1. POISON CONTROL & THE ROLE OF LABORATORY IN CLINICAL & FORENSIC TOXICOLOGY IN THE UK Prof. Robin Braithwaite* Regional Laboratory for Toxicology, City Hospital, Birmingham www.toxlab.co.uk *robin.braithwaite@kcl.ac.uk

2. POISONS CONTROL IN THE UK - 1 Approximately 100,000 admissions to hospital for poisoning each year Mortality in hospital very low (<0.1%) Most poison related deaths occur out of hospital Most deaths due to Pharmaceuticals, illicit drugs and alcohol Most accidental exposures to drugs and poisons occur in children

3. POISONS CONTROL IN THE UK - 2 Health Protection Agency (www.hpa.org.uk)www.hpa.org.uk Microbiological Hazards Division Nuclear Hazards Division Chemical Hazards and Poisons Division (CHaPD) National Poisons Information Service (NPIS)

4. POISONS CONTROL IN THE UK - 3 Chemical Hazards and Poisons Division (CHaPD) Provision of expert advice and support for chemical incidents across England and Wales Provides advice to NHS and other agencies about known health effects of chemicals poisons and other environmental hazards 24/7 service with close link to NPIS Head office in Oxford with 4 specialist centres in Birmingham, Cardiff, London and Newcastle

5. POISONS CONTROL IN THE UK - 4 National Poisons Information Service (NPIS) First established in 1963 Provides a clinical toxicology service for health care professionals (no public access) 24/7 telephone enquiry service with single national telephone number 4 centres in the UK Cardiff, Edinburgh, Newcastle and Birmingham

6. National Poisons Information Service (NPIS) Commissioned by the Health Protection Agency (HPA) through its Chemical Hazards and Poisons Division (CHaPD) * London ceased to be a center in 2005

7. POISONS CONTROL IN THE UK - 5 Each centre is located within a University hospital where there is experience in the diagnosis and management of poisoning Telephone system directs caller to relevant local centre, or redirects call if busy Single National Consultant Clinical Toxicology rota for out of hours referrals

8. POISONS CONTROL IN THE UK - 6 Toxbase – the primary clinical toxicology database of the NPIS Primary web based source of poisons information (www.toxbase.org) All NPIS units contribute and authenticate the database (~ 12,000 substances or products)

9. POISONS CONTROL IN THE UK - 7 Intended for use by all medical practitioners and other health care professionals in the NHS Toxbase is free to all NHS registered users Approximately 0.5 million poison – related enquiries to NPIS in 2005/6 – includes telephone and Toxbase log on

10. POISONS CONTROL IN THE UK - 8 NPIS uses technical information officers with back up from physicians experienced in poisons treatment NPIS also provides information to other government agencies - Medicines and Health Care Regulatory Agency (MRHA) - Department for Environmental Food and Research Affairs (DEFRA) - Pesticide Safety Directorate (PSD)

11. NPIS Telephone enquiries ( ) and TOXBASE ( ) sessions from 2000 to 2005/06

12. How poisons enquiries are answered in the UK Enquiries from professional colleagues (generally acute trust NHS staff/DH) NHS Direct/NHS 24 TOXBASE (www.toxbase.org) NPIS information scientists NPIS clinical consultants HPA CHaPH HQ Enquiries from the public If unresolved online then via the NPIS national telephone number Clinical support required if highly complex If population, political or media implications

13. POISONS CONTROL IN THE UK – 9 Types of Products involved in Telephone enquiries to NPIS in 2005/6 Pharmaceuticals 66% Industrial Chemicals 13% Household Products 11% Plants/Fungi 3% Agro Chemicals 1% Others 6% ____ TOTAL100%

14. POISONS CONTROL AND THE ROLE OF THE TOXICOLOGY LABORATORY – CLINICAL AND FORENSIC ASPECTS - 1 Clinical management of majority of acutely poisoned patients in UK hospitals require access to routine chemistry and haematology tests Some acutely poisoned patients require urgent access to simple toxicology tests e.g. paracetamol, salicylate, alcohol, drugs of abuse screening

15. POISONS CONTROL AND THE ROLE OF THE TOXICOLOGY LABORATORY – CLINICAL AND FORENSIC ASPECTS - 2 A proportion of severely poisoned patients and medico-legal cases requires access to more complex toxicology tests which are best provided by a specialist (Regional) Toxicology Laboratory. Investigation of unexpected or sudden deaths due to suspected poisoning carried out by both clinical or forensic toxicology laboratories

16. CITY HOSPITAL BIRMINGHAM Part of National Health Service (NHS) Inner City Teaching Hospital Links with University of Birmingham and Schools of Medicine, Biosciences and Occupational and Environmental Medicine Most active Emergency Department (A&E) in Region Location of Poisons Treatment Ward, Information Service (NPIS) and Regional Toxicology Laboratory (RTL)

17. THE REGIONAL LABORATORY FOR TOXICOLOGY -1 First established in 1972, City Hospital, Birmingham Part of the Division of Pathology within National Health Service (NHS) Hospital Provision of a Regional and National specialist clinical and Forensic Toxicology Service

18. THE REGIONAL LABORATORY FOR TOXICOLOGY - 2 Purpose built secure Laboratory (600 m 2 ) Access to a wide range of state of the art analytical techniques (e.g. GC-and LC-MS) Current staffing 26 Scientists and Support staff (excluding students/ trainees) Budget $2.5 million (2006/7)

19. ORGANISATION OF THE LABORATORY SERVICE - 1 Part of National Health Service (NHS) Close links with other pathology services on site (Biochemistry, Haematology & Cellular Pathology) Close links with Poisons Information Service (NPIS) and poisons treatment facilities on same site

20. ORGANISATION OF THE LABORATORY SERVICE - 2 Links to Health Protection Agency (HPA and CHaPD) 24/7 Clinical toxicology service Service provided to local health region (population approx. 8-10 million), also rest of UK ~55 million Strong research interests in field of analytical, clinical and forensic toxicology

21. LABORATORY SERVICES PROVIDED - 1 Therapeutic Drug Monitoring (TDM) Investigation of suspected poisoning – clinical diagnosis and management Investigation of suspected drug abuse – clinical, occupational & forensic cases

22. LABORATORY SERVICES PROVIDED - 2 Measurement of essential and non-essential Trace Elements – clinical, occupational and forensic cases Investigation of occupational and environmental exposure to chemical poisons Investigation of sudden or unexpected deaths on behalf of HM Coroner

23. TECHNIQUES AVAILABLE IN THE LABORATORY - 1 Simple colour tests UV and visible spectrophotometry Immunoassay Liquid chromatography (LC) and LC-Mass Spectrometry (LC-MS)

24. TECHNIQUES AVAILABLE IN THE LABORATORY - 2 Gas Chromatography (GC) and GC-Mass Spectrometry (GC-MS) Atomic Absorption Spectrometry (AAS) Inductively Coupled Plasma (ICP) - ICP-Mass Spectrometry - ICP-Atomic Emission Spectrometry

25. INVESTIGATION OF SUDDEN OR UNEXPECTED DEATHS (H.M CORONER) Traffic accidents Hanging, drowning, trauma Suspected alcohol, drug or substance misuse Suspected suicide Deaths in custody, hospital or care homes etc Cot deaths (SIDS)

26. REASON FOR PROVIDING A FORENSIC TOXICOLOGY SERVICE - 1 A growing number of clinical cases have a medico-legal dimension – e.g. paediatric poisoning, “spiked” drinks The majority of deaths involve former NHS patients Provides useful information on trends in drug related death e.g. relative toxicity of antidepressants and opioids

27. REASONS FOR PROVIDING A FORENSIC TOXICOLOGY SERVICE - 2 Trends in deaths related to alcohol and drug misuse e.g. heroin, cocaine and ecstasy Investigation of cot deaths (under 2 years of age) and perinatal mortality Better understanding of the mechanism of drug toxicity and causes of death in the population

28. COMMON DRUGS/POISONS AS A CAUSE OF DEATH - 1 Heroin/morphine Methadone Alcohol (and alcoholic keto-acidosis) Anti-depressants (dothiepin, amitriptyline, citalopram, venlafaxine) Dextropropoxyphene + paracetamol – far less recently

29. COMMON DRUGS/POISONS AS A CAUSE OF DEATH - 2 Carbon monoxide Cocaine Opiates (codeine, dihydrocodeine) + opioids (tramadol) Volatile substances (e.g. lighter fuel – butane) *Although death solely due to benzodiazepines is rare, they are one of the most common detected drug classes found in fatalities.

30. UNUSUAL DRUGS/POISONS AS A CAUSE OF DEATH - 3 Veterinary products (e.g. etorphine) Plant poisons (e.g. aconite, yew) Cyanide Strychnine Herbicides (e.g. paraquat) Chemicals/solvents (e.g. dichloromethane and ethylene glycol) Pesticides/rodenticides (e.g. aluminium phosphide and warfarin)

31. THERE ARE MANY ADVANTAGES IN BEING ABLE TO STUDY THE WHOLE DOSE – RESPONSE CURVE Therapeutic Dose Abuse/Excess Overdosage Death