharge to home, followed by stabilized diastolic BP, indicating that these factors probably were important in the SU treatment. The effects of characteristic features of an SU, such as a specially trained staff, teamwork, and involvement of relatives, were not possible to measure. Such factors might be more important than those actually measured.
This systematic review suggests a favourable effect of glycerol treatment on short term survival in patients with probable or definite ischaemic stroke but the confidence intervals were wide and the magnitude of the treatment effect may be only minimal. Due to the relatively small number of patients, and that the trials were 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.