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Advances, challenges, and controversies in poisoning
  1. A L Jones,
  2. P I Dargan
  1. National Poisons Information Service, Guy's and St Thomas' NHS Trust, Avonley Road, London, SE14 5ER, UK
  1. Correspondence to:
 Dr A L Jones;
 alison.jones{at}gstt.sthames.nhs.uk

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The treatment of self poisoned patients in the emergency department

Patients presenting with self poisoning constitute a significant and increasing workload in emergency medicine departments and rates in the UK (up to 347 per 100 000 per year) are among the highest in Europe.1,2 The severity of poisoning has decreased over the past decade with the introduction of safer drugs such as serotonin reuptake inhibitors over tricyclic antidepressants, but there are still more than 2000 deaths per year in the UK from self poisoning.3

CHALLENGES IN CLINICAL TOXICOLOGY

Recognition of severe poisoning

Fewer than 1% of people who present with self poisoning develop severe clinical effects.4 One of the main challenges in managing poisoned patients is to identify this group as early as possible so that appropriate supportive, and if necessary, specific management steps can be instituted to prevent serious complications. Equally importantly, the vast majority of patients (particularly children) require only supportive care and do not need to be exposed to unnecessary procedures. Meticulous supportive care is the most important aspect of the management of seriously poisoned patients.5 As a general rule complete elimination of a drug takes five half lives and seriously poisoned patients, who are often fit young adults, need to be kept alive to allow elimination of the drug. If organ failure ensues, extracorporeal removal of toxins may become necessary.

Drugs of misuse

Presentation to hospital with clinical effects from an ever growing number drugs of misuse is becoming more common, particularly in inner city areas.1,6 In addition to newer drugs such as GHB (gammahydroxybutyrate) combinations of drugs are often taken, for example, Sextasy (Ecstasy and Viagra).6 This issue of EMJ contains a reminder of the potential for methaemoglobinaemia from nitrite containing drugs of misuse such as “poppers”.7 Cocaine use is increasing as the price of cocaine has fallen in several inner city areas. Cocaine misuse can result in cardiovascular complications such as myocardial ischaemia/infarction, arrhythmias, and myocardial dysfunction.8 It is important that cocaine use is considered in all patients, especially young adults, presenting with acute coronary syndromes because this will change the management strategy. First line treatment for cocaine related myocardial ischaemia/infarction includes benzodiazepines and nitrates together with aspirin and oxygen; β blockers are contraindicated and thrombolysis should not be used routinely because the mechanism is coronary artery vasospasm rather than thrombosis.5,8 Alcohol remains the most widely used “drug of misuse” throughout Europe and the impact of a blood ethanol concentration of greater than 0.50 g/l on road accidents is shown by Fabbri et al.9

Worldwide: issue of chemical preparedness

The events of 11 September in the USA have alerted us to be more prepared for the unthinkable, including preparing for receiving victims exposed to biological or nerve warfare agents.10 Sarin exposure of the public in a subway happened in peacetime in Tokyo.11 Lessons learned from that tragedy included the need to have adequate decontamination facilities available, to avoid contamination of medical or nursing staff, and to have optimum procedures for admission and appropriate antidotal therapy for such patients.10,11 Further information is available from the UK Public Health Laboratory Service web site (http://www.phls.org.uk/facts/deliberate_releases.htm) and US Centers for Disease Control and Prevention website (http://www.bt.cdc.gov/Agent/AgentlistChem.asp).

Prevention of paracetamol poisoning

Paracetamol is the commonest drug taken in overdose in the UK, accounting for 50% of all self poisoning episodes and 100–200 deaths per year.1,3 In September 1998 legislation was introduced in the UK limiting pack sizes available for sale in an attempt to decrease the number and severity of paracetamol overdoses. A number of studies have attempted to assess the impact of this legislation with conflicting findings and it is probably too early to tell whether it has had any clinically significant impact yet.12 A number of other measures have been considered to reduce paracetamol overdoses. However, few of these are practical and some, such as the addition of methionine have potential safety issues, which make them unsuitable.13 Prevention of paracetamol poisoning is a significant issue, but it is not, however, likely to be something that individual accident and emergency departments are going to be able to have a significant impact on.

Optimising early care of poisoned patients

The mainstay of gut decontamination in poisoning is the administration of activated charcoal within one hour of ingestion of a toxin.14 However, recent studies have shown that as few as 15% of patients are seen in hospital in the first hour after self poisoning, and further delays can occur during triage, waiting to see a doctor, and because of transport delays in more remote, rural areas.15,16 It is important that those who have ingested a potentially serious overdose and have presented within the one hour interval are rapidly identified and “fast tracked” for activated charcoal therapy. Prehospital administration of charcoal by ambulance staff would allow earlier administration and may be one aspect of the future of the treatment of poisoned patients, though the potential risk of inducing vomiting and aspiration must be evaluated first.

To do simple things well. For example, weighing patients

The weight of patients is important in clinical toxicology because the toxic dose of many compounds is expressed in mg/kg body weight and the dose of some drugs used to treat poisoned patients (for example, N-acetylcysteine) is weight dependent. However, patients are often not weighed and doctors and nurses frequently estimate the weight of patients; these estimates of bodyweight are often inaccurate.17 A simple set of weighing scales should be standard equipment in all clinical areas treating poisoned patients and all patients presenting after taking an overdose should have a formal body weight measurement as a standard part of their management. All patients given medications based on bodyweight should also be formally weighed.

RECENT ADVANCES IN CLINICAL TOXICOLOGY

There have been a number of specific advances in the understanding of the mechanisms of poisoning and management of patients with poisoning over the past five years.

Improved understanding of mechanisms in poisoning, for example, late paracetamol poisoning

The mechanism of toxicity in early paracetamol poisoning is well established and N-acetylcysteine (NAC) protects against hepatotoxicity in these patients.18 Until recently, comparatively little was known about the mechanisms of toxicity in late paracetamol poisoning (more than 15 hours after ingestion). Recent studies have shown that factors such as production of cytokines and chemokines, nuclear transcription factors, free radicals, and caspases are involved in hepatotoxicity in late paracetamol poisoning.18 NAC is less effective in late paracetamol poisoning,18 and knowledge of the mechanisms of liver injury, at the haemodynamic and subcellular level, is important in the development of new treatments for paracetamol overdose, particularly for patients who present late. However, until these new treatments are available NAC remains the treatment of choice in patients presenting with late paracetamol poisoning.18

New antidotes, for example, 4-methylpyrazole in ethylene glycol and methanol poisoning

Ethylene glycol and methanol are metabolised to toxic metabolites by alcohol dehydrogenase and significant clinical effects including metabolic acidosis, CNS depression, and acute renal failure can occur in overdose. The mainstay of management is inhibition of alcohol dehydrogenase and thus reduction of toxic metabolite formation.19 Until recently the only agent available was ethanol, but treatment with ethanol causes CNS depression and hypoglycaemia and requires close laboratory monitoring of blood ethanol concentrations.19 A new alcohol dehydrogenase inhibitor is now available: 4-methylpyrazole (4-MP, fomepizole). 4-MP is well tolerated and blood concentrations are not required to monitor treatment; the main drawback of 4-MP is its cost of £1000–£2000 per treatment course. There have been three recently published multicentre prospective case series describing the successful use of 4-MP in adults with ethylene glycol and methanol poisoning.20–22 There have been no trials comparing ethanol and 4-MP and until these data are available, ethanol is generally the antidote of choice in ethylene glycol and methanol poisoning. However, there are certain circumstances where we would advocate the use of 4-MP. For example, in asymptomatic patients (particularly children) who present early after a witnessed large ingestion with biochemical evidence of poisoning (a raised osmolal gap, or if available a raised methanol/ethylene glycol concentration) and potentially in patients who have coingested CNS depressants, in whom additional CNS depression would be difficult to manage.

Novel treatment methods, for example, Haemofiltration, Molecular Adsorbent Recycling System (MARS)

Extracorporeal drug removal techniques such as haemoperfusion and haemodialysis are indicated in a minority of severe cases of poisoning.23 However, each technique has problems such as limited availability, poor tolerance in haemodynamically compromised patients, and poor removal of protein bound drugs.23

Haemofiltration is available in most intensive care units and is better tolerated in hypotensive patients but there are limited data on the use of haemofiltration in poisoned patients. Recent, in vitro studies have shown significant removal of salicylate by haemofiltration24 but further work is required before it can be recommended in the management of poisoned patients

MARS is an extracorporeal device that combines conventional haemodialysis with a secondary system containing an albumin impregnated dialysis membrane (with an albumin containing dialysate) in addition to anion-exchange and charcoal columns.25 It has been used in the management of acute liver failure25 and because it is able to remove protein bound substances could theoretically be used in the management of severe poisoning with highly protein bound drugs such as salicylates in the future, but for now it remains a research tool in the few centres in which it is available.

Better training: greater availability of information and courses

In the UK, several databases have been developed to meet the increasing needs of doctors and nurses for easy access to information on poisoning. TOXBASE (http://www.spib.axl.co.uk/), a computerised database run by the National Poisons Information Service, has been available over the internet to health professionals in the UK since 1999, having replaced the former Viewdata database of the same name that was developed in the 1970s. ISABEL (http://www.isabel.org.uk/) is a new medical information system, also delivered via the internet, that provides support in diagnosis and management of children and includes toxicology as one of its components. As well as an aid to the management of individual patients, both of these web sites can be used as an educational tool.

Poisoning is an important part of the workload in emergency medicine, general medicine, and intensive care. NPIS centres offer a wide range of training courses for doctors and nurses in all of these disciplines; details of these courses are available on TOXBASE (http://www.spib.axl.co.uk/).

THE FUTURE: DEVELOPMENT OF AN EVIDENCE BASE FOR THE MANAGEMENT OF POISONED PATIENTS

Guidelines for the management of poisoned patients should be evidence based.26 However, the level of evidence in toxicology is often poor and based on case reports/series or observational studies that have been performed on highly selected patients and so are subject to significant bias. There has been little hypothesis testing research performed in toxicology. Many management strategies have been developed as an extrapolation from the pharmacological effects of drugs or from animal data or generalisations from drugs within the same class, which is far from satisfactory.

There are a number of questions that need to be answered, including whether various gut decontamination methods have an impact on the outcome of patients with severe poisoning. In addition, there are a number of specific issues to be addressed such as the indications for hyperbaric oxygen in carbon monoxide poisoning, the optimum regimen and mechanism of action of sodium bicarbonate in tricyclic antidepressant poisoning, management of late paracetamol poisoning, and length of treatment with deferoxamine in iron poisoning to name but a few.

Clinicians in poisons centres need to work with those working in emergency medicine to develop modern, evidence based practice that recognises the sensitivity of this group of patients and their special needs. Large, multicentre studies across many hospitals in different regions are needed to study outcomes and treatment strategies and to collect data to optimise the management of poisoned patients. Let us hear from you and we can get started!

The treatment of self poisoned patients in the emergency department

REFERENCES

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