Escolar Documentos
Profissional Documentos
Cultura Documentos
com
06/01/09
are you ready for tolerating honesty ? 1
ABC in drug
Poisoning
) for education purposes only(
Objectives
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
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
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
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
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
Glucuronidation Sulfation
OH
P450
N-Acetyl-p-benzoquinonamine
NAPQI
Glutathione
Oxidant tissue Oxidant tissue
damage damage
Non-toxic
metabolites
25
Overdose
Rumack-Matthew
Nomogram for
Acute
Acetaminophen
Toxicity
28
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
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
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
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