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06/01/09
are you ready for tolerating honesty ? 1
 ABC in drug
Poisoning
) for education purposes only(

By Dr. Ahmed Shaker Ali

Please send any comments regarding this
lecture
06/01/09 AhmedShaker21@yahoo.com 2
3

Objectives

 General Principles in the Management

of Poisoning e.g charcoal √√
 Specific management options with
certain substances e.g
 Paracetamol√√
 Opiates )Heroin, Methadone, Morphine(
 NSAIDs )ibuprofen (
 Tricyclic Antidepressants )
4

Topics
 Introduction
 General guidelines ) most slides are optional
regarding the exam (
ABC, toxidromes, decontamination,
antidote
 Acetaminophen toxicity
 Heroin toxicity
 Optional ) Tricyclic antidepressant
toxicity (
5

Introduction
Types of Intoxication
A sudden and severe
Acute exposure to a toxic agent
Subacute Repeated exposures over a period
of hours or days
Chronic Repeated exposure over weeks or
even years
6

Assessment & management

History & Evaluation, diagnosis

life saving measures ) ABC .. (
Many steps may be
General measures : performed
simultaneously
o Stop Exposure:
o Limit GI Absorption

o Hasten Elimination

o Specific antidote
Further Investigations & follow up
7

General Management -1
 A )Airway(
 B )Breathing(
 C )Circulation(
 D )Disability-AVPU/ Glasgow Coma
Scale(
 DEFG ) Don’t ever forget the
Glucose(
 GET A SET OF BASIC
8

History
 Who – pt’s age, weight, relation to
others
 What – name and dose of medication,
coingestants and how much amount
ingested
 When – time of ingestion, single vs.
multiple ingestions
 Where – route of ingestion,
geographical location
 Why – intentional vs. unintentional,
Also consider : Psychiatric history & other Circumstances Drug
history, I
identify, keep any drugs came with the patients , or empty
containers
 9 Toxidromes =symptoms of
toxicity
 Physical Examination
 eye { pupil size, nystagmus
 CNS – level of arousal, GCS, mental status,
neurologic exam
 CVS – Blood pressure, Pulse rater, rhythm
 Respiration – pattern, depth, wheezing
 GI – bowel sounds, distention Vomiting
 Skin – color, temp, sweating, signs of trauma
 Other observations Odors
 :
 Essential Clinical laboratory
10
tests

 U & Es, LFTs , glucose, ABG,

clotting,
 Drug monitoring & Toxicology screening
 E.g Acetaminophen , salicylate , Antiepileptic , digoxin ,
selective screen ) e.g drugs of abuse (
 NB : Toxicology screening need urine samples+ blood
samples.

Other may be considered :
 urine analysis
 Serum osmolality and osmolar gap
 Osmolar gap = measure - calculated = 0 ± 5 ??
 Calculated Os = 2 Na+ glucose + BUN ??
 Summery of ABC Management
11
plan

 Supportive monitoring and

management of serious life
threatening problems
 Correct hypoxia, hypotension,
dehydration, hypo- hyperthermia, and
acidosis
 Control seizures
12
General measures
2- Decontamination

 Surface Decontamination
 Skin : protect yourself, remove contaminated clothes ,
washing, soap and shampoos for oily substances etc
 EYE : place the victim in supine position under tap water or
use IV tubing to direct a stream of water across the nasal
bridge into the medial aspect of the eye ) use at least 1L
/eye (
 Inhalation : remove the patient from exposure, subliminal
humidified oxygen, Assist vent. If necessary , Observe
closely for URT edema , and late onset pulmonary edema
etc
13

√GIT decontamination-3
Methods
 activated charcoal
 Gastric Lavage ?
 Whole bowel irrigation ?
 Emesis ????
 Cathartics????
 Surgery ????????
14

√√√Activated Charcoal
 Indications
 Within 1 hour of ingestion
 Nearly all suspected toxic ingestions except
) inorganic salts, acids, alkali, heavy metals, Iron,
alcohols , ethylene glycol (

 Contraindications : no absolute
contraindications
 Complications
 Intestinal impaction if multiple doses
 Distension of the stomach with potential of
pulmonary aspiration.
15
√√√Activated Charcoal

 1g/kg PO or NG at
least 10 times the
ingested dose.
 One or two
additional doses may
be used at 1-2 hr
intervals
16

Whole bowel irrigation

 PEG in a balanced electrolyte soln. via NG at 1-2 L/h )500cc/h in
peds( until effluent clear
 + activated charcoal 25-50 g / 2-3 hr
 Indications
 Large doses of SR or EC prep of dangerous drugs e.g
Theophylline , carbamazepine, aspirin etc
 Ingested packets of illicit drug )stuffers, packers(
 Substances not adsorbed by AC
 Iron ingestions
 Contraindications
 Ileus , Bowel perforation or obstruction, Intractable vomiting
 GI bleeding
 Unprotected airway
 Hemodynamic instability ??
 Complications
 Nausea, vomiting, cramps
 Aspiration
 Reduce effectiveness of charcoal
17
Emesis Ipecac –syrup‫????نفعه‬
‫اكثر من‬ ‫التقيىء‬
) not used‫ضرر‬in
‫ربما‬
hospitals (
 Emetic – both peripherally and central acting >90% effective
 Dose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 mo
 Indications
 Early pre-hospital management when activated charcoal is not
available , prolonged transport time to hospital
 Contraindications
 Unprotected or anticipated unprotected airway
 Hydrocarbons, crossover agent
 Substance likely to cause CNS depression or seizure in short time
 Obtunded, comatose or convulsive patients
 Cardiac and pulmonary patients
 < 6 month
 Complications ) many (
 Diarrhea, lethargy/drowsiness, prolonged vomiting, hemorrhagic
gastritis s
 A soapy water) dishwashing liquid or lotion , 2 teaspoonful in a
glass of water ( solution may be used as alternate emetic
18

Gastric Lavage
 Overview : Occasionally used in ER,, not necessary for small to moderate ingestion
of most substances if activated charcoal can be given promptly
 Indications
 Recent ingestion )<1-2 hr(
 Massive overdose or a particularly toxic subsetance
 Agents not adsorbed by AC
 Contraindications
 Obtunded, comatose or convulsive patients
 SR or enteric coated tab.
 Corrosives ??
 Hydrocarbons
 Risk of GI bleed or perforation
 Adverse effects :
 mostly from bad manipulation mechanical injury, Aspiration pneumonia
 , laryngospasm, hypoxia,, fluid/electrolyte imbalances
 Technique : protect airway, proper position, administer activated charcoal before
starting lavage
19

)Enhancing elimination) EE
Overview : Application of toxic kinetics is necessary for
appropriate use # 3 Q ?
 Q1: Does the patient need EE?
 Q2 : Is the drug accessible to the procedure ?
 this depends on PK ) vd, protein binding (
 Q3: Will the method work ?
 this depends on Total CL & t-half.
Methods avialble
 Urinary manipulation ) Alkalinization of urine for acidic
drugs or diuretics(
 Hemodialysis
Details are
 Hemoperfusion optional
 Hemofilteration
 Repeated dose activated charcoal ) Annex 2 (
20

Antidotes ANTAGONISING THE EFFECTS OF THE

)

POISON

Antidote Poison
N-acetylcysteine acetaminophen
atropine organophosphate
Ca gluconate or Ca Calcium channel blockers
chloride
Cyanide kit cyanide
Deferoxamine Iron
Fab digoxin Digoxin
Dimercaprol )BAL( Arsenic, mercury, lead
21

Antidotes
Antidote poison
ethanol MeOH, et glycol
flumazenil Benzodiazepine
Fomepizole MeOH
glucagon Β-blocker, CCB
Methylene blue methemoglobin
naloxone opioids
physostigmine anticholinergic
pralidoxime organophosphate
pyridoxine isoniazid
Sodium bicarbonate TCA, cocaine, salicylates
 Paracetamol toxicity
22
23
Toxicity

 Little to no toxicity in therapeutic

dosing
 With overdose:
 Hepatic toxicity progressing to
fulminant hepatic failure,
encephalopathy and death within
days
 Other systemic effects
24Pharmacological basis of
√√√√√ Acetaminophen toxicity
Acetaminophen
O
ll
HN-C-CH3

Glucuronidation Sulfation

OH

P450
N-Acetyl-p-benzoquinonamine
NAPQI

Glutathione
Oxidant tissue Oxidant tissue
damage damage
Non-toxic
metabolites
25
Overdose

 Normal conjugation metabolism

routes are saturated
 More NAPQI is produced
 Glutathione reserves fall below 30%
 Unable to detoxify all NAPQI formed
 Cellular injury results
26
Management

 NB in initial phases no clear

symptoms.
 Drug monitoring is very valuable if
done properly
 N-actylcystine is the anti-dote
 Use the Rumack-Matthew Nomogram
to identify the potential toxicity
27

Rumack-Matthew
Nomogram for
Acute
Acetaminophen
Toxicity
28

Opiate Poisoning- Features

 Heroin ) addiction (
 Methadone, analgesics
‫بئس المصير‬
 in Elderly
 General toxidromes.
 1. PINPOINT PUPILS
 2. RESPIRATORY DEPRESSION
 3.COMA
29 Opiate Overdose-
Management
 INITIAL MANAGEMENT
 A
 B
 C
 D
30 Opiate Overdose-
Management 2
 NALOXONE
 Opioid antagonist
 High Affinity for the opiate receptors
 Little other effects
 Rapid onset
 Effects last 2-4 hrs, may need
repeated doses
 Give I-M or I-V
31

References
You may visit these sites
 http://www.clintox.org

 http://www.aapcc.org

 TOXNET database

http://toxnet.nlm.nih.gov/index.htm/
 Text book : Poisoning and & drug

overdose
 Kent R OLSON 4th ed . LANGE P. 66-69 ,

286-289
32

) Optional section ) SDL

33

A irway
 Assessment :
 Patients awake )monitor closely (
 lethargic or obtunded ) consider management (
 Management :
 Optimize the airway position )practical skill (
o Sniffing position
o Jaw thrust
o Head down, left sided position
 Remove any obstruction or secretions
 Perform endotrachial intubations if indicated
o Nasotrachial or
o orotracheal
34

B reathing
1-Ventilatory failure
cause : CNS depression by opiates, barbiturates alcohol, Tricylic
antidepressants, etc ) R.O other causes (
Assessment : Arterial blood gases ) PCO2 > normal values(
indicate the need for assisted ventilation
Treatment : Assisted ventilation : optimal programming of the
ventilator

2- Hypoxia
cause : sedative hypnotic , opiates ,salicylates,) R.O other
causes (
Treatment : Correct hypoxia : Administer oxygen as indicated
based on arterial PO2
35

Breathing cont
3- Cellular hypoxia
cause : CO , Cyanide & hydrogen sulfide
Treatment : CO ) 100 % oxygen , consider hyperbaric oxygen ( refer to
the specific guide
4- Bronchospasm
Cause : Direct irritant ) gases, aspiration of petroleum distillates (
Pharmc effects of poisons or drugs ; e.g Organophosporous ,
carbamates insecticides, B-blockers .
Hypersensitivity : many drugs & poisons
Treatment :
o Administer oxygen, assist ventilation, endotrachial intubations if
needed ,
o Administer bronchodilators
o e.g albutrol 2.5-5 mg in nebulizer
o ibratroprium bromide 0.5 mg 4-6 h
o consider iV theophylline in case of B-blockers poisoning
36

C irculation
 I-General
Check BP , pulse rate & rhythm.
CRP ) cardiopulmonary resuscitation( if no pulse
ACLS [ Advanced cardiac life support ] for severe arrhythmia and shock
Begin cont EEG monitoring
Begin IV infusion of appropriate fluids
Secure venous access
 II: Bradicardia & AV block
no treatment unless the pt is symptomatic
Treatment include : maintain airway and assists ventilation if necessary
Atropine 0.01-0.03 mg/kg IV or
isopreternol 1-10 mcg/min,
ER pacemaker
Specific antidote if appropriate
o Glucogon for bet-blockers over dose
o Fab digoxin for digoxin toxicity
37

Circulation cont
 III-QRS INTERVAL
PROLONGATION
 >0.12S INDICATE POSIONING BY TCA OR OTHER MEMBRANE
DEPRESSANT DRUGS eg digitalis , b-blockers
 Treatment :
o maintain airway and assists ventilation if necessary
o Treat hyperkalimia and hypothermia if present
o Treat AV block by atropine , isoppteternol and pacemaker if
necessary
o for TCA or other sodium channel blockers give 1-2 mEq sod
bicarc IV bolus, repeat as needed

o
Other antidote if appropriate
38

Circulation
 III-Tachycardia
causes : many e.g sympathomimetic agents : Amphetamine ,
theophylline , cocaine
Treatment observation and sedation if no chest pain or hypotension
sympathomimetic induced : propranolol or esmolol
If tachycardia is anticholinergic induced ; consider use of neostigmine
these drugs should be avoided in case of TCA ) A systole additive depression of
conduction (

V-Ventricular arrhythmia
 Causes : many drugse.g exissive Sympathetic stimulation ) cocaine ,
amphetamine (
 Treatment : follow the standard guidelines for management of
arrhythmia with exception : Procanimide and bretylium should not be
used esp if TCA or B-blockers over dose is suspected.
39

Circulation cont
VI-Hypotension
 Causes : many drugs. Opiates , sedative hypnotics ,
theophylline , TCA
 Treatment :usually respond to simple measures Fluid therapy
and low dose of pressor drugs
 IF not resolved use systematic approach
 Which consider management of Airway, Arrhythmia,
hypothermia, dopamine ) nor-epinephrine in case of TCA
 Specific antidote
VII-Hypertension
 Causes : With Tachycardia : LSD, Cocaine, Amphetamine, TCA
 Treatment : it depends on other symptoms:
No Tachycardia : phentolamine or nitroprusside
Presence of Tachycardia : As above + propranolol or esmolol or
labetolol
NB : not use These drugs alone for treatment of hypertensive
crisis
40

Mental Status
 Coma and stupor
 Cause: many :Generalized CNS depressants & sympatholytic
 Treatment :
 1-Maintain airway , assists ventilation, administer oxygen if necessary
 2-DRUGS : Dextrose, Thiamine,
 Naloxone ) if respiratory depression,

Flumazenil ) If Benzodiazepine alone is suspected (
 Hypothermia : follow the guidelines
 Hyperthermia : follow the guidelines
 Key words :,, Treatment : immediate rapid cooling
 1- as above, 2- Fluids, 3- Control of seizure
4-External cooling with tepid sponging and fanning
5- specific drugs ,
neuromuscular paralysis by vecuronium
Malignant hyperthermia : Give dantrolene
neuroleptic malignant syndrome : Consider bromocriptine
serotonin syndrome : cryptoheptadine or methylsergide my helpful
41

Mental Status cont

Seizure :
 Causes : many drugs including adrenergic sympathomimetic agents
Antidepressants and antipsychotic
 Treatment :
 1- 1-Maintain airway , assists ventilation, administer oxygen if
necessary
 2- Nalxone : if seizure is due to narcotic
 3-correct hypoglycemia : dextrose and thiamine as for coma
 4- Appropriate anticonvulsant drug ) Diazepam, Lorazepam,
Midazolam, phenobarbital, pentoparbital, propofol , phenytoin }
 5-Specific antidote : Pralidoxime or atropine or both for
organophosphate or carbamate insectside
 Agitation, delirium or Psychosis follow the
guideline
42

Other complications
 Dystonic reactions
 Dyskinesia
 Rigidity
 Rhabdomylosis
 Anaphylaxis
 Anaphylactoid reactions
43

 Details of Enhanced
elimination
44

Hemodialysis
 Blood passed across membrane with countercurrent dialysate flow
 Toxins removed by diffusion
 Patient must be anticoagulated
Properties required:
 Molecular weight < 500 daltons
 High water solubility
 Low or saturable plasma protein binding
 Low Vd )<1L/kg(

Low endogenous clearance)<4ml/min/kg(
Complications
 Bleeding at venous puncture site
 hypotension
 DVT
 Bleeding due to systemic anticoagulation
 Infection
 Air embolus
45

Hemoperfusion
Overview : Blood passed through cartridge containing AC
 Toxins removed by adsorption
Advantages : Drug characteristics are less important
 Usually greater clearance rate
Disadvantages Systemic anticoagulant is required
 Thrombocytopenia is a common complication

 Properties required:
 Low Vd <1L/kg
 Low endogenous clearance
<4cc/min/kg
 Adsorbable to AC
46

Peritoneal dialysis
 Easer to perform than other dialysis
tech.
 Only 10-15 % as effective , slow Cl. rate
 Can be performed continuously
 24 hr Pr. D = 4 hr of Hemo. D.
47

Alkalinization
 Enhances elimination of weak
bases by ion trapping
 Useful for:
 Salicylates, phenobarbital,
chlorpropamide, methotrexate,
myoglobin
 NaHCO3 1-2 mEq/kg IV Q3-4H
 Aim for Urine pH 7-8
 Must replace K
48 Multiple Dose Activated
Charcoal
 Consider only if life-threatening amount
of:
 Carbamazepine
 Phenobarbital
 Dapsone
 Quinine
 Theophylline
 May also increase elimination of :
 amitriptyline, propoxyphene, digitoxin,
digoxin, disopyramide, nadolol,
phenylbutazone, phenytoin, piroxicam,
sotalol
49

Details of Toxicity of
Acetaminophen
50
Phase I

 0 to 24 hours
 Usually asymptomatic
 “silent overdose”:
 Importance of obtaining level
 Nausea, vomiting, abdominal pain
51
Phase II

 24-72 hours
 Resolution of initial physical
symptoms
 May develop right upper quadrant
pain
 Evolving liver injury
 Elevation of LFT, PT, Bilirubin
52
Phase III

 3 to 4 days
 Nausea, vomiting, and abdominal
pain reoccur
 Maximal manifestation of hepatic
injury-AST/ALT in 10,000s
 Coagulopathy, hepatic necrosis,
acidosis, encephalopathy
 Coma and anuria precede death
53
Phase IV

 Beyond 4 days
 Recovery phase
 LFTs will decrease, but bilirubin
may remain elevated for some
time
 May take several weeks for LFTs to
normalize
54
Other Overdose Sequelae

 Renal toxicity
 Occasionally renal failure can occur
from massive overdoses
 Possibly 2° to P450 activity in the kidney
 Pancreatitis
 Pneumonitis
 55
The Nomogram
 Is a guideline for determining who should
be treated for a single acute ingestion
 Is not a representation of the elimination
kinetics
 Serial levels not useful
 In US, line positioned 25% lower
 ↑ sensitivity – no missed cases
 ↓ specificity
 Important to use a 4-hour level whenever
possible
56
Ingestion of single dose

 Treatment indicated if:

 Level above 150mg/dL at 4 hours
 Ingestion of 150 mg/kg in children
 Ingestion of 7.5 g in adults
 Patient is unreliable or unconscious
57
N-acetylcysteine
58
Mechanism of N-acetylcysteine

 Restores glutathione:
 Allows NAPQI detoxification
 Augments sulfation reaction
 Direct anti-oxidant:
 Directly detoxifies NAPQI
 Improves organ function and limits
hepatocyte injury
59
Unknown ingestion time

 Treat if any sign of liver injury

even without history of APAP
ingestion
 Detectable APAP level in altered
patient
 If AST/ALT are normal
 And APAP is less than 10 µg/ml
 Do not treat
 Narrow window of risk
60
Laboratory Assessment

 If patient is sick, one should obtain

LFTs, PT, electrolytes, BUN/Cr,
amylase, lipase and glucose
 Late presenting sick patients will not
have detectable acetaminophen
levels
 Diagnosis can be more difficult
 They will require treatment
61 Repeat or Chronic
ingestion
 Nomogram does not apply
 Suggested threshold:
 150 mg/kg per 24 hours in children
 7.5 g per 24 hour period in adults
 Obtain acetaminophen level, AST,
ALT, PT, BUN/Cr and electrolytes
62 Repeat or chronic
ingestion
 Patients who should be treated
)similar to unknown ingestion
time(:
 Signs of hepatotoxicity )elevated AST(
 APAP level of ≈25 mcg/ml or greater
 Symptomatic
 “Gray area”: APAP 11-25 mcg/ml
and normal AST in asymptomatic
patient
63
Ethanol And Acetaminophen

 Ethanol is metabolized to some

extent by P450 system
 Chronic ethanol ingestion causes
increase in 2E1 P450 activity
 Acute acetaminophen ingestion is
treated the same in patients who
consume alcohol chronically
64
N-acetylcysteine
65
N-acetylcysteine

 Greatest benefit if administered within 8

hours:
 No clinical difference within the first 8 hours
 All patients that have a normal AST at time
of NAC initiation survive
 Treatment within 8 hours of single ingestion
completely prevents liver failure
 “Too Late” does not exist
 Improved mortality even in patients with
hepatic failure when initiated 2-3 days after
ingestion
66
Oral N-acetylcysteine

 Oral loading dose is 140 mg/kg

 Dilute 4:1 with palatable liquid
 Repeat doses are 70mg/kg every 4
hours
 Total of 17 doses for total of 72 hours
 Antiemetic treatment may be
required
 NAC is very foul “rotten egg” liquid
67
IV N-acetylcysteine

 Can cause anaphylactoid reaction

 Rash, hypotension, bronchospasm
and death
 Rate related; rare when given slowly
 Higher, continuous blood levels
obtained then oral NAC
 Bolus administered first, then
constant infusion rate may be
given
68
IV vs. Oral

 Both have their advantages and

disadvantages
 Each may be more appropriate in
certain settings
 No side by side studies to date
 Conclusions of relative benefits are
speculative