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MAIN TOPIC

Diagnosis of acute

As all chemicals can act as in the right quantity, effective lines of communication between the attending clinician or health worker, the laboratory and the toxicologist are essential.

Virtually all known chemicals can rating (LD50 < 400 mg/kg), 2 is edible’ substances ingested acci-

cause injury or death, depending intermediate (LD50 of 400 - 4 000 dentally is usually small. The aver-

on the dose of the substance. The mg/kg), and 1 is low (LD50 of age quantity of liquids swallowed lethal dose may vary widely. For 4 000 - 40 000 mg/kg). Safety, the accidentally by a child under the example, 4 000 mg/kg of table salt opposite of risk, is the probability age of 5 years is 5 ml, and that by will be lethal to 50% of a popula- that harm will not occur under an adult 15 ml. In contrast, the tion of experimental animals specified conditions.2,3 quantity swallowed intentionally

(expressed as the LD50), while the (by adults) is usually considerably

LD50 of trioxide is 1 - 2 larger, and should be taken into mg/kg, and that of botulinum consideration when potential haz- 0.00001 mg/kg. A number of fac- Virtually all known ard or risk is assessed. tors may contribute to : chemicals can cause Table I lists the most frequently physico-chemical characteristics injury or death, ingested household agents consid- such as the pKa, lipid solubility, ered ‘usually non-toxic’. This table the route of entry (e.g. orally or depending on the is intended as a guide only, and percutaneously), the nature of the dose of the sub- should be used in conjunction with exposure (e.g. acute or chronic) the information given above.4,5 and the susceptibility of the victim. stance. This refers to factors such as the For clinical purposes, poisons state of fetal development, child- (including therapeutic drugs) may ‘Non-toxic ’ refers to the hood, advancing age and underly- be divided into two broad cate- consumption of a non-edible agent ing pathology. In addition, the gories: or product usually not associated vehicle in which the agent is dis- with harmful effects. The practical solved or suspended, and other • Poisons (and their metabo- value of knowing that a product is formulation factors, may markedly lites) which directly cause ‘usually non-toxic’ prevents: influence toxicity. There is no irreversible or slowly reversible structural or entirely ‘safe’ chemical since all • an inappropriate response that functional tissue damage in have the potential to cause death causes panic and injury under specific circum- one or more organ systems. • over-treatment of the patient stances. It should also be empha- These are also considered com- • unnecessary visits to the doctor sised that some adverse reactions pounds with a high inherent or hospital emergency facility.4 to chemicals, such as allergic and toxicity (Table II). Arsenic and idiosyncratic reactions, are not For an agent to be considered the organophosphates are good dose-related.1,2 ‘usually non-toxic’, it should meet examples of poisons which may the following criteria: cause irreversible damage, long- In practice the critical factor is not lasting (slowly reversible) organ • positive identification of the whether or not a substance is poi- dysfunction, or lead to compli- product, its ingredients, and its sonous, but whether someone is at cations which may require concentration risk from exposure to it. Risk is extended periods of supportive the probability that a substance • positive assurance that it was therapy. Significant symptoms 1,4 will cause harm under specified the only product ingested. and signs of a substantial num- conditions. This is reflected in a Because of unpleasant or disagree- ber of poisons in this group may hazard rating on a scale of 1 - 3, able tastes, the quantity of ‘non- appear late (1 - 3 days post where 3 indicates a high hazard

438 CME August 2003 Vol.21 No.8 MAIN TOPIC Sweetening agents (saccharin, Silica 4 etroleum jelly (Vaseline) fluoride) Phenolphthalein laxatives (Brooklax) Play-DohRouge (without ) Vitamins Magic markersMineral oil (unless aspirated) Silly putty (99% silicones) Golf ball (core may cause mechanicalLaxatives rings (containing Teething Eye make-up Eye with permission 4 Most frequently ingested household agents considered ‘usually non-toxic’ Table I. Table Bleach (< 3.5% hypochlorite)Body conditioners Bubble-bath soaps additives Fish bowl Calamine lotionCalcium sulphate(plaster of Paris)Candles (beeswax or paraffin) Glues and pastes (for wood or paper) pistol, potas- Caps (toy sium chlorate)Chalk (calcium carbonate) Newspaper injury) Greases Hair products (dyes, sprays, tonics)Charcoal Motor oilCigarettes or cigars (nicotine) Homeopathic (excl. herbalClay (modelling)Colognes (medicinal 3%) P 3%Contraceptives Peroxide Ice bricks (water and edible thickener)Corticosteroids medicines) Cosmetics Hand lotions and creams ‘non-toxic’)Crayons (marked picture coating fluid Polaroid PlasticineDehumidifying packets Incense(silica or charcoal) Lanolin (not inhaled) Talc Ink (black and blue — non-permanent) cyclamate) Inedible markers Iron filings (chemical sets) food Pet (lead, graphite, colouring) Pencil Lipstick (indoor or latex) Paint water Toilet Putty (less than 60 g) Thermometers (elemental mer- Perfumes Vaseline if sterile) water, ink marking pens (koki) Porous-tip (ferricyanide) Zinc oxide Rubber cement (with or without Toothpaste colours Water cury or ) Zirconium oxide AbrasivesAdhesivesAntacidsAntibiotics (most) Detergents (phosphate type, anionic) Deodorants Deodorisers (spray and refrigerator) (without local anaesthetic) Lozenges Shampoos (non-pediculicides) Lubricating oils (lipid pneumonia tain aniline dyes) Lubricant when aspirated) from Ellenhorn and Barceloux, Adapted Shoe polish (most do not con- Sesame oil Baby products, cosmetics Baby Ballpoint pen inksBathtub floating toysBath oil (castor and perfume) added) Fertiliser (if no insecticides or herbicides softeners Fabric Matches liquid, facial) (eye, Make-up Suntan preparations Soap and soap products

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exposure). At this stage symp- which are rapidly and com- maintenance of normal respira- toms may not be expected, or pletely reversible. Although tory, circulatory and renal func- the incident may have been par- many agents in this category tion with monitoring of tially forgotten. This can mean have the potential to cause gases, acid/base balance, serum that the patient and/or doctor serious organ dysfunction or electrolyte and glucose levels, may not immediately (if at all) even death, appropriate support- etc. Benzodiazepines and opi- associate the cause of the symp- ive care during the acute phase ates taken in overdose, and even toms with exposure, leading to will ensure complete recovery in strychnine, are examples of poi- delayed optimal therapeutic most instances. Fortunately, sons with a relatively low inher- intervention. Examples include most potential poisons dealt ent toxicity. paracetamol and phal- with in the clinical setting fall When dealing with a suspected loides poisoning. into this category. Consequently, case of poisoning, one of the main • Poisons which do not cause most poisoned patients require priorities should be to attempt to tissue damage directly or treatment of symptoms and identify poisons with a high inher- which cause toxic effects appropriate supportive care ent toxicity as soon as possible only. ‘Supportive care’ is the

Table II. Examples of drugs and poisons with a high inherent toxicity*

Drug or Specific treatment† Reason for early antidotal/ active removal therapy

Carbon monoxide‡ Oxygen Tissue damage () Cyanide‡, § Oxygen. In serious poisoning: Extremely toxic, often with a morbid course and /sodium thiosulphate death or Kelocyanor (Restan) Digoxin Digoxin-specific antibodies With massive overdose poisoned membranes can no longer maintain electrolyte gradients; this leads to extremely high potassium levels Ethylene glycol‡, ¶ , haemodialysis Tissue damage (nervous system, kidney) Isoniazid‡ Pyridoxine, haemodialysis Tissue damage (nervous system) Lithium carbonate** Haemodialysis Tissue damage (nervous system, kidney) and Arsenic** , Tissue damage (nervous system, liver, kidney) Tissue damage (gastrointestinal, liver, CVS) Iron‡, ** Deferoxamine Tissue damage (nervous system) Lead** Dimercaprol, calcium disodium Tissue damage (nervous system, kidney) edetate Mercury** Dimercaprol, penicillamine ‡, ¶ Ethanol, haemodialysis Tissue damage (nervous system, blindness) Methyl bromide Dimercaprol, N- Tissue damage (nervous system, CVS, kidneys) — cyclopeptides as in Silibinin Tissue damage (liver, kidney, heart, pancreas) ** Organophosphates** chloride, To prevent extended periods of intensive care Paracetamol N-acetylcysteine Tissue damage (liver, kidney) Paraquat (diquat)**, †† Immediate, aggressive Multisystem failure (kidney, liver, nervous decontamination procedures plus system, heart, lungs) activated charcoal or a watery slurry of clay Salicylates‡ Haemodialysis Tissue damage (nervous system) Theophylline‡, ** Haemoperfusion Tissue damage (nervous system)

*Examples are those in which or special toxin removal procedures may prevent permanent tissue damage or serious complications (paraquat and carbon monoxide excluded). †The degree of poisoning, together with drug or poison levels, usually determines the specific treatment regimen. ‡Causes marked metabolic acidosis. §Included because of its potential to cause death within minutes. Most patients who recover have no permanent sequelae. ¶Causes alterations in the osmolar gap. **Gastrointestinal disturbances prominent. ††Survival only possible if oral activated charcoal or a watery slurry of clay combined with a cathartic (preferably magnesium sulphate or sorbitol), is given as soon as possible to prevent absorption. Once absorbed it is doubtful whether an or special toxin removal procedure will prevent tissue damage.

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(Table II). This allows timely anti- damaging potential often present may apply to more than one poiso- dotal or special decontamination with severe and persistent gastroin- nous agent and may even be mim- procedures so that severe tissue testinal symptoms and signs icked by a disease state unrelated damage and complications can be (Table II). Hypotension, cardiac to poisoning. Although toxidromes avoided. Agents with a low inher- dysrhythmias, , acid-base are useful when dealing with an ent toxicity need to be identified and electrolyte disturbances (aci- unidentified toxic agent, they may early where the use of a specific dosis and hyperkalaemia), and be misleading and their use fraught antidote may avoid relatively risky signs of liver and renal impairment with pitfalls for the unwary and treatment regimens. An example is usually also indicate serious poi- inexperienced. the treatment of an opiate overdose soning. (CNS)7 with , rather than with CNS depression is one of the most mechanical ventilation, which may common manifestations of acute predispose to respiratory infection poisoning. Substances usually and other complications.5,6 Patients who have implicated include alcohol, anti- ingested poisons convulsants, benzodiazepines, tri- GUIDELINES FOR EARLY with high inherent cyclic antidepressants, organophos- IDENTIFICATION OF A phates, carbamates and salicylates. POISON tissue-damaging A combination of alcohol with potential often pre- other CNS is particu- History sent with severe and larly hazardous. While vital functions are being assessed/stabilised, a proper history persistent gastroin- • Lateralising neurological signs. With the exception of should be obtained. Important testinal symptoms information includes the nature of transient inequality of pupil size, the poison, degree of exposure and and signs. lateralising neurological signs time since exposure. Since it is effectively exclude a diagnosis of often difficult to obtain a reliable acute poisoning unless the signs are due to a pre-existing condi- history from the poisoned patient Although the diagnosis of acute tion. (up to 50% of histories are incor- poisoning can seldom be made on rect as to the substance, quantity the basis of a single symptom or • Pyramidal tract signs.An or even actual exposure), the clini- sign, specific are associ- overdose of tricyclic antidepres- cian must rely on a high index of ated with clusters of clinical fea- sant agents, and the earlier gen- suspicion and be aware of the tox- tures which may be of diagnostic erations of antihistamines with ins that possess a high inherent value. In the context of a condi- prominent anticholinergic prop- toxicity (Table II). Communi- tion caused by a poisonous sub- cation with family, friends, tradi- stance, a set of associated symp- tional healers, general practitioners toms and signs is referred to as a and local pharmacists may provide toxidrome. Toxidromes may be useful information. Relatives or useful when attempting to identify friends should be asked not to the cause of a poison-induced leave the premises until the clini- symptom/sign complex. An exam- cian has had the opportunity to ple in point is the association of a question them. A special effort garlicky smell on the breath with should be made to obtain speci- , profuse bloody diar- mens and containers involved. rhoea, delayed and dis- tinctive lines in nails, which is Clinical evaluation/physical pathognomic of . examination Toxidromes and their causes are Symptoms and signs provide valu- listed in the introductory chapters able clues to the causative toxic of most standard text- agent. Although manifestations of books. A given toxidrome, howev- acute poisoning may be wide and er, must be interpreted with cau- varied, patients who have ingested tion since it may not be specific, poisons with high inherent tissue- and hence pathognomonic, but

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erties, often induces hypertonia, theophylline and cholinesterase Absence of clinical signs of toxicity hyperreflexia and extensor plan- inhibitors (nicotinic effect) all In poisoning with certain sub- tar responses. cause tachycardia. stances, the onset of toxic manifes- • Extrapyramidal signs.An • Bradycardia. Cholinesterase tations may be delayed. During overdose of metoclopramide, a inhibitors (via muscarinic this latent period clinical evalua- phenothiazine or a butyrophe- effects), digitalis, -blocking tion will reveal no clear abnormal none antipsychotic agent, may agents, central-acting sympa- findings. Symptoms and signs of induce an acute dystonic reac- tholytic antihypertensive drugs poisoning with Amanita phalloides tion. Dystonia also often occurs and opioids may all cause mushrooms, methyl bromide, in association with carbon bradycardia. organophosphates, paracetamol, monoxide poisoning. • . Antimuscarinic and the superwarfarin rodenticides, • Seizures. Compounds usually and sympathomimetic agents may not immediately be evident implicated include camphorated and, frequently, tricyclic antide- and may be delayed for varying oil, chlorinated hydrocarbons pressants (sympathomimetic periods of time — for hours (e.g. gamma benzene hexachlo- and antimuscarinic effects) may (organophosphates) or days ride), organophosphates and the be implicated. (Amanita phalloides mushrooms). carbamates. Medicinal agents Special investigations include carbamazepine, the sali- A sample of the suspected toxic cylates (aspirin and mefenamic A dry, hot, flushed substance or the material ingested acid), the tricyclic antidepres- skin is typical of is crucial for rapid and positive sants, theophylline, carbon identification of a poison. monoxide, caffeine and the sym- atropine poisoning. Identification can often be pathomimetic appetite suppres- achieved by simple inspection. sants. Health care providers should be • Agitation/restlessness. Over- • Hypotension. Tricyclic antide- encouraged to collect, inspect and dose with agents such as pressants (-blocking effects), send the suspected toxic material ethanol, tricyclic antidepres- antipsychotic drugs, -blocking to the laboratory as soon as possi- sants, theophylline and carba- agents, barbiturates, and central- ble. If the suspected toxic sub- mazepine is known to cause agi- acting antihypertensive drugs stance is not initially brought in tation. Other causes, such as may be implicated. with the patient, a special effort hypoxia, should always first be • ECG. See under ‘Special inves- should be made to send family or excluded. tigations’. friends, or even the police, to col- • Pupils. The opioids, cholin- Respiratory system lect specimens and containers. esterase inhibitors, barbiturates, Obtaining the original toxic sub- chloral hydrate, pilocarpine and • Hyperventilation. Salicylate, stance or container is more valu- the phenothiazines often induce theophylline and sympath- able and reliable for rapid and pos- miosis. In contrast, the omimetic drugs are often impli- itive identification of a poison than antimuscarinic and sympath- cated. depending on laboratory analysis omimetic agents, the tricyclic • . Opioids, of blood, urine or other body flu- antidepressants, carbamazepine sedative-hypnotics, cholines- ids.5 and diphenhydramine, among terase inhibitors, central-acting others, often cause mydriasis. sympatholytic drugs and The toxicology laboratory Non-medicinal chemicals that cyanide cause hypoventilation. Laboratory analyses play an impor- may induce dilated pupils Skin tant role in the identification or include ethanol, methanol, LSD, exclusion of poisons. In addition, cocaine, cyanide and certain Blisters on the skin are occasionally the laboratory may be able to assist neurotoxic snake . found in poisoned patients and are in quantifying the severity of expo- • Anosmia. Loss of the sense of associated with a wide variety of sure. Because of time limitations, smell is diagnostic of berg adder drug overdoses, but especially with expense, and the large number bite. phenobarbitone overdose. A dry, (thousands) of potentially toxic hot, flushed skin is typical of substances commonly encoun- Cardiovascular system atropine poisoning. Heavy perspi- tered, standard toxicology screen- • Tachycardia. Antimuscarinic ration is common in organophos- ing procedures cannot cover all the drugs, sympathomimetic drugs, phate poisoning and in latrodec- possibilities. Contrary to the per- tism.

442 CME August 2003 Vol.21 No.8 MAIN TOPIC ceptions of most clinicians, routine toxicology screening tests are pri- marily designed to identify, or eliminate, a limited number of drugs and non-drug chemicals which are commonly involved in poisoning. If none of the com- pounds for which the tests were designed are identified, the test is reported as being negative. Con- sequently, a negative screening test does not imply that poisoning has not occurred but only that the compounds tested for are not the culprits. In the normal course of events fewer than 50 compounds are routinely screened for. There- fore, the use of a toxicology screen without an understanding of its ins is needed for relatively few sub- of the prothrombin time or the possibilities and limitations may be stances, e.g. paracetamol, salicy- INR may be caused either by misleading or even hazardous. If lates, theophylline, lithium, digoxin ingestion of vitamin K antago- the screen is negative, but a diag- and metals. For some of these, nists (e.g. super warfarin rat poi- nosis of poisoning cannot be depending on the elimination rate sons), or by liver sec- excluded clinically, the toxicologist of the substance, two plasma levels ondary to paracetamol or hepa- should be consulted for an opinion some hours apart may be needed totoxic poisoning, on appropriate additional special to determine whether concentra- among others. A prolonged investigations and/or an appropri- tions are rising or falling, before clotting time may be indicative ate course of action. It needs to be deciding if a specific therapy is of boomslang bite. stressed that when a medical emer- needed or can be discontinued. • Hypoglycaemia. Low glucose gency is thought to be the result of concentrations may be due to an Non-toxicological investiga- an unidentified poison, efforts overdose of oral antidiabetic tions should be directed at identification agents (e.g. sulphonylureas) or or elimination of those agents with In most cases of poisoning, stan- insulin. It may also be a com- high inherent toxicity.5 dard special investigations, such as plication of severe paracetamol serum electrolyte, glucose, arterial or Amanita phalloides (hepato- blood gases, blood urea , toxic mushroom) poisoning. the ion and osmolal gap measure- In most cases of • Hyperglycaemia is often asso- ments, as well as liver and kidney ciated with an overdose of sym- poisoning, standard function tests, full blood count, pathomimetic agents or theo- special investiga- clotting profile (prothrombin time phylline. and INR), urinalysis and ECG, are • Liver function abnormalities. tions are often more often more rewarding for diagnos- Abnormalities, with or without tic purposes than a toxicology rewarding for diag- , are common with screen. nostic purposes advanced paracetamol, arsenic than a toxicology • Urine. Brown discolouration of or hepatotoxic mushroom (e.g. urine may be due to the pres- Amanita phalloides) poisoning. screen. ence of haemoglobin (due to • Nephrotoxicity. Acute renal intravascular haemolysis), myo- failure may occur in aminogly- globin secondary to rhabdomy- coside, heavy , arsenic and Effective lines of communication olysis (see later) or metabolites ethylene glycol poisoning. between the attending clinician or of paracetamol. Urinary oxalate Poisons that cause rhabdomyo- health worker, the laboratory and crystals are a common, but not lysis with myoglobinuria (many the toxicologist are essential. invariable, feature of ethylene poisons) may indirectly cause glycol intoxication. renal failure. Quantitative determination of tox- • Clotting profile. Prolongation • Hypocalcaemia. Low calcium

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levels are a complication of fluo- ously. It is a syndrome that pre- seizures, trauma, metabolic acido- ride and ethylene glycol poison- sents with at least 3 of the follow- sis, hypoxia, coma, immobilisation, ing. ing features: altered mental status muscle compression, or occlusion • ECG abnormalities. A num- (, hypomania), agitation, of the regional blood supply. Beta- ber of induce well-recog- myoclonus, hyperreflexia, sweating, receptor stimulation and hyperdy- nised ECG changes that are, to shivering, , diarrhoea, inco- namic states, such as malignant a greater or lesser extent, specif- ordination, and fever. The syn- hyperthermia, neuroleptic malig- ic and may confirm, or cast drome may be difficult to distin- nant syndrome, and hypokalaemia doubt on, the compound or guish from the neuroleptic malig- have been documented to cause substance thought to be nant syndrome. Hyperthermia is a , as well as pro- involved. These changes include characteristic finding. Tachycardia, longed physical activity, agitation, a prolonged QT interval (e.g. hypertension and tachypnoea are and compartment syndrome. common. Hypotension and respi- phenothiazines), a widened QRS References available on request. interval (e.g. tricyclic antide- ratory failure, and even a DIC, pressants and quinidine), atrio- may develop in severe cases. The ventricular conduction block creatine kinase (CK) levels are (e.g. digoxin, tricyclic antide- usually elevated. Patients being pressants and phenytoin) and treated with antidepressant agents ventricular arrhythmias (e.g. tri- who take drugs of abuse, such as IN A NUTSHELL cyclic antidepressants, digoxin the amphetamines and cocaine, are When dealing with a suspect- and theophylline).7 particularly vulnerable. This syn- ed toxic exposure or poison- • Water, electrolyte and acid- drome is often a complication of ing, one of the major priorities should be to attempt to identi- base disturbances are com- drug abuse in the ‘rave’ party set- ting.8 fy agents with a high inherent mon complications of acute poi- toxicity as soon as possible. soning and this topic is dis- Rhabdomyolysis Early identification will allow cussed in the article on p. 466. This is a syndrome resulting from timeous antidotal or special skeletal muscle damage, with decontamination procedures IMPORTANT CLINICAL release of muscle cell contents into so that severe tissue damage or complications can be avoid- ENTITIES WHICH MAY BE the plasma (myoglobinaemia), ed. ASSOCIATED WITH ACUTE manifesting as myoglobinuria. Renal failure can occur secondary Patients who have ingested POISONING poisons with a high inherent to rhabdomyolysis. Common tissue-damaging potential causes of rhabdomyolysis include often present with severe and This syndrome may be caused by drug abuse/overdose and alcohol persistent gastrointestinal drugs, or combinations of drugs, abuse, or following trauma, symptoms and signs. which increase serotonin activity in seizures, and infections. Although The suspected toxic substance the brain. It usually occurs when alcohol and drug abuse/overdose or the material ingested is cru- two or more drugs, which increase are implicated in many cases, the cial for rapid and positive iden- serotonin availability by different actual rhabdomyolysis may be due tification of a poison. mechanisms, are used simultane- to secondary causes, such as

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