CPD Bulletin CB V9 N3.indd

Many poisoned patients are treated with no laboratory help other than general clinical chemistry and haematology. However, some emergency toxicological analyses that could influence immediate patient management such as ethanol, iron, lithium, paracetamol (acetaminophen), and salicylates should be provided at hospitals with emergency departments on an urgent (24 h, maximum 2 h turnaround) basis. More complex, less frequently needed clinical toxicological assays are often provided from regional or national centres because of the need to make best use of resources. Regional centres normally offer specialized therapeutic drug monitoring, urine screening for drugs of abuse, and metals/trace elements analysis in addition to specialized toxicology tests such as ethylene glycol and methanol. Clinical interpretation of analytical results is the responsibility of the reporting laboratory, at least in the first instance. Introduction Acute poisoning is a common reason for presentation to hospital. With a few poisons analytical toxicology data can be important in establishing a diagnosis of poisoning and guiding treatment. Examples include iron, lithium, and paracetamol (acetaminophen). The availability of reliable analytical facilities can also assist in other clinical areas, such as assessing illicit drug use and the diagnosis and treatment of poisoning with environmental toxins such as lead, as well as in the management of incidents related to the accidental or deliberate release of chemicals into the environment (chemical incidents) and other aspects of chemical safety. Many acutely poisoned patients are treated successfully without any contribution from the laboratory other than routine clinical laboratory tests. This is true particularly for those cases where there is no doubt about the poison involved and when the results of an analysis would not inf luence therapy. At the other extreme, toxicological analyses can play a useful role if the diagnosis of poisoning or the nature of any poison(s) present is in doubt, the administration of certain antidotes is contemplated, or the use of active elimination therapy is being considered. Close collaboration between the analyst and the originator of the request is important if tests other than routine toxicological analyses are to be useful. However, many requests for emergency toxicological investigations are, in fact, requests for advice on the diagnosis or management of poisoning. TOXBASE (www.toxbase.org) is a database that can be accessed at any time by registered users in the UK and Eire from any computer that has access to the Internet and is the first line source of poisons information for health care professionals in the UK. If analyses are indicated, ideally liaison with the laboratory should commence before any specimens are collected in all but the most straightforward cases, as some analytes, toxic metals for example, require special precautions in specimen collection. On the other hand, residues of samples held in a clinical chemistry laboratory or by other departments, for example in the emergency department (ED) refrigerator, can be invaluable if the possibility of poisoning is raised in retrospect. Tests for poisons which a patient is thought to have taken and for which specific therapy is available will often take priority. However, a defined series of tests (a ‘screen’) is occasionally justified in the absence of clinical or other evidence to indicate the poison(s) involved. If possible this screen should be tailored to the poisons commonly encountered in a particular country in Western Europe and North America, for example, drugs (often accompanied by alcohol) will have been taken by most poisoned patients admitted to hospital. However, pesticides, ethnic medicines, and poisonous animals or plants are major concerns in many other countries. Screening in such circumstances is particularly difficult since such a wide variety of compounds may be encountered and may be guided by clinical and circumstantial evidence as indicated below. Diagnosis of Poisoning In suspected acute poisoning the clinician must ask a number of questions that may aid diagnosis. In the case of an unconscious (comatose) patient, the circumstances in which the patient was found and whether any tablet bottles or other containers, or paraphernalia of substance abuse (‘scene residues’), were present can be important. Unexplained confusion or coma in the absence of head injury is often due to poisoning, particularly in young adults. Blood glucose should be measured to Robert J Flanagan Toxicology Unit, Department of Clinical Biochemistry King s College Hospital NHS Foundation Trust Denmark Hill LONDON SE5 9RS Ian D Watson Department of Clinical Biochemistry Aintree Hospitals Lower Lane Liverpool L9 7AL Correspondence: Dr R J Flanagan Toxicology Unit Department of Clinical Biochemistry King s College Hospital NHS Foundation Trust Denmark Hill London, SE5 9RS Email: robert.f lanagan@kch. nhs.uk CPD Bulletin CB V9 N3.indd 79 4/3/2009 9:58:27 PM 80 CPD Clinical Biochemistry 2009; 9(3): 79–97 © 2009 Rila Publications Ltd. Laboratory Support for the Poisoned Patient exclude hypoglycaemia as the cause of coma. Convulsions may be due to poisoning. If the patient is conscious, information on the presence of poisons in the home or workplace may be available. The patient’s past medical history (including drugs prescribed, mental health) may also be helpful. The physical examination may indicate the poison or class of poison involved (Table 1). Thus, the combination of pin-point pupils, hyper salivation, incontinence, and respiratory depression suggests poisoning with a cholinesterase inhibitor such as an organophosphorus (OP) insecticide. However, the value of this approach is limited if a number of poisons with different actions have been ingested. Moreover, many drugs have similar effects on the body, whilst some clinical features may be the result of secondary effects such as anoxia. Thus, if a patient is admitted with depressed respiration and pin-point pupils this strongly suggests poisoning with an opioid such as heroin, especially if needle marks are discovered. However, if the pupils are dilated then other hypnotic drugs such as glutethimide may be present, or cerebral damage due to hypoxia may have occurred secondary to respiratory depression. Diagnoses other than poisoning must also be considered. Thus, coma may be caused by, for example, a cerebrovascular accident or uncontrolled diabetes as well as poisoning. Characteristic features traditionally associated with specific poisons may not be displayed depending on the dose taken, or the time-course of the episode. The availability of the results of biochemical and haematological tests is obviously important in these circumstances. Poisoning with certain compounds is sometimes misdiagnosed, especially if the patient presents in the later stages of poisoning. Examples include: cardiorespiratory arrest (cyanide), hepatitis (paracetamol), paraesthesia (thallium), progressive pneumonitis (paraquat), and renal failure (ethylene glycol). The analytical diagnosis of paracetamol poisoning is especially important since within the first 24 h the clinical features of potentially fatal poisoning typically are unremarkable. However, antidotal treatment must be instituted promptly if it is to be effective. Serious paracetamol poisoning is rare in children. However, lifethreatening overdoses are common in adults in the UK and in the US. An emergency paracetamol assay should be considered on samples from all overdose or suspected overdose patients aged 10 years or more presenting at hospital.2,9 Especial difficulties may arise in deciding on treatment (i) if the patient has taken more than one paracetamol overdose in the preceding 48 h or so, and (ii) if either an overdose of a sustained release paracetamol preparation has been taken , or paracetamol has been coingested with an opioid such as codeine or another drug that delays gastric emptying because in such cases the standard interpretative nomogram may mislead. Abdominal radiography may aid the diagnosis of poisoning, although a toxicological analysis is needed to establish the nature of the poison ingested if this is in doubt. Examples of radio-opaque poisons include enteric coated aspirin, ferrous sulphate, lead particles, sustained release potassium, and halogenated hydrocarbons such as chloroform and trichloroethylene. Radiography may also help detect and monitor movement of ingested batteries and of packages of illicit drugs which have been wrapped in aluminium foil or condoms. However, toxicological analyses are needed to monitor in vivo release of drug from such packages, or of mercury or other toxic metal ions from batteries, and may help indicate the need for surgical intervention. Poisons ‘Screening’ In clinical poisons screening the main aims are usually to detect poisons that act on the central nervous system (CNS) and to identify situations where active treatment of poisoning may be indicated. It may even be helpful to establish whether a clinical diagnosis of self-poisoning was correct in the face of denial of this possibility either from relatives, or indeed from the patient. The diagnosis of unauthorised drug administration to children or other dependents (Munchausen syndrome by proxy, induced illness) is a particularly specialised area with potentially farreaching implications. Advice should always be sought from the patient’s consultant if this is suspected. Chain of custody procedures and rigorous documentation of the analyses are required. Toxicological analyses may also be important in establishing a diagnosis of Munchausen syndrome (self-induced illness), and in alleviating anxiety in patients who believe they have been poisoned by incidental exposure to, for example, pesticides even though there is no evidence for this belief. All relevant information about a particular patient should be communicated to the analyst and appropriate specimens must be collected and properly labelled. Useful information might include the medical and social history, especially any history of substance abuse, treatment in hospital including drug therapy, and the results of laboratory and/or other investigations. It is also important to be aware of the timing of the sample(s) in relation to the time of the suspected ingestion or exposure as this may inf luence the interpretation of results. A request form must be completed to accompany the specimens to the laboratory with, as a minimum, adequate patient identification information and sufficient clinical information to guide the analyses. A note of a patient’s occupation or hobbies can be valuable as this may indicate access to particular poisons. Cyanide poisoning may result from accidents in electroplating establishments, for example, whilst poisoning with sodium barbital is now encountered most frequently amongst laboratory workers. Information on the drugs prescribed for the patient, and indeed the patient’s relatives, is especially important as this may not only indicate the poison(s) ingested, but also warns that a compound detected may be a drug prescribed for the patient. Even compounds given inadvertently can cause serious toxicity in exceptional circumstances. Benzyl alcohol used as a preservative in intravenous (i.v.) f luids has caused fatal poisoning in young children. Iodine used intra-abdominally after surgery has resulted in death. CPD Bulletin CB V9 N3.indd 80 4/3/2009 9:58:27 PM 81 CPD Clinical Biochemistry 2009; 9(3): 79–97 Laboratory Support for the Poisoned Patient © 2009 Rila Publications Ltd. Clinical Feature Poison(s) 1. Central Nervous System Acute confusion Amphetamines including MDMA, benzylpiperazine derivatives, cocaine, any compound that may cause coma (see below); withdrawal from drug usage Ataxia Bromides, carbamazepine, ethanol, hypnotics/sedatives, phenytoin, thallium Coma Alcohols, benzodiazepines and other hypnotics/sedatives including •hydroxybutyrate (GHB), hypoglycaemic agents, opioids, tranquillizers, tricyclic antidepressants (TCAs), and many other compounds Convulsions Amphetamines including MDMA, antiarrhythmics, anticonvulsants, clozapine and some other antipsychotics, cocaine, hypoglycaemic agents, lithium, monoamine oxidase inhibitors (MAOIs), orphenadrine, selective serotonin re-uptake inhibitors (SSRIs), strychnine, theophylline, TCAs, venlafaxine; withdrawal from alcohol or benzodiazepines 2. Respiratory Tract Respiratory depression Alcohols, hypnotics/sedatives, opioids, tranquillizers, many other compounds Pulmonary oedema Aspirin, chlorophenoxy herbicides, irritant gases, opioids, organic solvents, paraquat Hyperpnoea Aspirin, ethylene glycol, hydroxybenzonitrile herbicides, isoniazid, methanol, pentachlorophenol Respiratory distress Cadmium fume 3. Heart and Circulation Tachycardia Anticholinergics, sympathomimetics Bradycardia Cholinergics, •blockers, digoxin, opioids Hypertension Anticholinergics, sympathomimetics Hypotension Arsenic salts, cadmium fume, ethanol, hypnotics/sedatives, opioids, tranquillizers, many other compounds Arrhythmias •Blockers, chloroquine, cyanide, digoxin, phenothiazines, potassium salts, quinidine, sodium salts, TCAs, theophylline