Enlargement of the third ventricle and hyponatraemia in aneurysmal subarachnoid haemorrhage.

Hyponatraemia following aneurysmal subarachnoid haemorrhage is associated with an increased risk of cerebral infarction. Whether the development of hyponatraemia was related to enlargement of the third ventricle on the admission CT scan was investigated in a consecutive series of 133 patients who were seen within 72 hours of aneurysmal haemorrhage. Hyponatraemia occurred significantly more often in patients with enlargement of the third ventricle (with or without dilatation of the lateral ventricles) than in patients with a normal ventricular system (20/41 versus 24/92, p = 0.016). After ventricular drainage, the sodium levels returned to normal in two patients in whom the size of the third ventricle decreased and not in four patients with persistent enlargement of the third ventricle. The significant relationship between enlargement of the third ventricle and hyponatraemia remained after adjustment for the amount of cisternal blood, but not after adjustment for the amount of intraventricular blood. These results suggest that the size of the third ventricle is an important but not the only factor in the relationship between acute hydrocephalus and hyponatraemia in patients with aneurysmal subarachnoid haemorrhage

The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke

Background Only a few small trials have compared antithrombotic therapy (antiplatelet or anticoagulant agents) versus control in acute ischaemic stroke, and none has been large enough to provide reliable evidence on safety or efficacy. Methods The International Stroke Trial (IST) was a large, randomised, open trial of up to 14 days of antithrombotic therapy started as soon as possible after stroke onset. The aim was to provide reliable evidence on the safety and efficacy of aspirin and of subcutaneous heparin. Half the patients were allocated unfractionated heparin (5000 or 12 500 IU bd [twice daily]) and half were allocated “avoid heparin”; and, in a factorial design, half were allocated aspirin 300 mg daily and half “avoid aspirin”. The primary outcomes were death within 14 days and death or dependency at 6 months. 19 435 patients with suspected acute ischaemic stroke entering 467 hospitals in 36 countries were randomised within 48 hours of symptom onset. Results Among heparin-allocated patients, there were non-significantly fewer deaths within 14 days (876 [9·0%] heparin vs 905 [9·3%] no heparin), corresponding to 3 (SD 4) fewer deaths per 1000 patients. At 6 months the percentage dead or dependent was identical in both groups (62·9%). Patients allocated to heparin had significantly fewer recurrent ischaemic strokes within 14 days (2·9% vs 3·8%) but this was offset by a similar-sized increase in haemorrhagic strokes (1·2% vs 0·4%), so the difference in death or non-fatal recurrent stroke (11·7% vs 12·0%) was not significant. Heparin was associated with a significant excess of 9 (SD 1) transfused or fatal extracranial bleeds per 1000. Compared with 5000 IU bd heparin, 12 500 IU bd heparin was associated with significantly more transfused or fatal extracranial bleeds, more haemorrhagic strokes, and more deaths or non-fatal strokes within 14 days (12·6% vs 10·8%). Among aspirin-allocated patients there were non-significantly fewer deaths within 14 days (872 [9·0%] vs 909 [9·4%]), corresponding to 4 (SD 4) fewer deaths per 1000 patients. At 6 months there was a non-significant trend towards a smaller percentage of the aspirin group being dead or dependent (62·2% vs 63·5%, 2p=0·07), a difference of 13 (SD 7) per 1000; after adjustment for baseline prognosis the benefit from aspirin was significant (14 [SD 6] per 1000, 2p=0·03). Aspirin-allocated patients had significantly fewer recurrent ischaemic strokes within 14 days (2·8% vs 3·9%) with no significant excess of haemorrhagic strokes (0·9% vs 0·8%), so the reduction in death or non-fatal recurrent stroke with aspirin (11·3% vs 12·4%) was significant. Aspirin was associated with a significant excess of 5 (SD 1) transfused or fatal extracranial bleeds per 1000; in the absence of heparin the excess was 2 (SD 1) and was not significant. There was no interaction between aspirin and heparin in the main outcomes. Interpretation Neither heparin regimen offered any clinical advantage at 6 months. The results suggest that if heparin is given in routine clinical practice, the dose should not exceed 5000 IU subcutaneously twice daily. For aspirin, the IST suggests a small but worthwhile improvement at 6 months. Taking the IST together with the comparably large Chinese Acute Stroke Trial, aspirin produces a small but real reduction of about 10 deaths or recurrent strokes per 1000 during the first few weeks. Both trials suggest that aspirin should be started as soon as possible after the onset of ischaemic stroke; previous trials have already shown that continuation of low-dose aspirin gives protection in the longer term

How good are volunteers at searching for published randomized controlled trials? The OSTR Collaborative Group. Ottawa Stroke Trials Registry.

The Ottawa Stroke Trials Registry (OSTR) collects information on all randomized controlled trials (RCTs), in all languages, in which the primary focus is stroke. Published trials are added to the registry database once they have been identified by volunteers hand searching journals. We undertook this study to assess volunteer sensitivity, specificity, positive and negative predictive values, accuracy and reliability in identifying RCTs. Three volunteers participated in this study. The complete contents of five years of one journal were searched (n = 240) as were ten research reports from five journals. Volunteer sensitivity, specificity, positive and negative predictive values, and accuracy was 89.5%, 100%, 100%, 99.1%, and 99% respectively. Inter volunteer reliability was 0.87. Searching the published literature to identify RCTs is an enormous task. These results indicate that volunteers, with minimal training, can effectively contribute to this endeavour