Drug Poisoning(1)
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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