Poisoning in Children 3: Common Medicines

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Poisoning thioglycollate as an active ingredient. In Arch Dis Child: first published as 10.1136/adc.87.5.400 on 1 November 2002. Downloaded from ...... small quantities they cause oropharyn- geal irritation and burning if consumed. Larger amounts can cause corrosive Poisoning in children 3: Common injury or systemic toxicity. medicines ASTHMA MEDICATION Salbutamol is the most common asthma M Riordan, G Rylance, K Berry medication to be accidentally ingested by ...... children. In overdose salbutamol can induce tremor, tachycardia, agitation, A wide variety of medicines are ingested by children metabolic acidosis, hyperglycaemia, and hypokalaemia. Symptomatic ingestion is uncommon and associated with large n this, the third of a series of articles ORAL CONTRACEPTIVE PILLS doses (1 mg/kg). on the management of poisoning, we Accidental ingestion of oral contracep- Activated charcoal should be given if Ideal with medicines commonly in- tive pills rarely produces any toxic effect more than 1 mg/kg has been ingested. gested by children. other than transient gastrointestinal Asymptomatic children can be dis- upset on the following day. Parents charged at four hours post-ingestion. should be advised that vaginal bleeding Symptoms are generally short lived and 2 COUGH AND DECONGESTANT could occur, in girls of all ages, during resolve spontaneously. PREPARATIONS the first few days following ingestion. Theophylline is far more toxic in over- Proprietary preparations for the treat- dose but is encountered infrequently. ment of coughs, colds, and nasal conges- ANTIBIOTICS Symptoms include vomiting, tachycar- tion are frequently ingested accidentally. Accidental overdose of most commonly dia, tachypnoea, tremors, agitation, and Most preparations (75%) are made up of prescribed antibiotics is associated with convulsions. Metabolic disturbances in- more than one active ingredient. little in the way of adverse effects. clude hyperglycaemia, hypokalaemia, Sympathomimetic agents make up Transient gastrointestinal disturbance hypophosphataemia, metabolic acidosis, the largest group of ingredients. Their may occur. No treatment is required. and respiratory alkalosis. effects in overdose vary widely between Children who have consumed more agents. Individual susceptibility is also BENZODIAZEPINES than 15 mg/kg of theophylline require variable. Adverse effects are unusual and These are most frequently encountered hospital admission and treatment with occur fairly soon after ingestion. Severe by children in the form of sedatives or activated charcoal. Use of multiple doses cases are associated with hypertension, anxiolytics prescribed for adults. In over- of activated charcoal can enhance theo- reflex bradycardia, arrhythmias, convul- dose they produce drowsiness, ataxia, phylline elimination3; 0.5 g/kg should be sions, and coma. Treatment is support- hallucinations, confusion, and agitation. administered on a four hourly basis. ive. Respiratory depression, bradycardia, and Propanolol can be used to prevent the Paracetamol and aspirin make up the hypotension can also occur. metabolic disturbances caused by theo- second biggest group of ingredients. Activated charcoal should be adminis- phylline overdose (most are mediated by tered if presentation occurs within one β Their presence should not be overlooked direct sympathomimetic 2 http://adc.bmj.com/ as measurement of blood concentration hour of ingestion and conscious level is stimulation).4 When these metabolic not impaired. Asymptomatic children may be required, depending on the dose 1 abnormalities are established it is far less consumed. should be observed for four hours. efficacious.5 Hypokalaemia has been im- Opioid analgesics are found in a Symptomatic children require hospital plicated in the induction of cardiac admission. Treatment is largely support- number of preparations. Dextromethor- arrhythmias and convulsions which ac- ive. The use of flumazenil, a competitive 6 phan is most frequently encountered. It company theophylline poisoning. It antagonist to benzodiazepines, is not 7 has a low toxic potential and only should be corrected cautiously with generally indicated. Flumazenil can pro- produces side effects when ingested in intravenous supplementation. Hypergly- on October 2, 2021 by guest. Protected copyright. duce nausea, vomiting, flushing, and considerable quantity. Codeine is also caemia is transient and does not require transient hypotension. Its use should be found in a number of preparations. It is treatment. restricted to patients in whom adequate more toxic in overdose. Theophylline increases cardiac con- measures to protect the airway, support duction velocity,increases catecholamine Expectorants make up the final group respiration, and maintain circulation of ingredients. These are mucosal irri- have failed. Flumazenil may precipitate liberation, reduces coronary blood flow, tants or stimulants. Their putative mech- convulsions in patients on long term and decreases the ventricular fibrillation anism of action is to increase respiratory benzodiazepine treatment, for epilepsy. threshold. It can produce both supraven- tract fluid, thereby facilitating its expul- tricular and ventricular arrhythmias. sion. Expectorants include guaiphen- VITAMIN PREPARATIONS Arrhythmias are concentration depend- esin, ipecacuanha, ammonium salts, cin- Vitamin preparations are generally of ent and are exacerbated by hypoxia, eole, creosote, squill, and tolu. These low toxicity in overdose, but they may hypercapnia, and acidosis. Children are agents may act as emetics in overdosage contain iron and this may not be explicit less prone to theophylline induced ar- 5 but because of their low dosage, toxicity from the product name. rhythmias than adults. is generally overshadowed by other Propanolol is the first line treatment ingredients. TOPICAL MEDICINAL PRODUCTS for both supraventricular and ventricular The presence of several active ingredi- Most topical medicinal products are of arrhythmias. Esmolol is an alternative in ents in a single preparation may produce low toxicity when ingested. Nausea, asthmatic patients.5 Adenosine may also a confusing clinical picture and potenti- vomiting, and diarrhoea may occur. prove effective.1 ate adverse effects. Poison centre advice Exceptions include products with poten- should be sought if the maximum daily tially toxic active ingredients, for exam- ANTIHISTAMINES therapeutic dose of any preparation is ple, salicylates in wart and callus treat- Antihistamines cause central nervous exceeded. ments. Depilatory creams contain system depression and anticholinergic

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side effects in overdose. Hypotension, for nocturnal enuresis, chronic pain dis- with tricyclic antidepressants. While Arch Dis Child: first published as 10.1136/adc.87.5.400 on 1 November 2002. Downloaded from muscle weakness, paradoxical central orders, or attention deficit disorder. In these compounds are much safer in nervous system stimulation, and convul- overdose tricyclics produce anticholiner- overdose than tricyclic sions can also occur. gic symptoms, drowsiness, ataxia, and antidepressants,16 17 adverse effects have Antihistamine overdose can produce a agitation. Convulsions, central nervous been documented. Adverse effects in- variety of cardiac arrhythmias. For the system depression, and hypotension also clude vomiting, agitation, tremor, nys- majority of antihistamines this effect is occur. tagmus, and drowsiness. Convulsions mediated by myocardial sodium channel Cardiac arrhythmias occur frequently and arrhythmias18 have also been re- blockade—a quinidine like effect. Two of and are the most common cause of ported. the newer non-sedating antihistamines, death. The mechanism of cardiac toxicity A “serotonin syndrome” has been terfenadine and astemizole, cause de- is complex. Blockade of noradrenaline described. This most commonly occurs in layed cardiac repolorisation by potas- reuptake at the adrenergic synapse pro- adults receiving combinations of drugs, sium channel blockade. This is associ- duces initial stimulation followed by α two or more of which inhibit the ated with prolongation of the QT interval adrenergic blockade. Tricyclics also exert reuptake or metabolism of serotonin, or and may predispose to the development a quinidine like membrane stabilising enhance its release. Examples of such of ventricular tachyarrhythmias. effect. This causes delayed conduction drugs include selective serotonin re- Children should be observed for a and myocardial depression. The anti- uptake inhibitors, tricyclic antidepres- minimum of four hours following inges- cholinergic effects of tricyclics on the sants, monoamine oxidase inhibitors, tion. Symptomatic children, and those heart are not of major significance. and amphetamines. Symptoms include who have ingested terfenadine, astemi- Activated charcoal should be adminis- autonomic dysfunction, hyperpyrexia, zole, or slow release preparations, even in tered if the maximum recommended circulatory collapse, convulsions, and the absence of symptoms, require admis- daily dose has been exceeded. rhabdomyolysis.19 Reports suggest that sion. Activated charcoal should be con- A 12 lead ECG should be performed in this constellation of symptoms may also sidered up to four hours post-ingestion all cases. The best indicator of risk for occur following the ingestion of a single as gut motility is impaired. Treatment is cardiac toxicity is a QRS duration of agent.20 21 Treatment is supportive. otherwise largely supportive. more than 0.1 seconds.8 Sinus tachycar- While the anticholinergic side effects dia, QT or PR prolongation, and ventricu- IRON of antihistamines are unpleasant they lar ectopics are all common.9 Early features of iron poisoning include are not generally life threatening. The Asymptomatic children, with a nor- vomiting, diarrhoea, and abdominal majority of clinically significant effects mal ECG, should be observed for a mini- pain. Direct mucosal irritation by adher- of antihistamine poisoning are not anti- mum of six hours. Patients with any ECG ent tablets can cause gastrointestinal cholinergic mediated. For this reason abnormality should be monitored until haemorrhage. These effects usually settle acetylcholinesterase inhibitors, such as resolution of the abnormality.9 within six hours. physostigmine, are not recommended in Compromising arrhythmias should be Absorbed iron is rapidly cleared from antihistamine poisoning. treated with an initial bolus of 1 ml/kg of the circulation by cellular uptake. High Hypotension should be treated with 8.4% sodium bicarbonate. Arterial pH concentrations of intracellular iron dis- intravenous fluids. Where inotropes are should subsequently be maintained be- rupt mitochondrial function and result considered necessary, adrenaline should tween 7.45 and 7.55, using further doses in cell death. Signs of multiorgan failure be avoided as paradoxical hypotension of sodium bicarbonate as required. Ar- present at 12–48 hours post-ingestion. can occur.1 rhythmias unresponsive to sodium bicar- The liver is particularly prone to damage Convulsions and paradoxical excite- bonate may be treated with phenytoin, and symptoms of fulminant hepatic fail- http://adc.bmj.com/ ment can be treated with a benzodi- atenolol, or propanolol. Class Ia an- ure predominate. azepine. Phenothiazine based sedatives tiarrhythmic drugs should be avoided. A careful history must be taken as to should be avoided because of their Life threatening arrhythmias may re- the iron preparation consumed and the anticholinergic side effects. Continuous ECG monitoring is ad- spond to cardioversion. Survival has maximum quantity taken. Different iron vised for symptomatic children and been reported, in patients with tricyclic salts contain differing quantities of those who have ingested terfenadine or induced electromechanical dissociation, elemental iron: for example, 200 mg of astemizole. The management of arrhyth- following several hours of external car- ferrous sulphate contains 65 mg of on October 2, 2021 by guest. Protected copyright. mias in antihistamine poisoning can be diac massage. elemental iron; 300 mg of ferrous gluco- difficult. Sinus tachycardia is the most Hypotension unresponsive to intra- nate contains 35 mg. frequently seen abnormality. This can venous fluids should be treated with Asymptomatic children, with a defi- usually be managed conservatively. A sodium bicarbonate. Glucagon can also nite history of consuming less than 30 number of other arrhythmias can occur. be used to treat refractory hypotension. mg/kg of elemental iron, do not require Care must be taken in the choice of The large volume of distribution of tri- further investigation. Activated charcoal antiarrhythmic drugs. Sodium bicarbo- cyclic compounds means that they are does not bind iron. nate is the first drug of choice for QT not amenable to removal by extracorpor- Children who may have consumed 10–14 prolongation with sodium channel eal means. more than 30 mg/kg require hospital blocking antihistamines. Class Ia and III Poisoning by monoamine oxidase inhibi- admission and further investigation. An antiarrhythmic drugs should be avoided tors is uncommon following a decline in abdominal x ray examination should be in this situation. Magnesium sulphate their use. In overdose they produce anti- performed. If undissolved iron tablets may be considered for arrhythmias cholinergic effects, excessive central are visible on the abdominal film, whole caused by terfenadine or astemizole. nervous stimulation, convulsions, hyper- bowel irrigation should be undertaken. pyrexia, and rhabdomyolysis. Activated Irrigation should continue until abdomi- ANTIDEPRESSANTS charcoal should be administered follow- nal films are clear of undissolved Antidepressant medications include tri- ing ingestion. Treatment is supportive. tablets.22 In patients with tablets con- cyclic compounds, monoamine oxidase Dantrolene may be required to treat fined to the stomach, repeated gastric inhibitors, and selective serotonin re- hyperpyrexia. lavage or endoscopic removal are alter- uptake inhibitors. Selective serotonin reuptake inhibitor native strategies. The absence of iron Tricyclic compounds are prescribed as usage has increased in recent years tablets on abdominal x ray does not pre- antidepressants for adult patients. Chil- because of their efficacy and more toler- clude the presence of a significant inges- dren may be prescribed tricyclic drugs able side effect profile when compared tion. Vitamin tablets containing iron

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4 Kearney TE, Manoguerra AS, Curtis GP,

Gastrointestinal stricture formation, Arch Dis Child: first published as 10.1136/adc.87.5.400 on 1 November 2002. Downloaded from Table 1 Products of low toxicity et al. Theophylline toxicity and the caused by the corrosive effects of iron, beta-adrenergic system. Ann Intern Med Cold sore treatment can occur as a late complication of iron 1985;102:766–9. Ear and eye drops 5 Gaudreault P, Guay J. Theophylline poisoning. poisoning. Pharmacological considerations Hormone replacement tablets and clinical management. Med Toxicol Nasal drops 1986;1:169–91. Steroids INGESTIONS OF LOW TOXICITY 6 Boldy DAR, Buckley BM, Vale JA. Advances A wide range of medicines are acciden- in the treatment of poisoning I. J Clin Hosp Pharm 1984;(9):147–60. Note: Some of the products listed present tally ingested by children. Many are of a significant choking hazard that should 7 D’Angio R, Sabatelli F. Management considerations in treating metabolic not be overlooked. very low toxicity (see table 1). abnormalities associated with theophylline overdose. Arch Intern Med 1987;147:1837–8. SEEKING FURTHER ADVICE 8 Boehnert MT, Lovejoy FN. Value of the QRS may not be demonstrable radiologically. Specific, expert advice on all aspects of duration versus the serum drug level in If large quantities have been consumed, predicting seizures and ventricular poisoning is available to medical profes- arrhythmias after acute overdose of tricyclic whole bowel irrigation should be under- sionals in the United Kingdom via the antidepressants. N Engl J Med taken. National Poisons Information Service 1985;313:474–9. 9 Commerford PJ, Lloyd EA. Arrhythmias in In asymptomatic patients, a serum (NPIS). The regional centres that make patients with drug toxicity, electrolyte, and iron level should be determined at four up this service have recently introduced endocrine disturbances. Med Clin North Am 1984;68:1051–79. hours post-ingestion. This level should a single national enquiry number: 10 Pond SM. Extracorporeal techniques in the be repeated at eight hours if a sustained 0870 600 6266. treatment of poisoned patients. Med J Aust release preparation has been consumed. 1991;154:617–22. A wide range of easily accessible and 11 Bismuth C. Biological valuation of Patients with a serum iron level less than highly practical advice is available extra-corporeal techniques in acute poisoning. 55 µmol/lrequire no further treatment, through the NPIS website.23 This free Acta Clin Belg Suppl 1990;13:20–8. 12 Heath A, Wickstrom I, Martensson E, et al. and, provided gastric decontamination is service is restricted to medical profes- Treatment of antidepressant poisoning with not required, can be discharged. Patients sionals. On line registration is available resin hemoperfusion. Hum Toxicol with a serum iron level between 55 and 1982;1:361–71. at http://www.spib.axl.co.uk/toxbase/. 13 Henry JA. Can tricyclic antidepressants be 90 µmol/l require observation for at least removed by haemoperfusion? [editorial]. Hum Arch Dis Child 2002;87:400–402 24 hours. If they remain asymptomatic, Toxicol 1982;1:359–60. 14 Haapanen EJ. Hemoperfusion in acute no specific treatment is indicated. intoxication. Clinical experience with 48 Patients with a serum iron level ...... cases. Acta Med Scand Suppl µ Authors’ affiliations 1982;668:76–81. greater than 90 mol/l should receive 15 Catalano G, Cooper DS, Catalano MC, et treatment with intravenous desferriox- M F Riordan, Department of Pediatrics, Yale al. Pediatric sertraline overdose. Clin amine. University Medical School, USA Neuropharmacol 1998;21:59–61. G W Rylance, Department of General 16 Personne M, Sjoberg G, Persson H. Patients with symptoms suggestive of Paediatrics, Royal Victoria Infirmary, Newcastle Citalopram overdose—review of cases treated multiorgan failure require intensive sup- upon Tyne, UK in Swedish hospitals [published erratum port and immediate treatment with K Berry, Accident and Emergency Department, appears in J Toxicol Clin Toxicol Birmingham Children’s Hospital, Birmingham, 1997;35:577]. J Toxicol Clin Toxicol intravenous desferrioxamine. Expert ad- 1997;35:237–40. UK vice should be sought, as a higher total 17 Borys DJ, Setzer SC, Ling LJ, et al. Acute fluoxetine overdose: a report of 234 cases. daily dose may prove beneficial. As Correspondence to: Dr K Berry, Accident and Am J Emerg Med 1992;10:115–20. desferrioxamine interferes with serum Emergency Department, Birmingham Children’s 18 Graudins A, Vossler C, Wang R. Hospital, Steelhouse Lane, Birmingham Fluoxetine-induced cardiotoxicity with http://adc.bmj.com/ iron estimation, blood levels should be B4 6NH, UK; response to bicarbonate therapy. Am J Emerg taken prior to commencing treatment. [email protected] Med 1997;15:501–3. 19 Francois B, Marquet P, Desachy A, et al. Treatment, however, should not be de- Serotonin syndrome due to an overdose of layed whilst results are awaited. REFERENCES moclobemide and clomipramine. A potentially Desferrioxamine chelates free iron. life-threatening association. Intensive Care 1 Bates N, Edwards N, Roper J, et al. Med 1997;23:122–4. The chelate complex is excreted in the Paediatric toxicology: handbook of poisoning 20 Gill M, LoVecchio F, Selden B. Serotonin urine, giving it a pink-brown tinge (vin- in children. London: Macmillan Reference syndrome in a child after a single dose of Limited, 1997. fluvoxamine. Ann Emerg Med rosé). Should renal function be signifi- on October 2, 2021 by guest. Protected copyright. 2 Wiley JF, Spiller HA, Krenzelok EP, et al. 1999;33:457–9. cantly impaired this complex can also be Unintentional albuterol ingestion in children. 21 Mueller PD, Korey WS. Death by “ecstasy”: removed by haemodialysis. Pediatr Emerg Care 1994;10:193–6. the serotonin syndrome? Ann Emerg Med 3 Vale JA, Krenzelok EP, Barceloux GD. 1998;32(3 pt 1):377–80. Desferrioxamine treatment should be 22 Tenenbein M. Position statement: whole Position statement and practice guidelines on continued until symptoms have abated bowel irrigation. American Academy of the use of multi-dose activated charcoal in the Clinical Toxicology; European Association of and urine discolouration clears. Special- treatment of acute poisoning. American Poisons Centres and Clinical Toxicologists ist advice should be sought if therapy Academy of Clinical Toxicology; European [review]. 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