H.A. de Silva

Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial.

Summary Background High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs to lower their blood pressure. Methods In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140–220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day), started within 48 h of stroke onset, or to no glyceryl trinitrate (control group). A subset of patients who were taking antihypertensive drugs before their stroke were also randomly assigned to continue or stop taking these drugs. The primary outcome was function, assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment. This study is registered, number ISRCTN99414122. Findings Between July 20, 2001, and Oct 14, 2013, we enrolled 4011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls (difference −7·0 [95% CI −8·5 to −5·6] mm Hg/–3·5 [–4·4 to −2·6] mm Hg; both p<0·0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference −9·5 [95% CI −11·8 to −7·2] mm Hg/–5·0 [–6·4 to −3·7] mm Hg; both p<0·0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 (95% CI 0·91–1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90–1·22; p=0·55). Interpretation In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke. Funding UK Medical Research Council.

Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial

BACKGROUND Deliberate self-poisoning with yellow oleander seeds is common in Sri Lanka and is associated with severe cardiac toxicity and a mortality rate of about 10%. Specialised treatment with antidigoxin Fab fragments and temporary cardiac pacing is expensive and not widely available. Multiple-dose activated charcoal binds cardiac glycosides in the gut lumen and promotes their elimination. We aimed to assess the efficacy of multiple-dose activated charcoal in the treatment of patients with yellow-oleander poisoning. METHODS On admission, participants received one dose of activated charcoal and were then randomly assigned either 50 g of activated charcoal every 6 h for 3 days or sterile water as placebo. A standard treatment protocol was used in all patients. We monitored cardiac rhythm and did 12-lead electocardiographs as needed. Death was the primary endpoint, and secondary endpoints were life-threatening cardiac arrhythmias, dose of atropine used, need for cardiac pacing, admission to intensive care, and number of days in hospital. Analysis was by intention to treat. FINDINGS 201 patients received multiple-dose activated charcoal and 200 placebo. There were fewer deaths in the treatment group (five [2.5%] vs 16 [8%]; percentage difference 5.5%; 95% CI 0.6-10.3; p=0.025), and we noted difference in favour of the treatment group for all secondary endpoints, apart from number of days in hospital. The drug was safe and well tolerated. INTERPRETATION Multiple-dose activated charcoal is effective in reducing deaths and life-threatening cardiac arrhythmias after yellow oleander poisoning and should be considered in all patients. Use of activated charcoal could reduce the cost of treatment.

Liv.52 in alcoholic liver disease: a prospective, controlled trial

Liv.52, a hepatoprotective agent of herbal origin, is used empirically for the treatment of alcoholic liver disease in Sri Lanka. We conducted a controlled trial to assess the efficacy of Liv.52 in patients with alcoholic liver disease. Patients with evidence of alcoholic liver disease attending outpatient clinics were included in a prospective, double blind, randomized, placebo controlled trial. During the trial period, 80 patients who fulfilled inclusion criteria were randomly assigned Liv.52 (cases; n = 40) or placebo (controls) the recommended dose of three capsules twice daily for 6 months. All patients underwent clinical examination (for which a clinical score was computed), and laboratory investigations for routine blood chemistry and liver function before commencement of therapy (baseline). Thereafter, clinical assessments were done monthly for 6 months, while laboratory investigations were done after 1 and 6 months of therapy. There was no significant difference in the age composition, alcohol intake and baseline liver function between the two groups. The two-sample t-test was used to analyze data obtained after 1 and 6 months of therapy against baseline values. There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point. There were no reports of adverse effects attributable to the drug. Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease.

Alzheimer's disease with cerebrovascular disease: current status in the Asia–Pacific region

There is growing awareness of the coexistence of Alzheimers disease and cerebrovascular disease (AD+CVD), however, due to lack of well‐defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia.

Neurophysiological findings in patients 1 year after snake bite induced neurotoxicity in Sri Lanka.

Snake bite causes significant morbidity and mortality in Sri Lanka. Snake venoms contain neurotoxins that block neuromuscular junction transmission. Presynaptic neurotoxicity most commonly causes destruction of nerve terminals with recovery by regrowth, whilst postsynaptic neurotoxicity usually involves competition at the acetylcholine receptor. The aim of this study was to investigate whether there were long-term clinical or neurophysiological changes in snake bite survivors 1 year after their envenoming. Detailed neurophysiological tests and clinical examinations were performed on 26 snake bite victims who had presented with neurotoxicity 12 months previously, and their results were compared with controls recruited from the same communities. Significant differences were observed in some nerve conduction parameters in some snake bite victims compared with controls, predominantly in those thought to have elapid bites, including prolongation of sensory, motor and F-wave latencies and reduction of conduction velocities. There was no evidence of any residual deficits in neuromuscular junction transmission. These results suggest a possible demyelinating type polyneuropathy. None of the cases or controls had abnormalities on clinical examination. This is one of the few studies to report possible long-term neurological damage following systemic neurotoxicity after snake bite. The clinical significance of these neurophysiological abnormalities is uncertain and further studies are required to investigate whether the abnormalities persist and to see whether clinical consequences develop.

Multidose activated charcoal for yellow oleander poisoning

Sir—H A de Silva and colleagues (June 7, p 1935) report that multipledose activated charcoal (MDAC) confers a survival advantage over a single dose in patients with yellow oleander poisoning. We commend the researchers for addressing a serious health concern endemic to Sri Lanka. However, certain aspects of their study merit additional comment. The comparison of groups at baseline would benefit from additional specification. Because of the prognostic implications of varying degrees of depressed atrioventricular conduction and enhanced ventricular automaticity in such poisonings, a breakdown of arrhythmias and baseline heart rate would be more informative than simply categorising ventricular fibrillation and seconddegree atrioventricular block together. The early death rate for individuals with yellow oleander poisoning (one of 422 at 6 h, or 0·2%) in this study is remarkably low. Moreover, premonitory arrhythmias were reported in fewer than half of the deaths. The same researchers and others have previously suggested that deaths from yellow oleander poisoning often occur shortly after hospital admission, and are usually preceded by third degree atrioventricular block or ventricular tachyarrhythmias. Many of the deaths in this study are, therefore, unusual, yet they are essential to the study’s interpretation because the absolute number of events in the two groups are sufficiently low as to render the study’s conclusions statistically fragile. Another puzzling aspect of the trial is the sample size calculation, which is not straightforward. De Silva and colleagues estimate a 10% death rate for controls, citing previous work by Eddleston and colleagues, involving patients treated at remote hospitals often without the benefits of pacing or digoxin immune Fab. Why did the group not rely on their own previous research, reporting a death rate of 2·4%. Moreover, de Silva and co-workers anticipated a 75% reduction in the risk of death in patients treated with MDAC. The basis for such optimism is unclear, since MDAC has not been shown to improve clinical outcomes associated with cardiac glycoside toxicity. Two other aspects of the trial deserve comment. Although controversial, routine use of gastric lavage is difficult to justify, especially for late presentations (averaging 10 h in this study) after ingestion of a highly emetogenic substance. Finally, digoxin immune Fab should be standard care for patients with serious cardiac glycoside toxicity. Only seven of at least 21 patients (33%) with an absolute indication for the drug (lifethreatening arrhythmias) received it. Notwithstanding its limited availability and cost, withholding this essential antidote affects this study’s conclusions and generalisability. *David N Juurlink, Marco L A Sivilotti