Pediatric Poisonings

Pediatric Poisonings

Epidemiology 99% of ingestions by children under 6 are unintentional. Approximately 40% of ingestions reported to the poison center by adolescents are intentional. Approximately 56% of adolescent ingestions are by females.

Definiton The poison means to injure or kill with a substance that in known or discovered to be harmful . The term poisoning cannotes clinical symptomatology, it also implies that the toxic exposure is unintentional . The term overdose implies intentional toxic exposure , either in the form of a suicide attempt os as inadvertent harm secondary to puposeful drug abuse . The terms poisoning and drug overdose often are used interchargeably , especially when prescription drugs are the agents , even though definiton a drug overdose does not produce poisoning unless it causes clinical symtoms

The general approach to poisoning • 1.Stabilization • 2. Laboratory assessment • 3.Decontamination of the gastrointestinal tract , skin , eyes • 4.Administrate of an antidote • 5.Elimination enhacement of the toxin • 6.Observation and disposition

1.Stabilization • Resuscitation with establisment of the airway , adequate support of ventilation .Particular attention should be dirrected to abnormalities in the cervical spine and temporomandibular joint • Continous cardiac and pulse oximetry monitoring • Maintenance of blood pressure and tissue perfusion ( may require the peovision of volume , correction of acid –base disturbance , administration of pressor agents )

History The following questions may be revealing • What other medicines are in the house? • What was the patient doung that day? • Have there been recent emotionally or traumatic events ? • Is the patient eating a special diet or taking a new health food , alternative medication or performance enhancer ? • Could the patient inadvertently have taken too much of prescribed medication ? • If it can be identified , is the substance non toxic?

Physical examination • Body temperature – hypotermia( exposure to cold , hypoglicemia , barbiturates , ethanol ,overdose ) , hypertemia(LDS , cocaine , slicylates poisoning) • Bradycardia – overdose of digitalis ,beta blokers , calcium channel blokers but also it may be seen iwith hypotermia and spinal cord injury • Hypertension – intoxication with cocaine ,amphetamines , sympathomimetics • Lungs – inhalation of toxic gase s may produce wheezing - tricyclic antidepressant overdose – pulmonary edema - pneumothorax in patients who smoke cocaine , methamphetamina • Pupils – pinpoint pupils – overdose clonidine , opiates , organophosphate insecticids • Level of consciousness

2.Laboratory assessment Complet blood count Determination of serum electrolytes , glucose , BUN , creatinine and calcium , urinalysis ,prothrombin time , hepatic enzymes Pulse oxymetry , 12 lead electrocardiography Arterial blood gases The measurement of serum salicylate and acetaminofen levels is generally added in the case of the patient with overdose of un unknown substance , because these agents are often co- ingestants or are contained in combination drugs Performing a urine pregnancy test in teenager girls is wise Urinary drug screening Chest radiography – aspiration pneumonia , pulmonary edema , Ct scan – if underlying trauma is suspected Lumbar punction – for ruling out meningitis in a patient with fever and coma

3.Decontamination of the gastrointestinal tract , skin , eyes The range of dermal toxins is broad Most of these substances are corrosive agents capable of producing burns that may become full thickness( i.e third degree) Other types of agents are irritants , sensitizers , allergens , vesicants and exfoliants The skin of infants is notable for beeing more permeable than that of adults to substances of all classes If the victim is immersed in atoxic fluid , the first step is his or her extrication , the victim should be disrobe , wash with water Emmergency medical personel should provide themselves every level available of self- protection

3.Decontamination of the gastrointestinal tract , skin , eyes Initial management of all chemical ocular injuries requires immediate decontamination by irrigation Early application of a topical anesthetic is recomandated to facilitate irrigation and anhance the patient comfort The most commonly available solution include sterile water , normal saline an lactated Ringer The upper and the lower eyelids should be retracted ,inspected for retained solid material and injury and irrigated Immediate refferal to an ophthalmologist is necessary for all significant burns

3.Decontamination of the gastrointestinal tract , skin , eyes • Gastric lavage –involves blind placement of a large – bore gastric tube into the stomach , in a patient who can either protect his or her airway or in whom the airway has been protected by an endotracheal tube , with the goal of removing toxicant remaining in the stomach through a combination of instillation of water or physiological saline , followed by suction or gravity induced drainage The cycle of instillation/drainage is repeated until the effluent in clear or until several liters of water /saline have been passed through the tube.Left recumbent Trendelenburg’s position to reduce the risk of aspiration Indications – recent ingestion( less than 1 hr , unless the ingestion involves agents that decrease gastric motility such as anticholinergics) Contraindications – low –viscosity petroleum products , corrosive and inability to protect the aiway Adverse effects – hypoxia , perforation of the gastrointestinal tract or pharynx, aspiration pneumonitis , electrolyte abnormalities

3.Decontamination of the gastrointestinal tract , skin , eyes • Activated charcoal – binds to diverse substances , rendering them less available for systemic. absorbtion from the gastrointestinal tract Single Dose – 1 g/kg in children max dose 50 g , 25-100 g in adults , administred orally( in water ) or via nasogastric tube . Indication –, fenitoin, glutetimid , acetaminofen , benzodiazepine poisoning Contraindications – ingestion of caustics , in case of risk for gastrointestinal hemorrhage or perforation , in any patient in whom the airway protection is not assured , in case of ileus or mechanical bowel obstruction Adverse reactions and complications – vomiting , duarrhea and constipation , pulmonary aspiration , direct administration into the lungs via misplaced nasogastric tube

3.Decontamination of the gastrointestinal tract , skin , eyes • Multiple dose activated charcoal – used in the case of drugs that undergo extensive enterohepatic or enteroenteric circulation Indication – carbamazepine , dapsone , phenobarbital , quinine , theophyline Contraindications – same as for single dose - the presence of decreased peristalsis should provoke caution • Cathartics – magnesium salts and nondigestible sorbitol . May induce significant harm in children with renal disease .Manitol 20% - dose 4-5 ml/kg , Sorbitol 70% 1-2 ml /kg . Complications – nausea , vomiting , hypermagnesiemia and cardiac dysrhythmias , dehydratation .

3.Decontamination of the gastrointestinal tract , skin , eyes Whole bowel irrigation –involves administration , by mouth or nasogastric tube , of large amounts of an iso- osmotic polyethylene glycol electrolite solution with the goal of removing unabsorbrd toxicant from the gastrointestinal tract as rapidly as possible by rectal expulsion .Dose 25 ml /kg/hr for 4 -6 hr .Total dose 500 ml /hr under the age of 6 yrs , 1000ml /hr under the age of 10 yrs , 1500-2000 ml /hr in adolescents Indications – iron ,lithium , drug packets Contraindications – mechanical or functional obstruction , gastrointestinal haemorrhage

4.Administrate of an antidote • Only a small proportion of poisoned patients are amenable to antidotal therapy • Only a few poisoning is antidotal therapy urgent (e.g., CO, cyanide, organophosphate and opioid intoxication)

Specific Intoxications and Their Antidotes

5.Elimination enhacement of the toxin Forced diuresisby administering 2-3 times the maintenance fluid to achieve U.O = 2-5 cc/kg/hr (contraindicated in pulmonary or cerebral edema and renal failure) Urinary alkalinizationto eleiminate weak acids(salicylates, barbiturates and methotrexate), can be achieved by adding NaHCO3 to the IV fluids, the goal is urine pH of 7-8 Serum alkalinizationin triciclic antidepresant toxicity Hemodialysisin low molecular weight substances with low volume of distribution and low binding to plasma proteins (barbiturate , methanol, ettilenglicol , heavy metals , lithium) Hemoperfusion, protein binding is not a limitation

Special Pediatric Issues ALL THINGS TEND TO END UP IN THE MOUTHS OF YOUNG CHILDREN!!

Which is Candy?

Sweet Tarts vs. Ecstacy

Physiologic Differences • Blood brain barrier still more permeable to toxicologic substances until around 4 months. • No studies demonstrating increased permeability, rather this is an estimate based on toxicity noted with smaller doses than expected. • Higher metabolic demands. • Decreased ability to glucuronidate in the infant period. Second trimester pregnancies that were terminated showed only 10% activity of the P-450 system. • No better studies to date, but most believe between ages 2-4 years that glucuronidation is equivalent to adults. • Decreased glycogen stores.

Physiologic Differences • Increased body surface area can lead to thermoregulatory issues. • Children reside lower to the ground. This puts them at higher risk for ingesting compounds heavier than air. Often adults will NOT have the same exposure. • Inability to avoid hazards – they do not read warning labels or “Do Not Enter” signs.

Acquired methemoglobinemia - is caused by an external source, usually a drug or medication. Methemoglobin is an aberrant form of hemoglobin arising from oxidation of iron in the normal heme molecule from the ferrous form (Fe2+) to the ferric (Fe3+) form. The presence of ferric heme molecules causes a structural change in the hemoglobin molecule, resulting in reduced oxygen-carrying capacity and impaired unloading of oxygen at the tissue. This left shift in the oxygen saturation curve results in functional anemia. Typically, red blood cells maintain a steady-state methemoglobin level of less than 1% via 2 main enzymatic pathways. Elevation in methemoglobin levels can be caused by congenital enzyme deficiencies or exposure to exogenous oxidizing agents that disrupt the equilibrium established by these pathways. Causes – Nitrates fountain water in the first year of life , Sulfamides , EMLA cream(lidocaine and prolocain),Nitric oxid ,Metoclopramid , Anilin diapers

With a methemoglobin level of 3-15% skin can turn to a pale gray or blue (cyanosis). With levels above 25% the following symptoms may be present: Cyanosis unaffected by oxygen administration Blood that is dark or chocolate in color that will not change to red in the presence of oxygen Headache Weakness Confusion Chest pain When methemoglobin levels are above 70% death may result if not treated immediately. Blood from the heel sticks is chocolate-brown and does not become pink when exposed to room air. Management 1. Laboratory data – methemoglobin > 2% in new borne ,>1,5% in premature new borne Chemistry – serum electrolytes , liver enzyme , BUN , complete blood count ( CBC)

Management 2. Vital signs – cardiac and respiratory stabilisation, seizures treatment , O2 3.Decontamination – wash skin , gastric lavage( in case of ingestion) 4.For acquired methemoglobinemia the typical treatment is with methylene blue. This is administered with an IV over a five-minute period and results are typically seen within 20 minutes. Methylene blue reduces methemoglobin back to hemoglobin. Dose 1 mg/kg , (concentration 1%) , max dose 7 mg/kg If symptoms persist after 1 hour, repeat doses are given with caution, as accumulation of the drug can result in increased production of methemoglobin . 5 .Ascorbic acid 30 mg/kg iv 6.If symptoms persist despite the above-outlined therapy, hemodialysis might be required( metHb> 60% , hemolysis , sulfmethehemoglobinemia

Benzodiazepine Toxicity Depending on the drug preparation and the presence of co -ingestants , the time from ingestion to appearance of the drug in the systemic circulation is 10-20 min . After absorbtion , benzodiazepines are higly protein bound , ranging from 70%-99%. Protein binding is greatest with highly – soluble drugs(diazepam 99% bound) and least with more water soluble agents( alprazolam 70% bound) . Only unbound drug is available to cross the blood- brain barrier and interact with CNS receptors . Benzodiazepines are metabolized predominantly in the liver by oxidation and/or conjugation. Elimination of benzodiazepine metabolites usually occurs via renal clearance Respiratory failure – frequent -Triazolam ,Flunitrazepam ,

Paradoxical agitation Slurred speech Altered mental status, impairment of cognition Confusion Drowsiness Coma (Classic-isolated benzodiazepine overdose presents as coma with normal vital signs). Respiratory depression Hypotonia Diagnosis Qualitative urine screening for the presence of benzodiazepnes or their metabolites provide rapid useful information in evaluation of patients with un unknouwn cause of CNS depression. A negative screening result does not rule out the presence of a benzodiazepine. Qualitative screening of urine or blood may be performed but rarely influences treatment. Quantitative plasma measurements are not available in most hospitals and provide no significant therapeutic direction to the trating pshysician. Plasma concentration of benzodiazepines correlate very poorly with the severityof toxic effects( CNS depression) or mortality. Physical Examination

Treatment Single-dose activated charcoal is not routinely recommended as the risks far outweigh the benefit( fast absorbtion). Activated charcoal - single dose 1 g/kg Hypotension - use Dopamine Coma and respiratory depression - Flumazenil 0,1 mg /kg in 30 sec , if the patient is still in coma after 30 sec a second dose will be use. In long-term benzodiazepine users, Flumazenil may precipitate withdrawal and seizures; in patients taking benzodiazepines for a medical condition, flumanazenil may result in exacerbation of the condition. Respiratory support may be necessary

Barbiturate toxicity Long action > 48 hr ( fenobarbital , mefobarbital) Medium action (amobarbital) Short action 3-4 hr(ciclobarbital,secobarbital) VeryShort < 30 min (thiopental) Barbiturates mainly act in the CNS, though they may indirectly affect other organ systems. Direct effects include sedation and hypnosis at lower dosages 1. The CNS depressant effect mimics that of ethanol(ataxia ,slurred speech lethargy ,coma) 2. Coma - decreased pupillary light reflex ,decreased deep tendon reflexes , myosis in severe cases. 3. Respiratory exam -acute respiratory distress syndrome ,apnea,hypoxia 4. Cardiovascular exam –hypotension,tachycardia,bradycardia,diaphoresis,shock 5. Renal dysfunction due to acute tubular necrosis( muscle necrosis and calcification may be associated with acute renal failure) Physical Examination

6. Coma blisters are lesions that occur in the setting of a variety of neurological diseases. Although most commonly associated with barbiturate overdose, they can be seen in the setting of coma due to other etiologies. Blisters develop 48–72 h after the onset of unconsciousness.They typically appear as blanchable erythematous pathches at pressure points of the skin . A biopsy of the lesion shows epidermal or subepidermal blisters with characteristic necrosis of the sweat glands .Over the next 2-3 days these patches become blisters or erosions , but they usually heal spontaneously over 1-2 weeks Physical Examination

Management Attention to the airway and hypoxia Vital signs( risk of cardiovascular compromise and hypotermia) Ruling out hypoglicemia ( missing diagnosis can have grave consequences) Activated charcoal – 1 g/kg , for patients who have a compromised airway , endotracheal intubation is advised prior to giving charcoal Laboratory evaluation – basic electolites and glucose . Serum barbiturate levels can be useful in gauging the clinical course of therapy , screenin assays employing semiquantitative immunoassays of serum and urine are readly avilable . BUN , hepatic enzymes may have increased values . ECG ,EEG

Management • Urine alkalinization is of theoretical value in the treatment of phenobarbital overdose but not overdose of other barbiturates According of the theory of ion trapping , phenobarbital , as a weak acid , will be poorly reabsorbed by the renal tubules if it can be ionized in the milieu of an alkaline urine (NaHCO3 1-2 mEq/kg until urinay Ph 7,5- 8 ) Such alkalinization is rarely achieved in clinical practce without the unwanted effects of metabolic alkalosis or hypernatremia . • Multiple dose activated charcoal has been shown to be more effective in decreasing phenobarbital half life in adults and neonates . • Extracorporeal removal by hemodialysis or hemoperfusion is also effective in removing the barbiturates , although they are reserved for the most severe cases

Pesticides • Specifically organophosphates and carbamates. • They work by inhibiting acetylcholinesterase. • Present with cholinergic symptoms

Cholinergic Symptoms

Cholinesterase - 2 forms 1 . RBC form - true cholinesterase 2. plasma form - pseudocholinesterase. Cholinesterases →hydrolyzetheneurotransmitter acetylcholine into inactive fragments. Organophosphates form an initially reversible bond with the enzyme cholinesterase. The organophosphate-cholinesterase bond can spontaneously degrade, reactivating the enzyme, or can undergo a process called aging( the first 72 hours ,Oxime treatment can be used) The process of aging results in irreversible enzyme inactivation

Inactivation of the enzyme →acetylcholine will accumulate at the synapse, leading to overstimulation and disruption of nerve impulses. ▼ Nicotinic stimulation at the motor endplate(Skeletal-muscle depolarization and fasciculations ) Muscarinic effects occur at the postganglionic parasympathetic synapses, causing smooth-muscle contractions in various organs

Muscarinic Symptoms • Sweating • Miosis • Lacrimation and salivation • Bronchorrhea • Bradycardia • Emesis, diarrhea, Abdominal cramping and intestinal hypermotility • Urinary incontinence

Nicotinic Symptoms Remember the days of the week ! Mydriasis Tachypnea Weakness Tachycardia Fasiculations Pediatric patients tend to present with a predominance of nicotinic symptoms!!!

Central nervous system • Anxiety • Seizures • Central respiratory paralysis • Altered level of consciousness and/or hypotonia

Weakness from Pesticides

Intermediate Syndrome- IMS -proximal muscle weakness , weak neck flexors ,respiratory failure -onset 24- 72 h after acute cholinergic crisis , can last several days or weeks Delayed polyneuropathy -symmetric demyelinisation process • patient notice the onset of weakness and paresthesias about 3-6 month after initial ilness • no known treatment , resolution over 6 month to 1 year

Laboratory test • CBC count to rule out infectious causes. • Chemistry tests may be useful in ruling out electrolyte disturbances, renal and liver test • RBC cholinesterase tests may reveal decreased activity, which confirms the diagnosis. • Chest x ray , ECG

Treatment • Decontamination involves removing all of the patient's clothing and washing him or her with water and soap. • Ensure airway support and ventilation • Circulatory support with intravenous (IV) access, fluids, and cardiac and pulse oximetry monitoring • Gastric decontamination with activated charcoal should be performed in cases of ingestion.

Treatment Atropine 0.02 mg / Kg IV. Repeat as needed and titrate to respiratory secretions. It will likely take massive doses!!(every 3-5 min) Toxogonin (for Romania) – 4-8 mg/kg iv in 30 min , will adm again after 4-6 h Pralidoxime (2-Pam) 20-40 mg / Kg bolus followed by 10-20 mg / Kg /hour infusion. Fresh frozen plasma 10 ml/kg Remember to send RBC and Plasma Cholinesterase levels upon arrival and daily.

Corrosive injury

Pediatric Poisonings