Second CME and workshop on Critical

care

An approach to a poisoned
patient

Dr. J V Peter, MD, DNB (Med), FRACP

Christian Medical College & Hospital, Vellore
 Introduction

What is a poison?

In common usage - poisons are

chemicals or chemical products
that are distinctly harmful to
human

More precisely - a poison is a

foreign chemical (xenobiotic)
that is capable of producing a
harmful effect on a biologic
system
 Other terminology

What is a toxin?

It originally referred to a
poison of animal or plant
origin

Toxicant is the currently

preferred scientific term
for all poisons.
 Other terminology

What is a toxidrome?

Itis the association of several clinically

recognizable features, signs,
symptoms, phenomena or
characteristics which often occur
together, so that the presence of one
feature alerts the physician to the
presence of the others.
Common toxidromes
The cholinergic toxidrome
The cholinergic toxidrome
The cholinergic toxidrome
What toxidrome?
 The anticholinergic
toxidrome
Hot as a
hare
Dry as a
bone
Red as a
beet
Mad as a
hatter
Blind as a
bat
 The anticholinergic
toxidrome
Hot as a
hare
Dry as a
bone
Red as a
beet
Mad as a
hatter
Blind as a
bat
 The anticholinergic
toxidrome
Hot as a
hare
Dry as a
bone
Red as a
beet
Mad as a
hatter
Blind as a
bat
 What toxidrome?

disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic Phencyclidine
Benzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
 Hallucinogenic
Sympathomimetic
toxidrome
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic Phencyclidine
Benzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
 Hallucinogenic
Sympathomimetic
toxidrome
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic Phencyclidine
Benzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
 Hallucinogenic
Sympathomimetic
toxidrome
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic Phencyclidine
Benzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
Common toxidromes
Sedative/hypnotic toxidrome
Sedative/hypnotic toxidrome
Sedative/hypnotic
toxidrome
Common toxidromes
Opiate toxidrome
Opiate toxidrome
Opiate toxidrome
Common toxidromes
Serotonergic syndrome
Serotonergic syndrome
Serotonergic syndrome
 Recognition of poisoning
May be difficult because of non-specific symptoms

High index of suspicion - especially occult poisoning

history may be unreliable
look for corroborative history - missing pills, empty
container

Course that a poison runs (toxidromes) ! - may help

Toxicology screening - helpful only in a few

 Clinical manifestations

Very diverse and varied - depends on

the poison

Clinical examination should be

focused on the possible
manifestations of common poisons in
the geographical area
Clinical manifestations

Skin and mucosal damage

Neurotoxic manifestations

Cardiovascular manifestations

Metabolic consequences

Eye manifestations

Hepatic dysfunction
 When do you consider
ICU?
Respiratory

Airway protection

Respiratory failure

Cardiovascular

Hypotension despite fluid challenge

Heart block, arrhythmias, QTc prolongation as in TCA

 When do you consider
ICU?
Neurologic
GCS < 8
Seizures

Metabolic
Hypoglycaemia
Significant electrolyte abnormalities
metabolic acidosis
Hepatic failure
Coagulopathy with bleeding
Assessment & management

ASSESSMENT & THERAPY

should proceed in parallel
Clinical assessment
 Clinical assessment
Airway - ensure clear airway, clear
secretions, check for cough/gag

Breathing - check oxygenation,

supplemental O2, breathing pattern &
adequacy

Circulation - heart rate, rhythm, blood

pressure
 Clinical assessment
Neurologic - GCS, seizures, agitation,
spasms, pupils, autonomic dysfunction

Miscellaneous - odour, temperature,

pallor, cyanosis, jaundice

Abdomen - rigidity, bleeding, urine output

Laboratory assessment
 Laboratory assessment
Of limited value

Paracetamol levels, salicylate levels,

alcohol, Red cell/pseudocholinesterase,
anti-epileptic drug levels

Urinary drug screen - opiates,

barbiturates, benzodiazepines,
amphetamines, cocaine
 Laboratory assessment
Anion gap & Osmolal gap

Increased anion gap (Normal 12 4 mEq/L)

Ethylene glycol
Methanol
Salicylate poisoning

Increased osmolal gap (Normal 5 7 m

osmol/kg)
Ethylene glycol
Methanol
Acetone, ethanol, isopropyl alcohol, propylene glycol
 Laboratory assessment
Electrolytes
Hypokalemia
Oduvanthalai poisoning (Clistanthis collinis)
Diuretics, Methyl xanthine, Toluene
Hyperkalemia
Digoxin
Beta-blocker
Liver function tests
Acetaminophen, Ethanol, Carbon tetrachloride
Renal function tests
Ethylene glycol, NSAIDS
 Laboratory assessment
ECG

Digoxin toxicity

TCA overdose - sinus tachycardia, QT

prolongation, increased QRS

Beta-blockers - conduction abnormalities

Imaging

Limited value
Goals of treatment
 Goals of treatment

Reduce absorption of the toxin

(xenobiotic)

Enhance elimination

Neutralise toxin
Reduce absorption of the toxin
 Reduce absorption

Removal from surface skin & eye

Emesis induction
Gastric lavage
Activated charcoal administration & cathartics
Dilution - milk/other drinks for corrosives
Whole bowel irrigation
Endoscopic or surgical removal of ingested
chemical
 Reduce absorption

Skin decontamination

Important aspect not to be

neglected

Remove contaminated clothing

Wash with soap and water (soaps

containing 30% ethanol advocated)

However, no evidence for benefit

even in OP poisoning
 Decontamination

Gastric decontamination
Forced emesis if patient is awake
Gastric lavage
Activated charcoal 25 gm 2 hourly
Sorbitol as cathartic
 Reduce absorption
Gastric lavage

Gastric lavage decreases absorption by 42% if

done 20 min and by 16% if performed at 60 min

Performed by first aspirating the stomach and

then repetitively instilling & aspirating fluid
Left lateral position better - delays spont.
absorption
No evidence that larger tube better
Simplest, quickest & least expensive way - funnel
Choice of fluid is tap water - 5-10 ml/kg
 Reduce absorption

Gastric lavage

Preferrably done on awake patients

Presence of an ET tube does not preclude
aspiration, though preferred if GCS is low

No human studies in OP poisoning showing

benefit of gastric lavage
Enhance elimination
 Enhance elimination
Increased elimination is possible only if

the drug is distributed predominantly in the

ECF
has a low protein binding
the induced rate of elimination is faster than
the normal rate
hazards of having a longer time of exposure
to the drug are potentially fatal
 Enhance elimination
Methods

Keep a good urine output 150-200 ml/hr

Alkalinisation of urine - clinical efficacy
accepted for salicylate & phenobarbital
poisoning
Extracorporeal removal
Hemodialysis - Barbiturates, Salicylates,
Acetaminophen, Valproate, Alcohols,
Glycols
Hemoperfusion - theophylline, digitalis,
lipid soluble drugs
Neutralise toxin
Neutralise toxin-specific
antidotes
Neutralise toxin-specific
antidotes
 Summary
Poisoning a common problem in our country

A high index of suspicion required to diagnose

Know common toxidrome

Dont panic and follow a plan of action

Decreasing absorption
Enhancing elimination
Neutralising toxins

Avoid potentially harmful Rxs - risk vs benefit

Thank you
Organophosphate poisoning
Clinical features
Clinical manifestations
 Neurological manifestations

Neuromuscular weakness/paralysis
Type I, Type II and Type III paralysis (OPIDP)

Neuropsychiatric manifestations -COPIND

Extrapyramidal manifestations
Dystonia, resting tremor, rigidity, chorea

Neuro-ophthalmic manifestations
Optic neuropathy, retinal degeneration

Rarer manifestations
GBS, Ototoxicity, Sphincter involvement
Therapy of organophosphate
poisoning
 Management

Step I: Identify the nature of the poison

Organophosphate
Carbamate
Chloride
Pyrethroid
Neonicotinoids
 Management
Step II: Decontamination

Skin decontamination

Important aspect not to be

neglected

Remove contaminated clothing

Wash with soap and water (soaps

containing 30% ethanol advocated)
 Management
Step II: Decontamination

Care to be taken by health personnel

to avoid contamination

Reports of occupational illness in 3 staff

caring for OP poisoned patients

Another report 7 of 10 staff who cared for

a patient developed chest tightness or
discomfort
Geller RJ, Singleton KL, Tarantino ML, Drenzek CL, Toomey KE. Nosocomial
poisoning associated with emergency department treatment of organophosphate
toxicity Georgia 2000. J Toxicol Clin Toxicol 2001; 39: 109-11.
 Management
Step II: Decontamination
Skin decontamination is there
evidence for benefit?

Skin decontamination (15 minutes

post-VX on the ear) arrested the
development of clinical signs and
prevented further cholinesterase
inhibition and death in experimental
animals.

Hamilton MG, Hill I, Conley J, Sawyer TW, Caneva DC, Lundy PM. Clinical
aspects of percutaneous poisoning by the chemical warfare agent VX: effects of
application site and decontamination. Mil Med 2004; 169: 856-62.
 Management
Step II: Decontamination

Skindecontamination is there
evidence for benefit?

Cholinesterase sponges on surfaces

have been used called OP scavengers

Others have developed lotions

No human evidence for benefit of skin

contamination
 Management
Step II: Decontamination

Gastric decontamination
Forced emesis if patient is awake
Gastric lavage
Activated charcoal 25 gm 2 hourly
Sorbitol as cathartic
 Reduce absorption
Gastric lavage

Gastric lavage decreases absorption by 42% if

done 20 min and by 16% if performed at 60 min

Performed by first aspirating the stomach and

then repetitively instilling & aspirating fluid
Left lateral position better - delays spont.
Absorption
No evidence that larger tube better
Simplest, quickest & least expensive way -
funnel
Choice of fluid is tap water - 5-10 ml/kg
 Reduce absorption

Gastric lavage

Preferrably done on awake patients

Presence of an ET tube does not preclude
aspiration, though preferred if GCS is low

No human studies in OP poisoning showing

benefit of gastric lavage
 Management
Step III: Airways and Respiration
Maintain airway
Ensure adequate oxygenation
Watch for intermediate syndrome
(diplopia, extra-ocular muscle
weakness/neck muscle weakness)
Monitor respiratory rate/tidal volume/vital
capacity
Blood gas analysis

Step IV: Cardiac monitoring

Hemodynamic and monitor for
arrhythmias
 Management
Step V: Specific therapy
Atropine
Initiate as soon as diagnosis is
suspected
Adults 2 mg IV bolus - repeat dose
very 5-15 minutes till atropinised
children - 0.05 mg/kg initially then
0.02-0.05 mg/kg
Atropinisation
Heart rate about 100/mt
Pupils mid position
Bowel sounds just heard
Clear lung fields
 Remember
Steps I to V occur
simultaneously
Role of oximes
 Organophosphate poisoning

Are oximes beneficial in human OP

poisoning?

Subject of much debate & literature

Systematic review & meta-analysis

Organophosphate poisoning
Organophosphate poisoning
Organophosphate poisoning
OP - why no benefit with PAM
May be a true effect - it is not
effective!!

Type of compound
Poison load & dose
Time of administration
Ageing of the compound
Toxicity of the antidote
 Conclusions
The key to successful management in a
poisoning is early recognition and
appropriate management

Remember common toxidromes

OP poisoning very common in our part of

the world

Role of oximes still not established

THANK YOU
Is there a role?- nature of OP
compound
Human poisoning by OP bearing two
methoxy groups eg. malathion,
paraoxon-methyl, dimethoate and
oxydemeton-methyl is generally
considered to be rather resistant to
oxime therapy.

Failureattributed to megadose
intoxications and to prolonged time
intervals between poison uptake and
oxime administration

Dimethylphosphoryl-inhibited human cholinesterases:

inhibition, reactivation, and aging kinetics. Arch. Toxicol
1999; 73:7-14
 Is there a role?- dose related?
Invitro studies (isolated rat diaphragm) and in
vivo studies (cats). minimum-effective
plasma level for oxime therapy 4 mg/l..
higher doses may be required in severe cases
of OP poisoning

Case reports where even with high dose -

course is prolonged

MK Johnson et al. Evaluation of antidotes for poisoning by

organophosphorus pesticides. Emergency Medicine (2000) 12:22-
37.
Is there a role?- time of
administration
Electrophysiologicalimprovements
(present) when obidoxime administered
within 12 hours of poisoning. Minimal or
no improvement if treatment delayed
more than 26 hours.

Efficacy of obidoxime in human organophosphorus

poisoning: determination by neuromuscular transmission
studies. Besser R et al. Muscle Nerve 1995; 18:15-22

Vellore- in vitro study - re-activation of

AChe is poor if P2 AM is administered
after 12 hours of poisoning
Is there a role?- time of
administration
Obidoxime was quite ineffective
in oxydemetonmethyl poisoning
when the time elapsed between
ingestion and oxime therapy was
longer than 1 day..when
obidoxime was administered shortly
after ingestion (1 h) reactivation
was nearly complete

Cholinesterase status, pharmacokinetics and

laboratory findings during obidoxime therapy in
organophosphate poisoned patients. Thiermann H et
al (Germany). Hum Exp Toxicol 1997; 16:473-80
Is there a role?- ageing of OP
..believed that 1 day after intoxication
with a dimethyl OP insecticide, virtually
all the AChe will be in the aged inhibited
form, so that oxime therapy will be
useless after this time.

Ageing characteristics different for di-

methyl (half life 3.7 hours) and di-ethyl
(half life 33 hours) - therapeutic window
five times the half life

MK Johnson et al .Evaluation of antidotes for poisoning by

organophosphorus pesticides. Emergency Medicine 2000;
12:22-37
Is there a role?- toxicity

Formation of stable phosphoryl

oximes (POXs) with high
anticholinesterase activity

Obidoxime and other pyridinium-4-

aldoximes form these POXs

The phosphoryl oxime-destroying activity of human

plasma. Arch. Toxicol 2000; 74:27-32
 Toxicity of oximes - II
Pralidoxime in a volunteer study - dizziness
& blurring

Rapid administration of PAM - slow &

shallow resps

Cardiac arrhythmias - AF, VT, VFib, AV block

Liver function abnormalities with obidoxime

High dose oximes cause muscle weakness