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Home , Iron poisoning, Paracetamol poisoning

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Current Paediatrics (2005) 15, 563–568

www.elsevier.com/locate/cupe

Poisoning in children

Fiona JepsenÃ, Mary Ryan

Emergency Medicine, Royal Liverpool Children’s NHS Trust, Alder Hey, Liverpool L12 2AP, UK

KEYWORDS Summary accounts for about 7% of all accidents in children under 5 Poisoning; years and is implicated in about 2% of all childhood deaths in the developed world, Child; and over 5% in the developing world (National Information Service). In Accidents; considering this topic, however, it is important to differentiate accidental overdose Home (common in the younger age groups) and deliberate overdose (more common in young adults). Although initial assessment and treatment of these groups may not differ significantly, the social issues and ongoing follow-up of these children will be totally different and the treating physician must remain aware of this difference. The initial identification and treatment of these children remains the mainstay of management, and many ingested substances do not have a specific . Supportive treatment must be planned and the potential for delayed or long-term effects noted. The specific presentation and treatment of some of the commonly ingested substances will be addressed in this article, and guidance given on when to contact expert help. & 2005 Elsevier Ltd. All rights reserved.

Introduction such as bleaches, detergents and turpentine sub- stitutes. More than 100 000 individuals are admitted to Toxic compounds may be ingested or inhaled hospital in England and Wales annually due to either accidentally or deliberately. Accidental poisoning, accounting for 10% of all acute admis- poisoning can occur at any age, but is much more 1 sions.1 However, the true incidence of acute common in children. Peak incidence is around the poisoning may be 2–3 times greater.1 age of 2 years and boys are at more risk than girls. In England and Wales, analgesics account for Most incidents (80–85%) occur in the child’s home 20% of all cases of poisoning in children aged and in many cases the substances involved have not 14 years or less, with a further 40% ingesting been stored in their usual place or have been put 1 other pharmaceutical preparations. The remaining into a different container. 40% are poisoned by a variety of household products Household products are more commonly ingested than drugs by children and seasonal variability has ÃCorresponding author. Tel.: +44 151 2933623; been described. Pesticides and weed killers are fax: +44 151 2525088. more commonly ingested in the spring, berry E-mail address: [email protected] (F. Jepsen). poisoning occurs in the autumn, and cough and

0957-5839/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.cupe.2005.08.006 ARTICLE IN PRESS

564 F. Jepsen, M. Ryan cold remedies are more commonly ingested in the of body weight should be identified as accurately as winter. possible.2 Deliberate poisoning is more common in adults, In cases where poisoning is suspected, but cannot but is increasing in the teenage population; the be confirmed by clinical history, a detailed physical incidence of analgesic ingestion has particularly examination, including a full neurological assess- increased. Depression and deliberate self-harm are ment is an essential part of substance identifica- often found concurrently with analgesic overdose, tion.2 Initially, assessment and treatment of the and the particular needs of this population differs airway, breathing and circulation is mandatory. from adults. Treatment should first focus on supportive mea- Poisoning accounts for a very small proportion of sures, including use of high-flow oxygen and deaths in children under 10 years of age. This intravenous fluids. Depression of the nervous declining proportion of deaths in children may be system can occur and fitting should be treated with attributable to the widespread introduction of child- intravenous benzodiazepines. resistant closures on containers. However, other There is no place for the use of emetics in the factors, including greater emphasis on safety in the modern treatment of poisoning.3 The use of home, improved access to information on poisons and activated charcoal for reducing drug absorption improved treatment may also contribute to reducing should be considered if a patient presents within mortality. In England and Wales, carbon monoxide 1 h of taking the substance. A single dose of 1 g/kg remains the most common cause of childhood death body weight for children can be given by mouth or due to poisoning. Tricyclic antidepressant ingestion via naso-gastric tube up to 1 h after ingestion of a remains a significant contributor to mortality, potentially toxic amount of a well charcoal- although it is relatively infrequently ingested. adsorbed , and perhaps beyond an hour in cases involving sustained or modified-release drug preparation. A list of poisons for which activated charcoal has been proven to be ineffective is found in Table 1. The use of repeated doses of activated Initial approach, investigation and charcoal to remove undergoing enterohepa- treatment tic circulation is one of the simplest active elimination techniques.5 Table 1 lists the sub- The diagnosis of acute poisoning may be apparent stances for which this technique may be useful. from the clinical history. However, it should also be is not recommended by The considered in patients who present with altered American Academy of Clinical or the consciousness, those unable to give a history and European Association of Poisons Centres and Clin- those who present with an episode of deliberate ical Toxicologists unless a patient has ingested a self-harm. Wherever possible the constituents of potentially life-threatening amount of a poison and the substance ingested and its dosage per kilogram the procedure can be undertaken within 1 h of

Table 1 Poisons for which activated charcoal has been proven to be ineffective and substances for which the use of repeated doses of activated charcoal may prove useful.

Poisons for which activated charcoal has been proven Substances where repeat doses of activated charcoal to be ineffective may prove useful in enhancing clearance

Cyanide DDT Theophylline Essential oils Digoxin Organic solvents Salicylates Lead Phenylbutazone Mercury Dapsone Lithium Amanita phalloides Bleach Alkalis Quinine (i.e., , ethanol, ethylene glycol) Slow-release preparations Sotalol Piroxicam ARTICLE IN PRESS

Poisoning in children 565 ingestion.4 They also advise against the use of have taken very large overdoses, particularly of a emetics, and conclude that there is no evidence long-acting agent such as dihydrocodeine and from clinical studies that ipecacuanha improves the methadone, may need further doses of to outcome of poisoned patients.3 competitively antagonise the opioid agonist, and Urinary alkalinisation can be used to enhance the continuous intravenous infusion of naloxone, to- excretion of weakly acidic drugs.2 Dialysis, haemo- gether with intensive monitoring may be necessary perfusion and haemofiltration have all been used to in some cases. The use of flumazenil is not actively enhance excretion.2 recommended in the suspected overdose of benzo- diazepines because of the risk of fitting with co- ingestion of tricyclic antidepressants. Laboratory investigations

A careful history may obviate the need for blood 2 tests. Standard haematological investigations are Specific poisons rarely diagnostically helpful, although the pro- thrombin time may be prolonged after ingestion of anticoagulants or in case of hepatic damage (e.g. in ). Blood glucose estima- Children are more resistant to paracetamol-in- tion should be performed in all cases, as hypogly- duced damage than adults.8 The volume and caemia is typically caused by an overdose of insulin paracetamol concentration of the formulation or oral hypoglycaemic agents and complicates should be established from the packaging and the ethanol intoxication, particularly in children. Blood volume remaining should be measured.9 The max- gas analysis should be undertaken in any patient imum possible ingestion should be assumed. If the with respiratory insufficiency, hyperventilation or dose of paracetamol consumed is known with when metabolic acid–base disturbance is sus- absolute certainty to be below 150 mg/kg no pected.6 Hypokalaemia has been described as a further action is required.9 However, it is recom- of acute poisoning and electrolyte mended that paracetamol levels should be investi- estimation may be useful. gated at least 4 h after the time of ingestion in any Routine measurement of plasma paracetamol patient who has deliberately taken an overdose in should be performed in older children presenting order to commit deliberate self-harm. Samples with any deliberate ingestion. In one study, authors taken before this may be unreliable. found one in 500 adult overdose patients not Paracetamol levels should be compared with the suspected of having taken paracetamol had levels standard adult normogram to determine the need above the treatment threshold.7 The routine for treatment with N- (NAC). This measurement of salicylate is controversial, and may overestimate treatment required in children although done in practice, is only necessary when but there is at present no normogram available for symptoms become obvious. It is unlikely that a the paediatric population. Children at high risk clinically significant concentration will be present (i.e., those on enzyme-inducing in a patient without the typical signs of salicylism.6 drugs or those who are malnourished) should be Radiology can be used to confirm ingestion of treated as per the ‘high-risk line’. Patients who metallic objects or ingestion of elemental mercury have taken a staggered overdose should be started or iron salts. An electrocardiogram (ECG) is of on NAC without awaiting the result of paracetamol limited diagnostic value, although tachycardia with levels and then bloods taken for INR, LFTs, U/Es prolongation of the PR and/or QRS intervals in an after the NAC regimen has been completed. Those unconscious patient should prompt consideration of presenting more than 8 h post-ingestion should also tricyclic antidepressant overdose.6 be started on treatment immediately. NAC is given via intravenous infusion, and should Specific be administered when indicated using the normo- gram or in the situations already discussed. Adverse Antidotes should only be considered after the initial reactions such as , , flushing and supportive treatment has been started. An example urticarial rash can occur, usually within the first of an antidote is naloxone, a competitive anatago- 30 min of administration. This usually resolves once nist at the opioid receptor. It is effective in reversing the infusion is stopped and an is the symptoms of with all compounds given. Once the reaction has settled NAC infusion except buprenorphine (which is a partial agonist and can be recommenced at an infusion rate of 50 mg/ therefore not completely antagonised). Those who kg over 4 h. Further reactions are almost unknown. ARTICLE IN PRESS

566 F. Jepsen, M. Ryan

Blood should be taken for estimation of electro- tool. A partial response is an indication for a further lytes, , INR/prothrombin time and liver dose, although the patient may be sedated by function tests after the NAC regime has finished. A another central agent, such as baseline INR is sometimes useful before treatment. or a benzodiazepine.10 Clearly with opioid Abnormal results should prompt further advice the first priority is to ensure that respiration from a specialist liver centre and a further 16-h and circulation are adequate, and if the patient infusion of NAC should be commenced. appears to be close to respiratory arrest attention to the airway and provision of respiratory and cardiovascular support is more urgent than giving naloxone.10 The incidence of salicylate toxicity has declined considerably since the withdrawal of paediatric Compound analgesics aspirin preparations from the market in 1986.9 In children over the age of 4 years a mixed respiratory Compound analgesics are mixtures of paracetamol alkalosis and metabolic is the rule with or aspirin with a variety of opioids or other normal or high arterial pH (normal or reduced ingredients. When assessing overdose of compounds hydrogen ion concentration). In children aged 4 each active constituent must be considered sepa- years or less a dominant with rately. low arterial pH (raised hydrogen ion concentration) is common. Tricyclic antidepressants Plasma salicylate concentrations should be mea- sured for patients who are thought to have ingested Tricyclic overdoses produce anticholinergic symp- more than 120 mg/kg of aspirin. The sample should toms, including drowsiness, ataxia and agitation. be taken at least 2 h (symptomatic patients) or 4 h Convulsions, central nervous system depression and (asymptomatic patients) after ingestion, as it may can also occur. Increased tone and take several hours for peak plasma concentrations hyper-reflexia may be present with extensor to occur. There is no need to measure salicylate plantar reflexes. In deep all reflexes may be concentrations in conscious overdose patients who abolished. Cardiac arrhythmias secondary to the deny taking salicylate-containing preparations prolonged QT interval are the most common cause and who have no features suggesting salicylate of death.11 toxicity. Table 2 details further management after Activated charcoal should be administered within an overdose of aspirin. 1 h if more than 4 mg/kg tricyclic has been ingested by a child, provided the airway can be protected. A Opiates second dose of charcoal should be considered after 2 h in patients with central features of toxicity. Opioid toxicity produces the classic triad of reduced Investigations should include a 12-lead ECG to consciousness, pinpoint pupils, and a reduction of detect signs of cardiac toxicity. The patient should respiratory rate. These should be enough to lead to be observed for 6 h if asymptomatic and those who a rapid working diagnosis of opioid toxicity. Nalox- remain symptom free and have normal ECGs by 6 h one can be used as a diagnostic and therapeutic are unlikely to develop late complications.

Table 2 Management of aspirin poisoning.

Mild Moderate Severe

Plasma salicylate o350 mg/l (2.5 mmol/l) 4350 mg/l 4700 mg/l (5.1 mmol/l) Fluids Encourage oral fluids Intravenous fluids Intravenous fluids Sodium bicarbonate Yes Yes 1.26% to correct metabolic acidosis and alkalise the urine Consider repeated doses Yes Yes of activated charcoal Urgent referral for Yes haemodialysis ARTICLE IN PRESS

Poisoning in children 567

Iron throughout the , metabolic acidosis, hepatic failure, renal damage and altered Early features of include vomiting, level of consciousness.12 diarrhoea and . The vomitus and stools are often grey or black. Direct mucosal Essential oils irritation by adherent tablets can cause gastroin- testinal haemorrhage. These effects usually settle Essential oils are used in perfumery and aromather- 11 within 6 h. apy and are potentially very toxic. Initial effects A careful history must be taken to find out the include mucosal irritation, vomiting, epigastric iron preparation consumed and the maximum pain and diarrhoea. Convulsions, central nervous quantity taken as different iron salts contain system depression, and hepatic and renal failure 11 differing quantities of elemental iron. A child may follow. Asymptomatic children require 6 h who is asymptomatic and has ingested less than observation. Fluids should be encouraged. Sympto- 20 mg/kg body weight of elemental iron is said to matic children require hospital admission with have mild toxicity and does not require further supportive treatment and blood glucose monitor- investigation. Those who have ingested more than ing. Signs of respiratory distress may indicate oil 20 mg/kg body weight of elemental iron are aspiration.12 likely to develop features and so will warrant admission. Plants and berries A serum iron estimation taken at about 4 h after ingestion is the best laboratory measure of Ingestion of or exposure to potentially poisonous severity. Plain abdominal X-ray has been recom- plants is a relatively common presenting complaint in mended as a screening test within 2 h of a hospital paediatric departments, especially amongst suspected ingestion. If less than 2 h has elapsed toddlers.13 History taking needs to include the part of since the suspected ingestion, iron tablets are the plant that has been ingested, i.e., the berries or sometimes visible in the stomach or small bowel. leaves, as toxicity may differ. Activated charcoal is Later abdominal X-rays are of no value, as tablets recommended for initial management of ingestion of may have disintegrated thus giving a negative plants such as laburnum and deadly nightshade. It is result and the absence of iron tablets on abdominal recommended that the National Poisons Information X-ray does not preclude the presence of a 11 Service be contacted for advice regarding initial and significant ingestion. In patients with tablets continued care. confined to the stomach, repeated gastric lavage or endoscopic removal can be considered. Patients with a serum iron level greater than 90 mmol/l Alcohol should receive treatment with intravenous desfer- rioxamine, which chelates free iron, and expert The incidence of intoxicated children presenting advice should be sought. to the Emergency Department is increasing nation- ally. Children who have ingested the equivalent of 0.4 ml/kg pure ethanol should be observed for Turpentine substitute at least 4 h and hypoglycaemia must be investi- gated and corrected if present. The fatal dose of Turpentine oil has been largely replaced with white alcohol in children is approximately 3 g/kg body weight (4 ml/kg absolute ethanol). Crawford et spirit and turpentine substitute, which are of 14 relatively low toxicity when ingested. Their main al. demonstrated the effectiveness of referring toxicity relates to the risk of aspiration resulting in adult drinkers to alcohol health workers. Under- a chemical pneumonitis. For this reason gastric lying social issues of an intoxicated child should decontamination is contraindicated. All patients be addressed once the child is sober and consi- should be assessed for signs of respiratory distress, deration of referral to alcohol services may be which should include measurement of oxygen required. saturation. The majority of patients are asympto- matic and do not necessarily require observation. Advice must be given to return if children develop National poisons information service cough or fast, noisy breathing. Children can develop symptoms up to 24 h post-ingestion.12 This must be the first port of call in dealing with Hospital admission is mandatory for the ingestion any patient that presents after the ingestion of a of turpentine as it can cause irritation and burning ‘poison’. Poisons information specialists and nurses ARTICLE IN PRESS

568 F. Jepsen, M. Ryan answer telephone calls and consultant physicians for all treating physicians in the management of are available to provide clinical advice, and their poisoning. expertise is useful if a patient has presented with a toxidrome, i.e., a combination of symptoms sec- ondary to ingestion of an unknown substance. References ‘Toxbase’ (www.spib.axl.co.uk) is a database usually available to the treating physician in the 1. Meredith T. Epidemiology of poisoning. Medicine 1999; local Emergency Department. Another website 27:1–3. and programme that can be purchased is 2. Riordan M, Rylance G, Berry K. Poisoning in children 1: ‘TicTac’ (www.tictac.org) which contains a data- general management. Arch Dis Childhood 2002;87(5): 392–6. base of tablets allowing identification of unknown 3. Krenzelok EP, McGuigan M, Lheur P. Position statement: . ipecac syrup. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Clin Toxicol 1997;35(7):699–709. 4. Vale JA, Kulig K, Seger D, Meulenbelt J. Position paper: Conclusions gastric lavage. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Poisoning can occur either accidentally or deliber- Toxicologists. Clin Toxicol 1997;35(7):711–9. ately. Along with ascertaining a detailed history, 5. Vale JA, Krenzelok EP, Barceloux GD. Position statement and the ‘ABC’ approach to the initial management of practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American the patient must be adopted, along with the Academy of Clinical Toxicology; European Association of consideration of the use of charcoal and a specific Poisons Centres and Clinical Toxicologists. Clin Toxicol antidote, if one exists. 1997;35(7):721–41. Substances that are commonly ingested by chil- 6. Bradberry SM, Vale JA. Poisons initial assessment and dren include household products and drugs, the management. Clin Med 2003;3:107–10. 7. Ashbourne JF, Olson KR, Khayambashi H. Value of rapid ingestion of which may be deliberate or accidental. screening for acetaminophen in all patients with intentional Treating physicians must consider ingestion of . Ann Emerg Med 1989;18(10):1035–8. paracetamol in deliberate overdoses of any tablets 8. Rumack BH, Peterson RG. Acetaminophen overdose—inci- and be knowledgeable about the use of the dence, diagnosis, and management in 416 patients. Pedia- normogram with NAC. Aspirin toxicity is still seen trics 1978;62(5):898–903. 9. Riordan M, Rylance G, Berry K. Poisoning in children 2: either alone or due to the ingestion of compound painkillers. Arch Dis Childhood 2002;87(5):397–9. analgesics. Tricyclic antidepressant ingestion re- 10. Henry JA. Management of drug abuse emergencies. mains a significant cause of mortality in this group. J Accident Emerg Med 1996;13(6):370–2. Iron can be extremely toxic and the use of 11. Riordan M, Rylance G, Berry K. Poisoning in children 3: desferrioxamine may be required if a large amount common medicines. Arch Dis Childhood 2002;87(5):400–2. 12.RiordanM,RylanceG,BerryK.Poisoninginchildren4: has been taken. Turpentine substitutes and essential household products, plants, and mushrooms. Arch Dis Childhood oils have been included as these are commonly 2002;87(5):403–6. ingested accidentally. Ingestion of alcohol and street 13. Vichova P, Jahodar L. Plant in children in the drugs, such as ecstasy and cocaine, is on the Czech Republic, 1996–2001. Hum Exp Toxicol 2003;22(9): increase by the teenage population and the manage- 467–72. 14. Crawford MJ, Patton R, Touquet R, et al. Screening and ment of these should be known, as well as the referral for brief intervention of alcohol misusing patients importance of dealing with any social issues. If in in an emergency department: a pragmatic randomised doubt the Poisons Information Service is a resource controlled trial. Lancet 2004;364:1334–9.