Problem 3

PROBLEM 3
AMELIA
405140226
Intoxication
Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen’s Emergency Medicine
Concepts & Clinical Practice. 8th ed. Philadelphia: Elsevier; 2014.
Sherman SC, Weber JM, Schindlbeck MA, Patwari RG. Clinical Emergency Medicine.
USA: McGraw-Hill; 2014.
Sherman SC, Weber JM, Schindlbeck MA, Patwari RG. Clinical Emergency Medicine. USA: McGraw-Hill; 2014.
Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen’s
Emergency Medicine Concepts & Clinical Practice. 8th ed.
Philadelphia: Elsevier; 2014.
Sherman SC, Weber JM, Schindlbeck MA, Patwari RG. Clinical
Emergency Medicine. USA: McGraw-Hill; 2014.
Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen’s Emergency Medicine Concepts & Clinical Practice. 8 th ed.
Cyclic Antidepressant Intoxication
• Result from overdose of a TCA or drug-drug interactions
Clinical Presentation :
• History  determine the exact amount of drug ingested
Diagnostic Studies :
• Laboratory  serum CA concentrations
• ECG  sinus tachycardia with right axis deviation of the
terminal 40 msec of the QRS complex (terminal R-wave in
lead aVR) associated with prolongation of the PR, QRS, &
QT intervals  abnormalities develop within the first 6
hours of ingestion & typically resolve by 36-48 hours.
Sherman SC, Weber JM, Schindlbeck MA, Patwari RG.
Clinical Emergency Medicine. USA: McGraw-Hill; 2014.
Sherman SC, Weber JM, Schindlbeck
MA, Patwari RG. Clinical Emergency
Medicine. USA: McGraw-Hill; 2014.
Opioid Intoxication
• Toxicity occurs as a result of intentional overdose,
intentional abuse, or adverse effect of therapeutic use
• Well absorbed after gastrointestinal (oral and rectal) or
parenteral administration
• Opioids and their metabolites cross the blood-brain
barrier
• All opioids undergo hepatic metabolism and renal
elimination
Clinical features :
• Neurology :
Direct CNS depression, hypoxia from CNS and respiratory
depression
Hypertonicity, myoclonus, and seizures  overdose of the
synthetic opioids meperidine and propoxyphene
Dysphoria and acute psychosis with an agonist-antagonist
opioid
Parkinsonian symptoms
Psychomotor retardation, dysarthria, ataxia, tremor, and
other neurologic abnormalities
Serotonin syndrome  mental status changes, autonomic
instability, and neuromuscular changes  fatal
• Respiratory :
Decrease respiratory rate and tidal volume in a dose-
dependent manner
Central sleep apnea  long-term opioid use and also with
acute increased opioid use from baseline
Bronchospasm  severe, prolonged, and refractory to beta-
agonist therapy, and it may require mechanical ventilation
for several days
• Ophthalmologic  stimulation of mu receptors  miosis
(pin point pupils)
• Otologic  SNHL  acute and chronic use of heroin,
methadone, and hydrocodone, especially in combination
with acetaminophen
Tintinalli JE, Kelen GD, Stapczynski JS. Emergency Medicine : A
Comprehensive Study Guide. 6th ed. USA: McGrawHill; 2004.
• Cardiovascular :
Mild hypotension (typically orthostatic) and relative
bradycardia
Propoxyphene, norpropoxyphene  widening of the QRS
complex
Levomethadyl, Methadone  QTc prolongation
• GI :
Delayed gastric emptying, direct stimulation of the CTZ, and
vestibular stimulation  nausea, vomiting
Decreased gastrointestinal motility  ileus
Increased biliary tract pressures and choledochoduodenal
sphincter spasm
• Urologic :
Urinary retention from urethral sphincter spasm and decreased
detrusor tone
Glomerulosclerosis and renal amyloidosis  end-stage “heroin
nephropathy” of chronic opioid addicts
• Dermatologic :
Pruritus, erythema  localized to the area of injection
• Metabolic  hypoglycemia, hypothermia, hyperthermia
Marx JA, Hockberger RS, Walls RM, et al,

editors. Rosen’s Emergency Medicine Concepts
& Clinical Practice. 8th ed. Philadelphia:
Elsevier; 2014.
Tintinalli JE, Kelen GD, Stapczynski JS.
Emergency Medicine : A Comprehensive Study
Guide. 6th ed. USA: McGrawHill; 2004.
Diagnosis :
• Based on history and physical examination
• Carbon dioxide and oxygen saturation monitoring
• Chest radiograph  acute lung injury
• 12-lead ECG suspected dysrhythmia or evaluate for
QRS widening or QT prolongation if propoxyphene or
methadone overdose is suspected
• Abdominal radiograph
• Qualitative antibody-based enzymatic immunoassay
urine toxicology screens
Management :
• Gastrointestinal Decontamination
• Antidote with Opioid Antagonist  naloxone
• Supportive Care
– Bi-level positive airway pressure, continuous positive
airway pressure, or mechanical ventilation with positive
end-expiratory pressure
– Crystalloid infusion
– Correction of hypoxia, correction of hypoglycemia, or
administration of benzodiazepines
• Clonidine initial dose is 0.1 mg PO, repeated doses every 30 to
60 minutes
• Methadone initial dose 20 mg PO or 10 mg IM is 30 to 60
minutes
Acetaminophen Intoxication
• Absorbed rapidly, with peak plasma concentrations
generally occurring within 1 hour and complete
absorption within 4 hours
• In therapeutic doses  metabolized by conjugation with
glucuronide + sulfate into nontoxic metabolites (urine)
• <5% is oxidized by CYP2E1 to a highly cytotoxic metabolic
intermediary, N-acetyl-p-benzoquinoneimine (NAPQI)
• In therapeutic doses, NAPQI is short-lived, combining
rapidly with glutathione and other thiol-containing
compounds to form nontoxic metabolites that are
excreted in the urine
Marx JA, Hockberger RS, Walls RM,
et al, editors. Rosen’s Emergency
Medicine Concepts & Clinical
Practice. 8th ed. Philadelphia:
Elsevier; 2014.
Marx JA, Hockberger RS, Walls RM, et al, editors.
Rosen’s Emergency Medicine Concepts & Clinical
Practice. 8th ed. Philadelphia: Elsevier; 2014.
Management :
Limiting
Gastrointestinal
Absorption
N-Acetylcysteine
Sherman SC, Weber JM, Schindlbeck MA,
Patwari RG. Clinical Emergency Medicine.
Warfarin Intoxication
• Bound to albumin, metabolized by the liver, and excreted in
the urine
• Blocks activation of vitamin K and thereby interferes with
hepatic carboxylation of coagulation factors II, VII, IX, and X
• Warfarin dosing is guided by measurement of the
international normalized ratio (INR), a standardized
measurement of prothrombin time (PT)
Tintinalli JE, Kelen GD, Stapczynski JS. Emergency Medicine : A Comprehensive Study Guide. 6 th ed. USA: McGrawHill; 2004.
Patwari RG. Clinical Emergency Medicine. USA:
McGraw-Hill; 2014.
Digoxin Intoxication
• Orally administered digoxin begins to exhibit clinical effects
within 90 minutes of ingestion and typically reaches maximal
effect within 4-6 hours
• Eliminated by the kidneys with a usual half-life of 36-48 hours
• Although normal therapeutic concentrations generally range
between 0.5 and 2 ng/mL, given the significant toxicity and
narrow therapeutic window, the safest suggested
concentration with maximal therapeutic benefit is between
0.5 and 1 ng/mL
Tintinalli JE, Kelen GD, Stapczynski JS. Emergency Medicine : A
Comprehensive Study Guide. 6th ed. USA: McGrawHill; 2004.
Sherman SC, Weber JM, Schindlbeck MA, Patwari RG. Clinical Emergency
Medicine. USA: McGraw-Hill; 2014.
Tintinalli JE, Kelen GD, Stapczynski JS. Emergency Medicine :
A Comprehensive Study Guide. 6th ed. USA: McGrawHill;
2004.
CO Intoxication
• CO is generated through incomplete combustion of
virtually all carbon-containing products
• Structure fires (e.g., wood), clogged vents for home
heating units (e.g., methane), and use of
gasolinepowered generators indoors
• CO interacts with deoxyhemoglobin carboxyhemoglobin
(COHb)
• Hemoglobin binds CO tightly and forms a complex
• In muscle, CO binds myoglobin atraumatic rhabdomyolysis
• CO inhibits the final cytochrome complex involved in
mitochondrial oxidative phosphorylation  switch to
anaerobic metabolism and ultimately in cellular death
• Delayed-onset neurologic complications hypoxic insult;
reperfusion injury and lipid peroxidation related to platelet-
induced nitric oxide release
• By alteration of the platelet-associated nitric oxide cycle, the
microvascular endothelium of the central nervous system
undergoes free radical–mediated injury  localized
inflammation and dysfunction
Clinical features :
• Asphyxia  altered mental status, including coma and
seizures; hypotension, cardiac arrest; metabolic acidosis
• Mild CO poisoning  headache, nausea, vomiting,
dizziness, myalgia, confusion
• Neurologic assessment  normal or focal findings or
subtle perceptual abnormalities
• The often-touted cherry-red skin color  postmortem
finding
Diagnosis :
• Lab  co-oximetry, ABG, COHb levels, Serum lactate,
Serum cardiac marker, Creatine phosphokinase level
• ECG, Chest Xray, CT kepala
editors. Rosen’s Emergency Medicine
Concepts & Clinical Practice. 8th ed.
Patwari RG. Clinical Emergency Medicine.
Management 
Hyperbaric oxygen
(HBO) therapy
Hydrogen Cyanide Intoxication
• Hydrogen cyanide is a gas with many commercial uses,
particularly in synthetic fiber manufacture and
fumigation
• Odor of bitter almonds
• When cyanide salts are dissolved in water, hydrogen
cyanide can leave the surface, under acidic conditions
• Tissue hypoxia dysfunction of the heart, CNS  coma,
seizures, dysrhythmias, cardiovascular collapse
• Diffuse cellular dysfunction  elevated serum lactate
concentration  metabolic acidosis
Diagnosis  low arterial-venous oxygen difference, pulse
oxymetri, ABG, lactate concentration
Management :
• High-affinity source of ferric ions (fe3+)
• Sodium nitrite for a previously healthy adult is 300 mg
(10 ml of a 3% solution) given during 2 to 4 minutes
• Sodium thiosulfate 12.5 g intravenously (IV), which is
provided as 50 ml of 25% solution (2 ml/kg of 25%
sodium thiosulfate up to an adult dose in children)
• Vit B12 5 g IV during 15 minutes for adults and 70 mg/kg
IV for children, up to an adult dose
• Hyperbaric oxygen (HBO) therapy
Heavy Metal Intoxication
1. Iron
2. Lead
3. Arsenic
4. Mercury

editors. Rosen’s Emergency Medicine
Concepts & Clinical Practice. 8th ed.
Iron
Essential to the function of hemoglobin, myoglobin, many cytochromes, & many catalytic
enzymes, can be extremely toxic when levels are ↑after an overdose / from accumulation in
disease states.
Normal serum iron levels  50 - 150 µg/dL.
Pathophy Two distinct toxic effects:
siology (1) it causes direct caustic injury to the gastrointestinal mucosa
(2) it impairs cellular metabolism, primarily of the heart, liver, and CNS.
Clinical •Phase I : corrosive effects of iron on the gut  Vomiting (within 80 min),
Features diarrhea (can be bloody).
•Phase II : apparent (but not complete) recovery that lasts <24 hours, but can
extend up to 2 days. Most patients recover after this point.
•Phase III : recurrence of GI symptoms, severe lethargy / coma, anion gap
metabolic acidosis, leukocytosis, coagulopathy, renal failure, & cardiovascular
collapse.
•Phase IV : fulminant hepatic failure (2 - 5 days after ingestion). rare, dose
related, & is usually fatal.
•Phase V : consequences of healing of the injured GI mucosa. It is characterized
by pyloric or proximal bowel scarring, sometimes associated w/ obstruction.
Diagnostic •serum iron levels (are not immediately available)  ↑ of the
Strategies serum glucose level >150 mg/dL & leukocyte count > 15,000 
100% specific for prediction of serum iron levels of > 300 µg/mL.
Management •Gastric Emptying
•Deferoxamine  a continuous infusion at 15 mg/kg/hr for up to 24
hour.
Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen’s Emergency
Medicine Concepts & Clinical Practice. 8th ed. Philadelphia: Elsevier;
2014.
Lead
Most exposures  inhalation of lead dust / fumes / ingestion of contaminated
substances, such as paint chips ; Less often direct skin contact
Pathoph •no known physiologic need for lead.
ysiology •Lead binds to sulfhydryl groups & other ligands  interferes with
critical enzymatic reactions.
•toxic effects  most prominent in the hematopoietic, neurologic, &
renal systems
Clinical •Symptoms of chronic, mild lead poisoning are slow in onset &
Features nonspecific.
•Acute exposure  symptomatic  “Lead colic”  cramping abdominal
pain with nausea, vomiting, constipation, &, occasionally, diarrhea.
•Other  fatigue, anemia, peripheral neuropathy, renal impairment, &
hepatic & CNS dysfunction (mild headache / personality changes to full-
blown
encephalopathy with coma, convulsions, &papilledema)
Diagnostic •BLL
Strategies •Other ancillary data  CBC, serum glucose level, BUN, & creatinine
concentrations, electrolyte levels, & urinalysis.
Management •Acute Lead Encephalopathy :

Goals identification &
treatment of all life-
threatening conditions 
prevention of further
exposure to lead,
minimization of ingested lead
absorption, enhancement of
its elimination, & prevention
or reversal of pathologic cell
changes.
•Chelation Therapy : BLL > 70
µg/dL / signs of
encephalopathy
Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen’s Emergency
Medicine Concepts & Clinical Practice. 8th ed. Philadelphia: Elsevier;
2014.
Arsenic
•A tasteless, odorless substance that looks like sugar, has an infamous history as an
agent of homicide.
•Exposure  primarily environmental & occupational  found in smelters &
electric power plants that burn arsenic-rich coal ; used in industry as a wood
preservative & in the production of glass & microcircuits
•Inorganic arsenicals  used in rodenticides, fungicides, insecticides, paint,
&tanning agents & As defoliants in the cotton industry.
•Medicinal purposes  treatment of trypanosomiasis, amebiasis, & leukemia.
Normal arsenic levels  5 µg/L or less in blood or < 50 µg/day in a 24-hour urine
Diagnostic urine arsenic level  >100 µg/day or 50 µg/L  treatment
Strategies Other laboratory  Anemia, leukocytosis or leukopenia, &
erythrocyte basophilic stippling are seen in the CBC.
The results of renal function tests  may be abnormal 
proteinuria, hematuria, & pyuria.
Managements
•The initial management  address life
threatening condition with supportive
management of shock, dysrhythmias, &
seizures
•Hemodialysis removes arsenic in the
setting of acute renal failure
•Chelation  Intramuscular dimercaprol
•Workers should modify their habits to
avoid further absorption, & repeated
monthly 24-hour urine collections can
follow arsenic excretion.

Mercury
A silver-white metal, familiar to most as the only metal that is liquid at room
temperature.
Contain in  fluorescent lights, batteries, polyvinyl chloride, & latex paint, common
pollutant of air & water.
“Normal” mercury levels  <10 µg/l in the blood or <20 µg/l in the urine.
Pathophysi •No known physiologic role.
ology •Binds covalently to sulfhydryl groups, disturbing multiple cellular
enzyme functions.
Clinical Depend on the acuity of the exposure, the route of exposure, and the
Features chemical
Form of mercury
Diagnostic •24-hour urine mercury levels
Strategies •Blood levels >35 µg/L & urine levels > 150 µg/L  intervention.
Managements
•Supportive managements 
gastric lavage with protein-
containing solutions (e.G., Milk and
egg whites)
•Acute inhalational exposures, 
removed from the source &
supportive management
•Chelation therapy  BAL

editors. Rosen’s Emergency Medicine Concepts
& Clinical Practice. 8th ed. Philadelphia:
Elsevier; 2014.
CYANIDE
• binds readily to cytochrome oxidase 
inhibiting oxygen utilization within the cell 
cellular hypoxia and lactic acidosis
• Manifestations
– shortness of breath, agitation, and
tachycardia followed by seizures, coma,
hypotension, and death
– Severe metabolic acidosis
– venous oxygen content may be elevated
Katzung BG, Masters SB, Trevor AJ, Basic Clinical
• Treatment
– rapid administration of activated charcoal +
general supportive care
– nitrites induce methemoglobinemia, which binds
to free CN–
– thiosulfate is a cofactor in the enzymatic
conversion of CN–
– Hydroxocobalamin (one form of vitamin B12)
combines rapidly with CN– to form
cyanocobalamin
Katzung BG, Masters SB, Trevor AJ, Basic Clinical
ORGANOPHOSPORUS PESTICIDE
•  based on compounds such as soman, sarin,
and tabun, which were developed for use as
war gases
– used to combat a large variety of pests
• absorbed by the skin as well as by the

respiratory and gastrointestinal tracts
• Biotransformation is rapid
57
Agents
58
Human toxicology
• Inhibition of acetylcholinesterase through phosphorylation of the
esteratic site 
– accumulation of acetylcholine  direct cholinergic activity
– Manifestations
• Altered neurologic and cognitive functions
• Capable of phosphorylating another enzyme (neuropathy target

esterase) present in neural tissue 
– progressive demyelination of the longest nerves  paralysis and axonal
degeneration (organophosphorus ester-induced delayed
polyneuropathy/OPIDP)
– Manifestations
• burning and tingling sensations
• motor weakness a few days later
• ataxia may be present
• Central nervous system and autonomic changes 59
CARBAMATE PESTICIDES
• = organophosporus pesticides
• clinical effects due to carbamates are of shorter
• Spontaneous reactivation of cholinesterase is more
rapid
60
Management (organophosporus &
carbamate intoxications)
• Acute intoxication
– Dominant initial sign must be recognized
• miosis, salivation, sweating, bronchial constriction, vomiting, and
diarrhea
• CNS involvement (cognitive disturbances, convulsions, and coma)
• depolarizing neuromuscular blockade
– Therapy
• maintenance of vital signs
• decontamination to prevent further absorption
• atropine parenterally in large doses;
• Pralidoxime  NOT recommended for carbamate intoxication
• benzodiazepines for seizures
61
• Chronic exposure
– Sign & symptoms
• neuropathy target esterase (NTE) inhibition  weakness of
upper and lower extremities, unsteady gait in 1-2 weeks
• intermediate syndrome (muscle weakness) occurs 1–4 days
– Therapy
• Triorthocresyl phosphate (additive in lubricating oils)
• Preventive therapy
– Pyridostigmine
• prior binding to the enzyme  impedes binding of
organophosphate agents
62
KEROSENE POISONING
CLINICAL FEATURES
• Age – 1 to 3 years
• More than 70% symptomatic within
10 hours
SYMPTOMS
• RS – breathlessness, cough
• CNS – convulsions, coma
• GPE – fever, restlessness, cyanosis
• GI – vomiting, diarrhea
• Kerosene ingestion:
– Risk of aspiration
– GIT & Respiratory effects.
– Burning sensation, nausea and diarrhea
– Cough, chocking, gagging and grunting.
– CXR 2-8 hrs later: Pulmonary infiltrates or perihilar
densities.
– pneumatoceles, pleural effusion or pneumothorax
and bacterial superinfection
– Resolution 2-7 days.
LAB INVESTIGATION COMPLICATIONS
• Blood – Leukocytosis • Pneumothorax
• X – Ray changes = • Pneumatocoeles
Changes appear within one • Pleural effusion
hour • Bronchopneumonia
- commonly right basal • Coma
infiltrates
- emphysema
- pleural effusion
- pneumatocoeles
Management
• Avoid emetics
• Avoid gastric lavage – In case of massive amount use
a cuffed endotracheal tube
• After lavage leave magnesium or sodium sulphate in
the stomach
• Oxygen may be useful
• Assisted Ventilation
• Antibiotics - Penicillin
• Kanamycin
• Steroids – Not helpful
IRON TOXIC EFFECT
• (1) it causes direct caustic injury to the
gastrointestinal mucosa, and
• (2) it impairs cellular metabolism,primarily of the
heart, liver, and central nervous system(CNS).
• The caustic effects of iron on the gut cause the initial
symptoms of vomiting, diarrhea, and abdominal pain
• Hemorrhagic necrosis of gastric or intestinal mucosa
can lead to bleeding, perforation, and peritonitis.
IRON TOXIC EFFECT
• Unbound (free) iron moves into cells and
localizes near the mitochondrial cristae, resulting
in uncoupling of oxidative phosphorylation and
impairment of adenosine triphosphate synthesis.
• Cell membranes are injured by free radical–
mediated lipid peroxidation
• Iron increases capillary permeability and both
arteriolar dilation and venodilation, resulting in
hypotension
Phase iron toxicity
• Phase I = reflects the corrosive effects of iron
on the gut. Vomiting occurs within 80 minutes
of ingestion in more than 90% of symptomatic
cases. Diarrhea, which can be bloody, soon
follows.
• Phase II = represents an apparent (but not
complete) recovery that lasts less than 24
hours but can extend up to 2 days. Most
patients recover after this point.
Phase iron toxicity
• Phase III = is characterized by the recurrence of gastrointestinal
symptoms, severe lethargy or coma, anion gap metabolic acidosis,
leukocytosis, coagulopathy, renal failure, and cardiovascular
collapse.
– Serum iron levels may have fallen to normal during this phase because of
distribution of iron into the tissues.
– Metabolic derangements due to iron poisoning include hypoglycemia,
leukocytosis, and severe lactic acidosis from hypoperfusion and
interference with cellular respiration.
– Early coagulation defects are probably related to direct effects of iron on
vitamin K–dependent clotting factors.
– Later coagulation defects are due to hepatic failure.
– Hypoglycemia and elevations of bilirubin and aspartate and alanine
transaminases are other markers of hepatotoxicity.
Phase iron toxicity
• Phase IV = characterized by fulminant hepatic
failure, occurs 2 to 5 days after ingestion. This
is relatively rare, appears to be doserelated,
and is usually fatal.
• Phase V = represents the consequences of
healing of the injured gastrointestinal mucosa.
It is characterized by pyloric or proximal bowel
scarring, which is sometimes associated with
obstruction.
Diagnostic
• Serum iron level measured at its peak, 3 to 5
hours after ingestion, is the most useful
laboratory test to evaluate the potential
severity of an iron overdose
Treatment
• Whole-bowel irrigation is generally the
preferred method of decontamination for
significant iron ingestions
• For significant ingestions (>20 mg/kg of
elemental iron), especially when tablets are
identified on the abdominal radiograph, whole-
bowel irrigation with a polyethylene glycol–
electrolyte lavage solution (PEG-ELS; CoLyte,
NuLytely, or GoLytely) should be initiated
LEAD TOXICITY
• Most exposures are from inhalation of lead dust or
fumes or ingestion of contaminated substances, such as
paint chips
• Less often, it results from direct skin contact with organic
lead compounds or from retained bullets in or near joints
• Other sources of toxic lead ingestions include curtain
weights, buckshot, fishing weights, lead-contaminated
soil or water, bootleg whiskey (“moonshine”), food or
beverages stored or prepared in lead-soldered cans,
lead-glazed pottery, and lead crystal decanters
• Acute exposure to lead can result in symptomatic
poisoning. “Lead colic” is characterized by cramping
abdominal pain with nausea, vomiting, constipation, and,
occasionally, diarrhea
• Other characteristic symptoms and signs of acute toxicity

include fatigue, anemia, peripheral neuropathy, renal
impairment, and hepatic and CNS dysfunction.
• The CNS toxicity may be manifested as mild headache or

personality changes to full-blown encephalopathy with
coma, convulsions, and papilledema.
• Permanent neurologic and behavioral sequelae may occur.

• The Centers for Disease Control and Prevention has
defined a chronic BLL of more than 10 μg/dL as toxic
for a child. Acute exposure can result in levels above
100 μg/Dl
• A peripheral smear may show basophilic stippling
• Markers of hepatic injury may be elevated after acute

exposure,Because lead-containing paints and objects
are radiopaque when lead is present in sufficient
quantities, radiographs can confirm acute ingestion
and also monitor the effectiveness of whole-bowel
irrigation.
OPIOIDS
• Opioids are a class of drugs that have actions
similar to opium. Opioids act on the brain.
• Effects:
– Drowsiness: due to ‘depressant’ effect on the brain
– Suppression of cough: due to the effect of opioids
on the brain cough centre
– Constriction of the pupils in the eyes
– Constipation: due to the effect of opioids on the
gut system
• Some of the commonly used opioids include:
– Morphine
– Codeine
– Heroin
– Buprenorphine (commonly available as Tidigesic,
Lupigesic 2 )
– Pentazocine (commonly available as Fortwin )
– Dextropropoxyphene (commonly available as
Proxyvon, Spasmoproxyvon, Parvon Spas )
• Overdose occurs when a person takes opioid drugs or
opioids in combination with other drugs, in quantities
that the body cannot handle.
• As a result, the brain is not able to carry out normal

body functions  The person may pass out and stop
breathing, and in extreme cases, have heart failure, or
experience convulsions.
• Overdose can be fatal, and is one of the most common

causes of death among opioid dependent users
• Risks factors for Opioid Overdose
– Staying away from drugs
– Change in the purity of the opioids
– Mixing different type of drugs
– Physical illness or recent infections
– Mental health
– Past overdose events
– Using other drugs while on Opioid Substitution
Therapy
– Drug Interactions with antiretroviral and other
prescription medications
• Signs & Symptoms of Opioid Overdose
– Coma
– Pinpoint pupils
– Respiratory depression
• Warning Signs of Opioid overdose
– Can’t be woken up by noise or pain
– Blue lips and fingernails due to lack of oxygen
– Slow breathing (less than 1 breath every 5 seconds)
– Gasping, gurgling, or snoring
– Choking sounds
– Passing out
– Vomiting
– Pale face
– Tired body
• Preventing Overdose
– Avoid mixing drugs, and mixing drugs with alcohol. If you are drinking alcohol and
injecting together, inject first and wait for it to take effect before you start drinking
– When your tolerance is low divide the normal dose in half, do a tester shot and
allow the drugs to take effect before you try more. Try changing the route of
administration, that is, if you usually inject, try snorting.
– If you have a new dealer or unfamiliar supply, try a small amount at first to check
how strong it is
– Understand that medications prescribed by a doctor may interact with street

drugs and cause an overdose.
– Avoid using alone; if you overdose, you need someone around to help. For
example, put together a support team of people who know that you are going to
use drug alone and ask them to check on you
– Take care of your health. Eat well, drink plenty of water, and sleep properly.
Overdose Management
• check the following
– Is the person breathing?
– Is the person responsive (do they answer when
you shake them and call their name)?
– Does he/she respond to stimulation (such as
sternum rub)?
– Can the person speak?
– What is the colour of his/her skin?
ACETAMINOPHEN
• Acetaminophen is absorbed rapidly, with peak plasma
concentrations generally occurring within 1 hour and
complete absorption within 4 hours  inhibits prostaglandin
E2 (PGE2) synthesis (direct COX-2 inhibition or inhibition of
membrane-associated prostaglandin synthase)  antipyresis
and analgesia.
• After therapeutic ingestion  acetaminophen is primarily

metabolized by conjugation with glucuronide (40–67%) and
sulfate (20–46%) into nontoxic metabolites that are excreted
in the urine.
POISONING AND OVERDOSE
• A small percentage (<5%) is oxidized by cytochrome P450 2E1

to a highly cytotoxic metabolic intermediary, N-acetylp-
benzoquinonimine (NAPQI).
 In therapeutic doses : NAPQI is short-lived, combining
rapidly with glutathione and other thiol-containing
compounds to form nontoxic metabolites that are excreted
in the urine.
 Large ingestions or repeated supratherapeutic ingestions :
the amount of NAPQI produced begins to outstrip
glutathione stores and leading to unbound NAPQI 
initiates a cascade of events that lead to hepatic cellular
death.
Clinical Features
 Acetaminophen-induced liver damage initially occurs in hepatic zone III
(centrilobular) because oxidative metabolism is concentrated in this area
& renal failure.
 Multiorgan failure, systemic inflammatory response syndrome,
hypotension, cerebral edema, and death.
STAGE TIME COURSE NAME SYMPTOMS SIGNS

1 0–12 (up to 24–36) hr Preinjury Nausea, vomiting, anorexia,malaise Elevated serum
acetaminophen
concentration
2 8–36 hr Liver injury Nausea, vomiting, right upper
quadrant abdominal tenderness
Transaminitis (AST begins to
rise 8–36 hr after ingestion)
3 2–4 days Maximum liver injury Liver failure (encephalopathy,
coagulopathy, hemorrhage,
acidosis)
Hemorrhage, ARDS, sepsis/SIRS,
multiorgan failure, cerebral edema
4 >4 days Recovery None Complete hepatic histologic recovery
Diagnosis
 Acetaminophen exposures may be classified as acute or chronic.
 An acute ingestion is generally considered to be a single ingestion, arbitrarily
defined to be occurring within a 4-hour period.
 All other ingestions : accidental repeated supratherapeutic ingestions and
intentional ingestions spread over longer than 4 hours, can be considered to be
chronic.
Risk assessment with acute ingestion

 The first step is to determine the patient’s risk of acute acetaminophen
exposure.
 Next step is to establish a time of ingestion  determine serum
acetaminophen concentration 4 hours postingestion, or as soon as possible
after 4 hours. The serum acetaminophen concentration and the time of
ingestion determine the need for antidotal therapy by plotting the serum
acetaminophen concentration against the time since ingestion on the
treatment nomogram.
Risk assessment with chronic ingestion
 The initial steps include determining if the patient is at risk for hepatotoxicity,
evaluating the patient by measuring a serum acetaminophen concentration
and an AST, and initiating therapy with NAC.
Indications for Initiating Testing for Serum Acetaminophen Concentration

and AST in Chronic Acetaminophen Ingestions
Age ≥6 years old; Ingestion of 10 g/d (or 200 mg/kg/d) [whichever is smaller] over a 24-hr
period
or Ingestion of 6 g/d (or 150 mg/kg/d) [whichever is smaller] over a 48-hr
period
or Symptomatic (e.g., RUQ pain/tenderness, jaundice, vomiting)
Children <6 years old; Ingestion of 200 mg/kg/d over a 24-hr period
or Ingestion of 150 mg/kg/d over a 48-hr period
or Ingestion of 100 mg/kg/d over a 72-hr or longer period
or Symptomatic (e.g., RUQ pain/tenderness, jaundice, vomiting)
Spesific therapy
• Acetaminophen
 Acetaminophen level should be obtained in all multiple drug overdoses >4 hours after
ingestion.
 Antidote : N-acetylcysteine (NAC)
o Single acute dose 140 mg/kg, followed by
o 17 oral maintenance doses of 70 mg/kg administered 4
hours apart.
 NGT may needed for administration
 Antiemetic therapy
 If patient vomits the loading dose/any maintenance dose within 1 hour of administration 
the dose should be repeated.
 NAC IV loading dose 150mg/kg over 15 minutes, followed by
o 50mg/kg infused over 4 hours, then
o 100 mg/kg infused over 16 hours.
Szalados JE, editor. Adult Multiprofessional Critical Care Review. Rochester New York :
Society of Critical Care Medicine, 2007
 NAC is most effective in first 8 hours but is recommended up to 24 hours after substantial
ingestion.
 Late administration of NAC may be potentially benefical in fulminant hepatic failure caused by
acetaminophen toxicity.
o A marker of toxicity by evaluation AST-ALT >50 U/L or acetaminophen level
>10microgram/mL  course of NAC may be strongly considered.
 Activated charcoal = absorb acetaminophen and many coingestants
NAC FORMULATION COMMON SIDE EFFECTS SEVERE SIDE

EFFECTS
PO NAC Vomiting (50%) Very rare
IV NAC Mild anaphylactoid
reactions (e.g., rash,
flushing, pruritis,
vomiting),
2–18%
Severe
anaphylactoid
reactions
(e.g.,
hypotension) 1%editor. Adult Multiprofessional Critical Care Review. Rochester New York :
Szalados JE,
Society of Critical Care Medicine, 2007
DIGOXIN
• Used therapeutically:
– To increase the force of myocardial contraction to increase
cardiac output in patients with heart failure
– To decrease atrioventricular (AV) conduction to slow the
ventricular rate in atrial fibrillation.
• The basis for its first effect is inhibition of membrane
sodium-potassium–adenosine triphosphatase (Na+,K+-
ATPase), which increases intracellular sodium and
extracellular potassium concentrations
• Digoxin exerts direct and indirect effects on sinoatrial (SA)
and AV nodal fibers
• Digoxin also exerts three primary effects on Purkinje
fibers:
– Decreased resting potential, resulting in slowed phase 0
depolarization and conduction velocity
– Decreased action potential duration, which increases
sensitivity of muscle fibers to electrical stimuli
– Enhanced automaticity resulting from increased rate of phase
4 repolarization and delayed after depolarizations
• The volume of distribution (Vd) of digoxin is 5 L/kg for
adults but varies from 3.5 L/kg in premature infants to
16.3 L/kg in older infants.
• DigiFab
• Electrolyte Correction
• Atropine
• Pacing
• CSM
• Phenytoin and Lidocaine
WARFARIN
• Single ingestion of warfarin (10-20 mg) does not
cause serious intoxication.
• In contrast, chronic or repeated ingestion of even
small amounts of warfarin (2-5 mg/day)
eventually can lead to significant anticoagulation,
especially in the presence of interacting drugs.
• Patients with hepatic dysfunction, malnutrition,
or a bleeding diathesis are at the greatest risk of
toxicity from warfarin use.
DRUGS THAT INHIBIT WARFARIN METABOLISM
• Allopurinol
• Amiodarone
• Azole antifungals
• Capecitabine
• Cephalosporin antibiotics
• Chloramphenicol
• Chlorpropamide
• Cimetidine
• Cotrimoxazole
• Disulfiram
• Ethanol (acute ingestion)
• Flutamide
• Isoniazid (INH)
• Macrolide antibiotics
• Metronidazole
• Omeprazole
• Penicillin antibiotics
• Phenytoin
• Propafenone
• Propoxyphene
• Quinidine
• Quinolone antibiotics
• Statins (particularly lovastatin and pravastatin)
• Sulfinpyrazone
• Sulfonamides
• Tamoxifen
• Tolbutamide
• Zafirlukast
• Zileuton
Examination
• Bleeding is the only expected symptom of
significance. Internal bleeding may present
with a vast array of symptoms or be occult.
• Obtain an accurate history of the amount of
warfarin or superwarfarin ingested, when it
was ingested, and over what period it was
ingested
Lab testing
• The anticoagulant effect is best quantified by baseline and
daily repeated measurement of the PT and the INR, which
may not be elevated until 1-2 days postingestion. A
normal PT 48-72 hours after ingestion rules out significant
ingestion.
• Blood levels of vitamin K–dependent clotting factors (II,
VII, IX, and X) are decreased if measured, but these are
rarely available in a timely fashion and usually do not aid
in clinical management. However, depressed levels may
provide supporting evidence for suspected poisoning by
warfarin or superwarfarins
Treatment
Acute ingestion
• For acute ingestions, generally no evidence of bleeding is
present on the initial clinical examination, unless the
ingestion occurred more than 12-24 hours before
emergency department (ED) presentation
• Obtain a baseline PT/INR and make arrangements for a
repeat measurement in 24-48 hours. Administer
activated charcoal if it was not already given in the field.
Gastric lavage is unnecessary if rapid administration of
activated charcoal is feasible. Do not induce emesis.
• Treat any co-ingestions, evaluate the patient for suicidal intention, and refer
appropriately. Avoid drugs that may enhance bleeding or decrease
metabolism of the anticoagulant.
• Do not administer vitamin K1 prophylactically because (1) it is not needed in

most patients, and (2) its presence masks the onset of anticoagulant effects
in the few patients who do require prolonged treatment and follow-up care.
• If the PT is elevated, treatment with vitamin K1 is appropriate. Ten milligrams

orally is a reasonable daily dose. Since the pharmacologic effects of warfarin
wear off within days, otherwise healthy patients with acute warfarin
ingestions do not need supplemental vitamin K1 for more than several days.
In the setting of superwarfarin-induced coagulopathies, 50-200 mg daily is
recommended, and the duration of therapy may be many weeks.
• Note that if a patient has a critical need for ongoing anticoagulation (eg,
mechanical heart valve), heparin can be given as a temporary measure while
the effects of warfarin are fully reversed.
• Chronic intoxication
• Chronic intoxication resulting from the therapeutic use of
warfarin can be evaluated with a careful physical
examination and a measurement of the PT and INR.
• If the INR is higher than therapeutic levels but less than 5
and the patient is not bleeding, withhold warfarin for 2-3
days and restart when the INR approaches the therapeutic
range. If the patient requires more rapid reversal (eg,
elective surgery), administer 1-2.5 mg of vitamin K1 orally
with the expectation that the INR will begin to fall within 8
hours, with a maximal effect in about 24 hours.
• If the INR is higher than 5 but less than 9 and the patient is not
actively bleeding, withhold warfarin for the next 1 or 2 doses,
monitor the INR more frequently, and resume therapy at a lower
dose when the INR is at the therapeutic level.
• Another therapeutic approach would be to withhold 1 dose of

warfarin and orally administer vitamin K 1, 1-2.5 mg, particularly if
the patient is at increased risk of bleeding. For more rapid
reversal (eg, urgent surgery), administer vitamin K1, 2.5-5 mg,
orally (expected reduction of the INR should occur in about 24 h).
• If the INR is higher than 9 and the patient is not bleeding, a

higher daily dose of oral vitamin K1 (5-10 mg) may be
administered. In the setting of superwarfarin-induced
coagulopathies, 50-200 mg is recommended.
Treatment of serious hemorrhage
• Active, serious hemorrhage should be treated with FFP.
This therapeutic strategy immediately restores therapeutic
levels of coagulation factors. A volume of 15 mL/kg is
typically sufficient to completely reverse coagulopathy
• Alternatively, recombinant factor VIIa (rFVIIa) or

prothrombin complex concentrate, human (Kcentra) may
be used.
• Administer vitamin K1, 10 mg, by slow IV infusion. Using IV

vitamin K1 is rarely associated with acute cardiovascular
collapse (probably an anaphylactoid response) in a small
group of patients.
CARBON MONOXIDE
• Lethal concentration of carboxyhemoglobin found in 50% of
autopsied fire victims
• Higher metabolic rate of children, resulting in more rapid uptake

of CO, puts pediatric patients at greater risk
• Pathophysiology
– CO affinity to hemoglobin is 240 times greater than Hgb-O2 affinity
– CO-Hgb binding causes leftward shift in the oxyhemoglobin dissociation
curve, impeding oxygen delivery to tissues
– CO binds to myoglobin, cytochromes a and a3, and cytochrome c oxidase,
impeding O2 utilization and worsening cellular dysoxia
O2 saturation in CO poisoning
Pediatrics 1981; 68:218

CO poisoning: Therapy
• If comatose or hypercapneic, intubate
• Treat cerebral edema with hyperventilation, mannitol, and fluid

restriction
• Optimize hemodynamics/blood pressure
• Pharmacologic correction of mild acidosis discouraged--acidosis

shifts oxyhemoglobin dissociation curve to the right, facilitating
improved oxygen delivery
CO poisoning: Therapy
• Definitive therapy is 100% FiO2

– reverses arterial hypoxemia
– accelerates dissociation of CO from Hgb
– maintain until carboxyhemoglobin level <5%
• hyperbaric oxygen
• Consider empiric concomitant treatment for cyanide toxicity

CO exposure: Prognostic Factors
• Acidosis on admission reported to be a negative prognostic sign
• Reversal of coma within 48 hours associated with some degree

of recovery
• Correlation between LOC on admission and later

neuropsychiatric sequellae

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Marx JA, Hockberger RS, Walls RM, et al,

Marx JA, Hockberger RS, Walls RM, et al,

Management •Acute Lead Encephalopathy :

Marx JA, Hockberger RS, Walls RM, et al, editors. Rosen’s

Marx JA, Hockberger RS, Walls RM, et al,

• absorbed by the skin as well as by the

• Capable of phosphorylating another enzyme (neuropathy target

• Other characteristic symptoms and signs of acute toxicity

• The CNS toxicity may be manifested as mild headache or

• Permanent neurologic and behavioral sequelae may occur.

• A peripheral smear may show basophilic stippling

• Markers of hepatic injury may be elevated after acute

• As a result, the brain is not able to carry out normal

• Overdose can be fatal, and is one of the most common

– Understand that medications prescribed by a doctor may interact with street

• After therapeutic ingestion  acetaminophen is primarily

• A small percentage (<5%) is oxidized by cytochrome P450 2E1

STAGE TIME COURSE NAME SYMPTOMS SIGNS

Risk assessment with acute ingestion

Indications for Initiating Testing for Serum Acetaminophen Concentration

NAC FORMULATION COMMON SIDE EFFECTS SEVERE SIDE

• Do not administer vitamin K1 prophylactically because (1) it is not needed in

• If the PT is elevated, treatment with vitamin K1 is appropriate. Ten milligrams

• Another therapeutic approach would be to withhold 1 dose of

• If the INR is higher than 9 and the patient is not bleeding, a

• Alternatively, recombinant factor VIIa (rFVIIa) or

• Administer vitamin K1, 10 mg, by slow IV infusion. Using IV

• Higher metabolic rate of children, resulting in more rapid uptake

Pediatrics 1981; 68:218

• Treat cerebral edema with hyperventilation, mannitol, and fluid

• Optimize hemodynamics/blood pressure

• Pharmacologic correction of mild acidosis discouraged--acidosis

• Definitive therapy is 100% FiO2

• Consider empiric concomitant treatment for cyanide toxicity

• Reversal of coma within 48 hours associated with some degree

• Correlation between LOC on admission and later

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