William Stephen Waring

Hyperuricaemia does not impair cardiovascular function in healthy adults

Objective: To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis. Design: UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied. Main outcome measures: The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and l-NG-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques. Results: UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide dependent endothelial function. Conclusion: Unlike other risk factors associated with endothelial dysfunction, acute exposure to high concentrations of UA does not impair cardiovascular function in healthy men. These findings do not support a causal link between hyperuricaemia and atherosclerosis.

Survey of cases of paracetamol overdose in the UK referred to National Poisons Information Service (NPIS) consultants

Background: Paracetamol is the most common means of drug overdose in the UK. Guidance on management is available to junior doctors through TOXBASE, the online resource managed by the UK National Poisons Information Service (NPIS) and in poster form. TOXBASE is supported by NPIS units and further by a UK national rota of clinical toxicologists. A study was undertaken to examine reasons why calls about paracetamol are referred to consultants to better understand issues in managing this common poisoning. Methods: Calls relating to paracetamol overdose referred by a poisons information specialist to the duty NPIS consultant between 1 May 2005 and 30 April 2006 were identified from the database and the number of TOXBASE accesses during the same time period was determined. Enquiries that resulted in consultant referral were classified into six categories. Results: Calls referred to NPIS consultants pertain mainly to patients who present late, staggered overdoses, adverse reactions to N-acetylcysteine, and interpretation of blood results. This information has been used to inform the development of TOXBASE so that comprehensive advice is readily available to end users. Conclusions: The operation of a national consultant rota enables information on difficult or unusual cases of poisoning to be pooled so that treatment guidelines can be developed to optimise treatment throughout the UK.

Patterns of antiepileptic drug overdose differ between men and women: admissions to the Edinburgh Poisons Unit, 2000-2007

BACKGROUND AND AIMS Antiepileptic drugs are increasingly used in patients with psychiatric disorders who are at increased risk of self-harm. This might increase the likelihood that these agents are used as a means of overdose. This study was designed to examine the rate of occurrence of antiepileptic drug overdose between 2000 and 2007. METHODS A retrospective observational study examined patterns of antiepileptic drug overdose in patients admitted to the Edinburgh Poisons Unit, and compared prescription data for the corresponding region. Data were compared using chi-square trend tests. RESULTS There were 18 010 admissions to the Toxicology Unit, and 613 patients ingested at least one antiepileptic drug (3.4%). The most frequently implicated were carbamazepine, sodium valproate, phenytoin and lamotrigine, which corresponded with those most commonly prescribed. Women were more likely to ingest lamotrigine than men (P < 0.0001), and less likely to ingest sodium valproate (P = 0.0234). Patients that ingested antiepileptic drugs were more likely to be admitted to hospital for >1 day (22% vs. 8%, P < 0.0001) and need transfer to a psychiatric facility (14% vs. 7%, P < 0.0001). CONCLUSIONS Patients that ingested antiepileptic drugs required more intensive medical and psychiatric intervention compared to ingestion of other agents. Significant gender differences were noted in the specific antiepileptic drug ingested. Further work is required to establish whether this discrepancy may be explained by gender-based prescribing practices.

How Should Serum Uric Acid Concentrations be Interpreted in Patients with Hypertension

A large number of epidemiological studies have identified an association between high serum uric acid (SUA) concentrations and increased cardiovascular risk. However, the significance of this relationship has been difficult to interpret due to the co-existence of other cardiovascular risk factors. The relationship between SUA concentrations and morbidity appears particularly strong in patients with hypertension, and a number of recent studies have found that this relationship persists after adjusting for potential confounders. This paper reviews the potential mechanisms by which SUA might be causally related to cardiovascular disease in patients with hypertension. We critically appraise the evidence in favour of a causal, coincidental or compensatory relationship, and consider the potential outcomes of lowering SUA in patients with hypertension. The potential consequences of high SUA concentrations are discussed and, based on existing evidence, consideration is given to the potential therapeutic value of strategies to lower SUA as a means of cardiovascular risk reduction in patients with hypertension.

Lamotrigine overdose associated with generalised seizures.

This report describes the occurrence of generalised seizures in a 42-year-old woman who presented to hospital after deliberate lamotrigine overdose. Seizure activity was promptly terminated after intravenous benzodiazepine administration, and the patient subsequently made a complete recovery. Serum lamotrigine concentration was 30 mg/l at 1.3 h post-ingestion, which is substantially higher than the therapeutic reference range; the estimated elimination half life was 18.3 h. This case reminds us that lamotrigine toxicity may provoke generalised seizures in susceptible individuals.

Interpretation of clinical guidelines for poisoned patients: positive and negative effects of standard phrases used in TOXBASE.

IntroductionElectronic information sources are increasingly relied upon for clinical management advice. TOXBASE is a standardised online resource that offers clinical advice on the management of poisoned patients and is the first point of contact between clinicians and the National Poisons Information Service in the United Kingdom. Advice is delivered using a series of standard phrases. The present study examined how healthcare professionals interpret the phrases and studied their impact on clinical decision-making.MethodsA structured prospective written questionnaire was offered to healthcare staff in the Lothian region, and an electronic questionnaire issued to TOXBASE users across the United Kingdom. Participants were asked to respond to a variety of scenarios representing acutely poisoned patients. Clinical management advice was offered via TOXBASE using a variety of standard phrases, and participants were asked to express the likelihood that they would then administer gut decontamination treatment.ResultsThere were 70 respondents to written questionnaires, and 119 respondents to the electronic version. Phrases that included didactic instructions, for example ‘give’, ‘contraindicated’, ‘do’ and ‘perform’ were associated with strongly positive or strongly negative responses. In contrast, advice that consisted of open phrases such as ‘consider’, ‘benefit uncertain’, and ‘few data’ were associated with inconsistent responses.ConclusionDidactic words and phrases are associated with more consistent interpretation and response than open-ended words and phrases. The choice of words and phrases used in electronic systems can have an independent impact on clinical decision-making and require further consideration.

Acute liver impairment after sodium valproate overdose

Liver impairment is a recognised adverse effect of long-term sodium valproate treatment, but there are few reports concerning its occurrence after acute overdose. This report describes a 36-year-old woman who deliberately ingested 32 g of sodium valproate (Epilim). Serum valproate concentration was 4370 &mgr;mol/l (630 mg/l) at 4.3 h post-ingestion (therapeutic reference range: 300–600 &mgr;mol/l), and the elimination half-life was 14.1 h. Liver biochemistry tests were initially normal but gradually became impaired, and highest alanine aminotransferase (761 U/l) occurred 2.3 days after ingestion. Supportive measures alone were sufficient to allow recovery of liver function. This case indicates that sodium valproate overdose may cause acute hepatocellular injury, even in the absence of pre-existing liver disease.

Onset and recovery of hepatic and renal injury after deliberate acute paracetamol overdose.

A 54-year-old woman presented to hospital after deliberate acute ingestion of paracetamol 20 g. Despite early administration of a standardised acetylcysteine regimen, the patient developed acute liver impairment and acute renal impairment. Prolonged acetylcysteine administration and supportive measures allowed restoration of normal liver and renal function. Early presentation to hospital and prolonged duration of follow-up gave an unusual opportunity to examine the onset and duration of paracetamol-induced hepatic and renal impairment.