An approach to a poisoned

patient

Dr. J V Peter, MD, DNB (Med), FRACP
Christian Medical College & Hospital, Vellore

Second CME and workshop on Critical care
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?

It is 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
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
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
Acetaminophen N-acetyl cysteine
Anti-cholinergics Physostigmine
Benzodiazepenes Flumazenil
Ca channel blockers Glucagon, Insulin + dextrose, Calcium
Carbamate Atropine
Cyanide Thiosulphate, nitrate
Digoxin Digoxin antibodies
INAH Pyridoxine
Methanol Ethanol, Fomepizole
Glycol Ethanol, Fomepizole
Opioid Naloxone
Oral hypoglycaemics Glucose
Organophosphate Atropine,? P2AM
Warfarin Vitamin K

Neutralise toxin-specific
antidotes
Iron Desferroxamine
Copper Penicillamine, Dimercaprol, CaEDTA
Lead CaEDTA, Dimercaprol (BAL)
Mercury DMPS, DMSA, BAL
Arsenic BAL & derivatives
Antimony BAL & derivatives

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
Muscarinic Nicotinic Central receptors
Cardiovascular
Bradycardia
Hypotension
Respiratory
Rhinorrhea
Bronchorrhea/spasm
Cough
Gastrointestinal
Increased salivation
Nausea/vomiting
Abdominal pain
Diarrhoea
Fecal incontinence
Genitourinary
Urinary incontinence
Ocular
Blurred vision/miosis
Increased lacrimation
Cardiovascular
Tachycardia
Hypertension
Musculoskeletal
Weakness
Fasciculations
Cramps
Paralysis
Anxiety
Restlessness
Ataxia
Convulsions
Insomnia
Dysarthria
Tremors
Coma
Absent reflexes
CS respiration
Resp. depression
Circulatory collapse


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

Skin decontamination 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.

Failure attributed 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
Electrophysiological
improvements(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