Pediatric Toxicology Pills and poisonous bites High Yield

Pediatric Toxicology Pills and poisonous bites High Yield
Eiman Abdulrahman MD/MPH Pediatric Emergency Medicine Fellow Emory University 9/20/2018

Outline Important highlights in pediatric toxicology
Young children vs Adolescents Prevention Overview of pills potentially fatal in children even in small amounts Approach to management Snake and spider bites Not comprehensive will not cover toxic alcohol ingestions i.e ethyl glycol and Methanol, isopropill alcohol, hydrocarbons, carbon monoxide 9/20/2018

Epidemiology 1.25 million annual cases in <6years.
15,447 fatalities; 537 (3.7%) in <6yrs; 397 (2.6%) in <2yrs (since 1983) Of 27 deaths in 2004; 19 were caused by pharmaceuticals (analgesics and opioids) of which 14 were in <2yrs 12 deaths were pre-hospital More than 1 million involve children <3yr or younger 56% of pediatric exposures are due to cleaning products cosmetics vs 44% pharmaceuticals- majority of hospitalizations and fatalities are from pharmaceuticals Fortunately, fatalities are rare and most exposures are non-toxic 2004 AAPCC annual report 1.25 million cases Since 1983 AAPCC reporting data: 15,447 fatalities; 537 (3.7%) in <6yrs; 397 (2.6%) in <2yrs We will talk about the some of the medications that are toxic even in small amounts 9/20/2018

Pediatric Toxicology Young children vs Teenagers
79% of all pediatric exposures occur in <6years and approx 99% are unintentional Approx 40-45% of ingestions in adolescents are intentional and 56% are female (substance abuse vs suicide attempts) 51% of reported adolescent poisoning is intentional 9/20/2018

Young Children Without suicidal intent Usually one substance
Usually non-toxic Small amount Present for evaluation within one hour Most exposures are nontoxic because intent is exploration rather than self harm But in some cases even one pill can kill ie In most situations/exposures, a 10kg toddler would need to ingest 10 Ferrous sulfate 325 tablets before life threatening toxicity, however there are medication where one or two can kill 9/20/2018

Young children Physiologic considerations High Metabolic Demands
More permeable BBB until 4mos Decreased glycogen stores 9/20/2018

Adolescents 56% of seriously poisoned children
Overdose from suicidal attempt Adverse effect while trying seeking euphoria More frequently hospitalized than younger children ( includes psych) 42% of AAPCC reported adolescent fatalities from suicide vs 4% from medication errors and adverse reactions 9/20/2018

Prevention The Poison Prevention Packaging Act (PPPA) of 1972 has reduced pediatric mortality by 45% Mandatory child protective packaging in household products, medicines, solvents FDA 1997 regulation with packaging with blister packs of 30mg Iron tablets (overturned in 2003) Significant decline in iron overdose Small amounts of some substances can extremely toxic to children Unique poisoning in young children with significant morbidity and mortality are uncommon 9/20/2018

Lethal exposures Analgesics Sedative/hypnotic/psychotics
Antidepressants Stimulants and street drugs Cardiovascular drugs Alcohols Chemicals Gas and fumes Antihistamines Analgesics Sedative/hypnotics/psychotics Antidepressants Stimulants and street drugs Cardiovascular drugs Alcohols Chemicals Anticonvulsants Gases and fumes Antihistamines Muscle relaxants Hormones and hormone antagonists Cleaning substances Automotive products Cough and cold preparations Pesticides 9/20/2018

Lethal Drugs Antimalarials Antidysrhythmics Benzocaine β-blockers Calcium channel blockers (CCBs) Camphor Clonidine (and other imidazolines) Lomotil (diphenoxylate/atropine) Lindane Methyl salicylate Opioids Sulfonylureas Theophylline Tricyclic antidepressants (TCAs) 14 drugs lethal in small amounts in young children/toddler Camphor= waxy white or transparent solid w/ aromatic odor (found in wood of camphor laurel or large evergreen tree or synthetically from oil of turpentine) It is active ingredient in anti-itch gels and cooling gels has a (similar feeling as menthol) seen in also in Vicks Vaporubs Lomotil=anti-diarrheal; active ingredients diphenoxylate related to meperidine and atropine=anticholinergic Slows down the intestine Lindane used for lice/scabies 9/20/2018

General Approach Airway Breathing Circulation Disability Drugs
Decontamination Airway: Maintain patency, assess protective reflexes Breathing: Adequate tidal volume/ shallow breathing? ABG? Circulation: Secure IV access, assess perfusion Disability: Level of consciousness (AVPU alert, verbal, pain, unresponsive or GCS) Pupillary size, reactivity Drugs: Dextrose (cbg), Oxygen, Naloxone (Other ALS medications) Decontamination: Ocular—copious saline lavage Skin—copious water, then soap and water GI—consider options 9/20/2018

Focused history Three key questions: WHAT substance was ingested?
WHEN did the ingestion occur? HOW MUCH was ingested? Answers to these questions will answer: Severity of the ingestion Potential benefits/efficacy of gastrointestinal decontamination Whether or not therapeutic interventions will be potentially necessary Accurate interpretation of specific drug levels Disposition of patients 9/20/2018

Key PE Vital signs Level of consciousness, neuromuscular status
Eyes-pupils, EOM, fundi Mouth-corrosive lesions, odors CV- rate, rhythm, perfusion Resp- rate, chest excursion, air entry GI- motility Skin- color, bullae or burn, diaphoresis, piloerection, Eyes: pupillary size, symmetry and response to light , presence of nystagmus Oropharynx: moist or dry, + or – gag reflex, any odor Abdomen: + or – bowel sounds CNS: GCS, seizures + or – DTR’s 9/20/2018

Laboratory evaluation
CBC, co-oximetry ABG, serum osmolarity EKG/cardiac monitor CXR, abdominal xray Electrolytes, bun/cr, glucose, calcium, LFT, UA Urine tox screen Quantitative tests (esp acetaminophen) Urine screen: cocaine, amphetamines, barbituates, benzodiazepines, opiates, THC/marijuana, methadone Serum screen: alcohol, salicilates and acetaminophen Marijuana metabolites/THC Cocaine metabolites/Benzoylecgonine Opiates: morphine and codeine Phencyclidine Amphetamines: amphetamine and methamphetamine 9/20/2018

Assessment Clinical findings Toxidromes Laboratory abnormalities
Anion gap: (Na + K)-(Cl + HCO3) Osmolarity: (2x Na)+ (Bun/2.8)+(Glu/18) Osmolar gap: measured-calculated Clinical findings Laboratory abnormalities Anion gap: (Na + K) – (Cl + HCO3), nl = Osmolarity: (2 x Na) + (BUN/2.8) + (GLU/18) = 290 mOsm/kg Osmolar gap: measured – calculated, nl = < 10 Toxidromes 9/20/2018

Toxidromes 9/20/2018 Anticholin-ergics (Antihista-mines, Many Others)
Organophosphates (Insecticide Nerve Gases) Opiates Clonidine Barbiturates Sedative-Hypnotics Salicylates Theophylline Sympathomimetics (Amphetamines, Cocaine) MS/CNS Agitation, delirium, psychosis, convulsions Delirium, psychosis, coma, convulsions Confusion, fasciculations, coma Euphoria, somnolence, coma Somnolence, coma Lethargy, convulsions Agitation, tremor, convulsions Heart rate Increased Decreased (or increased) Decreased — Blood pressure Temp Respirations Pupils Large, reactive Large, sluggish Small Pinpoint Large Bowel sounds Present Diminished Hyperactive Skin Dry skin Flushed, dry Diaphoresis Misc “SLUDGE”a Vomiting Toxidromes Anticholinergics (atropine, antihistamines, TCA) Blind as bat, red as beet, hot as a hare, dry as bone, mad as hatter Blocks SLUD (salivation, lacrimation, urination and defecation) Only difference between anticholinergics and sympathomimietics is in the skin ( anticholinergics= dry) Cholinergics (organophospahtes) DUMB3ELS= Defecation Urinary incontinence Miosis Bradycardia/Bronchospasm/Bronchorrhea Emesis Lacrimation Salivation Opioids (codeine, morphine, heroin) VS bradycardia, bradypnea, hypotension CNS hyporeflexia euphoria to coma Eyes pinpoint pupils Sedatives/hypnotics ie ethanol VS bradycardia, bradypnea, hypotension CNS confusion to coma to ataxia Eyes nystagmus, miosis or mydriasis Salicilates VS fever, hyperpnea CNS lethargy to coma odor oil of wintergreen Misc vomiting 9/20/2018

Detoxification Reassess ABCDs GI decontamination:
Dilution, gastric emptying, Activated charcoal, catharsis, whole bowel irrigation Urgent antidotal therapy Consider excretion enhancement Diuresis, urine alkalinization, dialysis, hemoperfusion Reassess ABCDs Institute appropriate GI decontamination (if not already under way) Dilution, Gastric Emptying, Activated Charcoal, Catharsis, Whole Bowel Irrigation Urgent antidotal therapy Consider excretion enhancement Diuresis, Urinary Alkalinization, Dialysis, Hemoperfusion “Get the poison out” mainstay of toxicology until recently w/ controversy about different methods 9/20/2018

Case 1 “lethargic” 4 year old w/ ALOC
Grandmother called 911 when girl was not arousable VS: T 37.6 HR 60 RR 18 BP 80/60 Pulse Ox 98% Differential? 9/20/2018

Case 1 “lethargic” MNEMONIC FOR ALOC A- Alcohol E- Epilepsy
I- Insulin/intussusception O-Overdose U- Uremia T- Trauma I- Infection P- Psychiatric S- Shock 9/20/2018

Case 1 “lethargic” PE: 1mm pupils reactive Dry skin
No trauma except for “bandaid” on Rt knee Diagnosis? 9/20/2018

Case 1 “lethargic” Clonidine patch on Rt knee
Fluid resuscitation- NS20ml/kg Naloxone w/ no effect Admitted to PICU D/C next day Challenging Cases in Pediatric Emergency Medicine ACEP conference Marianne-Gausche-Hill MD, FACEP 9/20/2018

9/20/2018

Brown Recluse Spider (Loxosceles)
Southern and mid-western states Brown violin shaped mark on dorsum of cephalothorax Usually outdoors, but make indoor nests in closets Shy and will only attack when provoked Venom is cytotoxic and hemolytic Prefer warm, dry indoor areas such as sheds, cellars, and abandoned buildings 9/20/2018

Clinical presentation
2-8 hours Local reaction with mild-moderate pain (stinging sensation) Erythema, central blister or pustule 24 hours Fever, chills, malaise weakness, N/V, rash with petechiae, joint pain, DIC, hematuria, renal failure Subcutaneous discoloration that spreads over 3-4 days Spreads to cm Pustule drains leaving ulcerated crater that scars Scar formation is rare after 72 hrs Reaction varies according to amount of envenomation 9/20/2018

2-8 hours Local reaction with mild-moderate pain (initially stinging sensation then pruritis) Erythema, central blister or pustule 9/20/2018

24 hours Bite site becomes more red, edematous, and then acentral violaceous area appears (necrosis), often with rings separated by white areas of vasospasm (“red, white, and blue” or “bull’s eye” lesion) Severe cases Fever, chills, malaise weakness, N/V, rash with petechiae, joint pain, DIC, hematuria, renal failureSubcutaneous discoloration that spreads over 9/20/2018

Venom is hemolytic and cytotoxic enzymatically digests its prey
Venom is hemolytic and cytotoxic enzymatically digests its prey. Contains cytotoxin causes tissue necrosis by leukocyte aggregation and platelet plugging of arterioles and venules Eschar forms and sloughs away in several weeks leaving an ulcer 9/20/2018

Ulcer for months 9/20/2018

Management Unless spider is brought for ID, definitive diagnosis cannot be made Good local wound care If systemic symptoms, then CBC with platelets, U/A, BUN, creatinine Vigorous supportive care in PICU Surgical excision and skin grafting after necrosis is demarcated Steroids, heparin, and hyperbaric O2 don’t work No Dapsone for kids – methemoglobinemia No antivenom available Have wound rechecked daily for progression 9/20/2018

Male or female you have to fear?
9/20/2018

Black Widow Spider (Latrodectus)
Shiny black spider with brilliant red hourglass marking on abdomen Only the female bite is dangerous Male spiders are ¼ the size of females and bite cannot penetrate human skin Females not aggressive unless provoked or guarding egg sac Produces a neurotoxin Found in basements, woodpiles, and garages 9/20/2018

Clinical presentation
No local symptoms 1-8 hours after bite Generalized pain and muscle rigidity Cramping pain to abdomen, flanks, thighs, chest Chills Urinary retention Priapism Death from cardiovascular collapse Mortality 50% in young children Some cases progress to dramatic neuromuscular symptoms over the next mins but generally 6 hours Spasm, muscle cramps, and rigidity of major muscle groups at site of bite then spread Severe pain, fasciculations, weakness, vomiting, diaphoresis, priaprism, rare rhabdomyolysis Abdominal pain may mimic peritonitis Children: intractable crying Symptoms subside over several hours but recur for days to 1 week 9/20/2018

9/20/2018 Initial bite may or may not be noticed
Small papule or punctum 9/20/2018

Management Supportive ABC’s Tetanus
Treatment of spasm with narcortics and benzo’s Children < 40kg: Antivenin given as soon as bite confirmed Dose: 2.5ml (one vial) Children >40kg: not as urgent to give immediately unless having respiratory difficulty or significant hypertension Admit to PICU Calcium gluconate be used, but is short lived with variable effects Recluse= necrose Black widow minimal local rx lactro-wrecked-us 9/20/2018

9/20/2018

Other Spiders… Tarantulas Wolf Spider and Jumping spider
Do not bite unless provoked Venom is mild and not a problem Wolf Spider and Jumping spider Mild venom only causes local reaction Treatment is good local wound care 30,000 spiders worldwide all have venom but most not harmful b/c fangs cannot penetrate human skin. 9/20/2018

9/20/2018 Which ones are poisonous?
Notice the small and oval head with round pupils and NO pits between eyes and nostrils. Triangular vs oval shape 9/20/2018

This is all great to know in books and for tests but not recommended to be close to snake to identify headshape and eye shape Nonvenmous snakes flatten their heads when threatened 2) eye shape, head shape and tail of coral snakes are similar to non-poisonous snake 9/20/2018

Snake characteristics
cold blooded (seeks shelter at 55 degrees) - poor vision, great smell - slow but can strike 11 feet/sec. - Rattles are interlocking keratin rings - Jacobson’s organ at end of the forked tongue used to ID prey - venom with potent enzymes that effect coagulation, multi-organ function Play major role in ecosystem as rodent predators 9/20/2018

Snakes Bites Epidemiology approx 400,000 bites worldwide
Approx 45,000 bites in USA Approx 8,000 poisonous bites 5-15 deaths annually 9/20/2018

Snake Types Over 95% in the pit viper (Crotadilae) family:
Eastern diamondback rattlesnake (Crotalus) Copperhead (Agkistrodon) Cottonmouth (Agkistrodon) - 1% Coral snake(elapidae) family Georgia is home to 41 different snakes of which 6 are venomous Approximately 25%-50% of bites are dry bites with fang marks but no venom or envenomation 120 species of snakes in US only 26 are venomous Two families of venomous snakes native to US: Crotalinae (pit vipers i.e rattlesnakes, water moccasins, copperheads) 95% of the envenomation AND elapidae (coral snake) Still need to consider exotic snakes kept as snakes- clinician need to contact local poison control center- Antivenom index published by American Zoo and Aquarium Association and the American Association of Poison Control Centers: lists the locations, amounts, and various types of antivenom All states have at least one species of native venomous snake except for Hawaii, Alaska and maine 9/20/2018

Pit Vipers (Crotalinae)
Rattlesnakes, cottonmouths, water moccasins Proteolytic enzymes and anticoagulant esterases=> digest victim!! Mojave rattlesnake only pit viper with neurotoxin venom Elliptical pupil, triangular head, heat sensitive “pit” located midway between eye and nostril The pit allows the snake to see in infrared for warm blooded prey more efficiently Mojave rattlesnake: neurotoxin blocks N-type calcium channels (Mojave A neurotoxin and Mojave B neurotoxin and cytotoxin ( found in Phoenix AZ) 9/20/2018

Clinical Presentation
Local effects: edema within 1 hr (mod-severe bites) spreads centrally over 8-24hrs. Ecchymosis, Petechiae and Hemorrhagic bullae Systemic Effects: Nausea, vomiting, paresthesias, dizziness, and diaphoresis. In severe envenomations-hypotension, rhabdomyolysis, renal failure and AMS Coagulopathy: Increase in PT, PTT, thrombocytopenia and hemolysis. DIC in severe cases Need to mark leading edge of edema with pen every 30 min. Compartment syn can develop but is rare and overdiagnosed. Often difficult to separate loca effects of envenomation from compartment syndrome because they both cause the 5 P (Pallor, Pain, Parasthesia, Pressure) +/- Pulselessness Monitor capillary refill and consider consulting surgeon if elevated compartment pressures are suspected refractory to antivenom Most bites 9/20/2018

9/20/2018

Red on yellow= kill a fellow
Red on black= venom lack 9/20/2018

Coral snakes Eastern coral snake:AR, NC, SC, FL, GA, LA, MS, TX
Local damage usu mild and doesn’t correlate with severity of envenomation All confirmed coral snake envenomations are defined as severe and require antivenom 9/20/2018

Clinical Presentation
Mild local finding Venom potent neurotoxin Paresthesia, weakness, cranial nerve dysfunction, confusion, fasciculations, and lethargy Common early sx:diplopia, ptosis, and dysarthia Nausea, vomiting, and salivation are also common Respiratory paralysis common cause of death 9/20/2018

Lab evaluation CBC, coagulation studies, DIC panel
CK, renal function, UA Type and crossmatch in severe envenomations 9/20/2018

Prehospital treatment
Remove from vicinity of snake Immobilize bite site below heart level Minimize all physical activity (decrease absorption) DO not incise bite marks Transport to nearest hospital 9/20/2018

ED management ABC, IV hydration
Coral snakes: monitor neurologic sx (intubate if resp compromise) Antivenom (moderate to severe pit vipers and all confirmed eastern coral snake bites) Admission criteria: admit all pts w/ confirmed coral snake bites; if no envenomation observe for 6hr; if local pain or erythema, observe for 12hr; admit all pts with progressive symptoms to ICU; bitten by Mojave rattlesnake or exotic snake Is there envenomation? Moderate or severe two types polyvalent and Crofab Wyeth: made with horse serum; higher rate of anaphylaxis Skin test prior to innfusion very slowly and if positive then pretreat with benadryl, steroids, and even SQ epi CroFab: polyvalent immune Fab (ovine); highly purified, sheep derived antivenom; contains venomspecific Fab fragments that bind and neutralize venom; FDA approved for treatment of minimal to moderate envenomations; initial dose: 4-6 vials. Repeat in 1hr if further progression of symptoms. Some recommend 2 Units every 6hr for 3 doses after initial dose. Lower rate of acute reactions and serum sickness; some evidence of persistent coagulopathy in pt txt with CroFab 9/20/2018

Question 1 The four major steps in treatment of any poisoned
patient include all of the following EXCEPT: A. prompt hemodialysis or hemoperfusion B. decontamination and prevention of absorption, while preventing contamination of health care workers C. support of vital signs (ABCs) and symptomatic treatment specific antidote, if available D. enhancement of toxin excretion or elimination 9/20/2018

Question 2 Syrup of Ipecac is the first line
therapy for gastric decontamination of the poisoned patient: A. True B. False 9/20/2018

Question 3 Very few drugs are fatal for a 10 kg
toddler upon ingestion of one commercially available dose unit. Examples of drugs in which ingestion of one dose can be potentially fatal in this population include all of the following EXCEPT: A. Chloroquine B. TCA C. Calcium Channel Blockers D. SSRI’s Most toxic exposures in children are accidental, but intentional poisoning or drug abuse should be considered in any child over the age of 5-6 years. Most accidental pediatric toxic ingestions occur in children below age 5. Small, easily ingestible amounts of camphor and methylsalicylate can also be fatal to toddlers. Along with calcium channel blockers, beta blockers can be fatal as well. Also on this list are Benzocaine, Clonidine, Tricyclic antidepressants, Lomotil, Methadone, Glyburide, and phenothiazines. 9/20/2018

Question 4 Which of the following statements is TRUE
regarding intentional overdoses? A. Intentional overdoses are most commonly seen in the preschool age group. B. These overdoses are usually of one agent known to be lethal. C. Intentional overdoses frequently involve more than one agent Intentional overdoses are seldom fatal. D. None of the above are TRUE. Which of the following statements is TRUE regarding intentional overdoses? Intentional overdoses are most commonly seen in the preschool age group. These overdoses are usually of one agent known to be lethal. Intentional overdoses frequently involve more than one agent Intentional overdoses are seldom fatal. None of the above are TRUE. Always keep this point in mind. In trauma, poisoning, and in medicine in general, identification of one injury, toxic agent, or illness does not necessarily mean the search is over. Multiple toxins may be ingested intentionally or accidentally (e.g., the patient who attempts to overdose on opiates by ingesting a bottle of Tylenol tablets with codeine). Alcohol is frequently present as well. 9/20/2018

THANK YOU 9/20/2018

Reference Fine SJ. Pediatric Principles. Goldfrank LR et al. editors Goldfrank’s Toxicologic Emergencies. 8th Edition. Mc Graw-Hill; Henry K, Harris CR. Deadly Ingestions. Pediatr Clin N Am 53 (2006) Ranniger C. Roche C. Are one or two dangerous? Calcium Channel Blocker Exposure in Toddlers. Journal of Emergency Medicine. Vol 33 No , 2007 Eldridge DL, Van Eyk J, Kornegay C. Pediatric Toxicology. Emerg Med Clin N Am 15 (2007) Carson RH. The toxicology handbook for clinicians. Mosby, 2006 9/20/2018

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