Common poisonings (toxidromes)

B. Wayne Blount, MD, MPH

Epidemiology

US Poison Centers receive 1.5 million calls a year regarding pediatric ingestions.

79% of these calls involve children younger than age six.

56% of pediatric exposures are from products around the house including medicines, cleaning agents, pesticides, plants and cosmetics.

Acute Poisoning in the Emergency Department

Common - 3-5% of ED attendances2000 Deaths per year

Often multiple drugsDON’T FORGET ALCOHOL !!

Epidemiology: “the numbers”Nearly 90% of exposures occur at homeDuring pre-adolescence: slight male

predominanceThis reverses in ages 13-19 with females

accounting for 55 %Children, especially under age 6, are

more likely to have unintentional poisonings

About half of all poisonings among teens are classified as suicide

Epidemiology: “the numbers”

Approximately 1/3 of ingestions of toxic medications occur with meds intended for someone else

DefinitionsArtery: The Study of Paintings

ObjectivesGeneral Principles in the Management of

ANY PoisoningSpecific management options with certain

substancesSalicylates Ethylene GlycolAcetominophen PesticidesIron LeadTricyclics Hydrocarbons

General Management -HistoryApplies to ANY episode of PoisoningWHATHOW MUCH (Ideally mg/Kg)WHENWHAT ELSE (Including Alcohol)WHYUse Paramedics, friends, relatives, anyone!!

General Management -1A (Airway)B (Breathing)C (Circulation)D (Disability-AVPU/ Glasgow Coma Scale)DEFG ( Don’t Ever Forget the Glucose)G (Get a set of basic observations)

General Management -2Use all your senses, search for the cluesLOOK

Track MarksPupil Size

HearType Breathing (Kussmaul, Hyperventilation)

FEELTemperature, Sweating

SMELLAlcoholFruityI would NOT taste

Specific Management Options-1

DECREASING DRUG ABSORPTION

Decontaminate

Gastric Lavage ( Unpopular - need to protect the airway, may push drug through pylorus into small bowel.)

Absorbants ( Activated Charcoal , usually within 1 hour of ingestion, longer repeated doses in drugs that delay gastric emptying e.g. Aspirin)

Specific Management Options -2

INCREASING DRUG ELIMINATIONAlkaline Diuresis (Aspirin)

Hemodialysis (Aspirin)

Specific Management Options - 3

ANTAGONISING THE EFFECTS OF THE POISON

Desferrioxamine (IRON)Naloxone (OPIATES)N Acetylcysteine (Acetominophen)Digibind (Digoxin)Flumazenil (Benzodiazepines)

DefinitionsBariumWhat doctors do when patients die

DiagnosisPhysical Exam:

Vital signs and general appearanceThorough PEClose attention to neuro exam

Pupils Reflexes and posture Mental status

Bowel soundsMucous membranes and skin moisture/appearanceCharacteristic odorsNosebleeds, needle tracks, blistering

Physical Exam FindingsSympathomimetic (meth, amphetamines, cocaine,

opiate withdrawal, PCP) Hyperthermia, tachycardia, hypertension, mydriasis,

warm/moist skin, agitatedCholinergic (organophosphates, betel nut, VX,

Soman, Sarin) SLUDGE (Salivation, Lacrimation, Urinary incontinence,

Diarrhea/Diaphoresis, GI upset/hyperactive bowel, Emesis)Anticholinergic (antihistamines, atropine,

phenothiazines, TCA) Hyperthermia, tachycardia, HTN, hot/red/dry skin,

mydriasis, unreactive pupils, unrinary retention, absent bowel sounds

Opioids (codeine, dextromethorphan, heroin) Miosis, respiratory depresssion, mental status depression

Diagnostic ConsiderationsBefore proceeding, consider other aspects of the

differential diagnosis ( CVA, trauma, meningitis, post-ictal state, behavioral or psych disorders).

Labs to evaluate glucose, acid-base status and electrolytes, BUN/Cr, carboxyhemoglobin, hepatic enzyme levels, urinalysis (UA preg), serum osmolality, serum acetaminophen levels

EKGSave samples of blood, urine, gastric contentsGeneral qualitative tox screens of little value

(except when abuse is suspected), but are rapid and could offer clue to antidote; may have role in the difficult dx or critically ill; Quantitive measurements in certain toxic exposures

Diagnostic ConsiderationsOcular/dermal:

pH testing may reveal acid or alkali Hypoxemic while asymptomatic may suggest

methemoglobinemiaCardiac

EKG shows arrhythmia (TCA) Blood color on filter paper that remains brown after air

exposure suggests methemoglobinemia (possibly from benzocaine-containing products, aniline dyes, nitrites)

Signs of hypocalcemia in ethylene glycol, hydrofluric acid

Urine fluorescence in ethylene glycolFerric Cl creates purple reaction with salicylates and

phenothiazines in urineSmall opacities on x-ray may show halogenated

toxins, heavy metals, lithium, densely packed products, phenothiazines, enteric-coated meds

Diagnostic ConsiderationsMUDPILES CAT for high anion gap acidosis

Methanol or metforminUremiaDKAParaldehyde or phenforminIron, INH, IbuprofenLactic acidosisEthylene glycolSalicylatesCyanideAlcohol or acids (valproate)Toluene or Theophylline

Diagnostic ConsiderationsToxins requiring quantitative levels at a set

point:AcetaminophenCarbon monoxideEthanol, ethylene glycolHeavy metals (24 hour urine)IronMethanolMethemoglobin

Toxins requiring quantitative serial levelsAspirin/salicylates, tegretol, digoxin, phenobarbital,

phenytoin, VPA, theophylline

DefinitionsDilateLive longer than your kids

Common Toxidrome FindingsPhysical Findings Adrenergic

Anti-

cholinergic

Anti-

cholinesteraseOPIOID

Sedative-

hypnotic

RR Increased No change No change Decreased Decreased

HR Increased Increased Decreased Normal/

decreased

Normal/

decreased

Temp Increased Increased No change Normal/

decreased

Normal/

decreased

BP Increased NoChange/increased

No change Normal/

decreased

Normal/

decreased

Common Toxidrome FindingsPhysical Findings Adrenergic

Anti-

cholinergic

Anti-

cholinesterase

OPIOIDSedative-

hypnotic

Mental status

Alert/

agitated

Depressed/

Confused/

hallucinate

Depressed/

Confused/

Depressed Depressed

pupils Dilated Dilated Constrict Constrict Normal

Mucus membrane

Wet Dry Wet Normal Normal

skin Diaphoretic Dry Diaphoretic Normal Normal

Salicylates

PharmacologyIrreversibly inhibits the enzyme

cyclooxygenase. This inhibits prostaglandin synthesis.

Since prostaglandins are not synthesized, their downstream byproducts are never released such as: IL-6, TNF, and alpha and beta interferons.

Believed to directly inhibit neutrophils to decrease the inflammatory response.

PathophysiologySalicylates stimulate the brainstem to cause

hyperventilation (respiratory alkalosis).

Multifactorial renal impairment leads to accumulation of sulfuric and phosphoric acids.

Interfere with the Krebs Cycle limiting substrates for ATP generation.

Pathophysiology ContinuedUncouples oxidative phosphorylation

which leads to increased pyruvic and lactic acid level and generates heat.

Causes salicylate induced fatty acid metabolism which produces ketone bodies. This ketoacidosis contributes a significant portion to the overall metabolic acidosis.

Salicylate Poisoning

Ingestion of 150 mg/kg of salicylates causes intoxication.

Level of 50-80 mg/dL causes moderate symptoms.

Severe symptoms are associated with blood levels > 80 mg/dL.

Clinical ManifestationsEarly symptoms are usually non-specific such as nausea

and vomiting.

Tinnitus with or without hearing loss can also be an early sign.

Hyperventilation is often a warning sign of a significant ingestion. (respiratory alkalosis)

CNS signs can vary from vertigo to hallucinations to stupor. Coma is rare except in massive overdoses.

In large overdoses, almost every organ system becomes involved.

TreatmentAddress the A,B, C’s.Detailed history and exam.Laboratory evaluation and consider a blood

gas if your history suggests an ingestion.Activated charcoal should be given.

Evidence for multidose charcoal is equivocal.

The use of sodium bicarbonate.Measure serial salicylate levels and

chemistries.

Sodium Bicarbonate TherapyThe goal is to titrate the urinary pH to 8.

BUTExcretion of hydrogen will make it “nigh on

to” impossible to titrate your therapy to a urinary pH of 8.

Potassium must be monitored closely because if the potassium drops, the kidney will retain the potassium and excrete hydrogen.

Urine is alkalinized by administering 1-2 mEq/kg of sodium bicarbonate at

half hourly intervals for 4 hours in alkaline urine, salicylates do not

diffuse back into the tubular cells from the lumen.

Potassium salts should be given (3-5 mEq/kg/day) to replace the potassium losses

Indications for HemodialysisRenal failure.Congestive heart failure (relative).Acute lung injury.Persistent CNS disturbance.Severe acid-base or electrolyte imbalance,

despite appropriate treatment.Hepatic compromise with coagulopathy.Salicylate concentration (acute) >100

mg/dL.

DefinitionsImpotentDistinguished, Well Known

Ethylene Glycol and Methanol

fomepizole

Mg, B6

folate

thiamine

The Osmolar Gap

TreatmentFomepizole or ethanol – both inhibit

alcohol dehydrogenase. Cofactors

PyridoximeFolateMagnesiumThiamine

Fomepizole DosingLoading dose

15 mg / Kg

Next 4 doses10 mg / Kg

Subsequent doses15 mg / Kg

Dosing schedule is every 12 hours except during dialysis. Then it is every 4 hours during dialysis as it gets dialyzed off.

DefinitionsNitratesCheaper than day rates

PesticidesSpecifically

organophosphates and carbamates.

They work by inhibiting acetylcholinesterase. So…

Present with cholinergic symptoms

Organophosphorus (insecticides and pesticides) Poisoning

Organic phosphate insecticides cause irreversible inhibition of the enzyme cholinesterase. As result acetylcholine accumulates in various tissues. Excessive parasympathetic activity occurs. These agents are absorbed by all routes including skin and mucosa.

Cholinergic Symptoms

Symptoms manifest quickly usually

within a few hours Include weakness, blurred vision,

headache, giddiness, nausea, and pain in chest.

Sweat profusely. papilledema may occur.

Reflexes absent and sphincter control lost.

Nicotinic SymptomsThink the days of the week !M ydriasisT achypneaW eaknessT achycardiaF asiculationsW eekend: “Wee” ones : Pediatric patients

tend to present with a predominance of nicotinic symptoms!!!

Weakness from Pesticides

TreatmentIf the insecticide was in contact with

skin or eyes, Wash thoroughly .

Atropine 0.02 mg / Kg IV. Repeat as needed and titrate to respiratory secretions. It will likely take massive doses!!

Pralidoxime (2-Pam) 20-40 mg / Kg bolus followed by 10-20 mg / Kg /hour infusion.

Remember to send RBC and Plasma Cholinesterase levels upon arrival and daily.

DefinitionsRectumDamn near killed him

In overdose situations, liver enzymes become saturated, glutathione is depleted, NAPQI(N-acetyl-p-benzoquinoneimine) accumulates, and hepatic necrosis occurs

PharmacokineticsAbsorption

Rapidly absorbed from the GI tractPeak concentration usually occurs between 60 and 120 minutes

Peak plasma levels almost always occur within 4 hours

Half life

Average 2 hours– range 0.9 to 3.25 hours

No age related differencesNo change in patients with renal diseaseWith liver dysfunction, may increase to 17

hours

ToxicityFactors involved in predicting hepatotoxicity

total quantity ingestedtime from ingestion to treatmentage of the patientalcoholenzyme inducing medications

serum concentration in relation to Rumack nomogram

Toxic dose

In adults, threshold for liver damage is 150 to 250 mg/kg

Children under 10 appear to be more resistant

Potential liver damage

Adults: > 150 mg/kg in acute dose

Adults: > 7.5 Grams in 24 hours (chronic)

Children (<10 yrs): > 200 mg/kg

4 Stages of Acetaminophen Poisoning

Phase I (30 minutes to 4 hours)

Within a few hours after ingestion, patients experience anorexia, nausea, pallor, vomiting, and diaphoresis. Malaise may be present.

Patient may appear normal

Phase II (24 to 48 hours)

SX Less severe. May seem like recovery. Right upper quadrant pain may be present due to hepatic damage.

Liver enzymes become abnormal. Prothrombin time may be prolonged. Renal function may begin to deteriorate.

Phase III (3 to 5 days)

Characterized by symptoms of hepatic necrosis. Coagulation defects, jaundice, and renal failure have been noted. Hepatic encephalopathy has been noted. Centrilobular necrosis. Nausea and vomiting . Death due to hepatic failure.

Phase IV (4 days to 2 weeks)

Complete resolution or death

Activated charcoalShould not be withelddose 50-100 Grams

Catharticutilized to speed transit time

HemodialysisLimited benefitDamage occurs quickly

HemoperfusionNo benefit

Peritoneal dialysisNo benefit

Blood Sample

4 hour post ingestion APAP levellevels drawn earlier may be erroneous

levels may be accurate out to 18 hours

Plot level on Rumack-Matthews nomogram

150 mg/dl at 4 hours is possibly toxic

Do not use therapeutic “normal” values to determine potential toxicity!

Baseline CBCCreatinine, BUN, blood sugar, electrolytesProthrombin timesAST, ALT

repeat q 24 hourselevations typically seen 24-36 hours

post ingestion

mcg/ml 4 8 12 16 20 24Hours After Acetaminophen Ingestion

150

5

10

50

500

Rumack and Matthew Nomogram

100

Late

Not valid after 24 hours

If APAP level plots above the possible risk line administer N-acetylcysteine (NAC).

If NAC is indicated, full regimen should be followed. Do not stop NAC early if nomogram indicates toxic possibility

N-acetylcysteine (NAC)Mechanism of action

glutathione substitutemay supply inorganic sulfur, altering

metabolism

Route of administrationOrally

IV not approved in the U.S.

NAC dosing

Oral 72 hour protocolLoading dose is 140 mg/kg

Maintenance doses: 70 mg/kgGiven every 4 hours x 17 doses starting 4 hours after loading dose

NAC supplied as 10 or 20% oral solutiondilute to 5% final concentration with

juice or soft drink

May be administered via NG tube

If emesis occurs within 1 hour of administration, repeat the dose

DefinitionsTabletA small table

Acetominophen SummaryIn overdose, APAP may overwhelm the liver stores of glutathione. A rise in liver enzymes may occur. Timely administration of NAC may protect the patient from hepatic damage. Therapy should be initiated as soon as possible, but NAC is beneficial at any time. If APAP levels cannot be obtained, assume a toxic dose has been ingested, initiate NAC, and continue until regimen complete.

Points to rememberAPAP is present in many poly drug overdoses No symptoms may be present…screen150 mcg/ml at 4 hours is a “treat” levelNAC loading dose is 140 mg/kgNAC maintenance doses are 70 mg/kgOnce NAC is started, DO NOT DCMetoclopramide 0.1-1.0 mg/kg is very

effective in controlling nausea/vomiting associated with APAP toxicity

SummaryEpidemiologyApproach to the poisoned pateintSpecific toxidromesOther than the General approach, will

probably have to look up treatmentsCall the Poison Hot Line

DefinitionsBenignWhat you be after you be 8

IronThe most common

cause of death in toddlers.

Classically taught as having five clinical stages.

Remember prenatal vitamins, supplements, and “natural products”.

IronToxic doses occur at 10-20mg/Kg of

elemental iron.

Prenatal vitamins typically contain about 65 mg of elemental iron.

Childrens vitamins contain about 10-18 mg of elemental iron.

The Five StagesStage 1

Nausea, vomitting, abdominal pain and diarrhea.Stage 2

This is the latent phase often between 6-24 hours as the patient resolves GI symptoms.

Stage 3Shock stage involving multiple organs including

coagulopathy, poor cardiac output, hypovolemia, lethargy and seizures.

Stage 4Continuing of hepatic failure and ongoing oxidative

damage by the iron in the reticuloendothelial system.Stage 5

Gastric outlet obstruction secondary to scarring and strictures.

ManagementDetailed history and physical including a rectal

exam for frank blood.Aggressive fluid resuscitation and intravenous

access.Whole bowel irrigation and KUB to look for pills.Laboratory analysis for CBC, chemistry, and iron

levels (peak around 4 hours).Will often require repeat levels with a repeat

chemistry.TIBC has no utility in the acute overdose setting.

Management

ManagementIf the patient is in shock, remember to at least

type and screen (if not cross match) for blood.Give deferoxamine before iron level is back if

the patient is in shock.Deferoxamine was derived from streptomyces

pilosus.Hypotension and allergic reactions are seen.ARDS is a known complication and usually

limit its use to 24 hours or less.

Review ArticlesMichael JB, Sztanjnkrycer MD. Deadly pediatric

poisons: nine common agents that kill at low doses. Emergency Medicine Clinics of North America 2004; (22): 1019-1050.

Bar-Oz B, Levichek Z, Koren G. Medications that can be fatal for a toddler with one tablet or teaspoonful. Pediatric Drugs 2004; 6(2): 123-126.

TCA Overdose- Clinical features ANTICHOLINERGIC EFFECTS

Dry Mouth, Dry Eyes, Dilated Pupils, Urinary Retention, Blurred Vision, Dizziness, Palpitations, Pyrexia without sweating

CNS Effects- Confusion, Delerium, Coma, Convulsions, Myoclonus and Respiratory Depression

TCA Overdose Clinical FeaturesCardiac Toxicity (quinidine effects)

Heart Block, Asystole, Bradycardia, Tachycardia, Ventricular Dysrythmias

ECG Changes - broadening of QRS complex, Widened QT Interval

TCA Overdose- Management 1Mainstay of initial management is

Supportive. Try not to give other drugs ontop with a few specific exceptions

A- May need intubatingBC- Give IV fluids if low BPD -Control convulsions with Diazepam

TCA Overdose Management 2Activated Charcoal if more than 4 mg/Kg

within 1 hour.N.B WATCH OUT FOR THE AIRWAY

Correct Hypoxia with OxygenCorrect Acidosis with Na BicCorrect any arrythmias with Na Bic (i.e

start by controlling the acid base disturbance)

• Epidemiology• Clinical features• Investigation• Treatment

Epidemiology Accidental – 33 to 60% in India &

other developing countries

Reasons for high incidence1. Extensive use for cooking & lighting in

low socioeconomic status2. Stored in soft drink bottles, beer bottles

within reach of children

Clinical featuresAge – 1 to 3 years more than 70% symptomatic within

10 hours

SYMPTOMS

RS – breathlessness, coughCNS – convulsions, coma GPE – fever, restlessness, cyanosisGI – vomiting, diarrhea

Lab InvestigationsBlood – Leukocytosis

X – Ray changes

Changes appear within one hour - commonly right basal infiltrates - emphysema - pleural effusion - pneumatocoeles

Severity scorePARAMETERSPARAMETERS ABSENTABSENT PRESENTPRESENT OTHERSOTHERS

FEVER FEVER 00 11 00

SEVERE SEVERE MALNUTRITIONMALNUTRITION

00 11 00

RESP. DISTRESSRESP. DISTRESS 00 22 44

CNS SYMPTOMS CNS SYMPTOMS 00 22 44

• >4 – Significant• <7 – Likely to survive• >8 –– Risk of death is increased

ManagementAvoid emeticsAvoid gastric lavage – In case of massive

amount use a cuffed endotracheal tubeAfter lavage leave magnesium or sodium

sulphate in the stomachOxygen may be usefulAssisted VentilationAntibiotics - Penicillin G 50000/Kg/24 hrs IV

qid Kanamycin – 10-15mg/Kg/24 hrs - IM bdSteroids – Not helpful

Complications• Pneumothorax• Pneumatocoeles• Pleural effusion• Bronchopneumonia• Coma

Pralidoxime (PAM) is given in dose of

25-50 mg/kg IM or IV over 30 min infusion. The dose may be repeated in 1-2 hours, then at 6-12 hour intervals as needed. Monitor for hypertension. Never inject morphine, theophylline, aminophylline or chlorpromazine. Intravenous fluids should only be given with caution. No oral tranquilizers are administered. Artificial respiration may be necessary to sustain life.

Hydrocarbon PoisoningThese may be divided into aliphatic or

aromatic compounds. Aliphatic hydrocarbons include kerosene, turpentine, lubricating oils, tar and have greatest risk of aspiration and pulmonary symptoms. Aromatic compounds have mainly neurological and hepatic toxicity and include benzene compounds.

Type of toxicity with a hydrocarbon

depends on its volatility, viscosity or surface tension. The lower is viscosity, more is the risk of pulmonary aspiration. Mineral spirit, kerosene and furniture polish have both low volatility and viscosity and thus carry a higher risk of aspiration pneumonia.

Benzene derivates, toluene and xylene

are components of various solvents and degreasers. These are highly volatile but have low viscosity. Inhalation is the primary route of toxicity which manifests with CNS symptoms. Gasoline and naphtha are constituents of lighter fuel and lacquer diluent and primarily cause depression of the central nervous system (CNS).

Turpentine oil is highly volatile but has low

viscosity also. Toxicity results from inhalation and gastrointestinal absorption. They can also cause CNS toxicity.

Halogenated hydrocarbons are used as solvents and spot removers. Freon is used as a refrigerant.

Toxic exposure to hydrocarbons may result in cardia, gastrointestinal, neurological, pulmonary, renal, hepatic, metabolic and hematological manifestations.

Induced emesis or gastric lavage is

contraindicated for kerosene oil poisoning. It is done only when large quantities of turpentine have been ingested or the hydrocarbons product contains benzene, toluene, halogenated hydrocarbons, heavy metals, pesticides or aniline dyes. Other specific modalities including steroids and antibiotics are not efficacious.

Carbon Monoxide PoisoningClinical manifestations include

headache, cyanosis, convulsions, and coma.

Patients are administered 100 percent oxygen and

if carboxyhemoglobin levels are above 40 percent, hyperbaric oxygen therapy is considered.

Lead PoisoningExposure to lead occurs from old lead

based deteriorated house paint (in old houses) and dust and soil contaminated with lead such as from leaded gasoline, lead electrode plates from old automobile batteries, adultered food, folk remedies, broken lead typesets scattered around old printing establishments. Food may be adulterated with colored metallic salts or the black collyrium used as surma may contain a proportion of black oxide of lead.

Lead Poisoning Chronic lead intoxication occurs

usually in children who eat non-edible substances (pica) and manifests as pain in abdomen and resistant anemia. Lead is deposited in the bones. Acute infections may mobilize lead from storage areas in bones and cause acute lead poisoning leading to acute lead encephalopathy.

In these cases the child may be left

with neurological sequelae. Lead inhibits sulfhydryl enzymes and formation of heme. Heme precursors such as porphyrins accumulate in the blood and are excreted in the urine. Screening for lead intoxication is done by measuring zinc protoporphyrin or blood lead levels.

TreatmentIn symptomatic children, therapy is

usually started with dimercapol (BAL) (75 mg/m2 every 4 hourly IM). BAL may be stopped after 48 hours, while calcium disodium edetate is used for another 3 days but at a lower dosage of 50 mg/kg or 1000 mg/M2 per 24 hours by continuous IV infusion.

Maximum daily dose should not

exceed 500 mg/kg. Stop BAL when blood lead level falls below 60 microgram/dL. Give a second course of edetate alone if blood lead rebounds to 45-69 microgram/dL. A second course of edetate in combination with BAL is recommended for rebound lead level of >70 microgram/dL. Wait for 5-7 days in between the two courses.

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

Which is Candy?

Sweet Tarts vs. Ecstacy

Physiologic DifferencesBlood brain barrier still more permeable to toxicologic

substances until around 4 months. No studies demonstrating increased permeability, rather this is

an estimate based on toxicity noted with smaller doses than expected.

Higher metabolic demands.

Decreased ability to glucuronidate in the infant period. Second trimester pregnancies that were terminated showed only 10% activity of the P-450 system. No better studies to date, but most believe between ages 2-4

years that glucuronidation is equivalent to adults.

Decreased glycogen stores.

Physiologic DifferencesIncreased body surface area can lead to

thermoregulatory issues.

Children reside lower to the ground. This puts them at higher risk for ingesting compounds heavier than air. Often adults will NOT have the same exposure.

Inability to avoid hazards – they do not read warning labels or “Do Not Enter” signs.

The Expanded “One Pill Kill”

The Deadly Pediatric PoisonsCalcium Channel

BlockersCyclic

AntidepressantsLomotilOpiates / Opioids

Salicylates (methyl)Toxic AlcoholsSulfonylureasCamphorClonidine and

imidazolinesAntimalarials

Calcium Channel BlockersThree major classes

PhenylalkylamineBenzothiazepineDihydropyridine

Block L-type channelsCause hypotension,

bradycardia, and arrythmias.

Immediate and sustained release.

Usually not the childs medication.

Calcium Channel BlockersManage A, B, C’sCheck Labs and

EKGFluidsCalciumGlucagonPressorsHigh Dose InsulinAtorpine and Pacing

Calcium Channel BlockersMay be able to wean

pressors with insulin.Insulin dosage is 1

unit / kg bolus and 0.5 units / kg / hour drip.

Monitor sugar Q20 minutes for the first few hours.

Most will NOT become hypoglycemic.

Cyclic AntidepressantsThey were the leading cause of poisoning

fatality until 1993.They interfere with reuptake of biogenic

amines and serotonin at the nerve terminal.Manifest toxicity by anticholinergic effects,

alpha-1 inhibition, sodium channel blockade, and can inhibit GABA.

Cause CNS and cardiovascular toxicity with arrythmias leading to mortality.

EKG Findings

EKG Findings

Cyclic Antidepressant ManagmentManage A, B, C’s aggressivelyOptimize electrolytesFollow serial EKG’s and use Bicarb if:

QRS >100 or 110 msecaVr > 3 mm

If bicarbonate and magnesium are not effective, lidocaine is the antidysrhythmic of choice.

Norepinephrine is the pressor of choice for refractory hypotension.

Is it the Sodium or the Bicarb?The answer is

BOTH!

Sodium overcomes the partial blockade from cyclic antidepressants.

Alkalinization does change binding properties.

How does the bicarb work?Initially thought to increase protein binding

thus limiting free drug in the bloodRat study using alpha-1 acid glycoprotein

(AAG) only decreased arrhythmias at massive doses. AAG is a proven TCA binder.

Current theories is that the ionic form of the TCA binds to the sodium channel causing blockade and the bicarbonate changes the TCA from the ionic form to the neutral form causing less blockade.

LomotilAntidiarrheal agent containing both

diphenoxylate and atropine.

Both agents are absorbed by the GI tract and absorption may be delayed in overdose due to inhibitory effects on smooth muscle motility.

Diphenoxylate is an opoid that is metabolized to difenoxin which is 5 times more potent than the parent compound and has half life of 12-14 hours.

LomotilPatients manifest

signs and symptoms of opiate toxicity.

Respond well to naloxone and supportive care.

Current recommendations are for a minimum of 24 hour observation.

Opiates / OpioidsTypically present with respiratory

depression, altered mental status, and miosis.

Address the patient like any other “altered mental status”

Key point is to remember to consider an opiate ingestion.

Naloxone DosingUsually start with 0.01-0.1 mg / Kg.

Repeat as frequently as needed to reverse symptoms.

If a drip is required, calculate how much naloxone was used in the first hour and start the drip at 2/3 that dose.

Sulfonylureas

Mechanism of ActionSulfonylureas keep

the potassium efflux channel closed.

This keeps the cell depolarized which allows the voltage-gated calcium channel to remain open.

This stimulates insulin release.

SulfonylureasSince sulfonylureas stimulate insulin

release, this can result in prolonged hypoglycemia.

Continued doses of dextrose will continue to stimulate insulin release.

Octreotide works by antagonizing insulin release. Exact mechanism is still being debated.

OctreotideThe dose is 1-2 mcg / Kg bolus IV or SC.

Some papers suggest a continuous infusion while others suggest an every 8 hour dosing regimen.

If placed on an octreotide regimen, the octreotide must be off a minimum of 24 hours without another episode of hypoglycemia before discharge.

Key FactsA retrospective study showed 4 of 25 patients

developed delayed hypoglycemia including 1 at 16 hours post ingestion.

If a sulfonylurea is ingested, a minimum of 24 hours of observation is recommended.

CamphorAromatic ketone

derived from plants.Acts as a topical

rubefacient.Usually ingested as

a liquid.Often in

preparations combined with other medicines such as salicylates.

CamphorInitial symptoms are gastrointestinal distress

and generalized feelings of warmth.Symptoms usually progress quickly to

nervous system involvement from restlessness to seizures.

Delayed seizures have been reported up to 9 hours after ingestion.

CamphorIngestions of 1-2 grams have been fatal in

children.A 19 month old died after ingesting 5 ml

of 20% camphorated oil.Asymptomatic patients should be

observed 6-8 hours and discharged if not developing symptoms.

Remember about hydrocarbon aspiration if product is an oil with a history of coughing or vomitting.

Clonidine and ImidazolinesClonidine is an alpha-2 agonist that is used

for hypertension.Imidazolines, such as oxymetazoline (afrin)

are used as decongestants.Symptoms typically present like an opiate

overdose ?

Why?

? Like an Opiate Overdose ?They are NOT structurally related to opiates.The alpha-2 receptor targeted by clonidine

has significant functional overlap with the opiate receptor. Both may be located on the same neuron, both coupled by via G-protein to the same potassium channel.

May require larger doses of naloxone to reverse symptoms.

AntimalarialsThese include cloroquine,

hydroxychloroquine, quinine and their relatives.

They work by both sodium channel blockade as well as blockade of the potassium rectifier channel.

These lead to QRS widening as well as QT prolongation.

Torsades is a known complication of overdose.

SymptomsSmall therapeutic index.Presents with symptomatology known as

“cinchonism” which is tachycardia, nausea, vomitting, hearing loss, tinnitus, headache, vertigo, dystonia, and diarrhea.

Patients often known to have a flushed appearance.

TreatmentThese patients require aggressive

management of electrolytes.If the QRS widens, treatment with sodium

bicarbonate is indicated.Magnesium should be used for Torsades.If ventricular arrythmias occur despite

optimal management, lidocaine is the treatment of choice. (Avoid class 1a, 1c)

Selected Toxic Dosages

• Epidemiology• Clinical features• Investigation• Treatment

Epidemiology Accidental – 33 to 60% in India &

other developing countries

Reasons for high incidence1. Extensive use for cooking & lighting in

low socioeconomic status2. Stored in soft drink bottles, beer bottles

within reach of children

Clinical featuresAge – 1 to 3 years more than 70% symptomatic within

10 hours

SYMPTOMS

RS – breathlessness, coughCNS – convulsions, coma GPE – fever, restlessness, cyanosisGI – vomiting, diarrhea

Lab InvestigationsBlood – Leukocytosis

X – Ray changes

Changes appear within one hour - commonly right basal infiltrates - emphysema - pleural effusion - pneumatocoeles

Severity scorePARAMETERSPARAMETERS ABSENTABSENT PRESENTPRESENT OTHERSOTHERS

FEVER FEVER 00 11 00

SEVERE SEVERE MALNUTRITIONMALNUTRITION

00 11 00

RESP. DISTRESSRESP. DISTRESS 00 22 44

CNS SYMPTOMS CNS SYMPTOMS 00 22 44

• >4 – Significant• <7 – Likely to survive• >8 –– Risk of death is increased

ManagementAvoid emeticsAvoid gastric lavage – In case of massive

amount use a cuffed endotracheal tubeAfter lavage leave magnesium or sodium

sulphate in the stomachOxygen may be usefulAssisted VentilationAntibiotics - Penicillin G 50000/Kg/24 hrs IV

qid Kanamycin – 10-15mg/Kg/24 hrs - IM bdSteroids – Not helpful

Complications• Pneumothorax• Pneumatocoeles• Pleural effusion• Bronchopneumonia• Coma

Pralidoxime (PAM) is given in dose of

25-50 mg/kg IM or IV over 30 min infusion. The dose may be repeated in 1-2 hours, then at 6-12 hour intervals as needed. Monitor for hypertension. Never inject morphine, theophylline, aminophylline or chlorpromazine. Intravenous fluids should only be given with caution. No oral tranquilizers are administered. Artificial respiration may be necessary to sustain life.

Hydrocarbon PoisoningThese may be divided into aliphatic or

aromatic compounds. Aliphatic hydrocarbons include kerosene, turpentine, lubricating oils, tar and have greatest risk of aspiration and pulmonary symptoms. Aromatic compounds have mainly neurological and hepatic toxicity and include benzene compounds.

Type of toxicity with a hydrocarbon

depends on its volatility, viscosity or surface tension. The lower is viscosity, more is the risk of pulmonary aspiration. Mineral spirit, kerosene and furniture polish have both low volatility and viscosity and thus carry a higher risk of aspiration pneumonia.

Benzene derivates, toluene and xylene

are components of various solvents and degreasers. These are highly volatile but have low viscosity. Inhalation is the primary route of toxicity which manifests with CNS symptoms. Gasoline and naphtha are constituents of lighter fuel and lacquer diluent and primarily cause depression of the central nervous system (CNS).

Turpentine oil is highly volatile but has low

viscosity also. Toxicity results from inhalation and gastrointestinal absorption. They can also cause CNS toxicity.

Halogenated hydrocarbons are used as solvents and spot removers. Freon is used as a refrigerant.

Toxic exposure to hydrocarbons may result in cardia, gastrointestinal, neurological, pulmonary, renal, hepatic, metabolic and hematological manifestations.

Induced emesis or gastric lavage is

contraindicated for kerosene oil poisoning. It is done only when large quantities of turpentine have been ingested or the hydrocarbons product contains benzene, toluene, halogenated hydrocarbons, heavy metals, pesticides or aniline dyes. Other specific modalities including steroids and antibiotics are not efficacious.

Carbon Monoxide PoisoningClinical manifestations include

headache, cyanosis, convulsions, and coma.

Patients are administered 100 percent oxygen and

if carboxyhemoglobin levels are above 40 percent, hyperbaric oxygen therapy is considered.

Lead PoisoningExposure to lead occurs from old lead

based deteriorated house paint (in old houses) and dust and soil contaminated with lead such as from leaded gasoline, lead electrode plates from old automobile batteries, adultered food, folk remedies, broken lead typesets scattered around old printing establishments. Food may be adulterated with colored metallic salts or the black collyrium used as surma may contain a proportion of black oxide of lead.

Lead Poisoning Chronic lead intoxication occurs

usually in children who eat non-edible substances (pica) and manifests as pain in abdomen and resistant anemia. Lead is deposited in the bones. Acute infections may mobilize lead from storage areas in bones and cause acute lead poisoning leading to acute lead encephalopathy.

In these cases the child may be left

with neurological sequelae. Lead inhibits sulfhydryl enzymes and formation of heme. Heme precursors such as porphyrins accumulate in the blood and are excreted in the urine. Screening for lead intoxication is done by measuring zinc protoporphyrin or blood lead levels.

TreatmentIn symptomatic children, therapy is

usually started with dimercapol (BAL) (75 mg/m2 every 4 hourly IM). BAL may be stopped after 48 hours, while calcium disodium edetate is used for another 3 days but at a lower dosage of 50 mg/kg or 1000 mg/M2 per 24 hours by continuous IV infusion.

Maximum daily dose should not

exceed 500 mg/kg. Stop BAL when blood lead level falls below 60 microgram/dL. Give a second course of edetate alone if blood lead rebounds to 45-69 microgram/dL. A second course of edetate in combination with BAL is recommended for rebound lead level of >70 microgram/dL. Wait for 5-7 days in between the two courses.