Multicenter trial of hemodilution in acute ischemic stroke. I. Results in the total patient population. Scandinavian Stroke Study Group. Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial. A randomized controlled trial of hemodilution therapy in acute ischemic stroke. Ancrod for the treatment of acute ischemic brain infarction. The Ancrod Stroke Study Investigators. Adjusted hypervolemic hemodilution in acute ischemic stroke. Double-blind randomised trial of intravenous glycerol in acute stroke. Hydroxyethyl starch for hypervolemic hemodilution in patients with acute ischemic stroke: a randomized, placebo-controlled phase II safety study. Hypervolemic hemodilution treatment of acute stroke. Results of a randomized multicenter trial using pentastarch. The Hemodilution in Stroke Study Group. Custom-tailored hemodilution with albumin and crystalloids in acute ischemic stroke. Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial. A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population. Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit: a randomized pilot study.
Hemodilution by the combination of venesection and dextran 40 administration has previously been reported to enhance neurologic recovery in the acute phase of ischemic stroke. To study this therapeutic principle in its "natural habitat," a stratified and randomized multicenter trial involving 15 large and small hospitals was performed. Patients with acute ischemic stroke of less than 48 hours' duration and with hematocrits of 38-50% on admission were randomized to a hemodilution (183 patients, mean age 72.0 years) or a control group (190 patients, mean age 71.6 years). The two groups did not differ in sex distribution or medical history. Hematocrit, blood pressure, and neurologic score were closely similar at entry. By graded venesection (250-1000 ml) during the first 2 days and dextran 40 infusions (500 ml daily) during 5 days, the mean hematocrit was reduced from 44.2 to 37.1%. Three-month survival expressed as life table product was 0.84 in hemodilution and 0.88 in control patients. In survivors, neurologic score and activities of daily living performance during 3 months of follow-up were not improved by hemodilution. Length of stay in an acute-care hospital and the need for long-term institutional care was not reduced among patients in the hemodilution group. Major cardiovascular events occurred somewhat more often and there was an apparent increase in mortality during the first few days of hemodilution therapy. However, the differences were not significant. We conclude that the present standardized treatment with moderate hemodilution has no overall beneficial effects in general patients with acute ischemic stroke. Intravenous tissue plasminogen activator is the only approved specific treatment for acute ischaemic stroke. Ancrod, a natural defibrinogenating agent from snake venom, has proved to have a favourable effect when given within 3 h after an acute ischaemic stroke. The European Stroke Treatment with Ancrod Trial was undertaken to assess the effects of ancrod when given within 6 h.
                1222 patients with an acute ischaemic stroke were included in this randomised double-blind placebo-controlled trial. Brain CT scans were done to exclude intracranial haemorrhages and large evolving ischaemic infarctions. Patients were randomly assigned ancrod (n=604) or placebo (n=618). The primary outcome was functional success at 3 months (survival, Barthel Index of 95 or 100, or return to prestroke level). The analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, trial number NCT00343174.
                Functional success at 3 months did not differ between patients given ancrod (42%) and those given placebo (42%) (p=0.94, OR=0.99, 95% CI, 0.76-1.29).
                On the basis of our findings, ancrod should not be recommended for use in acute ischaemic stroke beyond 3 h. Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection (250-650 ml during the first 2 days) and administration of low-molecular weight dextran was evaluated in a prospective controlled trial. Fifty-two patients were randomized to hemodilution therapy and 50 to a control group; the two groups were comparable in important prognostic variables. Mean hemoglobin was reduced from 147 to 127 g/l, hematocrit from 43 to 37% and, in a subsample of patients, whole-blood viscosity at a shear rate of 23 sec-1 from 7.0 to 4.3 cps over the first 2 days. Hemodilution was then maintained by repeated dextran infusions. Of the hemodiluted patients, 85% improved in neurological scoring over the first 10 days as compared to 64% of the control patients (p less than 0.025). The case fatality rate during the first 3 months was little affected by hemodilution. Among the survivors, 8% of the hemodiluted and 31% of the non-hemodiluted patients were unable to walk at 3 months. The proportion of surviving patients still hospitalized at the 3-month follow-up was 13% in the hemodilution group and 39% in the control group (p less than 0.01). The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infarction, and it improves the overall clinical outcome over the first 3 months. There is no acute therapy proven to be of benefit for ischemic stroke. Ancrod is a potentially effective therapy because of the advantageous consequences of fibrinogen lowering.
                We studied the safety and efficacy of ancrod in patients with acute ischemic stroke administered within 6 hours of stroke onset. In a double-blind, randomized, placebo-controlled trial 64 patients received intravenous ancrod and 68 received placebo for 7 days. Neurological outcome, disability, and brain infarct volume were measured.
                There was no significant difference in overall mean scores on the Scandinavian Stroke Scale. No increase in bleeding occurred in the ancrod-treated patients. The target reduction of plasma fibrinogen levels of less than 100 mg/dL was achieved in only 15 (23%) of 64 ancrod-treated patients. Those patients with ancrod-induced 6-hour fibrinogen levels 130 mg/dL or less had a marginally significantly better neurological outcome on the Scandinavian Stroke Scale, mortality, and Barthel Index than ancrod-treated patients with higher fibrinogen levels.
                Ancrod appears safe and potentially effective when administered to patients within 6 hours of onset of ischemic stroke. We prospectively randomized 47 patients with acute ischemic stroke of the middle cerebral artery of less than 24 hours' duration to either adjusted hypervolemic hemodilution or control treatment and followed them up for 90 days. Rapid hemodilution to a target hematocrit of 30-35% as monitored with bedside determinations was achieved by using infusions of dextran 40, venesections, and infusions of additional crystalloid solution when necessary. There was no difference in the death rate between the two treatment groups. Of these 47 patients, 37 (19 in the hemodilution group and 18 in the control group) could be followed up for the entire study period of 3 months. The relative improvement in neurologic function from day 1 to days 8, 21, and 90 was significantly better in the hemodilution group than in the control group. In accordance, special tests for fine motor control of the paretic arm disclosed better performance in the hemodilution group. The frequency of patients with severe disability was significantly lower in the hemodilution group on days 8 and 21. Plasma viscosity (measured in 11 patients) was not affected by infusions of dextran 40. Vigorous hypervolemic hemodilution in patients with acute ischemic stroke is well tolerated and improves early neurologic outcome with an effect lasting at least 3 months. 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. Hypervolemic hemodilution (HH) with hydroxyethyl starch (HES) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. The objective of this study was to investigate the safety of a 10% solution of HES 130/0.4 versus 0.9% saline solution in acute ischemic stroke by the incidence of adverse events (AEs).
                In a controlled, double-blind, randomized, multicenter, phase II, parallel-group study, 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a randomization ratio of 2:1 in favor of HES therapy.
                There were no significant differences between the groups with regard to the incidence of the specific AEs (cardiovascular events, bleeding complications, allergic reactions) assessed over days 1-30, or mortality over days 1-8. In addition, global tests of efficacy showed a trend towards a better functional outcome with HES therapy; however, the study was not designed to prove efficacy.
                High-dose HH with HES or NaCl was generally safe and well tolerated. Safety profiles were similar for the two treatment groups, and there was a nonsignificant trend towards a better functional outcome with HES therapy.
                Copyright 2002 S. Karger AG, Basel Patients with acute ischemic stroke were randomized less than 24 hours after onset to standard (S) therapy (n = 43) or to hypervolemic hemodilution (HH) with pentastarch (n = 45). The therapeutic goal of hypervolemic hemodilution was to rapidly reduce hematocrit to 33%, to raise cardiac output, and to continue hypervolemic hemodilution for 3 days. A graded neurologic examination was scored by a blinded observer at randomization (baseline), at the end of treatment or after 72 hours, and at a 3-month follow-up; each patient was also rated using Barthel's disability scale at the 3-month follow-up. Group demographics and results of the graded neurologic examination were similar at baseline, except that the HH group contained twice the number of patients with severe strokes and fewer patients randomized within 12 hours compared with the S group. The HH group improved an average of 7 points in neurologic score from baseline to the end of treatment (the S group deteriorated 1 point) and 24 points by the 3-month follow-up (the S group improved 16 points; p = 0.11). The HH group reached an average Barthel disability scale index of 85 while the S group averaged 70 (p = 0.8). Deaths associated with cerebral edema occurred in five patients with severe stroke (four in the HH group vs. one in the S group, p = 0.36). The following subgroups of HH patients showed better overall improvement in neurologic scores: patients entered within 12 hours after stroke onset, patients with a 15% decrease in hematocrit, and patients with a 10% increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) Hemodilution in the acute phase of ischemic stroke is still controversial. Multicenter studies have failed to demonstrate any benefit. The present study focuses attention on analysis of circulation in stroke and on individual restabilization of circulation.
                The Amsterdam Stroke Study is a prospective, single-center, randomized clinical trial (n = 300). Normovolemic hemodilution is accomplished in a customized procedure by administration of 20% albumin plus crystalloids under hemodynamic and rheological monitoring in the acute phase of stroke. All patients receive general intensive care treatment and monitoring with a pulmonary artery catheter. This custom-tailored fluid therapy is guided on the basis of a target pulmonary capillary wedge pressure (12 +/- 3 mm Hg) and hematocrit (0.32 +/- 0.02). The control group receives only customized rehydration by infusion of crystalloids.
                We obtained significant (p less than 0.05) reduction in mortality at 3 months (from 27% to 16%) and an increase in independence at home (from 35% to 48%) after viscosity reduction by means of hemodilution with albumin in the subgroup with a hematocrit less than 0.45 (n = 201) (specific viscosity effect). We also obtained a significant (p less than 0.005) reduction in mortality at 3 months (from 27% to 8%) and an increase in independence (from 35% to 59%) after only rehydration with crystalloids in the subgroup with overt dehydration (hematocrit greater than or equal to 0.45; n = 51) as compared with the normal-hematocrit group without signs of dehydration (hematocrit less than 0.45; n = 103) (specific rehydration effect).
                This study may provide an explanation for the failures in former hemodilution trials and may re-establish proper hemodilution and rehydration as a valuable therapy in the acute phase of stroke, thus reducing mortality and improving independence after 3 months. Approved treatment options for acute ischemic stroke in the United States and Canada are limited at present to intravenous tissue-type plasminogen activator, but bleeding complications, including intracranial hemorrhage, are a recognized complication.
                To evaluate the efficacy and safety of the defibrinogenating agent ancrod in patients with acute ischemic stroke.
                The Stroke Treatment with Ancrod Trial (STAT), a randomized, parallel-group, double-blind, placebo-controlled trial conducted between August 1993 and January 1998.
                Forty-eight centers, primarily community hospitals, in the United States and Canada.
                A total of 500 patients with an acute or progressing ischemic neurological deficit were enrolled and included in the intent-to-treat analysis.
                Patients were randomly assigned to receive ancrod (n=248) or placebo (n =252) as a continuous 72-hour intravenous infusion beginning within 3 hours of stroke onset, followed by infusions lasting approximately 1 hour at 96 and 120 hours. The ancrod regimen was designed to decrease plasma fibrinogen levels to 1.18 to 2.03 micromol/L.
                The primary efficacy end point was functional status, with favorable functional status defined as survival to day 90 with a Barthel Index of 95 or more or at least the prestroke value, compared by treatment group. Primary safety variables included symptomatic intracranial hemorrhage and mortality.
                Favorable functional status was achieved by more patients in the ancrod group (42.2%) than in the placebo group (34.4%; P=.04) by the prespecified covariate-adjusted analysis. Mortality was not different between treatment groups (at 90 days, 25.4% for the ancrod group and 23% for the placebo group; P=.62), and the proportion of severely disabled patients was less in the ancrod group than in the placebo group (11.8% vs 19.8%; P=.01). The favorable functional status observed with ancrod vs placebo was consistent in all subgroups defined for age, stroke severity, sex, prestroke disability, and time to treatment (< or = 3 or > 3 hours after stroke onset). There was a trend toward more symptomatic intracranial hemorrhages in the ancrod group vs placebo (5.2% vs 2.0%; P=.06), as well as a significant increase in asymptomatic intracranial hemorrhages (19.0% vs 10.7%; P=.01).
                In this study, ancrod had a favorable benefit-risk profile for patients with acute ischemic stroke. To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects.
                Single-blinded randomized control trial.
                Outpatient rehabilitation.
                Forty-eight community-dwelling ischaemic stroke patients (38 independently mobile, 9 requiring assistance, 1 non-ambulatory) were randomly assigned to intervention or control groups by concealed allocation.
                The trial consisted of a 10-week schedule with measures taken at weeks 1 and 10. Both groups continued usual care (excluding aerobic exercise); intervention subjects attended 16 cycle ergometry sessions of aerobic-training intensity and two stress-management classes.
                Cardiac risk score (CRS); VO(2) (mL O(2)/kg per minute) and Borg Rate of Perceived Exertion (RPE) assessed during a standardized ergometry test; Hospital Anxiety and Depression Scale (HADS); Frenchay Activity Index; Fasting Lipid Profiles and Resting Blood Pressure.
                Group comparison with independent t-tests showed significantly greater improvement at follow-up by intervention subjects than controls in VO(2) (intervention 10.6 +/-1.6 to 12.0 +/- 2.2, control 11.1 +/-1.8 to 11.1 +/-1.9 t=4.734, P<0.001) and CRS (intervention 13.4 +/-10.1 to 12.4 +/-10.5, control 9.4 +/-6.7 to 15.0 +/-6.1 t=-2.537, P<0.05). RPE rating decreased in intervention subjects (13.4 +/-12.2 to 12.4 +/-2.0) and increased in controls (13.8 +/-1.8 to 14.4 +/-1.6); Mann-Whitney U (U = 173.5, P<0.05). Within-group comparison showed significant decrease in the HADS depression subscale in the intervention group alone (5.1 +/-3.4 to 3.0 +/-2.8) (Wilcoxon signed ranks test Z=-3.278, P<0.001).
                Preliminary findings suggest non-acute ischaemic stroke patients can improve their cardiovascular fitness and reduce their CRS with a cardiac rehabilitation programme. The intervention was associated with improvement in self-reported depression. Pathophysiological considerations and observational studies indicate that elevated body temperature, hypoxia, hypotension, and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome.
                Both units were organized with the same standard care and multidisciplinary approach to nursing and rehabilitation. A blinded observer assessed functional outcome at 3 months with the modified Rankin scale (mRS) and Barthel Index (BI). End points were (1) poor outcome, defined as either mRS > or =4 or BI <60 or the need for institutional care and (2) mortality.
                Fifty-four patients meeting the inclusion criteria were randomized. The groups were well matched for baseline characteristics, stroke subtype, stroke severity, vascular risk factors, and prognostic factors. Poor outcome was seen in 7 (25.9%) patients in the SCMU group and in 13 (48.1%) in the SU group (P=0.16). Mortality was lower in the SCMU group than in the SU group (1 [3.7%] vs 7 [25.9%]; odds ratio, 0.11 [95% CI, 0.02 to 0.96], P=0.05).
                This pilot study suggests that admission of acute stroke patients to an SCMU may reduce mortality and poor outcome. A larger trial is required to confirm these findings.
The overall results of this review are compatible both with modest benefit and moderate harm of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome.