Drug intoxication (pediatrics)

Drug intoxication is the most common reason for consultation of the Toxicology Information Center (TIS) in children and adults. The usual cause of drug poisoning in children under 5 years of age is accidents and medical errors (mixing up of drugs, their inappropriate use or incorrect dosage), a serious course of poisoning is an exception. In adolescents, it is mainly suicide attempts, and mostly in girls. In recent years, serious drug poisonings have decreased, mainly due to the fact that a number of very dangerous pharmaceutical preparations have been replaced by more modern active substances with lower toxicity. However, the current problem is extended-release preparations, which usually contain a larger amount of the active substance in one dose and where, due to the prolonged release, the course of the poisoning is unpredictable.

The most important thing is education and prevention (do not offer medicines under the pretext that they are treats, keep medicines in inaccessible places, do not throw leftover medicines in waste bins, watch children during visits,...).

Intoxication according to the age of the child
The most critical period for acute intoxication is the second year of a child's age, when motor skills, dexterity and the way of learning about the environment by putting objects in the mouth are developing. The severity of intoxication often depends on the environment in which the child grows up. In the household of young and healthy parents, intoxications usually occur with pharmaceutical preparations that are not serious in nature. The risk is higher in households where there are chronically ill or elderly individuals with chronic diseases of the circulatory system, psychiatric diagnoses, diabetes, obstructive pulmonary disease or pain conditions requiring opioid analgesics. In many cases, the daily medicine dispenser is emptied by the toddler. It is often not clear whether the child has eaten the medicine or just scattered it around, however, it is necessary to calculate the maximum possible dose, which is why observation in the children's inpatient ward is often necessary.

Medicines are often confused with newborns and infants, for example Kanavit ( vitamin K1 - recommended 1 drop per week) and Vigantol ( vitamin D3 - recommended 1 drop per day). In addition, there may be incorrect use of the medicine (for example, orally instead of nasally), incorrect dosage (number of milliliters instead of the number of drops) or multiple administration of the same dose by different members of the household.

Frequent accidental ingestion of medicines by children

 * Contraceptive Pills
 * NU (several pieces): nausea, possibly vomiting, sometimes several hours after ingestion.
 * First aid: administration of several tablets (1–3–8) of activated carbon (e.g. Carbosorb or Carbotox ), crushed into a favorite drink or into fruit pulp, puree or yogurt.


 * Tablets containing sodium fluoride to prevent tooth decay ( Zymafluor, Natrium fluoratum )
 * the active substance of these preparations is toxicologically very serious, but in tablets for children it is contained in such a small amount that intoxication does not occur even after eating several dozen pieces;
 * first aid: giving milk or another liquid milk product - the calcium contained in it reacts with fluorine to form calcium fluoride, which protects the gastric mucosa from the irritating effects of sodium fluoride and at the same time prevents the same reaction with calcium ions in the blood, which would occur if large doses of the drug were ingested caused poisoning with tetanic convulsions and other changes that could be fatal in severe cases.


 * Expectorants containing ambroxol ( Mucosolvan, Ambrobene )
 * even emptying the contents of an entire bottle of syrup for children (120 ml/360 mg ambroxol) should not cause anything more serious than indigestion and increased mucus secretion.

The most dangerous drug intoxication

 * calcium channel blockers ,
 * beta blockers or digoxin ,
 * theophylline preparations,
 * tricyclic antidepressants and carbamazepine ,
 * oral antidiabetic drugs ,
 * colchicine or preparations containing iron,
 * paracetamol and others

Clinical manifestations
Upraveno a doplněno podle N. C. Singh, Manual of Pediatric Critical Care

Paracetamol intoxication

 * 1) Loss of appetite, nausea and vomiting, malaise (sometimes leads to further administration of paracetamol!)
 * 2) first phase symptoms recede, pain or pressure in the right subcostal region may appear, hepatomegaly, oliguria ; increased bilirubin and liver enzymes , prolonged prothrombin time
 * 3) 48–120 hours after ingestion, loss of appetite, nausea, vomiting, and malaise again, but with signs of liver failure ( jaundice, hypoglycemia , coagulopathy , and encephalopathy ); sometimes the development of renal failure and cardiomyopathy
 * antidote: N-acetylcysteine ​​- good efficacy demonstrated when administered within 10-12 hours of intoxication
 * within 6–8 hours after paracetamol ingestion, administration of activated charcoal is effective, but reduces the effect of oral N-acetylcysteine
 * other measures: rest, diet, vitamins, hepatoprotectants and ursodeoxycholic acid in the cholestatic form, corticoids in severe liver damage (uncertain effect), liver transplantation in fulminant liver failure.

Intoxication calcium channel blockers

 * Verapamil, nifedipim, amlodipine, felodipine, isradipine,... ;
 * one of the most insidious and difficult to treat drug poisonings;
 * small therapeutic range;
 * bradycardia (slowing down of conduction of impulses through the myocardium, reduction of contractility) up to AV block or asystole;
 * arterial hypotension on the basis of peripheral vasodilation;
 * hyperglycemia caused by suppression of insulin release from the pancreas;
 * unconsciousness and convulsions due to cerebral hypoperfusion;
 * first aid: activated carbon (well absorbable);
 * the necessity of ECG and blood pressure monitoring (preferably invasive);
 * treatment: bolus of crystalloids, calcium chloride (an attempt to compensate for the blockage of calcium transport on cell membranes by administering preparations containing easily available calcium), infusions of adrenaline or noradrenaline (to reduce peripheral vasoconstriction, improve cardiac output), glucose with insulin (need to monitor potassium levels).

Intoxication beta-blockers

 * cardio-selective (beta-1-receptors in the myocardium, including the transmission system): atonolol, metoprolol, acebutolol,... ;
 * cardio-non-selective (beta-2-receptors in the wall of blood vessels, bronchi and adipose tissue): metipranolol, bopindolol, propranolol,... ;
 * alpha and beta-blockers: labetalol, carvedilol ;
 * competence with catecholamines at beta-adrenergic receptors;
 * small therapeutic breadth and different individual receptivity;
 * bradycardia, reduced myocardial contractility, prolonged QRS and QT interval, varying degrees of AV blockade, arterial hypotension ;
 * unconsciousness and convulsions ( metoprolol, propranolol, sotalol );
 * hypoglycemia, hyperkalemia , increased creatine kinase , thrombocytopenia ;
 * first aid: activated carbon (well absorbable);
 * the necessity of ECG and blood pressure monitoring;
 * treatment: crystalloids, adrenaline infusion, atropine (in case of significant bradycardia), glucagon (inotropic effect independent of beta receptors), glucose with insulin, bicarbonate, calcium.

Intoxication with tricyclic antidepressants

 * anticholinergic action – increased muscle tone, dryness of mucous membranes and circulatory symptoms (arterial hypotension);
 * blocking of the so-called fast, voltage-dependent sodium channels in the CNS and in the myocardium and potassium channels;
 * slowed conduction of the impulse, which is manifested by the widening of the QRS complexes;
 * arterial hypotension;
 * first aid: activated carbon (well absorbable);
 * treatment: bicarbonate, noradrenaline (dobutamine contraindicated).

Opioid intoxication

 * codeine, slow-release morphine tablets , buprenorphine (Subutex);
 * stimulation of specific opiate receptors in the CNS;
 * first euphoria, then depression of consciousness and depression of the respiratory center with subsequent hypoventilation (hypoxia with cyanosis) up to apnea ;
 * significantly narrowed pupils; severe cerebral hypoxia is followed by mydriasis ;
 * bradycardia, hypotension due to peripheral vasodilatation ;
 * antidote: naloxone (quick application can cause a rise in catecholamine levels with risks of arrhythmia, pulmonary edema - "heroin lung", asystole, convulsions); the action of naloxone is shorter compared to other opiates (30-45 minutes), and therefore there is a risk of repeated depression of the respiratory center;
 * adequate breathing support, monitoring of vital functions.

Investigation
For a number of drugs, it is possible to determine the plasma level, and for drugs, it is also possible to detect it in the urine. For some drugs, the value of the plasma level and its dynamic development is crucial for deciding on the method of treatment (paracetamol, salicylates, digoxin, theophylline, barbiturates , carbamazepine, phenytoin).

Treatment
Consultation with TIS on telephone lines 224 919 293 and 224 915 402.

Treatment options : primary elimination of the drug from the body (before its absorption), symptomatic care, antidote and secondary elimination methods (after absorption of the drug into the circulation and tissues). Primary elimination from the body is achieved by removing the substance from the stomach by inducing vomiting, by suctioning the stomach contents or by washing the stomach and administering activated charcoal, or a combination of administration of activated charcoal and a laxative, the so-called gastrointestinal lavage. These interventions are most effective within an hour of ingestion, within 15 minutes for liquids. The exception is the ingestion of drug forms with prolonged release, drugs with anticholinergic effects and serious poisoning associated with atony of the stomach and intestines.

As part of supportive treatment, monitoring of basic vital functions and parameters of the internal environment is necessary.

Vomiting

 * Risk of aspiration of vomitus and injury in the oral cavity - the risks usually outweigh the possible benefits;
 * indicated only in absolutely exceptional situations - after ingestion of substances and doses that threaten the child with very serious or fatal poisoning, especially when it is not possible to ensure rapid administration of activated charcoal, or when activated charcoal does not bind the ingested substance, or the child is allergic to activated charcoal.

Gastric lavage
Indicated only after ingestion of toxicologically very serious drugs in doses that significantly threaten the patient's health or life. The effectiveness of gastric lavage and the administration of emetics in eliminating the harmful substance from the stomach decreases significantly after 1 hour after ingestion of the toxic substance, while most patients arrive at the hospital after more than 3 hours after intoxication. Based on experiments on animals and volunteers, the importance of the time factor on the effectiveness of the procedure was clearly demonstrated. When performed within 5 minutes of ingestion, up to 90% of the substance was removed, up to 45% within 10 minutes, 25% within 30 minutes and approx. 10% within 60 minutes..

Procedure

 * In a conscious patient, it is performed in a position on the left side, if possible with the head down to avoid possible aspiration of vomit, or in a sitting position; immobilization by personnel is often required; prior intubation is required in an unconscious patient;
 * a probe of the largest possible diameter (at least 9–11 mm) is introduced, the length from the root of the nose to the xiphoideus process plus 10 cm;
 * it is possible to make sure of the correct location by aspiration of the contents or, in case of doubt, by insufflation of air with simultaneous listening in the stomach area;
 * gastric contents are aspirated, then tepid saline (5–10 ml/kg) is applied and again aspirated – this is repeated until clear gastric contents are obtained; a larger amount of liquid instilled at once can counterproductively accelerate the passage of gastric contents into the duodenum;
 * at the end, a dose of activated carbon (up to 1 g/kg) is applied.

Rare complications: laryngospasm, hypoxia , mechanical injury to the pharynx, esophagus or stomach, aspiration pneumonia , ion and water imbalance.

Contraindications to lavage: unconsciousness with reactivity of the patient, ingestion of detergents, lyes and acids or kerosene - organic oils, kerosene, diesel, gasoline.

Administration of activated carbon
As the most effective method of elimination, the administration of activated charcoal comes to the fore as a "universal antidote" (the recommended dose is governed by the amount of drug ingested; doses vary from 0.5-2.5 g/kg per dose, can be repeated indefinitely - repetition is appropriate if ingested drug undergoes enterohepatic circulation). Timely submission is important. It can also be administered at home, the condition for safe administration is the cooperation of the child (especially with sedatives). Contraindications are ileus and intestinal obstruction.

Substances absorbable and non-absorbable on activated carbon

 * Good absorption: acetaminophen (paracetamol), amitriptyline, amphetamine, acetylsalicylic acid and its salts, chlorpromazine, codeine, diazepam, digoxin, imipramine, morphine, pentobarbital, strychnine;
 * poor absorption: boric acid, ethyl alcohol, methyl alcohol, ethylene glycol, Li, Fe, kerosene and other kerosenes, strong acids and bases.

Administration of the antidote

 * (*) Antidotum je třeba podat do 60 minut od požití toxické látky.
 * (**) Antidotum je třeba podat do 120 minut.

Gastrointestinální laváž
Při odstraňování na aktivní uhlí neabsorbovatelných škodlivin a depotních, retardovaných forem léků či obsahu malých baterií, jež dítě spolklo.
 * přípravky s obsahem natrium fluoratum, vysoce ionizované soli v podobě železitých preparátů k léčbě anémie nebo antidepresiv s obsahem lithia, přípravky s boritany, s etanolem apod., nebo jde o požití tablet s řízeným uvolňováním.

Aplikace vodného roztoku makrogolu (např. Fortrans) žaludeční sondou v dávce 35 ml/kg/h, nebo dětem od 9 měsíců do 5 let 500 ml/h, do 12 let 1 000 ml/h.

V případě požití retardovaných tablet, jejichž účinná látka se váže na aktivní uhlí, je možné v intervalech 2–3 hodin podat zároveň i dávku aktivního uhlí 0,5–1 g/kg.

Masivní odchod stolice nastává za 1–2 hodiny po zahájení aplikace makrogolu. Jeho podávání se ukončí ve chvíli, kdy odchází čistý střevní obsah nebo obsah s přítomností aktivního uhlí.

Sekundární eliminace
Indikována po vstřebání léku do oběhu a tkání – metody: forsírovaná diuréza, peritoneální dialýza, extrakorporální metody jako hemodialýza a hemoperfuze. Forsírovaná diuréza má sporný efekt a poměrně vysoké riziko vzniku vodní a iontové dysbalance. Pro dialýzu jsou vhodné látky s nízkou molekulární hmotností, s malým distribučním prostorem a malou vazbou na bílkoviny plazmy (např. salicyláty, metanol, etylenglykol, litium, isopropanol). Hemoperfuze je vhodná pro látky s nízkou rozpustností ve vodě a vysokou afinitou k absorbentům a nízkou afinitou k plazmatickým bílkovinám (karbamazepin, barbituráty, teofylin). Hemofiltrace odstraňuje látky i s větší molekulární hmotností.

Lipidové emulze
Indikovány při akutních otravách kardiotoxickými léky, kdy těžké kardiální příznaky nelze zvládnout jiným způsobem. Předpokladem je rozpustnost v tucích. Využívá se při terapii otrav některými beta-blokátory, blokátory kalciového kanálu, ale i některými kardiotoxickými antidepresivy, antiepileptiky, antipsychotiky.

Postup

 * Intravenózní podání 20% Intralipidu (1,5 ml/kg jako bolus, následně 0,25–0,5 ml/kg/min. po dobu 30–60 minut do úvodního maxima 500 ml; bolus lze 1–2× zopakovat; rychlost podání se titruje podle klinické odpovědi).

Laická první pomoc
Obecné zásady laické první pomoci:
 * Zachovat klid;
 * nikdy nevyvolávat zvracení;
 * je-li dítě bez příznaků, může dostat napít vodu nebo čaj, ne mléko;
 * zjistit, co dítě požilo, v jakém množství a kolik času od požití uplynulo;
 * kontaktovat Toxikologické informační středisko (TIS) na telefonních linkách 224 91 92 93 nebo 224 91 54 02, případně dětského lékaře, pohotovostní službu nebo nemocnici;
 * nejčastěji lékař TIS doporučí podání tablet aktivního („černého“ či „živočišného“) uhlí;
 * v případně potřeby šetrná doprava do nemocnice (riziko poranění či aspirace zvratků), s sebou vzorek toho, co dítě požilo.