management of acute poisoning anish final

Management of Unknown Acute Poisoning

Dr. ANISH JOSHIMD, FNB CRITICAL CARE,

INDIAN DIPLOMA IN CRITICAL CARE,

FELLOW OF COLLEGE OF CHEST PHYSICIANS,

FELLOW OF COLLEGE OF CRITICAL CARE MEDICINE

2

Agents commonly responsible for acute Poisoning

Pesticides:Organophosphates, Carbamates,

Organochlorines, Synthetic pyrethroids, Rodenticides, Herbicides, Fumigants, Unlabelled powders sold by hawkers

Household chemicalsAcids, Bleach,Grain preservatives, Drain

cleaners,Naphthalene balls, CuSO4, Cosmetics

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Agents responsible for acute Poisoning contd.

Industrial Chemicals

Irritant gases like Chlorine and Ammonia, Acid fumes like Oleum, MethHb forming agents such as Nitrobenzene, Solvents like acetonitrile, Intermediates released during the manufacture of Dyes and Pharmaceuticals

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Pharmaceuticals

Sedatives and hypnotics (mostly benzo-diazepines) either alone or in combination with alcohol, phenobarbital, Chlorquine, antidepressants, drugs used in treatment of major psychotic disorders like schizophrenia, OTCs, antihistaminics, Mixed ingestions

Agents responsible for acute PoisoningAgents responsible for acute Poisoning contd.contd.

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Plant Poisonings

Datura, Argemone (Epidemic dropsy)

Plants with digitalis like effect Animal Toxins

Snake bites, scorpion bites

Agents responsible for acute Poisoning contd.

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4 situations

1. History of ingestion(mostly), poison is known and treatment is known

2. History of ingestion, poison is known but the physician is not very confident about the treatment

3. History of ingestion but poison is unknown

4. ? Poisoning e.g pt is unconscious

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Situation 1 – does not need any discussion

Situation 2 – Ask the Poison Center

Tel: + 91 - 79 - 2755 35 94 / 95 (10 am – 5.30 pm), Monday to Friday

At other times – see website www.inchem.org

Situation 1 & 2Situation 1 & 2

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Situation 3 and 4

1. First attend to the patient then poison

Resuscitate the patient without contaminating yourself

2. Be patient with the relatives and insist on seeing the empty container or a leaflet

3. Location and occupation of the patient can be a pointer to the poison

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Management Guidelines

If the patient is unconscious and poisoning is doubtful then look for other causes such as Trauma or Metabolic causes ( Poisoning and trauma may co-exist)

Symptom complexes or Toxidromes may help

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Gastrointestinal decontamination

Induction of emesis, Syrup of Ipecac not available & its role is being questioned in countries where it is available

Gastric lavage is the only way to remove unabsorbed poison, but it needs to be with care, aspiration pneumonitis common, should not be done with ingestions of corrosive substances and hydrocarbon ingestions

What is a Toxidrome?

Several clinically recognizable features, s/s, phenomena or characteristics which often occur together, so that presence of one feature alerts the physician to the others

Narrows the differential diagnosis to a specific class of poisons

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Toxidrome Features Drugs/Toxins Drug Treatment

“DUMBELS” D -DiarrhoeaU- Urinary frequency,

M- miosis,

B - bradycardia, bronchorrhoea bronchoconstriction,

E - emesis,

L - lacrimation

S – salivation

OrganophosphatesCarbamatesPhysostigminePilocarpine

Atropine

Oximes for Organophosphates

The Cholinergic ToxidromeThe Cholinergic Toxidrome

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The Anticholinergic ToxidromeThe Anticholinergic Toxidrome

Toxidrome Features Drug Toxin Drug Treatment

Hot as HareDry as a boneRed as a beet Mad as a hatter

Altered mental statusSedationMydriasisTachycardiaFeverDry skinDry mucous membranesDecreased bowel sounds FlushingUrinary Retention

AntihistaminicsAtropineBaclofenBenztropineDaturaTCAPhenothiazinesScopolamine

For life threatening events use Physostigmine*Not indicated for TCA as it may worsen conduction disturbances

*not available in India

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Sedative Hypnotic ToxidromeSedative Hypnotic Toxidrome

Features Drug Toxin Drug Treatment

Slurred speechConfusionStupor ComaApnoea

AnticonvulsantsAntipsychoticsBarbituratesBenzodiazepinesEthanolOpiates

NaloxoneFlumazenilUrinary alkalinization for Phenobarbital

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Narcotic ToxidromeNarcotic Toxidrome

Features Drug Toxin Drug Treatment

Altered Mental StatusSlow shallow breathsMiosisBradycardiaHypotesionHypothermiaDecreased Bowel Sounds

DextromethorphanOpiatesPentazocinePropoxyphene

Naloxone

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Extrapyramidal ToxidromeExtrapyramidal Toxidrome

Features Drug Toxin Drug Treatment

RigidityTremorOpisthotonusTrimusHyperreflexiaChoreoathetosis

HaloperidolPhenothiazinesRisperidoneOlanzapine

DiphenhydramineBenztropine

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Serotonin ToxidromeSerotonin Toxidrome

Features Drug Toxin Drug Treatment

IrritabilityHyperreflexiaFlushing DiarrheaDiaphoresisFeverTrismusTremorMyclonus

FluoxetineParoxetineSertralineTrazodoneClomipramine

BenzodiazepinesWithdrawal of drugCyprohepatidine (?)

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Solvent ToxidromeSolvent Toxidrome

Features Drug Toxin Drug TreatmentLethargyConfusionHeadacheRestlessnessIncoordinationDepersonalization

HydrocarbonsTolueneAcetoneNaphthaleneChlorinatedHydrocarbons

Withdrawal of toxinAvoid catecholamines

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EpileptogenicEpileptogenic

Features Drug Toxin Drug Treatment

TremorsHyperreflexiaTonic clonic seizuresHyperthermiaMay mimic stimulant patterns

Organochlorine pesticides like Endosulfan, LindaneIsoniazidCamphorStrychninePhencylidineCocaineXanthines

Antiseizure medicationsPyridoxine for IsoniazidAvoid phenytoin for theophyllineInduced seizures

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Hallucinogenic ToxidromeHallucinogenic Toxidrome

Features Drug Toxin Drug Treatment

HallucinationsPsychosisPanicFeverMydriasisHyperthermiaSynesthesia*

AmphetaminesCannabinoidsCocaineLSDPhencyclidine(May present with miosis)

Benzodiazepines

* Synesthesia :One sensory experience described in terms of * Synesthesia :One sensory experience described in terms of another sensory experience.another sensory experience.

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Limitations of diagnosis based on toxidromes

Toxidromes are most clinically useful when the patient has been exposed to a single drug.

Many toxidromes have several overlapping features.

For example, anticholinergic findings are highly similar to sympathomimetic findings, with one exception being the effects on sweat glands: anticholinergic agents produce warm, flushed dry skin, while sympathomimetic produce diaphoresis.

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Limitations of diagnosis based on toxidromes

Toxidrome findings may also be affected by individual variability, comorbid conditions, and co-ingestants.

For example, tachycardia associated with sympathomimetic or anticholinergic toxidromes may be absent in a patient who is concurrently taking ᵝ blockers.

When multiple drugs have been ingested, conflicting clinical effects may negate each other and cloud the clinical picture.

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Pesticide Poisoning

Commonest cause of Self-poisoning or Deliberate self-harm (DSH)

Accidental poisoning : may occur in children Occupational poisoning: In farmers during

spraying or pesticide formulatorsRoutes of exposure:

Most pesticides can be absorbed by all routes including dermal route and inhalation route, though toxicity and mortality are highest when ingested for self-harm as usually persons take a large amount

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Insecticides

Organophosphates e.g.malathion, chlorpyriphos, monocrotophos, dimethoate, phorate, quinalphos, ethion, Fenthion

Carbamates: Propoxur, Carbaryl Organochlorines: DDT, BHC,

Lindane, Endosulfan Synthetic pyrethroids: Cypermethrin,

Deltamethrin, Fenvalerate Neonicotinoids: Imidacloprid

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Organophosphates

Some are also used nerve agents for terrorist attacks

Sarin gas was released in the Tokyo subway system by the Aum Shinrikyo Cult, creating more than 5,000 victims and causing 12 deaths. (1995)

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Organophosphorus pesticides inhibit the enzyme Organophosphorus pesticides inhibit the enzyme

acetylcholinesteraseacetylcholinesterase in synapses and on RBC membranes, in synapses and on RBC membranes,

and and butyrylcholinesterasebutyrylcholinesterase in plasma. in plasma. Although acute butyrylcholinesterase inhibition does Although acute butyrylcholinesterase inhibition does

not seem to cause clinical features, not seem to cause clinical features, acetylcholinesteraseacetylcholinesterase

inhibition results in accumulation of acetylcholine and inhibition results in accumulation of acetylcholine and

overstimulation of acetylcholine receptors in synapses of the overstimulation of acetylcholine receptors in synapses of the

ANS, CNS, and N-M junctions. ANS, CNS, and N-M junctions.

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NN

Autonomic Nervous SystemAutonomic Nervous System Somatic Central Somatic Central

ParasympatheticParasympathetic Sympathetic Sympathetic

NN NN NN

ACAChh ACAChh ACAChhACAChh

ACAChh

MM

MM

ACAChh ACAChh

AA AA

EpinephrineEpinephrine NorepinephrineNorepinephrine

NN

ACAChh

Sweat GlandsSweat Glands

GlandsGlandsBladderBladder

GutGutHeartHeart

HeartHeartBlood PressureBlood Pressure Neuromuscular Neuromuscular

JunctionJunction

BrainBrain

AutonomicAutonomicGangliaGanglia

End End OrganOrgan

MM

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Acute Cholinergic Crisis

Clinical features depend on the type of receptors stimulated by acetylcholine and their location

Muscarinic receptors (parasympathetic): diarrhoea, urinary frequency, miosis, bradycardia, bronchorrhoea and bronchoconstriction, emesis, lacrimation, salivation (DUMBELS), hypotension & cardiac arrhythmias

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Nicotinic (sympathetic)

Tachycardia

Mydriasis

Hypertension

Sweating

Nicotinic (N-M Jn) Muscular weakness

Paralysis

Fasciculation

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Acute Cholinergic Crisis

Tacchycardia can also be caused by hypovolaemia, Tacchycardia can also be caused by hypovolaemia, hypoxia, previous doses of atropine, and alcohol hypoxia, previous doses of atropine, and alcohol

withdrawalwithdrawal

Nicotinic & Muscarinic (CNS)Nicotinic & Muscarinic (CNS) ConfusionConfusion AgitationAgitation ComaComa Respiratory failureRespiratory failure

Result of Result of centrally or peripherally mediated centrally or peripherally mediated mechanisms. mechanisms. Occurs during the acute cholinergic crisis (type I Occurs during the acute cholinergic crisis (type I paralysis) or during an apparent recovery phase paralysis) or during an apparent recovery phase (intermediate syndrome, or type II paralysis). (intermediate syndrome, or type II paralysis). Weakness of neck flexors Weakness of neck flexors is an early sign of is an early sign of significant muscle weakness.significant muscle weakness.

Respiratory failure in OP poisoningRespiratory failure in OP poisoning

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Causes of High Case Fatality

High toxicity Difficulty in transporting patients over long

distances from rural areas Lack of treatment facilities at PHC & even

district hospitals Lack of training in management of pesticide

poisoning

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Diagnosis

Ask the relatives. Clinical picture, smell of pesticides or solvents Typical s/s When in doubt quantification of butyrylcholinesterase

or acetylcholinesterase is helpful. Cholinesterase ≤ 80% of the lower reference range is

probably indicative. In very severe poisonings, may be zero

Source: Eddleston et al;Lancet online August, 2007Source: Eddleston et al;Lancet online August, 200732

Variable onset: Most patients develop severe toxicity within six hours. Patients remaining asymptomatic for 12 hours after ingestion are unlikely to develop major clinical toxicity

Exceptions exist with some highly lipophilic organophosphorus compounds (most importantly fenthion), which produce only subtle cholinergic features initially then progressive muscle weakness, including respiratory failure requiring intubation

Source: Managing acute organophosphorus pesticide poisoning. Darren M Roberts, Source: Managing acute organophosphorus pesticide poisoning. Darren M Roberts, Cynthia K Aaron; BMJ,2007Cynthia K Aaron; BMJ,2007

Diagnosis

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Principles of Treatment

ABC, Oxygen Muscarinic antagonist (Atropine) Acetylcholinesterase reactivator (Oxime) Gastric decontamination only after

patient has been fully resuscitated and stabilized

Careful observation for changing atropine needs, respiratory function and recurrence of cholinergic crisis

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Initial Stabilization Medical emergency Start two I/V lines. Give I/V saline to keep SBP ≥ 80

mm of Hg Patient should be placed in left lateral position with

neck extended Watch out for convulsions and give I/V diazepam Record a baseline GCS

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Gastric lavage

Gastric lavage is useful if done within 1-2 hours First aspirate and then do a lavage with 200-300

ml of tap water Comatosed patients should be intubated prior

to lavage with a cuffed endotracheal tube Do not carry out lavage in an unwilling

conscious patient

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Skin Decontamination

If there is suspicion of dermal exposure, remove all clothes and wash the skin thoroughly with soap and plenty of warm water

Give special attention to skin folds, hair, nails and areas like axillae and groins

Use adequate personal protection like gloves and apron

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Antimuscarinic agents

Atropine Before giving atropine, record pulse rate, BP, pupil

size, presence of sweat and auscultatory findings Give 1-3 mg bolus of atropine depending on

severity and then loading dose of PAM After 5 minutes of atropine, check all parameters

again and if no improvement has taken place double the dose of atropine

Continue to review every 5 minutes and doubling doses of atropine

Once the patient is stable start an infusion of atropine with 10-20% of the total dose needed to stabilize the patient38

Antimuscarinic agents

Target end-points Target end-points ::

•Clear chest on auscultation with no wheezeClear chest on auscultation with no wheeze

•HR ≥ 80 per minuteHR ≥ 80 per minute

•Pupils no longer pinpointPupils no longer pinpoint

•Dry axillaeDry axillae

•SBP ≥ 80 mm HgSBP ≥ 80 mm Hg

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Aim of Atropine Therapy:

• No need to aim for a heart rate of 120-140/min.No need to aim for a heart rate of 120-140/min.

• Tachycardia can be caused by hypoxia, agitation, Tachycardia can be caused by hypoxia, agitation, alcohol withdrawal, pneumonia, hypovolemia and fast alcohol withdrawal, pneumonia, hypovolemia and fast oxime administration & are not a C/I for atropineoxime administration & are not a C/I for atropine

• Glycopyrrolate: Glycopyrrolate: In patients with atropine toxicity, but In patients with atropine toxicity, but it it does not counteract CNS effects of OPsdoes not counteract CNS effects of OPs

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Glycopyrrolate

• Similar outcomes using continuous infusion.Similar outcomes using continuous infusion.

• Ampoules of 7.5 mg can be added to 200 ml of saline Ampoules of 7.5 mg can be added to 200 ml of saline and infusion can be titrated to drying of secretions. and infusion can be titrated to drying of secretions. Atropine can be added as a bolus if heart rate goes below Atropine can be added as a bolus if heart rate goes below 60/min.60/min.

• It may be used where the secretions are difficult to It may be used where the secretions are difficult to control.control.

• Or when it is difficult to differentiate altered level of Or when it is difficult to differentiate altered level of consciousness due to atropine toxicity or relapse of OP consciousness due to atropine toxicity or relapse of OP poisoningpoisoning41

Why Oximes have been shown to be ineffective in some studies ?

Reasons could be Insufficient dose or duration High dose of poison and rapid reinhibition of

reactivated enzyme Ageing of inhibited AChE Poor affinity for the particular OP-AChE complex

Many patients in the trials presented late and had taken dimethyl pesticides

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Pralidoxime in the blood might required to be higher to antagonise the toxic effects of many pesticides.

Thus a bolus-loading infusion followed by a maintenance infusion might be the best regimen.

On this basis, the WHO has proposed that patients be given about 30 mg/kg pralidoxime salt as a loading dose, followed by an infusion of at least 8 mg/kg/h (in a 50 kg south Asian patient this is roughly equivalent to 1–2 g bolus followed by 0·5 g/h).

Dose of Oximes

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Oximes

• Pralidoxime is the only oxime available in India.Pralidoxime is the only oxime available in India.

• Dose: Give 2gm I/V over 20-30 minutes and then an Dose: Give 2gm I/V over 20-30 minutes and then an infusion of 0.5-1gm/hour till atropine is not needed infusion of 0.5-1gm/hour till atropine is not needed for 12-24 hours and the patient has been extubated.for 12-24 hours and the patient has been extubated.

• Treatment for poisoning with dimethyl pesticides Treatment for poisoning with dimethyl pesticides must be started much earlier than for other diethyl must be started much earlier than for other diethyl pesticidespesticides

• Rapid infusion may cause vomiting, tachycardia and Rapid infusion may cause vomiting, tachycardia and diastolic hypertensiondiastolic hypertension

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Benzodiazepines

• Patients poisoned with OP frequently develop agitated Patients poisoned with OP frequently develop agitated delirium. delirium.

•Cause: Pesticide itself, atropine toxicity, hypoxia, Cause: Pesticide itself, atropine toxicity, hypoxia, alcohol, and medical complications.alcohol, and medical complications.

• Diazepam Diazepam is first line of treatment for seizures with OP is first line of treatment for seizures with OP poisoning though seizures are uncommon in well poisoning though seizures are uncommon in well oxygenated patientsoxygenated patients

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Carbamate Pesticides

Commonest is Baygon which is used as a household pesticide

Clinical picture similar to OP poisoning but CNS toxicity is less

Plasma and RBC cholinesterase may be depressed for short time but quickly recover

Prognosis good

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Carbamate Pesticides

Atropine, Role of PAM is not clear Complications mostly due to aspiration

pneumonitis (while doing gastric lavage). Many carbamate formulations are made in

petroleum product base. Pulmonary oedema and poor oxygenation may not respond to Atropine and such cases have to be managed as cases of ARDS

Carbamates used for agricultural purpose such as Carbofuran, Aldicarb and Methomyl are highly toxic47

Organochlorine pesticides

Examples are DDT, BHC, Lindane, Endosulfan DDT and BHC already discontinued except for

public health programs Endosulfan is one of the most commonly used

agricultural pesticides Patient will present with convulsions No lab test available for diagnosis Treat with Diazepam, Phenobarbital or other

anticonvulsants

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Fumigants: Aluminium phosphide (AlP):

It is available as 3 gm tablets known as Celphos, Alphos, Quickphos

It is used for storage of wheat On coming in contact with moist air or

gastric contents, releases Phosphine (PH3) gas

It is highly toxic and even ½ tablet can be fatal

There is no antidote49

Aluminium phosphide

Signs and Symptoms: Epigastric pain, retrosternal burning, vomitus

smells of decaying fish Severe hypotension or shock is the cardinal

feature & is often unresponsive to vasopressors Cardiac arrhythmias and metabolic acidosis Liver damage, Renal failure and ARDS may

develop after 24-48 hours Patient remains conscious till the end

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Though there are not many published reports, but administration of coconut oil (about 200 ml) has been reported to prevent release of phosphine gas. Role of gastric lavage is not clear

Give I/V fluids and vasopressors like dopamine There is no antidote After giving this first aid, shift the patient to an ICU This is one poisoning where quick first aid can

make a difference

Aluminium phosphideAluminium phosphideAluminium phosphide

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Ethylene dibromide (EDB)

Sold as a liquid in an ampoule Used for grain storage Causes hepatic and renal damage Initially patient may present with

vomiting and drowsiness, second day pt. may look better, but next day s/s of hepatic damage and anuria develop

Treatment symptomatic, no antidote, high fatality

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Rodenticides

Types:

1. Single dose : Zinc phosphide, Thallium, Red squill, Sodium monofluroacetate, Barium salts like carbonate, hydroxide and chloride

2. Multiple dose: Warfarins and Superwarfarins

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Zinc phosphide

It is greyish powder, smells of decaying fish Toxicity is similar to ALP but it is slower in

onset as release of phosphine is slow S/S are nausea, vomiting, shock, oliguria,

metabolic acidosis, pulmonary oedema, hepatotoxicity, ECG changes, convulsions, coma

No specific antidote, treatment is supportive and symptomatic

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Barium salts

Interfere with Na-K pump and cause paralysis of muscles

Barium carbonate can cause toxicity at a dose of 0.5 gm and Barium chloride is toxic in a dose of 1-10 gm.

S/S repeated vomiting, loose motions and abdominal pain

Tightness of muscles of face and neck, muscle tremors, difficulty in breathing

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Convulsions and cardiac arrhythmias Wide complex tachyarrhythmias including

VPCs, VT & VF Perioral paraesthesias which may spread

to other parts of body Ascending quadriparesis Hypokalaemia is common

Barium salts s/s contd.

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Gastric lavage followed by instillation of magnesium sulphate to form insoluble barium sulphate

Do not give mag sulphate by I/V route as ppt of barium sulphate may cause renal failure

Monitor arrhythmias and adequately treat hypokalaemia

Rx.

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Warfarins and Superwarfarins

They are coumarin derivatives and are used as anticoagulants

Inhibiting vitamin K dependent clotting factors II, VII, IX and X causing ↑ PT

Superwarfarins like bromadiolone, brodifacoum, difenacoum and diaphacinone are more potent and have a long duration of action

Bleeding may occur as petechial hemorrhages, haematuria, and occult blood in stools

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Toxicity is monitored by serial measurements of PT

Effect is usually seen after 48 hours and for most ingestions no treatment is required

Vitamin K1 is given by I/V route if PT is prolonged 10 mg upto 5 times a day (Do not give K3 or K4)

FFP / BT

Warfarins and Superwarfarins

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Corrosive PoisoningCorrosive Poisoning

• An average home contains a dozen different cleaning An average home contains a dozen different cleaning products. products. • Responsible for a large number of accidental and Responsible for a large number of accidental and intentional poisoningsintentional poisonings• Three types:Three types:

ACIDACIDALKALIALKALIOXIDIZING AGENTSOXIDIZING AGENTS

• > 100-150 ml is massive poisoning> 100-150 ml is massive poisoning

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Endoscopy

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Treatment of Corrosive Poisoning

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When to start feeding ?

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Poisoning with Sedative /Hypnotic drugs

Can be easily detected by urine drug screens Relatively safe drugs unless ingested with other

sedatives like alcohol or TCAs The elderly are more sensitive to the CNS

depressant effect and those suffering from COPD are more susceptible to respiratory effects.

Paradoxical reactions of agitation, aggression, hallucinations and combativeness may uncommonly occur; children are more susceptible.

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Treatment of Benzodiazepine Overdose:

Close observation and supportive care  Secure airway and adequate ventilation Flumazenil is a specific antidote, but is very short

acting. Should not be routinely used. Flumazenil may precipitate seizures in case TCA are

also taken with BZD Induction of acute withdrawal in those suffering

benzodiazepine dependence may also trigger seizures or pulmonary aspiration.

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Acute Methemoglobinemia

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Clinical Presentation

• Methemoglobin is an abnormal hemoglobin Methemoglobin is an abnormal hemoglobin • Usual reduced Ferrous state (Fe2Usual reduced Ferrous state (Fe2++) of the heme ) of the heme

iron is oxidized to Ferric form (Fe3iron is oxidized to Ferric form (Fe3++))• Deeply cyanosed yet completely asymptomatic Deeply cyanosed yet completely asymptomatic

at Meth-Hb conc. less than 10-15%. at Meth-Hb conc. less than 10-15%. • At higher concentrations, signs and symptoms At higher concentrations, signs and symptoms

of anoxia appearof anoxia appear

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Clinical Presentation

Meth-Hb levelsMeth-Hb levels Signs and SymptomsSigns and Symptoms20-30%20-30% Headache, fatigue, nauseaHeadache, fatigue, nausea30-45%30-45% DOE, lethargy & tachycardiaDOE, lethargy & tachycardia50-70%50-70% Arrhythmias, coma, Arrhythmias, coma,

seizures, resp. distress,seizures, resp. distress,lactic acidosislactic acidosis

>70%>70% Cardiovascular collapse,Cardiovascular collapse,DeathDeath

Anemic patients have symptoms at lower meth-Hb Anemic patients have symptoms at lower meth-Hb levelslevels

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Treatment

-Supportive: OSupportive: O22, decontamination of skin, , decontamination of skin, - Antidote : Methylene blue Antidote : Methylene blue if Meth-Hb levels are if Meth-Hb levels are ≥ 30% or patient is showing s/s of anoxia≥ 30% or patient is showing s/s of anoxiaDose: Dose: 1mg/kg body wt of 1% solution slowly over 1mg/kg body wt of 1% solution slowly over a period of 5 minutesa period of 5 minutes. Repeat after 1 hour if . Repeat after 1 hour if patient is still symptomatic. Some chemicals may patient is still symptomatic. Some chemicals may need many doses but need many doses but do not exceed 7 mg/kgdo not exceed 7 mg/kg

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Role of Intensivist

All poisoning requires intensive care atleast for initial time period

Multiorgan involvement & Multimodality treatment

Real time critical decisions Cordination with other superspecialities (if

required)

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Thankyou !Thankyou !

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Paracetamol (Lethal dose:7.5-10 gm)

Mechanism of toxicity

At therapeutic doses, 90% of acetaminophen is converted to non-toxic glucuronide and sulfate conjugates and 5% is excreted in the urine unchanged.

The other 5% is oxidized in the liver by P450 enzymes to NAPQI(N-acetyl-p-benzoquinoneimine). At therapeutic amounts glutathione binds with NAPQI to form a non-toxic conjugate

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In overdose, glucuronide and sulfate conjugation becomes saturated and an increased proportion of NAPQI is formed. Glutathione levels are depleted.

NAPQI remains in its toxic form in the liver. This can cause hepatocellular damage

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Four phases

PHASE 1 (0.5 to 24 hours): Few s/s: malaise, anorexia, nausea, vomiting, pallor

PHASE 2 (24 to 72 hours): Right upper quadrant pain may appear indicating hepatic damage with

associated raised hepatic transaminases. INR increases. Renal function may begin to deteriorate

PHASE 3 (72 to 96 hours): Continuing hepatic centrilobular necrosis with associated coagulation defects,

hypoglycemia, metabolic acidosis, and jaundice. Renal failure and cardiac complications frequently occur. Hepatic encephalopathy and death may ensue.

PHASE 4 (4 days to 2 week): If phase 3 is survived complete resolution of hepatic and renal function is

usual.

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Treatment

Decontamination with activated charcoal is effective within 2 hours

Rapid measurement of plasma acetaminophen (paracetamol) level is necessary.

N-acetylcysteine is a life-saving antidote, and while its efficacy declines after approximately eight hours of the acetaminophen (paracetamol) ingestion, it should be administered to all patients with a potentially toxic overdose, regardless of time

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Antidote

N-acetylcysteine:

Administer: 150 mg/kg in 200 mL diluent IV D5 or NS over 15 minutes

Followed by 50 mg/kg in 500 mL diluent IV over 4 hours

Followed by100 mg/kg in 1,000 mL diluent IV over 16 hours

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Antidote Endpoint

At the end of the infusion regimen the patient’s hepatic transaminases, INR and S.creat. should be determined. If these are normal, or normalizing, further N-acetylcysteine is not required.

If not, the infusion must continue at a rate of 100 mg/kg in 1,000 mL diluent over 16 hours, until hepatic transaminase levels and INR decline and renal function improves.

Supportive care

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Chloroquine – acutely toxic drug

Many cases with chloroquine ingestion Dramatic toxicologic syndrome GI upset followed by cardiotoxicity manifested

as hypotension, vasodilatation, ECG abnormalities particularly QRS widening and cardiovascular collapse

Acute ingestions of 5 gm or more may be fatal

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Chloroquine (contd.)

Life saving treatment regimen for acute chloroquine intoxication

Epinephrine infusion which begins at a rate of 0.25 ug/kg per minute, rapid-sequence intubation, mechanical ventilation, diazepam 2 mg/kg, and immediate GI decontamination

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Examples of toxidromes

Sedative/hypnotic: coma, decreased reflexes, hypotension, hypothermia, dilated or small pupils

examples: sedatives, barbiturates Tricyclic antidepressants: initially agitated

then coma, resp., dilated pupils, QT interval prolongation, conduction defects, hyperreflexia, convulsions,,

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Organophosphorus pesticides

Most are agricultural pesticides, highly toxic, absorbed by all routes including skin

Signs and symptoms typical, often patient needs ventilatory support for days

High doses of atropine needed, dose determined by clinical signs mainly drying of secretions

Dose of PAM still not definite, some recommend continuous infusion

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Organophosphorus pesticides (contd.)

Plasma and RBC cholinesterase good markers for diagnostic purpose, no prognostic value

Some patients may develop intermediate syndrome after 2-3 days characterized by weakness of neck flexors & proximal limb muscles, cranial nerve palsy and paralysis of respiratory muscles, needs good ventilatory and general support, prognosis good

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Organophosphorus pesticides (contd.)

OPIDN (organophosphate induced delayed neuropathy) may occur in few cases, takes long time to recover

Prognosis of OP poisoning is good and patients make a complete recovery if treatment is not delayed

Some Ops like Chlorpyrifos have a very long effect and may need hospitalization for weeks

Other common OPs are Dimethoate, Monocrotophos and Phorate

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Carbamate Pesticides

Commonest is Baygon which is used as a household pesticide

Clinical picture similar to OP poisoning but CNS toxicity is less

Plasma and RBC cholinesterase may be depressed for short time but quickly recover

Prognosis good

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Carbamate Pesticides (contd.)

Complications mostly due to aspiration pneumonitis (while doing gastric lavage)

Atropine is the only recommended treatment but PAM does not seem to do any harm

Carbamates used for agricultural purpose such as Carbofuran, Aldicarb and Methomyl are highly toxic

90

Organochlorine pesticides

Examples are DDT, BHC, Lindane, Endosulfan Endosulfan is the most commonly used

agricultural pesticide Patient will present with convulsions No lab test available for diagnosis Treat with Diazepam, Phenobarbital or other

anticonvulsants

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Fumigants: Aluminium phosphide (AlP): known as

Celphos, highly toxic, high fatality, patient presents with shock, cardiac arrhythmias, severe metabolic acidosis, later on renal failure and liver damage, ARDS

Treatment is supportive, treat metabolic acidosis, shock and arrhythmias

Role of Magnesium sulfate to treat arrhythmias is controversial

92

Fumigants (contd.)

Ethylene dibromide (EDB): sold as a liquid in an ampoule, used for grain storage, causes hepatic and renal damage

Initially patient may present with vomiting and drowsiness, second day pt. may look better, but next day s/s of hepatic damage and anuria develop

Treatment symptomatic, no antidote, high fatality