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1、Pediatric Poisonings,Mark Sutter,MD,Overview,Epidemiology Important Legislation Packaging and Marketing Problems Physiologic Differences Iron Pesticides Deadly Pediatric Poisons,Epidemiology,US Poison Centers receive 1.5 million calls a year regarding pediatric ingestions.79%of these calls involve c
2、hildren younger than age six.56%of pediatric exposures are from products around the house including medicines,cleaning agents,pesticides,plants and cosmetics.,Epidemiology,99%of ingestions by children under 6 are unintentional.Approximately 40%of ingestions reported to the poison center by adolescen
3、ts are intentional.Approximately 56%of adolescent ingestions are by females.,Epidemiology,Legislation,The Poison Prevention Packaging Act of 1970.(PPPA)Requires child protective packaging of hazardous household products.Over the last 30 years the list of substances regulated by the PPPA have expande
4、d to include medicines,solvents,and oils.Data shows reduction of 45%mortality of pediatric patients since the introduction and expansion of PPPA.,Special Pediatric Issues,ALL THINGS TEND TO END UP IN THE MOUTHS OF YOUNG CHILDREN!,Which is Candy?,Sweet Tarts vs.Ecstacy,Poison Center Campaign,Physiolo
5、gic 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
6、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 are
7、a 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.,Iron,The most common cause o
8、f death in toddlers.Classically taught as having five clinical stages.Remember prenatal vitamins,supplements,and“natural products”.,Iron,Toxic doses occur at 10-20mg/Kg of elemental iron.Prenatal vitamins typically contain about 65 mg of elemental iron.Childrens vitamins contain about 10-18 mg of el
9、emental iron.,The Five Stages,Stage 1Nausea,vomitting,abdominal pain and diarrhea.Stage 2This is the latent phase often between 6-24 hours as the patient resolves GI symptoms.Stage 3Shock stage involving multiple organs including coagulopathy,poor cardiac output,hypovolemia,lethargy and seizures.Sta
10、ge 4Continuing of hepatic failure and ongoing oxidative damage by the iron in the reticuloendothelial system.Stage 5Gastric outlet obstruction secondary to scarring and strictures.,Management,Detailed history and physical including a rectal exam for frank blood.Aggressive fluid resuscitation and int
11、ravenous access.Whole bowel irrigation and KUB to look for pills.Laboratory analysis for CBC,chemistry,and iron levels(peak around 4 hours).Will often require repeat levels with a repeat chemistry.TIBC has no utility in the acute overdose setting.,Management,Management,If the patient is in shock,rem
12、ember to atleast type and screen(if not cross match)for blood.Give deferoxamine before iron level is back if the patient is in shock.Deferoxamine was derived from streptomyces pilosus.Hypotension and allergic reactions are seen.ARDS is a known complication and usually limit its use to 24 hours or le
13、ss.,Pesticides,Specifically organophosphates and carbamates.They work by inhibiting acetylcholinesterase.Present with cholinergic symptoms,Cholinergic Symptoms,Nicotinic Symptoms,Remember the days of the week!MydriasisTachypneaWeaknessTachycardiaFasiculationsPediatric patients tend to present with a
14、 predominance of nicotinic symptoms!,Weakness from Pesticides,Treatment,Atropine 0.02 mg/Kg IV.Repeat as needed and titrate to respiratory secretions.It will likely take massive doses!Pralidoxime(2-Pam)20-40 mg/Kg bolus followed by 10-20 mg/Kg/hour infusion.Remember to send RBC and Plasma Cholineste
15、rase levels upon arrival and daily.,The Expanded“One Pill Kill”,The Deadly Pediatric Poisons,Calcium Channel BlockersCyclic AntidepressantsLomotilOpiates/Opiods,Salicylates(methyl)Toxic AlcoholsSulfonylureasCamphorClonidine and imidazolinesAntimalarials,Calcium Channel Blockers,Three major classesPh
16、enylalkylamineBenzothiazepineDihydropyridineBlock L-type channelsCause hypotension,bradycardia,and arrythmias.Immediate and sustained release.Usually not the childs medication.,Calcium Channel Blockers,Manage A,B,CsCheck Labs and EKGFluidsCalciumGlucagonPressorsHigh Dose InsulinAtorpine and Pacing,C
17、alcium Channel Blockers,May be able to wean pressors with insulin.Insulin dosage is 1 unit/kg bolus and 0.5 units/kg/hour drip.Monitor sugar Q20 minutes for the first few hours.Most will NOT become hypoglycemic.,Cyclic Antidepressants,They were the leading cause of poisoning fatality until 1993.They
18、 interfere with reuptake of biogenic amines and serotonin at the nerve terminal.Manifest toxicity by anticholinergic effects,alpha-1 inhibition,sodium channel blockade,and can inhibit GABA.Cause CNS and cardiovascular toxicity with arrythmias leading to mortality.,EKG Findings,EKG Findings,Cyclic An
19、tidepressant Managment,Manage A,B,Cs aggressivelyOptimize electrolytesFollow serial EKGs and use Bicarb if:QRS 100 or 110 msecaVr 3 mmIf bicarbonate and magnesium are not effective,lidocaine is the antidysrhythmic of choice.Norepinephrine is the pressor of choice for refractory hypotension.,Is it th
20、e Sodium or the Bicarb?,The answer is BOTH!Sodium overcomes the partial blockade from cyclic antidepressants.Alkalinization does change binding properties.,How does the bicarb work?,Initially thought to increase protein binding thus limiting free drug in the bloodRat study using alpha-1 acid glycopr
21、otein(AAG)only decreased arrhythmias at massive doses.AAG is a proven TCA binder.Current theories is that the ionic form of the TCA binds to the sodium channel causing blockade and the bicarbonate changes the TCA from the ionic form to the neutral form causing less blockade.,Lomotil,Antidiarrheal ag
22、ent containing both diphenoxylate and atropine.Both agents are absorbed by the GI tract and absorption may be delayed in overdose due to inhibitory effects on smooth muscle motility.Diphenoxylate is an opoid that is metabolized to difenoxin which is 5 times more potent than the parent compound and h
23、as half life of 12-14 hours.,Lomotil,Patients manifest signs and symptoms of opiate toxicity.Respond well to naloxone and supportive care.Current recommendations are for a minimum of 24 hour observation.,Opiates/Opiods,Typically present with respiratory depression,altered mental status,and miosis.Ad
24、dress the patient like any other“altered mental status”Key point is to remember to consider an opiate ingestion.,Naloxone Dosing,Usually start with 0.01-0.1 mg/Kg.Repeat as frequently as needed to reverse symptoms.If a drip is required,calculate how much naloxone was used in the first hour and start
25、 the drip at 2/3 that dose.,Salicylates,Pharmacology,Irreversibly inhibits the enzyme cyclooxygenase.This inhibits prostaglandin synthesis.Since prostaglandins are not synthesized,their downstream byproducts are never released such as:IL-6,TNF,and alpha and beta interferons.Believed to directly inhi
26、bit neutrophils to decrease the inflammatory response.,Salicylate Metabolism,Pathophysiology,Salicylates stimulate the brainstem to cause hyperventilation(respiratory alkalosis).Multifactorial renal impairment leads to accumulation of sulfuric and phosphoric acids.Interfere with the Krebs Cycle limi
27、ting substrates for ATP generation.,Pathophysiology Continued,Uncouples oxidative phosphorylation which leads to increased pyruvic and lactic acid level and generates heat.Causes salicylate induced fatty acid metabolism which produces ketone bodies.This ketoacidosis contributes a significant portion
28、 to the overall metabolic acidosis.,Clinical Manifestations,Early symptoms are usually non-specific such as nausea and vomiting.Tinnitus with or without hearing loss can also be an early sign.Hyperventilation is often a warning sign of a significant ingestion.CNS signs can vary from vertigo to hallu
29、cinations to stupor.Coma is rare except in massive overdoses.In large overdoses,almost every organ system becomes involved.,Treatment,Address the A,B,Cs.Detailed history and exam.Laboratory evaluation and consider a blood gas if your history suggests an ingestion.Activated charcoal should be given.E
30、vidence for multidose charcoal is equivocal.The use of sodium bicarbonate.Measure serial salicylate levels and chemistries.,Sodium Bicarbonate Therapy,The goal is to titrate the urinary pH to 8.Potassium must be monitored closely because if the potassium drops,the kidney will retain the potassium an
31、d excrete hydrogen.Excretion of hydrogen will make it impossible to titrate your therapy to a urinary pH of 8.,Indications for Hemodialysis,Renal failure.Congestive heart failure(relative).Acute lung injury.Persistent CNS disturbance.Severe acid-base or electrolyte imbalance,despite appropriate trea
32、tment.Hepatic compromise with coagulopathy.Salicylate concentration(acute)100 mg/dL.,Toxic Alcohols,Ethylene GlycolAntifreezeCoolant MixturesMethanolWindshield wiper fluidMoonshine,Ethylene Glycol and Methanol,fomepizole,Mg,B6,folate,thiamine,The Osmolar Gap,Clinical Symptoms,Treatment,Fomepizole or
33、 ethanol both inhibit alcohol dehydrogenase.CofactorsPyridoximeFolateMagnesiumThiamine,Fomepizole Dosing,Loading dose15 mg/KgNext 4 doses10 mg/KgSubsequent doses15 mg/KgDosing schedule is every 12 hours except during dialysis.Then it is every 4 hours during dialysis as it gets dialyzed off.,Sulfonyl
34、ureas,Mechanism of Action,Sulfonylureas keep the potassium efflux channel closed.This keeps the cell depolarized which allows the voltage-gated calcium channel to remain open.This stimulates insulin release.,Sulfonylureas,Since sulfonylureas stimulate insulin release,this can result in prolonged hyp
35、oglycemia.Continued doses of dextrose will continue to stimulate insulin release.Octreotide works by antagonizing insulin release.Exact mechanism is still being debated.,Octreotide,The dose is 1-2 mcg/Kg bolus IV or SC.Some papers suggest a continuous infusion while others suggest an every 8 hour do
36、sing regimen.If placed on an octreotide regimen,the octreotide must be off a minimum of 24 hours without another episode of hypoglycemia before discharge.,Key Facts,A retrospective study showed 4 of 25 patients developed delayed hypoglycemia including 1 at 16 hours post ingestion.If a sulfonylurea i
37、s ingested,a minimum of 24 hours of observation is recommended.,Camphor,Aromatic ketone derived from plants.Acts as a topical rubefacient.Usually ingested as a liquid.Often in preparations combined with other medicines such as salicylates.,Camphor,Initial symptoms are gastrointestinal distress and g
38、eneralized feelings of warmth.Symptoms usually progress quickly to nervous system involvement from restlessness to seizures.Delayed seizures have been reported up to 9 hours after ingestion.,Camphor,Ingestions of 1-2 grams have been fatal in children.A 19 month old died after ingesting 5 ml of 20%ca
39、mphorated oil.Asymptomatic patients should be observed 6-8 hours and discharged if not developing symptoms.Remember about hydrocarbon aspiration if product is an oil with a history of coughing or vomitting.,Clonidine and Imidazolines,Clonidine is an alpha-2 agonist that is used for hypertension.Imid
40、azolines,such as oxymetazoline(afrin)are used as decongestants.Symptoms typically present like an opiate overdose?Why?,?Like an Opiate Overdose?,They are NOT structurally related to opiates.The alpha-2 receptor targeted by clonidine has significant functional overlap with the opiate receptor.Both ma
41、y be located on the same neuron,both coupled by via G-protein to the same potassium channel.May require larger doses of naloxone to reverse symptoms.,Antimalarials,These include cloroquine,hydroxychloroquine,quinine and their relatives.They work by both sodium channel blockade as well as blockade of
42、 the potassium rectifier channel.These lead to QRS widening as well as QT prolongation.Torsades is a known complication of overdose.,Symptoms,Small therapeutic index.Presents with symptomatology known as“cinchonism”which is tachycardia,nausea,vomitting,hearing loss,tinnitus,headache,vertigo,dystonia
43、,and diarrhea.Patients often known to have a flushed appearance.,Treatment,These patients require aggressive management of electrolytes.If the QRS widens,treatment with sodium bicarbonate is indicated.Magnesium should be used for Torsades.If ventricular arrythmias occur despite optimal management,li
44、docaine is the treatment of choice.(Avoid class 1a,1c),Selected Toxic Dosages,Summary,Remember the“Deadly Pediatric Poisons”Dont be fooled if the“look good”as significant toxicity is still possible.Contact the poison center early as knowing the dosage and time of ingestion can influence your managem
45、ent,Review Articles,Michael JB,Sztanjnkrycer MD.Deadly pediatric poisons:nine common agents that kill at low doses.Emergency Medicine Clinics of North America 2004;(22):1019-1050.Bar-Oz B,Levichek Z,Koren G.Medications that can be fatal for a toddler with one tablet or teaspoonful.Pediatric Drugs 2004;6(2):123-126.,
