A guide to the basics of poisoning in the pediatric population.

1. A Guide to Understanding the
Poisoned Child
Fatima Farid
Ped Resident

2. 2

3. Contents
• Incidence & statistics
• Focus on “one pill can kill” drugs
• Basic toxidromes
• Principles of clinical assessment
• Directed investigations
• Treatment overview with focus on antidotes
• Individual analysis of common poisons
3

4. Section I
General Concepts
4

5. Introduction
• More than 50% of all USA poisonings occur in children younger than 6 years
• Almost all these exposures are unintentional
• More than 90% of toxic exposures in children occur in the home & most involve a single
substance
• Ingestion accounts for most exposures, with only a minority occurring via the dermal,
inhalational and ophthalmic routes
5

6. 6

7. Toxins
• Approximately 50% of cases involve
non- drug substances (cosmetics,
personal care items, cleaning
solution, plants and foreign bodies)
• Pharmaceutical preparations account
for the remainder of exposures, and
analgesics, topical preparations,
cough & cold products and vitamins
are the most commonly reported
categories
7

8. Do you think a poisoned child’s
age can give us any hints?
8

9. 9

10. 0- 6 years
• Occur primarily due to exploratory nature of
children in this age group, with only 2% mortality
rate
• Most can be managed without direct medical
intervention either because the product involved is
not inherently toxic or the quantity of the material
involved is not sufficient to produce clinically
relevant toxic effects
• However, several substances are potentially
highly toxic to toddlers in small doses
10

11. 11

12. 6- 12 years
• A second peak in pediatric exposures occurs in
adolescence, involving only 6% of reported
pediatric toxic exposures
• Exposures in the adolescent age group are
primarily intentional (suicide or abuse/ misuse of
substances) and this result in more severe toxicity
• OTC, prescription medications and even
household products (inhalants) are common
sources of adolescent exposures
12

13. Section II
One pill can kill
13

14. ONE PILL CAN KILL
15 meds fatal to toddlers
Small dose = 1- 2 pills
or max 5 mL
14

15. Fatal Meds
1. Methylsalycylates  tachypnea, metabolic acidosis & seizures
2. Opioids (esp. methadone, suboxone & Lomotil)  CNS and respiratory depression
3. B- blockers (lipid soluble (propranolol) more toxic than water soluble (atenolol) 
bradycardia, hypotension & hypoglycemia
4. CCB  bradycardia, hypotension & hyperglycemia
5. Clonidine  lethargy, bradycardia & hypotension
6. Phenothiazines (chlorpromazine + thioridazine)  seizures & cardiac arrhythmias
15

16. Fatal Meds
7. Oral hypoglycemics (SU + meglitinides)  hypoglycemia & seizures
8. TCAs  CNS depression, seizures, cardiac arrhythmias, hypotension
9. MAO inhibitors  hypertension followed by delayed cardiovascular collapse
10. Theophylline  seizures & cardiac arrhythmias
16

17. Fatal Meds
11. Anti- malarial (chloroquine + quinine)  seizures & cardiac arrhythmias
12. Lindane  seizures
13. Atropine  CNS and respiratory depression
14. Camphor  seizures
15. Benzocaine  methemoglobinemia
17

18. Section III
Common Toxidromes
18

19. Sympathomimetic Toxidrome
• Sympathomimetic: {amphetamine, cocaine,
ecstasy, theophylline, caffeine,
pseudoephedrine}
a. VS: hypertension, tachycardia,
hyperthermia
b. CNS: agitated, delirium, psychosis
c. Eyes: dilated
d. Skin: diaphoretic
e. BS: normal or increased
19

20. Anticholinergic Toxidrome
• Anti- cholinergic same except skin is dry &
BS decreased
• {TCA, anti- histamine, atropine,
phenothiazine, jimson weed}
20

21. Cholinergic Toxidrome
• Cholinergic: {OP, nerve gas, Alzheimer meds}
a. VS: bradycardia or tachycardia, normal BP
and temp
b. CNS: confusion, coma, hallucinations
c. Eyes: constricted
d. Skin: diaphoresis
e. BS: hyperactive
f. Urination + bronchorrhea + emesis +
salivation + diarrhea
21

22. Opioids & Sedative Hypnotic
Toxidromes
• Opioids: {morphine, methadone, suboxone, oxycodone,
heroin}
a. VS: respiratory depression, bradycardia,
hypotension, hypothermia
b. CNS: depression, coma
c. Eyes: pinpoint
d. Skin: normal
e. BS: normal or low
• Sedative hypnotic: same but VS may be normal or low
with resp depression + small pupils (not pinpoint) {BZD,
barbiturates, ethanol}
22

23. Salicylate Toxidrome
• Salicylates: {aspirin, bismuth subsalicylate
(peptobismol), methylsalicylates}
a. VS: tachycardia, tachypnea, hyperthermia
b. CNS: agitation, confusion, coma + tinnitus
c. Eyes: normal
d. Skin: diaphoretic
e. BS: normal, nausea, vomiting
f. 1ry resp alkalosis + 1ry met acidosis
23

24. Serotonin Toxidrome
• Serotonin syndrome: {SSRI, MAOi, linezolid,
lithium, tramadol, dextromethorphan,
meperidine}
a. VS: tachycardia, hyperthermia, BP high
or low (autonomic instability)
b. CNS: agitation, confusion, coma + NM
excitability (LL > UL) clonus &
hyperreflexia
c. Eyes: dilated
d. Skin: diaphoretic
e. BS: increased
24

25. Section IV
Good Hx & Exam
25

26. General
• Obtaining an accurate problem- oriented history is of paramount importance
• Intentional poisonings (suicide attempt, drug abuse/ misuse) are typically more severe then unintentional
exploratory ingestions
• In patients without a witnessed exposure, features suggesting poisoning are:
1. Age (toddler or adolescent)
2. Acute onset of symptoms without prodrome
3. Sudden alteration of mental status
4. Multiple organ system dysfunction
5. High levels of household stress
26

27. What is the best approach to a
poisoned child?
27

28. ABCDE
• The initial approach to the patient with a witnessed or suspected poisoning should be no
different than that in any other sick child – starting with stabilization and rapid assessment
of airway, breathing, circulation and mental status
• A serum dextrose concentration should always be obtained early in the evaluation of a
patient with altered mental status
• A targeted history and physical exam serve as the foundation for a thoughtful DDx, which
can then be further refined through labs & other Dx studies
28

29. What was the toxin?
• Household and workplace items: name (brand, generic, chemical) & specific ingredients
should be checked from product label
• If child is found with an unknown pill in their mouth, history must include a list of all
medications in the child’s environment including meds that their grandparents, caregivers,
or other visitors may have brought into the house
• In case of an unknown exposure, clarifying where the child was found (i.e garage, kitchen,
laundry room, bathroom, backyard, workplace) can help generate a list of potential toxins
29

30. When & how much?
• Next it is important to clarify the timing of ingestion and to obtain an estimate of how much
was ingested
• In general, it is better to overestimate the amount ingested in order to prepare for the worst-
case scenario
• Counting pills or measuring the remaining volume of liquid ingested can sometimes be helpful
in generating estimates
• For inhalational, dermal and ocular exposures, the concentration of the agent & length of
contact time should be determined if possible
30

31. Symptoms & more Hx
• Ask for timing of symptom onset relevant to time of exposure, & also progression
• Symptoms can guide towards a toxidrome or specific poisoning syndrome
• PMHx: underlying diseases can make a child more susceptible to the effects of a toxin. Concurrent drug therapy
can also increase susceptibility because certain drugs may interact with the toxin. Pregnancy is a common
precipitant in adolescent’s suicide attempt and can influence further evaluation/ management. A hx of psychiatric
illness can make patients more prone to substance abuse, misuse, or intentional ingestions.
• Dev Hx: ensure hx is concurrent with ability of a normal child at that age- may catch red flags for abuse (e.g
report of a 6-month-old picking up a large container of laundry detergent and drinking it)
• Social Hx: members of family, stressors, main caregivers/ screen for any possible abuse/ neglect
31

32. Physical Exam
• Initial efforts should focus on patient stabilization, then once achieved one can proceed towards
extensive general physical exam
• Key features that may point to a toxidrome:
1. Vital signs
2. Mental status
3. Pupils (size, reactivity, nystagmus)
4. Skin
5. Bowel sounds
6. Odors
32

33. Odors
• Bitter almonds = cyanide
• Acetone= isopropyl alcohol, paraldehyde,
salicylates, methanol
• Alcohol = ethanol
• Wintergreen = methylsalycylate
• Garlic = arsenic, thallium, OP, selenium
33

34. Section V
Investigation
34

35. Labs
• Based on the clinical presentation, lab tests that may
be helpful include:
• VBG (high AG implies certain drugs)
• CBC
• LFT
• Urea/ electrolytes
• Renal function
• Serum osmolarity (toxic alcohols)
• Urinalysis (crystals)
• Creatine kinase
35

36. High anion gap metabolic
acidosis
(MUDPILES)
• Methanol & metformin
• Uremia
• DKA
• Paraldehyde & phenformin
• Isoniazid, iron & massive ibuprofen
• Lactic acidosis (cyanide & carbon
monoxide)
• Ethylene glycol & ethanol
• Salicylates
36

37. 37

38. 38

39. 39

40. 40

41. 41

42. 42

43. Elevated osmolar gap
• Alcohols:
• Ethanol
• Isopropyl
• Methanol
• Ethylene glycol
43

44. 44

45. 45

46. 46

47. 47

48. Hypoglycemia
(HOBBIES)
• Hypoglycemics: SU & meglitinides
• Others: quinine, unripe ackee fruit
• B- blockers
• Insulin
• Ethanol
• Salicylates (late)
48

49. Hyperglycemia
• Salicylates (early)
• CCB
• Caffeine
49

50. Hypocalcemia
• Ethylene glycol
• Fluoride
50

51. 51

52. Rhabdomyolysis
• Statins
• Diphenhydramine (antihistamine)
• Doxylamine (antihist + antiAch)
• NMS
• Mushrooms
• Any toxin causing prolonged
immobilization (opioids) or excessive
muscle activity/ seizures
(sympathomimetics)
52

53. Drug level
• For the below list of meds, obtaining a serum drug
concentration is integral to Dx & Mx:
a. Salicylates
b. Acetaminophen
c. Certain anticonvulsants
d. Iron
e. Digoxin
f. Methanol & ethylene glycol
g. Lithium
h. Theophylline
i. Carbon monoxide
53

54. Acetaminophen screen
• Acetaminophen is a widely available medication and a commonly detected co- ingestant
with the potential for severe toxicity
• Given that a patient may be asymptomatic initially & fail to report acetaminophen as a co-
ingestant, an acetaminophen level should be checked in all patients who present after an
intentional exposure/ ingestion
• Remember, in any clinical situation with potential medicolegal implications, any positive
drug screen should be confirmed by GC/ MS (more sensitive and specific)
54

55. Drug screen
• For most other exposures, quantitative measurement is not readily available and is not likely to alter the
management
• Comprehensive drug screens vary widely in their ability to detect toxins and generally add little
information to the clinical assessment, particularly if the agent is known and the patient’s symptoms are
consistent with that agent
• If a drug screen is ordered, it is important to know which agents are included within it, what the lower
threshold for detection is, and to bear in mind the chance of false positive/ negatives
• Most standard urine drug screens will not be positive after ingestion of a synthetic opioid (methadone and
suboxone) Although the presence of some drugs (i.e marijuana) might not be clinically useful, it can
identify use of “gateway drugs” and an adolescent at risk for drug abuse
55

56. In a medicolegal case of ANY AGE (e.g alleged
or suspected child abuse/ neglect)  a
toxicology screen with any positive result 
must be confirmed with gas chromatography/
mass spectroscopy (GC/ MS) which is
considered the gold standard for legal
purposes
56

57. Additional testing
• ECG
a. Prolonged PR interval
b. Wide QRS
c. Prolonged QTc
• CXR
a. Pneumonitis
b. Pulmonary edema
c. Foreign body
• AXR
a. Radio-opaque tablets
b. Bezoar
c. Drug packets (body packer)
• Endoscopy
57

58. PR interval prolongation
• Digoxin
• Lithium
58

59. QRS prolongation
A widened QRS interval, putting
the patient at risk for
monomorphic ventricular
tachycardia, suggests blockade
of fast sodium channels
1. TCA
2. Carbamazepine
3. Propranolol
4. Lamotrigine
5. Cardiac glycoside
6. Phenothiazines
7. Diphenhydramine
8. Chloroquine, hydroxychloroquine
9. Quinine, quinidine, procainamide, disopyramide
10. Cocaine
11. Propoxyphene
12. Bupropion, venlafaxine (rare)
59

60. QTc prolongation
A widened QTc interval suggests
effects at the potassium rectifier
channels and portends a risk of
torsades de pointes (polymorphic
ventricular tachycardia)
1. Clarithromycin & erythromycin
2. Fluconazole, ketoconazole, itraconazole
3. Amiodarone
4. Phenothiazines
5. Sotalol
6. Antipsychotics (typical & atypical)
7. Citalopram & other SSRIs
8. Methadone
9. Arsenic
10. Cisapride
11. Disopyramide, dofetilide, ibutilide
12. Pentamidine
60

61. Radio-opaque substances
(CHIPPED)
• Chloral hydrate, calcium carbonate
• Heavy metals (lead, zinc, barium, arsenic,
lithium, bismuth)
• Iron
• Phenothiazines
• Play doh, potassium chloride
• Enteric coated pills
• Dental amalgam
61

62. 62
Iron tabs Bismuth (Pepto-Bismol)

63. Section VI
Management
63

64. General TTT
• Principles:
1. Supportive care
2. Decontamination
3. Enhanced elimination
4. Antidote administration & ILE
• Only a few patients qualify for all 4 interventions, but the physician should apply these to all cases to
avoid missing potentially useful therapies
• Antidotes are available for only a few poisons, further emphasizing the importance of excellent supportive
care and meticulous cardiopulmonary monitoring
64

65. Supportive care
65

66. Airway & breathing
• Careful attention is paid first to the “ABCs” of airway, breathing, and circulation; there should be a low
threshold to aggressively manage the airway of a poisoned patient because of the patient's propensity to
quickly become comatose.
• In fact, endotracheal intubation is often the only significant intervention needed in many poisoned
patients.
• An important caveat is the tachypneic patient with a clear lung examination and normal oxygen
saturation. This should alert the clinician to the likelihood that the patient is compensating for an
acidemia. Paralyzing such a patient and underventilating might prove fatal.
• If intubation is absolutely necessary for airway protection or a tiring patient, a good rule of thumb is to
match the ventilatory settings to the patient's pre- intubation minute ventilation.
66

67. Circulation
• Hypotensive patients often are not hypovolemic but are poisoned, and aggressive fluid
resuscitation may lead to fluid overload.
• If hypotension persists after 1 or 2 standard boluses of crystalloid, infusion of a direct-
acting vasopressor, such as norepinephrine or epinephrine, is preferred.
• Dysrhythmias are managed in the standard manner, except for those caused by agents
that block fast sodium channels of the heart, for which boluses of sodium bicarbonate are
given.
67

68. More supportive care
• Seizures should primarily be managed with agents that potentiate the γ- aminobutyric acid
(GABA) complex, such as benzodiazepines or barbiturates.
• The goal of supportive therapy is to support the patient's vital functions until the patient
can eliminate the toxin.
• Patients with an elevated creatine phosphokinase (CPK) should be aggressively hydrated
with crystalloid, with a goal urine output of 1-2 mL/kg/hr and close monitoring of CPK
trend.
68

69. Decontamination
69

70. Decontamination
• The majority of poisonings in children are from ingestion, although exposures can also
occur by inhalational, dermal, and ocular routes.
• The goal of decontamination is to minimize absorption of the toxic substance.
• The specific method employed depends on the properties of the toxin itself and the route
of exposure.
• Regardless of the decontamination method used, the efficacy of the intervention
decreases with increasing time since exposure.
70

71. When to decontaminate?
• Decontamination should not be routinely employed for every poisoned patient.
• Instead, careful decisions regarding the utility of decontamination should be made for
each patient and should include consideration of the toxicity and pharmacologic
properties of the exposure, route of the exposure, time since the exposure, and risks vs
benefits of the decontamination method.
71

72. Eye, skin & airway decontamination
• Dermal and ocular decontamination begins with removal of any contaminated clothing and particulate matter, followed by
flushing of the affected area with tepid water or normal saline (NS).
• Treating clinicians should wear proper protective gear when performing irrigation.
• Flushing for a minimum of 10-20 min is recommended for most exposures, although some chemicals (e.g., alkaline corrosives)
require much longer periods of flushing.
• Dermal decontamination, especially after exposure to adherent or lipophilic (e.g., organophosphates) agents, should include
thorough cleansing with soap and water.
• Water should not be used for decontamination after exposure to highly reactive agents, such as elemental sodium, phosphorus,
calcium oxide, and titanium tetrachloride.
• After an inhalational exposure, decontamination involves moving the patient to fresh air and administering supplemental oxygen
if indicated.
72

73. GI decontamination
• Gastrointestinal decontamination strategies are most likely to be effective in the 1 or 2 hours after an acute ingestion.
• GI absorption may be delayed after:
• ingestion of agents that slow GI motility (anticholinergic medications, opioids)
• massive amounts of pills
• sustained-release (SR) preparations, and agents that can form pharmacologic bezoars (e.g., enteric-coated salicylates).
• GI decontamination more than 2 hr after ingestion may be considered in patients who ingest toxic substances with these
properties.
• However, even rapid institution of GI decontamination with activated charcoal will, at best, bind only approximately 30% of the
ingested substance.
• GI decontamination should never supplant excellent supportive care and should not be employed in an unstable or persistently
vomiting patient.
73

74. Methods
1. Induced emesis with syrup of ipecac
2. Gastric lavage
3. Activated charcoal
4. Cathartics
5. Whole bowel irrigation
• Of these, only activated charcoal and WBI are of potential benefit
74

75. Syrup of ipecac
• Syrup of ipecac contains 2 emetic alkaloids that work in both the central nervous system
(CNS) and locally in the GI tract to produce vomiting.
• Many studies have failed to document a significant clinical impact from the use of ipecac
and have documented multiple adverse events from its use.
• The AAP, the American Academy of Clinical Toxicology (AACT), and the AAPCC have all
published statements in favor of abandoning the use of ipecac.
75

76. Gastric lavage
• Gastric lavage involves placing a large tube orally into the stomach to aspirate contents, followed by flushing
with aliquots of fluid, usually water or NS.
• Although gastric lavage was used routinely for many years, objective data do not document or support clinically
relevant efficacy.
• This is particularly true in children, in whom only small-bore tubes can be used.
• Lavage is time-consuming and painful and can induce bradycardia through a vagal response to tube placement.
• It can delay administration of more definitive treatment (activated charcoal) and under the best circumstances,
only removes a fraction of gastric contents.
• Thus, in most clinical scenarios, the use of gastric lavage is no longer recommended.
76

77. Single dose activated charcoal
• Activated charcoal is a potentially useful method of GI decontamination.
• Charcoal is “activated” by heating to extreme temperatures, creating an extensive network of pores that
provides a very large adsorptive surface area that many (but not all) toxins will bind to, preventing absorption
from the GI tract.
• Charcoal is most likely to be effective when given within 1 hr of ingestion.
• Administration should also be avoided after ingestion of a caustic substance, as it can impede subsequent
endoscopic evaluation.
• A repeat dose of activated charcoal may be warranted in the cases of ingestion of an extended-release product
or, more frequently, with a significant salicylate poisoning as a result of its delayed and erratic absorption
pattern.
77

78. Contraindications
1. Heavy metals (i.e lead)
2. Iron
3. Lithium
4. Caustics: acids & alkalis
5. Alcohols
6. Hydrocarbons
7. Cyanide
78

79. Administration
• The dose of activated charcoal, with or without sorbitol, is 1 g/kg in children or 50-100 g in adolescents
and adults.
• Before administering charcoal, one must ensure that the patient's airway is intact or protected and that
the patient has a benign abdominal examination.
• In the awake, uncooperative adolescent or child who refuses to drink the activated charcoal, there is little
utility and potential morbidity associated with forcing activated charcoal down a nasogastric (NG) tube,
and such practice should be avoided.
• In young children, practitioners can attempt to improve palatability by adding flavorings (chocolate or
cherry syrup) or giving the mixture over ice cream.
79

80. Precaution
• Approximately 20% of children vomit after receiving a dose of charcoal, emphasizing the
importance of an intact airway and avoiding administration of charcoal after ingestion of
substances that are particularly toxic when aspirated (e.g., hydrocarbons).
• If charcoal is given through a gastric tube in an intubated patient, placement of the tube should
be carefully confirmed before activated charcoal is given.
• Instillation of charcoal directly into the lungs can have disastrous effects.
• Constipation is another common side effect of activated charcoal, and in rare cases, bowel
perforation has been reported.
80

81. Cathartics
• Sorbitol, magnesium sulfate, magnesium citrate have been used in conjunction with
activated charcoal to prevent constipation and accelerate evacuation of the charcoal-toxin
complex.
• There are no data demonstrating their value and numerous reports of adverse effects
from cathartics, such as dehydration and electrolyte imbalance.
81

82. Whole bowel irrigation
• Whole-bowel irrigation (WBI) involves instilling large volumes (35 mL/kg/hr in children or 1-2 L/hr in adolescents) of a
polyethylene glycol electrolyte solution (e.g., GoLYTELY) to “wash out” the entire GI tract.
• This technique may have some success for:
• ingestion of SR preparations
• substances not well adsorbed by charcoal
• transdermal patches
• foreign bodies
• drug packets
• In children, WBI is most frequently administered to decontaminate the gut of a child whose abdominal radiograph demonstrates
multiple lead paint chips.
• Careful attention should be paid to assessment of the airway and abdominal exam before initiating WBI.
82

83. 83

84. Method
• WBI should never be given to a patient with signs of obstruction or ileus or with a compromised airway.
• Given the rate of administration and volume needed to flush the system, WBI is typically administered by
NG tube.
• WBI is continued until the rectal effluent is clear.
• If the WBI is for a child with ingested paint chips, the end-point will be clearing of the chips from the bowel
based on repeat radiographs.
• Complications of WBI include vomiting, abdominal pain, and abdominal distention.
• Bezoar formation might respond to WBI but may also require endoscopy or surgery.
84

85. Enhanced elimination
85

86. Enhanced elimination
• Enhancing elimination results in increased clearance of a poison that has already been
absorbed.
• It is only useful for a few toxins and in these cases is a potentially lifesaving intervention.
• Methods of enhanced elimination include:
1. urinary alkalinization
2. hemodialysis
3. multidose activated charcoal
86

87. Urinary alkalinization
• Urinary alkalinization enhances the elimination of drugs that are weak acids by forming charged molecules,
which then become trapped in the renal tubules.
• Charged molecules, being polar and hydrophilic, do not easily cross cellular membranes, thus they remain in the
renal tubules and are excreted.
• Urinary alkalinization is accomplished by a continuous infusion of sodium bicarbonate– containing IV fluids, with
a goal urine pH of 7.5-8. Serum pH should be closely monitored and not exceed a pH >7.55.
• Alkalinization of the urine is most useful in managing salicylate and methotrexate toxicity.
• Complications of urinary alkalinization include electrolyte derangements (e.g., hypokalemia, hypocalcemia), fluid
overload, and excessive serum alkalinization. Patients unable to tolerate the volumes required for alkalinization
are those with heart failure, kidney failure, pulmonary edema, or cerebral edema.
87

88. Hemodialysis
• Few drugs or toxins are removed by dialysis in amounts sufficient to justify the risks and
difficulty of dialysis.
• Toxins amenable to dialysis have the following properties:
• low volume of distribution (<1 L/kg) with a high degree of water solubility
• low molecular weight
• low degree of protein binding
88

89. Uses
1. Toxicity from:
• methanol & ethylene glycol
• salicylates
• theophylline
• Bromide
• Lithium
• valproic acid
2. To correct severe electrolyte disturbances and acid-base derangements resulting from the ingestion
(e.g., severe metformin-associated lactic acidosis).
89

90. Multidose activated charcoal
• Whereas single-dose activated charcoal is used as a method of decontamination, multidose
activated charcoal (MDAC) can help to enhance the elimination of certain toxins.
• MDAC is typically given as 0.5 g/kg every 4-6 hr (for 4 doses).
• Enhances elimination by 2 proposed mechanisms:
• interruption of enterohepatic recirculation
• GI dialysis: using the intestinal mucosa as a dialysis membrane and pulling toxins from
the bloodstream back into the intraluminal space, where they are adsorbed to the
charcoal
90

91. Uses
• The AACT/European Association of Poisons Centres and Clinical Toxicologists position
statement recommends MDAC in managing significant ingestions of:
1. Carbamazepine
2. Dapsone
3. Phenobarbital
4. Quinine
5. Theophylline
91

92. Method
• As with single-dose activated charcoal, contraindications to use of MDAC include an
unprotected airway and a concerning abdominal examination (e.g., ileus, distention, peritoneal
signs).
• Thus the airway and abdominal exam should be assessed before each dose.
• A cathartic (e.g., sorbitol) may be given with the 1st dose, but it should not be used with
subsequent doses because of the risk of dehydration and electrolyte derangements.
• Although MDAC reduces the serum level of an intoxicant quicker than without MDAC, it has
not been shown to have a significant impact on outcome.
92

93. Antidotes & ILE
93

94. Antidotes
94

95. 95

96. 96

97. 97

98. 98

99. 99

100. Intra- lipid emulsion therapy
• Intralipid emulsion (ILE) therapy is a potentially lifesaving intervention:
1. Sequesters fat-soluble drugs, decreasing their impact at target organs.
2. It also enhances cardiac function by supplying an alternative energy source to a
depressed myocardium.
3. Acts on calcium channels in the heart, increasing myocardial calcium and thus
cardiac function.
• Intralipid is most effective as a reversal agent for toxicity from inadvertent intravenous (IV)
injection of bupivacaine.
100

101. Technique
• Using the same 20% Intralipid used for total parenteral nutrition, a bolus dose of 1.5
mL/kg is given over 3 min, followed by an infusion of 0.25 mL/kg/min until recovery or until
a total of 10 mL/kg has been infused.
• Lipophilic drugs, those in which the logarithm of the coefficient describing the partition
between 2 solvents (hydrophobic phase and hydrophilic phase) is >2, have the most
potential to be bound by ILE.
• These include, but are not limited to, calcium channel blockers (verapamil, diltiazem),
bupropion, and tricyclic antidepressants.
101

102. Section VII
Specific substances
102

103. Acetaminophen
103

104. Acetaminophen
• Acetaminophen (APAP) is the most widely used analgesic and antipyretic in pediatrics,
available in multiple formulations, strengths, and combinations.
• Consequently, APAP is commonly available in the home, where it can be unintentionally
ingested by young children, taken in an intentional overdose by adolescents and adults,
or inappropriately dosed in all ages.
• In the United States, APAP toxicity remains the most common cause of acute liver failure
and is the leading cause of intentional poisoning death.
104

105. Pathogenesis
• APAP toxicity results from the formation of a highly reactive intermediate metabolite, N-
acetyl-p-benzoquinone imine.
• In therapeutic use, only a small percentage of a dose (approximately 5%) is metabolized
by the hepatic cytochrome P450 enzyme CYP2E1 to N-acetyl-p-benzoquinone imine,
which is then immediately conjugated with glutathione to form a nontoxic mercapturic acid
conjugate.
• In overdose, glutathione stores are overwhelmed, and free N-acetyl-p-benzoquinone
imine can combine with hepatic macromolecules to produce hepatocellular necrosis.
105

106. 106

107. Dose
• The single acute toxic dose of APAP is generally considered to be >200 mg/kg in children and
>7.5-10 g in adolescents and adults.
• Repeated administration of APAP at supratherapeutic doses (>90 mg/kg/day for consecutive
days) can lead to hepatic injury or failure in some children, especially in the setting of fever,
dehydration, poor nutrition, and other conditions that serve to reduce glutathione stores.
• Any child with a history of acute ingestion of >200 mg/kg (unusual in children younger than 6
yr old) or with an acute intentional ingestion of any amount should be referred to a healthcare
facility for clinical assessment and measurement of a serum APAP level.
107

108. 108

109. Dx
• The diagnosis of APAP toxicity cannot be based on clinical symptoms alone, but instead requires consideration
of the combination of the patient’s history, symptoms, and laboratory findings.
• If a toxic ingestion is suspected, a serum APAP level should be measured 4 hr after the reported time of
ingestion.
• For patients who present to medical care more than 4 hr after ingestion, a stat APAP level should be obtained.
• APAP levels obtained <4 hr after ingestion, unless “nondetectable,” are difficult to interpret and cannot be used
to estimate the potential for toxicity.
• Other important baseline labs include hepatic transaminases, renal function tests, and coagulation parameters
109

110. Treatment
• When considering the treatment of a patient poisoned or potentially poisoned with APAP,
and after assessment of the ABCs, it is helpful to place the patient into one of the
following 4 categories:
1. Prophylactic
2. Hepatic injury
3. Acute liver failure
4. Repeated supra- therapeutic ingestions
110

111. Prophylactic
• By definition, these patients have a normal aspartate aminotransferase (AST).
• If the APAP level is known and the ingestion is within 24 hr of the level being drawn, then treatment
decisions are based on where the level falls on the Rumack- Matthew nomogram.
• Any patient with a serum APAP level in the possible or probable hepatotoxicity range per the nomogram
should be treated with N-acetylcysteine (NAC).
• This nomogram is only intended for use in patients who present within 24 hr of a single acute
APAP ingestion with a known time of ingestion.
• If treatment is recommended, they should receive either oral Mucomyst or IV Acetadote for 24 or 21 hr,
respectively.
111

112. 112

113. Early NAC
• The importance of instituting therapy with either IV or oral NAC no later than 8 hr from the
time of ingestion cannot be overemphasized.
• No patient, no matter the size of the ingestion, who receives NAC within 8 hr of overdose
should die from liver failure. The further out from the 8 hr mark the initiation of therapy is
delayed, the greater the risk of acute liver failure.
• Any patient presenting close to that 8 hr mark or beyond it after an APAP overdose should
be empirically started on NAC pending lab results.
113

114. When to stop NAC?
• Repeat AST and APAP concentration drawn toward the end of that interval should be obtained.
• If the AST is normal and the APAP becomes nondetectable, then treatment may be discontinued.
• If the AST becomes elevated, then the patient moves into the next category of treatment (injury).
• If APAP is still present, treatment should be continued until the level is nondetectable.
• In the case of a patient with a documented APAP level, normal AST, and an unknown time of ingestion,
treatment should ensue until the level is nondetectable, with normal transaminases.
114

115. Hepatic injury
• These patients are exhibiting evidence of hepatocellular necrosis, manifested first as
elevated liver transaminases (AST rises first, then the alanine aminotransferase), followed
by a rise in the INR.
• Any patient in this category requires therapy with NAC (IV or oral). When to discontinue
therapy in the clinically well patient remains controversial, but in general, the
transaminases and INR have peaked and fallen significantly “toward” normal (they do not
need to be normal).
• Most patients’ liver enzymes will peak 3 or 4 days after their ingestion.
115

116. Acute liver failure
• The King’s College criteria are used to determine which patients should be referred for consideration of
liver transplant. These criteria include:
a. acidemia (serum pH <7.3) after adequate fluid resuscitation
b. coagulopathy (INR >6)
c. renal dysfunction (creatinine >3.4 mg/dL)
d. grade III or IV hepatic encephalopathy
• A serum lactic acid >3 mmol/L (after IV fluids) adds to both the sensitivity and specificity of the criteria to
predict death without liver transplant.
• The degree of transaminase elevation does not factor into this decision-making process.
116

117. Repeated supra- therapeutic ingestion
• APAP is particularly prone to unintentional overdose through the ingestion of multiple medications containing the drug or simply
because people assume it to be safe at any dose.
• Ingestion of amounts significantly greater than the recommended daily dose for several days or more puts one at risk for liver
injury.
• Because the Rumack-Matthew nomogram is not helpful in this scenario, a conservative approach is in order:
• In the asymptomatic patient, if the AST is normal and the APAP is <10 μg/mL, then no therapy is indicated. A normal AST
and an elevated APAP warrants NAC dosing for at least long enough for the drug to metabolize while the AST remains
normal.
• An elevated AST puts the patient in the “hepatic injury” category described above.
• A patient presenting with symptoms (i.e., right upper quadrant pain, vomiting, jaundice) should be empirically started on
NAC till pending lab results.
117

118. NAC
• NAC is available in oral and intravenous forms, and both are equally efficacious.
• The intravenous form is used in patients with intractable vomiting, those with evidence of hepatic failure, and pregnant patients.
Oral NAC has an unpleasant taste and smell and can be mixed in soft drink or fruit juice or given via nasogastric tube to improve
tolerability of the oral regimen.
• Administration of IV NAC (as a standard 3% solution to avoid administering excess free water, typically in 5% dextrose),
especially the initial loading dose, is associated in some patients with the development of anaphylactoid reactions (non–
immunoglobulin E mediated). These reactions are typically managed by stopping the infusion; treating with diphenhydramine,
albuterol, and/or epinephrine as indicated; and restarting the infusion at a slower rate once symptoms have resolved. IV NAC is
also associated with mild elevation in measured INR (range: 1.2-1.5).
• IV dosing does, however, deliver less drug to the liver compared with the oral regimen. As a result, many toxicologists now
recommend higher doses of the IV formulation in patients with large overdoses.
118

119. Follow- up
• Transaminases, synthetic function, and renal function should be followed daily while the patient is being
treated with NAC.
• Patients with worsening hepatic function or clinical status might benefit from more frequent lab
monitoring.
• A patient-tailored approach is the norm for when to stop NAC therapy, for deciding whom to refer for
transplantation evaluation, and often for the dose of IV NAC in patients with either very high APAP levels
or signs of significant injury.
• Consultation with the regional poison center and medical toxicologist can help streamline the care of
these patients, ultimately shortening their length of stay with potentially improved outcomes.
119

120. Salicylates
120

121. Salicylates
• The incidence of salicylate poisoning in young children has declined dramatically since APAP and
ibuprofen replaced aspirin as the most used analgesics and antipyretics in pediatrics.
• However, salicylates remain widely available, not only in aspirin-containing products but also in:
• antidiarrheal medications
• topical agents (e.g., keratolytics, sports creams)
• oil of wintergreen
• some herbal products
• Oil of wintergreen contains 5 g of salicylate in 1 teaspoon (5 mL), meaning ingestion of very small
volumes of this product has the potential to cause severe toxicity.
121

122. Pathophysiology
• Salicylates lead to toxicity by interacting with a wide array of physiologic processes, including:
• direct stimulation of the respiratory center
• uncoupling of oxidative phosphorylation
• inhibition of the tricarboxylic acid cycle
• stimulation of glycolysis and gluconeogenesis
• The acute toxic dose of salicylates is generally considered to be >150 mg/kg. More significant
toxicity is seen after ingestions of >300 mg/kg, and severe, potentially fatal, toxicity is
described after ingestions of >500 mg/kg.
122

123. Clinical features
• Salicylate ingestions are classified as acute or chronic, and acute toxicity is far more common in pediatric
patients.
• Early signs of acute salicylism include nausea, vomiting, diaphoresis, and tinnitus.
• Moderate salicylate toxicity can manifest as tachypnea and hyperpnea, tachycardia, and altered mental status.
The tachycardia results in large part from marked insensible losses from vomiting, tachypnea, diaphoresis, and
uncoupling of oxidative phosphorylation. Thus, careful attention should be paid to volume status and early
volume resuscitation in the significantly poisoned patient.
• Signs of severe salicylate toxicity include hyperthermia, coma, and seizures.
• Chronic salicylism can have a more insidious presentation, and patients can show marked toxicity at significantly
lower salicylate levels than in acute toxicity.
123

124. Labs
• Classically, lab values from a patient poisoned with salicylates reveal a primary
respiratory alkalosis and a primary, elevated anion gap metabolic acidosis.
• Early during acute salicylism, respiratory alkalosis dominates. As the respiratory
stimulation diminishes, the patient will move toward the metabolic acidosis.
• Hyperglycemia (early) and hypoglycemia (late) have been described.
• Abnormal coagulation studies and acute kidney injury may be seen but are not common.
124

125. Monitoring
• Serial serum salicylate levels should be closely monitored (every 2-3 hr initially) until they are consistently
down trending. Salicylate absorption in overdose is often unpredictable and erratic, especially with an
enteric coated product, and levels can rapidly increase into the highly toxic range, even many hours after
the ingestion. The Done nomogram is of poor value and should not be used.
• Serum and urine pH and electrolytes should be followed closely.
• An APAP level should be checked in any patient who intentionally overdoses on salicylates, because
APAP is a common co- ingestant and because people often confuse or combine their nonprescription
analgesic medications.
• Salicylate toxicity can cause a noncardiogenic pulmonary edema, especially in chronic overdose;
consequently, a chest x-ray is recommended in any patient in respiratory distress.
125

126. Treatment
• For the patient who presents soon after an acute ingestion, initial treatment should include gastric
decontamination with activated charcoal.
• Salicylate pills occasionally form concretions called bezoars, which should be suspected if serum
salicylate concentrations continue to rise many hours after ingestion or are persistently elevated despite
appropriate management.
• Gastric decontamination is typically not useful after chronic exposure.
• Initial therapy focuses on aggressive volume resuscitation and prompt initiation of sodium bicarbonate
therapy in the symptomatic patient, even before obtaining serum salicylate levels. Therapeutic salicylate
levels are 10-20 mg/dL, and levels >30 mg/dL warrant treatment.
126

127. Urinary alkalinization
• The primary mode of therapy for salicylate toxicity is urinary alkalinization.
• Urinary alkalinization enhances the elimination of salicylates by converting salicylate to its
ionized form, “trapping” it in the renal tubules, and thus enhancing elimination.
• In addition, maintaining an alkalemic serum pH decreases CNS penetration of salicylates
because charged particles are less able to cross the blood–brain barrier.
127

128. Method
• Alkalinization is achieved by administration of a sodium bicarbonate infusion at approximately 2 times
maintenance fluid rates.
• The goals of therapy include a urine pH of 7.5-8, a serum pH of 7.45-7.55, and decreasing serum
salicylate levels.
• In general, in the presence of an acidosis, an aspirin-poisoned patient’s status can be directly related to
the patient’s serum pH. The lower the pH, the greater the relative amount of salicylate in the
uncharged/nonpolar form and the greater the penetration of the blood–brain barrier by the drug.
• Careful attention should also be paid to serial potassium levels, because hypokalemia impairs
alkalinization of the urine; potassium is often added to the bicarbonate drip.
128

129. More Mx
• Repeat doses of charcoal may be beneficial because of the often delayed and erratic absorption of
aspirin.
• Parenteral glucose should be provided to any salicylate poisoned patients with altered mental status as
they may have CNS hypoglycemia not noted in a peripheral serum glucose test.
• In cases of severe toxicity, hemodialysis may be required. Indications for dialysis include severe acid–
base abnormalities (specifically severe acidosis and acidemia), a rising salicylate level despite adequate
decontamination and properly alkalinized urine, pulmonary edema, cerebral edema, seizures, and renal
failure.
• Serum salicylate concentrations should always be interpreted along with the clinical status of the patient;
on their own they are not a clear indicator of the need for dialysis.
129

130. Ibuprofen/ NSAIDs
130

131. Ibuprofen
• Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) are often involved in
unintentional and intentional overdoses owing to their widespread availability and
common use as analgesics and antipyretics.
• Fortunately, serious effects after NSAID overdose are rare owing to their wide therapeutic
index.
131

132. Pathophysiology
• NSAIDs inhibit prostaglandin synthesis by reversibly inhibiting the activity of cyclooxygenase (COX), the primary enzyme
responsible for the biosynthesis of prostaglandins.
• In therapeutic use, side effects include GI irritation, reduced renal blood flow, and platelet dysfunction.
• In an attempt to minimize these side effects, NSAID analogs have been developed that are more specific for the inducible form
of COX (the COX-2 isoform) than the constitutive form, COX-1.
• However, overdose of the more selective COX-2 inhibitors (e.g., celecoxib [Celebrex]) is treated the same as overdose of
nonspecific COX inhibitors (e.g., ibuprofen) because at higher doses, COX-2–selective agents lose their COX inhibitory
selectivity.
• Ibuprofen, the primary NSAID used in pediatrics, is well tolerated, even in overdose. In children, acute doses of <200 mg/kg
rarely cause toxicity, but ingestions of >400 mg/kg can produce more serious effects, including altered mental status and
metabolic acidosis.
132

133. Clinical features
• Symptoms usually develop within 4-6 hr of ingestion and resolve within 24 hr.
• If toxicity does develop, it is typically manifested as nausea, vomiting, and abdominal pain.
• Although GI bleeding and ulcers have been described with chronic use, they are rare in the
setting of acute ingestion.
• After massive ingestions, patients can develop marked CNS depression, anion gap metabolic
acidosis, renal insufficiency, and (rarely) respiratory depression.
• Seizures have also been described, especially after overdose of mefenamic acid.
133

134. Labs
• Specific drug levels are not readily available, nor do they inform management decisions.
• Renal function studies, acid–base balance, complete blood count, and coagulation
parameters should be monitored after very large ingestions.
• Co- ingestants, especially APAP, should be ruled out after any intentional ingestion.
134

135. Mx
• Supportive care, including use of antiemetics and acid blockade as indicated, is the primary therapy for
NSAID toxicity.
• Decontamination with activated charcoal should be considered if a patient presents within 1-2 hr of a
potentially toxic ingestion. There is no specific antidote for this class of drugs. Given the high degree of
protein binding and excretion pattern of NSAIDs, none of the modalities used to enhance elimination are
particularly useful in managing these overdoses. Unlike in patients with salicylate toxicity, urinary
alkalinization is not helpful for NSAID toxicity.
• Patients who develop significant clinical signs of toxicity should be admitted to the hospital for ongoing
supportive care and monitoring. Patients who remain asymptomatic for 4-6 hr after ingestion may be
considered medically cleared.
135

136. Opioids
136

137. Opioids
• Opioids are a commonly abused class of medications in both their IV and oral forms.
• Two specific oral opioids, buprenorphine and methadone, merit mention because of potential life-
threatening toxicity in toddlers with ingestion of even 1 pill.
• Both agents are used in managing opioid dependence, although buprenorphine is the drug of choice.
Methadone is also widely used in the treatment of chronic pain, meaning multiday prescriptions can be
filled. Both drugs are readily available for illicit purchase and potential abuse.
• Both drugs are of great potential toxicity to a toddler, especially buprenorphine, owing to its long half-life
and high potency.
137

138. Pathophysiology
• Methadone is a lipophilic synthetic opioid with potent agonist effects at μ-opioid receptors, leading to both its
desired analgesic effects and undesired side effects, including sedation, respiratory depression, and impaired GI
motility. Methadone is thought to cause QTc interval prolongation via interactions with the human ether-a-go-go–
related gene (hERG)-encoded potassium rectifier channel. Methadone has an average half-life of >25 hr, which
may be extended to >50 hr in overdose.
• Suboxone is a combination of buprenorphine, a potent opioid with partial agonism at μ-opioid receptors and
weak antagonism at κ-opioid receptors, and naloxone. Naloxone has poor oral bioavailability but is included in
the formulation to discourage diversion for intravenous use, during which it can precipitate withdrawal.
Suboxone is formulated for buccal or sublingual administration; consequently, toddlers can absorb significant
amounts of drug even by sucking on a tablet. Buprenorphine has an average half-life of 37 hr.
138

139. Assessment
• In children, methadone and buprenorphine ingestions can manifest with the classic opioid toxidrome of
respiratory depression, sedation, and miosis. Signs of more severe toxicity can include bradycardia,
hypotension, and hypothermia.
• Even in therapeutic use, methadone is associated with a prolonged QTc interval and risk of torsades de pointes.
Accordingly, an ECG should be part of the initial evaluation after ingestion of methadone or any unknown opioid.
• Neither drug is detected on routine urine opiate screens, although some centers have added a separate urine
methadone screen. Levels of both drugs can be measured, although this is rarely done clinically and is seldom
helpful in the acute setting. An exception may be in the cases involving concerns about neglect or abuse, at
which point urine for gas chromatography/mass spectroscopy, the legal gold standard, should be sent to confirm
and document the presence of the drug.
139

140. Antidote
• Patients with significant respiratory depression or CNS depression should be treated with the opioid
antidote, naloxone.
• In pediatric patients who are not chronically on opioids, the full reversal dose of 0.1 mg/kg (max: 2
mg/dose) should be used. In contrast, opioid-dependent patients should be treated with smaller initial
doses (0.01 mg/kg), which can then be repeated as needed to achieve the desired clinical response,
hopefully avoiding abrupt induction of withdrawal.
• Because the half-lives of methadone and buprenorphine are far longer than that of naloxone, patients
can require multiple doses of naloxone. These patients may benefit from a continuous infusion of
naloxone, typically started at two-thirds of the reversal dose/hr and titrated to maintain an adequate
respiratory rate and level of consciousness.
140

141. Monitoring
• Patients who have ingested methadone should be placed on a cardiac monitor and have serial ECGs to monitor
for the development of a prolonged QTc interval. If a patient does develop a prolonged QTc, management
includes close cardiac monitoring, repletion of electrolytes (potassium, calcium, and magnesium), and having
magnesium and a defibrillator readily available should the patient develop torsades de pointes.
• Given the potential for clinically significant and prolonged toxicity, any toddler who has ingested methadone,
even if asymptomatic, should be admitted to the hospital for at least 24 hr of monitoring.
• Some experts advocate a similar approach to management of buprenorphine ingestions, even in the
asymptomatic patient. As we gain more experience with pediatric buprenorphine exposures, some patients who
remain asymptomatic for 6-8 hr after ingestion and have a stable social setting may be candidates for earlier
discharge. In the meantime, these cases should be discussed with a poison control center or medical
toxicologist before determining disposition.
141

142. Section IIX
Prevention
142

143. 143

144. Prevention
• Poison prevention education should be an integral part of all well child visits,
starting at the 6 months visit
• Product safety measures, poison prevention education, early recognition of
exposures, and around the clock access to poison control services all
contribute to the fact that only 2% of the reported deaths occur in 0- 6 years
age group
• Pediatricians should be aware of the signs of drug abuse or suicide ideation in
this population & should aggressively intervene
• Counsel about:
1. Potential poisoning risks
2. How to poison proof a child’s environment
3. What to do if an ingestion or exposure occurs to diminish morbidity/
mortality
4. Poison prevention materials & poison control phone number
144

145. PCC
• Parents should be instructed to call the poison control center (1-800-222-1222 ) for any concerning
exposure.
• PCC specialists can assist parents in assessing the potential toxicity and severity of the exposure. They
can further determine which children can be safely monitored at home and which children should be
referred to the emergency department for further evaluation and care.
• Although up to one third of calls to PCCs involve hospitalized patients, and 90% of all calls for exposures
in children <6 yr old are managed at home.
• The AAPCC has generated consensus statements for out of hospital management of common ingestions
(e.g., acetaminophen, iron, calcium channel blockers) that serve to guide poison center
recommendations.
145

146. Thanks for
listening!
Reference: Nelson Textbook of Peds
19th Ed
146