PEDIATRICTOXICOLOGY2005

Adel M A Hassan, M.D

Sen. Cons. Anesthesia, ICU, Interventional Pain Management.

dradel.hassan@gmail.com

Epidemiology

• 64 Poison Centers serving 295 million people• 2.4 million exposures last year

– 39% are children younger than 3 years– 52% in children younger than 6 years

• 106 deaths in age <19 for 2003

2003 Annual report of the American Association of Poison Control Centers Toxic Exporure Surveillance System – Watson et. al

Epidemiology

• Most commonly fatal classes of poisoning– Analgesics (375)

• 62 Tylenol only, 52 Tylenol + 1 other, 100 Tylenol combination products (Lortab, etc.)

• 23 ASA – more than half did not have ASA levels >100mg/dl – early and more aggressive dialysis recommended

– Street drugs (124)

– Antidepressants (112)• Amitriptyline

Epidemiology

• Most common Pediatric Exposure– Cosmetics and personal care products (13%)

– Cleaning substances (10%)

– Analgesics (7.8%)

– Foreign Bodies (7.4%)

– Topicals (7.4%)

– Cold and Cough Preparations (5.5%)

– Plants (4.6%)

– Pesticides (4.1%)

Epidemiology

• Unintentional (1-2 years)– Exploratory

– Boys > girls

– Unable to discriminate safe from unsafe liquid

• Intentional (adolescent)– Purposeful

– Girls > boys

Epidemiology

• Around meal time• Grandparents home• Kerosene or gasoline in a soda bottle• Older sibling can pharmaceutically treat younger

sibling

Evaluation of Suspected Poisoning

• ABC’s and routine ICU management• Establishing the diagnosis

– Must consider poisoning, especially in “at risk” age groups

• Less than 6 year old with acute decompensation (AMS, arrhythmias, hypotension, metabolic acidosis, etc.)

Evaluation

• History of poisoning• Physical Examination• Laboratory studies• Gastrointestinal decontamination

History

• What?• When?• How much?• Reliability…

What?

• Medication• Illicit drug• Hazardous chemical

What forms?

• Pill• Solid• Liquid• Gaseous

What route?

• Ingestion• Inhalation• Topical • Intravenous

When?

• Elapsed time

How much?

• Estimate amount• Concentration

PICU Admission

• Tricyclic antidepressants (TCA)• Anticonvulsants• Digoxin • Opiates• Hydrocarbon-based household products

Toxic Exposure - Death

• Analgesics• Sedative-hypnotics• Alcohols• Gases & fumes• Cleaning substances

Toxidromes

• Anticholinergics– Atropine, scopolamine, TCA’s, phenothiazines,

antihistamines, mushrooms, jimson weed

– “Hot as a hare, dry as a bone, red as a beet, mad as a hatter”

– Neuro: agitation, hallucinations, coma, extrapyramidal movements, mydriasis, hyperthermia

– CV: tachycardia, hypotension, hypertension, arrhythmia

– GI/GU: decreased bowel sounds, urinary retention

Toxidromes

• Cholinergics– Organophosphates and carbamates

Muscarinic Effects of Organophosphate Poisoning

• S alivation *D iaphoresis/diarrhea

• L acrimation *U rination

• U rination *M iosis

• D efecation *B radycardia/bronchospasm

• G I secrestion/upset *E mesis

• E mesis *L acrimation excess

*S alivation excess

Nicotinic Effects of Organophosphate Poisoning

• Muscle fasciculation• Cramping• Weakness (extreme is diaphragmatic failure)• Autonomic nicotinic effects include hypertension,

tachycardia, pupillary dilation, and pallor

CNS Effects ofOrganophosphate Poisoning

• Anxiety

• Restlessness

• Confusion

• Ataxia

• Seizures

• Insomnia

• Dysarthria

• Tremors

• Coma

Toxidromes

• Opiates: – Morphine, Methadone, Dextromethorphan

Toxidromes

• Opiates– Morphine, methadone, dextromethorphan

– Resp: decreased respiratory rate, pulmonary edema

– CV: hypotension, bradycardia

– Neuro: miosis, AMS, coma, hypothermia, seizures

Toxidromes

• Sedatives/hypnotics– Benzodiazepines, barbiturates

– Resp: slow respirations

– CV: tachycardia, hypotension

– Neuro: AMS, coma, seizures, hypothermia

Toxidromes

• Tricyclic antidepressants– Amitryptiline, nortryptiline, etc.

– See anticholinergic effects

– CV: arrhythmias, hypotension

– Neuro: coma, seizures

Toxidromes

• Salicylates– ASA, oil of wintergreen

– Resp: tachypnea

Laboratory Tests Suggestive ofPoisoning

• Elevated osmolar gap (>10)– Serum osm = (Na x 2) + BUN/2.8 + glucose/18– Volatile alcohols, mannitol

• Elevated anion gap (>12)– MUDPILES

• Low anion gap– Lithium, iodine, bromine, fluoride

• Hyperkalemia– Postassium, lithium, digoxin, fluoride

• Hypokalemia– Theophylline, toluene

Laboratory Tests Suggestive ofPoisoning

• Hyperglycemia– ASA, theophylline, caffeine, iron

• Hypocalcemia– Ethylene glycol, ASA

• UA– Glowing urine – ethylene glycol

– Calcium oxalate crystals – ethylene glycol

Laboratory Testing

• What is in a “urine drug screen”?– Amphetamines, Barbiturates, Cocaine, Benzodiazepine,

Opiates, THC, PCP

• What is in a “serum drug screen”?– Acetaminophen, ETOH, Salicylate, TCA

• What is in a “comprehensive drug screen”?– Barbiturates, Salicylates, Cannabinoids, PCP, TCA,

Sedatives, Benzodiazepines, Stimulants, Opium alkaloid, Synthetic Narcotics, Tranquilizers, Cocaine

Laboratory Testing

• Grady unfortunately doesn’t do HPLC anymore

• Options for more “comprehensive” screen– Quest lab – if needed in 24 hours or less

– ARUP – 2-4 days turn around• SERUM: Acetaminophen, alcohols, barbiturates, benzodiazepines,

carbamazepine, carisoprodol, disopyramide, meprobamate, phenytoin, primidone, salicylate, theophylline, tricyclic and other antidepressants

• URINE: acetaminophen, alcohols, barbiturates, benzodiazepines, carbamazepines, carisoprodol, chlorpheniramine, cocaine & metabolites, diphenhydramine,ethchlorvynol, ibuprefen, lidocaine, meprobamate, narcotics & synthetics, phencyclidine, phenothiazines, phenytoin, primidone & metabolites, pyrilamine, salicylate, sympathomimetic amines, theophylline, tricyclic and other antidepressants, trimethoprim

Laboratory Testing• Additional testing is helpful if you have a specific substance that

you suspect• Usually less helpful as a “fishing expedition” and won’t affect

management• Am J Emerg Med. 1999 May:17(3):221-4. Belson MG, Simon HK

– Evaluate the clinical utility and cost-effectiveness of the limited component vs the HPLC component of comprehensive toxicologic screens in children

– Retrospective from HSCH ED Jan 1994-July 1995– The comprehensive test included a broad-spectrum HPLC component as

well as a limited component that examined serum for ethanol, aspirin, and acetaminophen and urine for benzodiazepines, barbiturates, amphetamines, cocaine, phencyclidien, and opiates

– Comprehensive toxicology screens were performed in 463 cases during the study period; 234 (51%0 were positive for exogenous toxin

Laboratory Testing• In 227 of 234 positive screens (97%), toxins were either suspected

by history and/or physical, were present on the limited portion of the toxicology screens, or were clinically insignificant

• The remaining 7 of the 234 positive screens (3%) were clinically significant and detected solely by the broad-spectrum HPLC portion of the comprehensive screen

• However, in none of these 7 cases was patient management clinically altered as a result of the positive screen

• The total additional cost of the HPLC component was $16,205 ($35x464), an average distributive charge of $2,315 per patient in whom the HPLC portion provided additional clinical information ($16,205/7)

• Although adding significant charges to the evaluation of suspected toxic exposures in children, the HPLC component of the comprehensive drug screen was of no additional clinical benefit compared with its limited component alone

Urine Drug Screens

• THC 1-3 weeks*

• Cocaine 2-4 days

• Amphetamine 2 days

• Barbiturates 1-2 days

• Opiates 1-2 days

• PCP 5-7 days

• LSD 1-2 days

• Steroids 3 days or longer

* Longer if prolonged exposure

Antidotes

Poison Antidote

Tylenol NAC

Anticholinergics

Beta Blockers

Carbon Monoxide

Cyanide

Ethylene Glycol

Antidotes

Poison Antidote

Tylenol NAC

Anticholinergics Physiostigmine

Beta Blockers

Carbon Monoxide

Cyanide

Ethylene Glycol

Antidotes

Poison Antidote

Tylenol NAC

Anticholinergics Physiostigmine

Beta Blockers Glucagon, catecholamine

Carbon Monoxide

Cyanide

Ethylene Glycol

Antidotes

Poison Antidote

Tylenol NAC

Anticholinergics Physiostigmine

Beta Blockers Glucagon, Catecholamine

Carbon Monoxide Oxygen

Cyanide

Ethylene Glycol

Antidotes

Poison Antidote

Tylenol NAC

Anticholinergics Physiostigmine

Beta Blockers Glucagon, Catecholamines

Carbon Monoxide Oxgygen

Cyanide Amyl Nitrate, Sodium Nitrate, Sodium Thiosulfate

Ethylene Glycol

Antidotes

Poison Antidote

Tylenol NAC

Anticholinergics Physiostigmine

Beta Blockers Glucagon, Cateholamines

Carbon Monoxide Oxygen

Cyanide Amyl nitrate, Sodium Nitrate, Sodium Thiosulfate

Ethylene Glycol Dialysis, Fomepizole, Ethanol

Antidotes

Poison Antidote

Iron

Isonazid

Lead/Heavy Metals

Methemoglobin Producing agents

Narcotics

Organophosphates

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid

Lead/Heavy Metals

Methemoglobin Producing agents

Narcotics

Organophosphates

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid Pyridoxine

Lead/Heavy Metals

Methemoglobin Producing agents

Narcotics

Organophosphates

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid Pyridoxine

Lead/Heavy Metals DMSA, BAL, EDTA

Methemoglobin Producing agents

Narcotics

Organophosphates

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid Pyridoxine

Lead/Heavy Metals DMSA, BAL, EDTA

Methemoglobin Producing agents

Methylene blue

Narcotics

Organophosphates

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid Pyridoxine

Lead/Heavy Metals DMSA, BAL, EDTA

Methemoglobin Producing agents

Methylene blue

Narcotics Narcan

Organophosphates

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid Pyridoxine

Lead/Heavy Metals DMSA, BAL, EDTA

Methemoglobin Producing agents

Methylene blue

Narcotics Narcan

Organophosphates Atropine, Pralodixime

Phenothiazines

Antidotes

Poison Antidote

Iron Desferoxamine

Isonazid Pyridoxine

Lead/Heavy Metals DMSA, BAL, EDTA

Methemoglobin Producing agents

Methylene blue

Narcotics Narcan

Organophosphates Atropine, Pralodixime

Phenothiazines Benadryl

Elimination of Poisons

• Surface decontamination– Reduce any additional absorption

• Ipecac– Not routinely recommended anymore

– Possible useful in an observed, in hospital poisoning

• Gastric Lavage– Most effective 1-2 hours after ingestion

• Can be effective later in drugs that delay gastric emptying

Elimination of Poisons• Activated charcoal

– Adsorbs many drugs, thus decreasing systemic absorption• Doesn’t work well for lithium, iron, hydorcarbons, alcohols, solvents,

acid/alkali ingestions

– Role of charcoal in gastrointestinaldialysis

• Cathartics– Not generally used– Some charcoal has sorbitol in it

• Whole bowel irrigation– Golytely infusions– Initially done with success in iron ingestions– Used mostly for drugs that charcoal doesn’t work well with

Elimination of Poisons

• Diuresis +/- alteration of urine pH– Obviously, only useful for renally excreted drugs

– Altering pH example• ASA – pkA3

– At a pH of 3, there is a 1:1 ratio of ionized/unionized

– At a pH of 7.4, the ratio is 25,000:1

– Ionized form can’t cross cell membranes – so when you dump ASA into the tubule, if the pH is 4.5 you would have about 5,00:1 ratio, if you increase urine pH to 8.0, then essentially all of it is in the ionized form, and can’t get reabsorbed

Elimination of Poisons

• Altering pH– Alkalinize the urine – ASA, isoniazid, phenobarb

• Use bicarb in the fluids

• Don’t use acetazolamide (Diamox) in ASA poisoning– Metabolic acidosis increases unionized form which can cross

into CNS, worsening poisoning

– Acidify the urine (usually not needed) – quinidine, PCP, fenfluramine, amphetamine

Elimination of Poisons

• Dialysis– What makes things “dialyzable”

• Low molecular weight

• Low volume of distribution

• Low protein binding

• Charge

– Methods• Intermittent Hemodialysis

• CVVH/CVVHD/CVVHDF– Albumin dialysis

Elimination of Poisons

• Charcoal hemoperfusion– Clear chemicals by direct adsorbtion with charcoal in

an extracorporeal circuit

– Doesn’t depend of molecular size, protein binding

– Can be used for a variety of otherwise difficult to manage poisonings

• Digoxin, ASA, barbiturates, TCA’s, theophylline

• Not used that much anymore

Elimination of Poisons

• Plasmapheresis– Works very well with highly protein (albumin) bound

drugs

– Not a routine methodology, but has been used to remove theophylline and digoxin/digibind complexes

• Exchange transfusion– Use in smaller infants where vascular access for

extracorporeal techniques can’t be done

Tylenol Ingestion

• Clinical manifestations– Stage 1

• First 12-24 hours

• Nausea, vomiting, anorexia

• No CNS involvement – of you see it, think of polysubstance ingestion

– Stage 2• Resolution of GI symptoms

• 36 hours after ingestion see biochemical evidence of liver dysfunction – AST/ALT, bilirubin, PT

Tylenol Ingestion

• Clinical manifestation– Stage 3

• Liver dysfunction reaches a peak on day 3-4• Start GI symptoms again• High transaminases (>10,000) do not necessarily predict liver

failure• Fulminant liver failure can occur

– Stage 4• Recovery stage – lasts 7-8 days• Chronic hepatitis does not occur – LFT’s/biopsy return to

normal

Tylenol Ingestion

• Prediction of toxicity– Rumack nomogram for single ingestion

– Rough guide for potential toxicity• Children – 150 mg/kg

• Adults – 7.5 gm– Uncommon 150mg/kg

– 50% with 250 mg/kg

– 100% with 350mg/kg

Tylenol Ingestion

• Therapy– N-acetylcysteine (Mucomyst)

• Oral – 140 mg/kg load, followed by 70mg/kg q4 hours for 17 doses

– Repeat dose if vomits within 1 hour

– Can mix with carbonated drinks or grapefruit juice

• Intravenous – 150 mg/kg load over 15 minutes, then 50mg/kg over 4 hours, then 100mg/kg over 16 hours

Volatile Alcohols

• Diagnosis– High index of suspision

– Elevated osmolar gap

– Volatile alcohol screen + separate test for ethylen glycol

– Methanol and ethylene glycol – no ketones

– Isopropyl alcohol – marked acetone

– Ethanol – acetoacetate and B-hydroxybutyrate

Volatile Alcohols

• Isopropyl Alcohol– Toxic dose is 1 ml/kg of 70% solution

• More than one swallow in children should be presumed toxic

– About 20% is broken down by liver ADH to acetone– Symptoms are like ethanol ingestion

• Nystagmus is common• More CNS depressant than ETOH, because acetone is a CNS depressant

as well

– Management• Supportive (without hypotension essentially 0% mortality)• Levels don’t mean much prognostically• Dialysis will remove it

– Coma + hypotension – 30% mortality– Level over 400 (implied severe ingestion)

Volatile Alcohols

• Methanol– No safe dose. 5ml is lethal in toddler age and can cause

blindness in adults. 1ml/kg is lethal in adults

– Metabolism• 30% excreted by lungs

• 5% kidneys

• Rest to liver to make toxic metabolites

Volatile Alcohols

• Methanol– Clinical symptoms – Biphasic

• Initial – CNS depression secondary to direct action of methanol on CNS

• Delayed– Visual disturbances

» Photophobia, “snowflakes”, blurred vision» CAN HAVE FIXED DILATED PUPILS

– Metabolic acidosis

– Laboratory• Elevated anion gap is due to formic acid and lactate• Retinal damage is due to locally produced formic acid

Volatile Alcohols

• Methanol– Treatment

• Supportive

• Ethanol/dialysis

• Fomepizole +/- dialysis now

Volatile Alcohols

• Ethylene Glycol– Minimum lethal dose is 1.4-1.6 ml/kg– Clinical symptoms

• Severe neurotoxicity, metabolic acidosis, renal failure, cardiovascular collapse

• 1st phase – 30 min –12 hours – CNS symptoms, N/V– If LP – pleocytosis and elevated protein

• 2nd phase – cardiorespiratory failure with pulmonary edema• 3rd phase – renal failure

– Metabolism• 25% excreted unchanged by kidneys• Remainder rapidly metabolized by liver and kidneys to toxic

metabolites

Volatile Alcohols

• Ethylene Glycol– Lactic acidosis develops secondary to altered

NADH/NAD ratio

– Oxalic acid chelates calcium• Tetany and myocardial dysfunction

– Renal failure is likely due to glycoaldehyde, glycolic acid, glyoxylic acid

• Most recover – can be prolonged up to 2 months

• Can see calcium oxalate crystals in urine

Volatile Alcohols

• Ethylene Glycol– Treatment

• Fomepixole +/- dialysis

Cyanide Poisoning

• Exposures– Mostly from fires in children

– Acetonitrile in some cosmetics reported lethal

– “Vitamin B17” – cyanogenic glycosides – sold in health food stores – from pits of apricots and bitter almonds

– Laetrile – only when given orally or rectally

– Nipride – use sodium thiosulfate to reduce incidence – 1 gram per 100mg of Nipride

Cyanide Poisoning

• Pathophysiology– Reversible binding to a-a3 cytochrome

– Halts aerobic metabolism and ATP formation• Pushes to anaerobic metabolism and resultant lactic acidosis

– Inability to use oxygen at the cellular level• Normal oxygen content and oxygen delivery

Cyanide Poisoning

• Treatment– 100% oxygen always

– Eli Lilly Cyanide Antidote Kit No M-76• Amyl nitrate pearls – inhale for 15-30 secs

– Produces about 5% methemoglobinemia

• IV sodium nitrite

• IV sodium thiosulfate

– Aiming for methemoglobin of 30%

Hydrocarbon Ingestion

• Unintentional vs intentional• Clinical presentation

– Respiratory distress• Hydrocarbons dissolve the lipid layer in the lung

– Surfactant inactivation, distal airway closure, hypoxemia, V/Q mismatch

• Can progress to ARDS

– CNS abnormalities• Mostly due to hypoxia

– GI abnormalities

Hydrocarbons Ingestion

• Clinical presentation– Fever and leukocytosis common in first 24-48 hours

• Treatment– Supportive

– Treat the hypoxia

– No induction of vomiting

Iron Intoxication

• Relatively common ingestion• About 5-10% require hospitalization• Can be lethal

– <20 mg/kg elemental Fe – insignificant

– 20-60 mg/kg mild toxicity

– >60 mg/kg moderate to severe toxicity

– >200 mg/kg rapidly lethal if not treated

Iron Intoxication

• Pathophysiology– Huge uptake of iron from small bowel– Overwhelm transferrin’s ability to bind and thus get

free iron circulating in blood• Disruption of CMS, GI, CV systems• Major oxidant stress – possibly shunts electrons away from

cytochromes in the mitochondria• Interferes with activation of thrombin and clot formation,

leading to coagulopathy

– Direct gut toxicity with hemorrhagic gastritis and bowel perforation

Iron Intoxication

• Clinical manifestation– 1st phase – GI symptoms (N/V/D, hemorrhagic gastritis,

GI bleed) – direct effect– 2nd phase – temporary recovery – 6-12 hours from

ingestion – can last several days– 3rd phase – return of GIU symptoms and MSOF

• Metabolic acidosis, shock, CNS depression, liver dysfunction, renal failure, coagulopathy, etc.

• Die or get better

– 4th phase – 4-6 weeks out – pyloric, gastric, or intestinal obstruction – due to healing of initial damage

Iron Intoxication

• Prognosis– Ingestion size

– Serum iron levels• Peak 2-6 hours after ingestion

– <100 – unlikely toxicity

– 100-300 minimal

– 300-500 moderate

– 500-1,000 severe

– >1,000 potentially lethal

• After 6 hours even in large ingestion, level may be normal

Iron Intoxication

• Therapy– Role of gastric lavage

– Desferoxamine – iron chelator• Binds iron to form ferrioxamine which can be safely excreted

renally– Red (“vin rose”) color to urine

• Also has a protective effect of increasing intracellular binding of iron, reducing toxicity

– Not dialysable

Beta Blockers

• Widely prescribed and available• Phamacology

– Lipophilicity

– Membrane stabilizing effect

• Selective vs non-selective agents• Propranolol is most common and most dangerous

Beta Blockers

• Toxic dose– 2-3 times therapeutic dose

• Signs and symptoms– Bradyarrhythmia

– Hypotension

– Decrease LOC

– Respiratory depression

– Seizure

– Ventricular arrhythmia

Beta Blockers

• Prehospital management– Aggressive airway management

– PALS protocol

– Atropine 1mg prn (max 3 mg)• Peds 0.02 mg/kg

– Transcutaneous pacemaker• Do not delay in symptomatic bradycardia

Beta Blockers

• Prehospital management– Glucagon 5mg IV bolus

• Peds 0.2 mg/kg IV bolus

– Fluid resuscitation – peds 20 ml/kg

– Pressors• Dopamine 5-10 mcg/kg/min

• Epinephrine drips– Titrate to response. May need bigger than normal dose

Beta Blockers

• Other management issues– Treat dysrhytmia

– Pediatric patient• Hypoglycemia more common

• Seizures more likely than adult

– Consider heroic measures - ECMO

Calcium Channel Blocker

• Pharmacology– Negative inotrope

• Blocks flow of calcium ions through slow channels

• Decreased amount of calcium from sarcoplasmic reticulum

– Negative chronotrope• Decrease automaticity in SA node and AV junction

– Reduction in PVR

Calcium Channel Blocker

• Agents– Verapamil

• Significant cardiac depressant– Vasodilation

– AV slowing

– Diltiazem

– Nifedipine

– Felodipine

– Amlodipine

Calcium Channel Blocker

• Toxicity– Hypotension

– Bradycardia

– Arrhythmias

– Respiratory depression

– Neurologic disorders• Seizures etc.

Calcium Channel Blocker

• Prehospital management– Aggressive airway management

– PALS protocol

– Atropine 1 mg prn (max 3mg)• Peds 0.02 mg/kg

– Atropine most often not effective

– Transcutaneous pacemaker• Do not delay in symptomatic bradycardia

Calcium Channel Blocker

• Prehospital management– Calcium chloride 250-500 mg IV

• Peds 20mg/kg

– Glucagon 5mg IV bolus• Peds 0.1 mg/kg IV bolus

– Fluid resuscitation – peds 20 ml/kg

Calcium Channel Blocker

• Other management issues– Pressors prn

• Dopamine 5 mcg/kg/min

• Epinephrine drip 2 mcg/kg/min– Titrate to response, may need bigger dose than normal

– Treat dysrhythmias

– Pediatric patient• Small dose can be lethal

• Seizures are more likely than adult

– Consider heroic measures - ECMO

Digoxin

• Toxicity– Dysrhythmias

• PVC’s

• Slow A-fib

• Bradycardia, V-fib. V-tach

– Hypotension

– Hyperkalemia ( Renal insufficiency is a risk factor)

– CNS• Delirium, hallucinations, lethargy, agitation

• Ocular disturbances

Digoxin

• Treatment– Basic management (ABC’s etc.)

– Electrolyte disturbances• Hyperkalemia

– Atropine/Pacemaker

– Manage dysrhythmias

– Digoxin specific antibody

Digoxin

• Treatment – Digibind– Indication

• Life threatening CV toxicity

• K > 6.5 mEq/L (except in chronic renal failure)

• Steady state level >10 ng/ml

• Ingested dose >10mg (adult)