Drug

Poisoning

Objective Approach to patient with drug

poisoning 1 -2 -How to manage patient with

drug poisoning3- Common poisoning special

treatment-Paracetamol poisoning-Aspirin poisoning-Iron poisoning-Tricyclic antidepressant4- strategies for primary

prevention

Approach to a patient with suspected or witnessed poisoning:

o Primary surveyo Historyo Physical examinationo Investigation

Primary Survey

Stabilization and rapid assessment of AirwayBreathingcirculation

mental status

History

o Witnessed Poisoning (suicide attempts, abuse or misuse).

o Unwitnessed Poisoning . History of Presenting Symptoms o Age ( toddlers or adolescent ).o Onset of symptoms ( usually acute onset

of symptoms without prodrome with sudden alteration of mental status ).

o Progression of the symptoms.

Description of the exposure:o Place (where the child was found) in case

of unknown exposure to generate a list of potential toxins.

o Product (name; brand, generic or chemical, concentration)

o Duration + Amount of drug:1- For ingested substances: Count the

remaining pills or measure the remaining volume of liquid ingested.

2-For inhalational, ocular or dermal exposure: ask about the concentration of the agent and the length of contact time with the material.

o Note: parents should be instructed to bring the products, pills, and/or containers with them to identify and quantify the exposure.

o If the pills are unknown, make a list of ALL medications in the child's environment including medications of grandparents and visitors

Past Medical History:o Underlying illnesses (toxic dose of the

drug or drug-drug interaction).o Psychiatric illness (patients more

prone to substance abuse, misuse, or intentional ingestions).

Social History:o New baby, parent’s illness or financial

stress can lead to serious neglect or intentional abuse.

Physical Examination

Targeted physical exam is done to:• Identify the toxin.• Assess the severity of the exposure.

In poisoned patient, the KEY features of the physical exam are:

• Vital signs.• Mental status.• Pupils (size, reactivity, nystagmus).• Skin (diaphoretic, dry or normal)• Bowel sounds.• Odor of the patient (aceton, alcohol or garlic).

Laboratory Investigation

o CBC.o Serum electrolyte.o Select intoxications (salicylates,

iron, theophylline, acetaminophen and carbon monoxide).

o Urine analysis.o Toxicology screen.o LFTo RFT

Additional tests:• ECGProlong PR interval (digoxin).Prolong QRS interval (cocaine,

propranolol).• Chest X-raypulmonary edema[salicylate toxicity].pneumonitis [hydrocarbon ingestion].• Abdominal X-ray.• Further investigation is based on the

DD and pattern of presentation

Mangment

Decontamination

ipecac

Gastric

lavage

cathartics

charcoal

WBI

Elimination

MDACUrinar

y alkalization

dialysis

Antidote

Supportive care

DecontaminationRouts of poisoning in children:oIngestion (the commonest).oInhalation.oDermal exposure.oOcular exposure.The goal of decontamination is to prevent absorption of toxic substance

Before applying decontamination method, you have to consider the following:oProperties of the toxin.oRoute of exposure.oTime since exposure (the efficacy of decontamination method decreases with oincreasing time since exposure).Risks vs. Benefits of the decontamination method

Gastrointestinal (GI) decontamination:

It is most likely to be effective in the first hour after an acute ingestion.

Consider GI decontamination after 1 hour of ingestion of toxic substance with one of the following properties:

Ipecac syrupIt’s an emetic drug . It's

contraindicated after the ingestion of caustics (acids and bases)

Gastric lavage

Place a tube into the stomach to aspirate contents, and then flush with normal saline.

Single-dose activated charcoalCharcoal is “activated” via heating to

extreme temperatures, providing a very large adsorptive surface area. Many toxins are adsorbed onto its surface, thus preventing absorption from the GI tract.Charcoal is most likely to be effective

when given within 1 hr of ingestion. Approximately 20% of children vomit after receiving a dose of charcoal, so it's important to: 1. protect the airway to avoid

aspiration pneumonia.2. ensure normal abdominal exam.

Substances POORLY adsorbed by activated charcoal:

o Alcohols.o Caustics (acid & alkaline).o Cyanide.o Heavy metals (lead & iron).o Lithium.

Adverse effects:oConstipation (common).oBowel perforation (rare).

Cathartics

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. Cathartics should never be used in multiple doses because of the risk of dehydration and electrolyte imbalance.

Whole bowl irrigation (WBI)

1. 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 “cleanse” the entire GI tract.

2. WBI can be combined with activated charcoal or with substances are not well adsorbed .

Multiple-dose activated charcoal (MDAC):

MDAC enhance elimination via two mechanisms:• Interruption of enterohepatic recirculation.• GI dialysis which uses the intestinal mucosa

as the dialysis membrane and pulls toxins from the bloodstream back into the intraluminal space, where they are adsorbed to the charcoal.

• Contraindications to use of MDAC include an unprotected airway and a concerning abdominal exam; thus the airway and abdominal exam should be assessed before each dose.

Urinary alkalization

1. elimination of some drugs that are weak acids which is accomplished with a continuous infusion of sodium bicarbonate–containing intravenous fluids, with a goal urine pH of 7.5-8.

2. It is most useful in managing salicylate, methotrexate and phenobarbital toxicity.

3. Serum PH should be closely monitored.

Dialysis

Toxins that are amenable to dialysis have the following properties:

• Low volume of distribution (<1 L/kg).• Low molecular weight.• Low degree of protein binding.• High degree of water solubility.• Examples: methanol and ethylene glycol.

Supportive careThe goal is to support the vital functions of the

patient until the patient can eliminate the toxin from the system.

Supportive care includes:o Careful attention to airway support.o Ventilator management.o Blood pressure support.o Appropriate and timely management

of seizures, dysrhythmias, conduction delays, and electrolyte and metabolic derangements.

Acetaminophen

poisoning

• In the US there were 70,984 acetaminophen-related cases reported to the American Association of Poison Control Centers in 2006

• There were 1045 cases of major acetaminophen toxicity and 110 cases of acetaminophen-related deaths

• In most developing countries, the incidence of acetaminophen poisoning rarely approximates that of the US or UK

Epidemiology

Pathophisology

Acetaminophen

Sulfate Glucouronid

Oxidized by cytochrom p450

N-acetyl p- benzoquinon eimin

Detoxified by glutathione

Cystein mercopturic

Saturated Mainly by cytochrom

p450

Not detoxified by glutathione

React with cellular membrane . Hepatocyte damage and death

Presentation

Stage4

Stage3

Stage2

Stage1

Stage 1 : Symptoms: anorexia . Nausea .

Vomiting . Diaphoresis . Neurological . CVS. Resp “ rare

affected“ Sign : pallor . diaphoresis . Hydration

Lab : ALT . AST elevated

Stage 2

o After 24 hours lasted to 48 hourso Symptoms: symptoms of stage 1

resolve or decrease . Pain . Tenderness at Rt upper Quadrant

o Sign : hepatomegaly . Decrease urine output .tachycardia . Hypotension

o Acute pancreatitis “abdominal pain. Increase lipase . Amylase

o Lab : ALT . AST elevated , PT prolonged . Nephrotoxcity

Stage 3 From 3-5 day o Symptoms: anorexia . Nausea.

Vomiting . Jaundice o Signs: abdominal pain . Jaundice .

GI bleeding Encephalopathy . Cerebral edema . Cardiomyopathy o Lab: PT prolong . ALT.AST elevated “

> 10,000” Elevated total biliruibin “ >4 mg\dl .

Hyperammonemia

Stage 4 From 5-14 day lasted 21 day A. recover: period for

normalization may take several week

B. death

Investigation

1- history and physical examination

2-Rumack-Matthew nomogram3- LFT

4- radiological studies

Rumack-Matthew nomogram

used to interpret acetaminophen

values to assess hepatotoxicity risk

in patients. It was initially

developed for single ,acute ingestions of acetaminophen is based on observational data from

patients who overdosed and who did not receive antidote

therapy.

Radiology o - CT scan indicate for patient

who developed altered mental status or encephalopathy

o - ultrasonoghraphy : to defined either hepatic or renal abnormality

Risk factors for chronic acetaminophen toxicity include

o sustained administration of high doseso fevero poor oral intakeo young age

Management 1- ABC 2- stander of care for

acetaminophen “ N-actyl cystin antidote ” to patient who present within not more than 24 hours

3- GI decontaminated : with active charchol and gastric lavage

4- surgical “ liver transplant “

salicylates

(Aspirin) poisoning

EPIDEMIOLOGY

The number of pediatric exposures to salicylates reported has

declined in the last two decades.

Deaths from exploratory salicylate overdose in children are rare.

PHARMACOKINETICS AND TOXICOKINETICS

salicylate ingestion

absorbed from jejunum

bind with plasma protein

In therapeutic dose, In overdose, 80% of salicylate over saturation of

is protein-bound. protein- binding sites and that will

lead to toxicity

In Fatal salicylate intoxication can occur after the ingestion

of 3 g by children

3 g = 36 tablets of baby aspirin(81 mg)

MECHANISM OF ACTION

Activation of the respiratory

center

increased RR, increase the elimination of CO2,

respiratory alkalosis

increased renal elimination of HCO3 to compensate

Stimulation of the chemoreceptor trigger zone

Nausea Vomiting

K depletion

Inhibition of cyclooxygenase

(decreased synthesis of prostaglandins,

and thromboxanes)

bruising or bleeding

Interference with cellular metabolismmetabolic acidosis

Hyperpyrexiahypoglycemia

o Hypoxia o increased RR, temperature, and

HR.o Seizureso Tinnituso Nausea and vomiting : loss of

potassium o Pulmonary edema

CLINICAL MANIFESTATIONS OF SALICYLATE OVERDOSE

(salicylism)

o bruising or bleedingo metabolic acidosiso respiratory alkalosis: loss of HCO3- due to

compensationo Glucose:

in early stage, there will be hyperglycemia from glycogenolysis. And after a period of time, as glucose

stores are depleted, hypoglycemia may started.

INVESTIGATIONS

o plasma salicylate concentration: if you suspect any one with salicylate intoxication, you

must do this test.o ABGo CBC and PTo Electrolytes and glucoseo Plasma creatinineo Urinalysiso Chest radiographo Electrocardiogram

DIFFERENTIAL DIAGNOSIS

oDiabetic ketoacidosis: Polyphagia, polydipsia, polyuria

oSepsis:Fever, signs of septic shock

oIron intoxication:By plasma iron concentration

MANAGEMNT

o Airwayo Breathingo Circulationo Supplemental glucose o Potassium repletion o Gastrointestional

decontamination:o Urine alkalinization

Clinical and laboratory features

Common: tachypnea, tinnitus, nausea, vomiting, acid-base abnormalities

Severe cases: hyperthermia, altered mental status, pulmonary edema

Diagnostic evaluation

Plasma salicylate concentration, arterial blood gas (ABG), basic electrolytes, BUN and creatinine, chest radiograph

Repeat salicylate concentration every two hours until it is declining

Repeat ABG every two hours until acid-base status stable or improving

Treatment

Avoid intubation if at all possible

Administer supplemental oxygen as needed

Volume resuscitate unless cerebral or pulmonary edema is present

Administer multiple doses of activated charcoal (first dose: 1 g/kg orally up to 50 g)

Administer supplemental glucose in patients with altered mental status, even if serum glucose concentration is normal: IV dextrose 50 g as 100 mL of 50 percent dextrose

Alkalinize with sodium bicarbonate

Bolus therapy: sodium bicarbonate, 1 to 2 mEq/kg (maximum 100 mEq) IV push over 3 to 5 minutes

Maintenance therapy: 100 to 150 mEq sodium bicarbonate in 1 L of D5W, run at 250 mL/hour in adults OR run at 1.5 to 2 times maintenance in children

Correct hypokalemia, hypocalcemia and other electrolyte abnormalities. IV sodium bicarbonate is NOT compatible with calcium salts.

Alkalemia (arterial pH up to 7.55) is NOT a contraindication to sodium bicarbonate therapy

DO NOT USE ACETAZOLAMIDE TO ALKALINIZE THE URINE

Alert nephrology team early in the patient's clinical course; indications for hemodialysis include:

Profoundly altered mental status

Pulmonary or cerebral edema

Renal insufficiency that interferes with salicylate excretion

Fluid overload that prevents the administration of sodium bicarbonate

A plasma salicylate concentration >100 mg/dL (7.2 mmol/L) in acute ingestion OR >60 mg/dL (4.3 mmol/L) in chronic ingestion

Clinical deterioration despite aggressive and appropriate supportive care

Iron

toxicity

EPIDEMIOLOGYo Almost 16,000 iron exposures annually are

reported in children less than six years of age in the United States.

o The number of major effects and death in children are improved when compared to the period from 1990 to 2000.

EtiologyIngestion of:oPure iron preparations containing(ferrous sulfate tablets), (more elemental iron per tablet (60 to 65 mg) than other iron preparations).               

        

Why !!!They are often:o Brightly coloredo Sugar-coated o Have the appearance of candy 

Pathophysiology & clinical manifestation

Pathophysiology & clinical manifestation :

o To show signs of toxicity : 10-20 mg/kg of elemental iron.

o Serious toxicity : more than 60 mg/kg

o Iron Toxicity Manifestations = Metabolic Acidosis 

1.Initial phase (up to 6 hours post ingestion ):Large dose of elemental iron ---->GI

mucosal irritation ---->vomiting and diarrhea (may be bloody), Abdominal pain..

2.Latent Period (after 6 Hours):hypovolemia ----> Shock ----

>drowsiness,coma and METABOLIC ACIDOSIS ----> liver failure, hypoglycemia and convulsions ..

3.Long term (several days to weeks):Gastric strictures ..

How to diagnose!!? History :o  HPIo  Does anybody at home Use Iron Tablets ?! (Who & from where &

when)o How many Tablets has been ingested &the formulation of iron in

the supplement ?! (How did you know)o Is it the first time ?! 

Examination :o Abdominal tenderness o Signs of dehydration and Shocko Signs of systemic acidosis 

Investigations :o CBCo Serum Iron level o Blood Gases o Chemistry (electrolytes & enzymes)o RBGo Abdominal X-ray

D/DD/D :o Gastroenteritis o DKA o Sepsis o Myocarditis

RxRx:o Intravenous Desferrioxamine (both

bowel decontamination with whole bowel irrigation and chelation)

o Gastric lavage in severe cases (only if < 1 hour after ingestion) 

Tricycle antidepressants poisoning

among 12,234 tricyclic antidepressant exposures reported by poison centers

in United States in 2004 9% in children < 6 years old

epidemiology

Possible risk factors

* Munchausen syndrome by proxyform of abuse in which caregiver causes injury to a victim

( usually a child ) that leads to unnecessary and harmful or

potentially harmful medical care. *child abuse

*homicidal intent

1-Inhibition of presynaptic neurotransmitter reuptake (norepinephrine and serotonin) “reuptake 1 inhibitor “.

TCAs have several important cellular effects, including

2-Antagonism of peripheral alpha-1 adrenergic receptors

“alpha-1 adrenergic receptors action is to reduce nor adrenaline and adrenaline“ 3-Blockade of cardiac fast sodium

channels 4-Antagonism of central and peripheral muscarinic acetylcholine receptors “atropine like effect”

5-Antagonism of histamine (H1) receptors

6-Antagonism of CNS gamma-aminobutyric acid (GABA) A receptors

Symptoms and sings

1-Inhibition of presynaptic neurotransmitter reuptake (norepinephrine and serotonin) “reuptake 1 inhibitor “.reuptake 1 inhibitor :NET (norepinephrine transporter) is also commonly called uptake 1 or reuptake 1. NET can be inhibited by cocaine and tricyclic antidepressant drugs, resulting in an increase of transmitter activity in the synaptic cleft.

2-Antagonism of peripheral alpha-1 adrenergic receptors

“alpha-1 adrenergic receptors action is to reduce nor adrenaline and

adrenaline “

Agitation, confusion, Respiratory depression , Hypotension

Sinus tachycardia*

*So as a net result of those 2 actions the body is loaded with

epinephrine and nor epinephrine with high

concentration and freely acting..

3-Blockade of cardiac fast sodium channels:The NA ions is substantial to myocardium action

potential; ThereforeThe cardiac conduction system needs abet longer time

to complete action potential .This delayed is obvious in QRS complex QRS complex delayed = QT interval prolonged =

ventricular tachycardia

QRS > 0.1 second(>2.5 small boxes) in lead II

4-Antagonism of central and peripheral muscarinic acetylcholine receptors “atropine like effect”

blurred vision ,warm, fever, dry skin ,dry mouth and

urinary retention

traditionally characterized as "blind as a bat, mad as a hatter,

red as a beet, hot as a hare, dry as a bone"

5-Antagonism of histamine (H1) receptors

6-Antagonism of CNS gamma-aminobutyric acid (GABA) A receptors:

*So if the main inhibitory mechanism get lost may lead to abnormal electrical activity appears with motor, sensory or psychomotor experiences That what’s called seizure.

History and Physical exam

Chief concern (CC): Cardio vascular system tachycardiacentral nervous system effects

Drowsiness ,confusion, delirium,coma,respiratory depression,seizures

other anticholinergic effectsblurred vision warm, dry

skin ,fever ,dry mouth ,urinary retention

History of present illness (HPI) :

onset of effect usually within 2 hours after tricyclic antidepressant ingestion but may be up to 5 hoursthorough history for patient with acute altered mental status may requireinterview with family and friendsinterview with emergency medical services personnelinspection of medication packaging if availableask aboutidentity of medicationtime ingestion occurred*

known or estimated amount ingested query patient's pharmacy to determinewhat prescription medications are available to patientrecent filling datestransdermal patche

Past medical history (PMH): ask about depression, attempted suicideSocial history (SH): ask about history of substance abuse

General physical: assess airway, breathing, and circulationcommon features on presentation after tricyclic

antidepressant overdosehypotensiontachycardiaurinary incontinencecoma

HEENT: dilated pupilsexternal ophthalmoplegia (divergent squint) in

comatose patientsNeuro: myoclonus, tremorsconfusion, delirium, agitationseizureassess level of consciousness with formal coma scale

such as Glasgow Coma Scale (score < 8 associated with high risk of serious

complications)

Investigations

Blood tests :blood gas analysisassess blood pH for acidosis on initial evaluation and monitor during alkalinization treatmentvenous sample acceptable alternative to arterial sample unless suspect hypoxia or hypoventilation

Electrocardiography (ECG)

toxicology screen:quantitative general toxicology screen usually not useful for management of acute toxicityqualitative toxicology urine screens may be useful eitherif abuse suspected in pediatric casesfor legal, forensic, or social service documentation

Activated charcoal if within 1 hourCardiac monitoring

Treat arrhythmias conservatively with sodium bicarbonate

Correct metabolic acidosisTreat convulsions with diazepam

Treatment

Prevention

Prevention strategies for poisonings

1- primary (pre-event)2-secondary (event)3-tertiary (post-event)

Primary prevention

Primary prevention encompasses all of the activities that prevent a poisoning event from occurring. Activities such as

o legislation o product engineeringo educational efforts o Anticipatory guidance

1-Legislation legislation and regulatory means

were implemented to protect children, adolescents, and adults from toxic exposures

2- Product engineering :

oStorage and locking devicesoThe addition of bittering agents to make dangerous substances unpalatableoThe use of poison warning labels or stickers that may alert adults and older children to the toxic hazard

3- Education :Primary prevention also includes

educational efforts targeted toward avoidance of poisoning exposure

4- Anticipatory guidance : Periodic anticipatory guidance for

poisoning prevention is recommended by the American Academy of Pediatrics (AAP)

Secondary prevention

Secondary prevention involves interventions that prevent injury or illness once a poisoning exposure has occurred

Poison centers Education

Decontamination

Poison centers o Poison information: telephone

management, advice, and consultation about toxic exposures

o Hazard surveillance to achieve hazard elimination

o Professional and public education in poison prevention, diagnosis, and treatment

Education

Decontamination Decontamination is another method of

modulating poisoning injury after poisoning exposure has occurred

Tertiary prevention

o involves interventions that minimize injury or toxic effects once symptoms have appeared

o administration of antidotes, vary depending upon the particular exposure (eg, N-acetylcysteine for acetaminophen exposure)

Reference

• nelson textbook• Pediaitric uptodate

•Illustrated pediatric 3rd edition•Medscap

Done by Noor MarwasNajlaa baddour Rand MelibariIsraa Mahmoud Sader Fatimah Hamza

Monitor Rafat Mosalli MD,FRCPC,FAAP,UTP (McMaster Univ.) Assistant professor of pediatrics