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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
3
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
4
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.
5
Plant Poisonings
Datura, Argemone (Epidemic dropsy)
Plants with digitalis like effect Animal Toxins
Snake bites, scorpion bites
Agents responsible for acute Poisoning contd.
6
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
7
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
8
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
9
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
10
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
11
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
12
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
13
Sedative Hypnotic ToxidromeSedative Hypnotic Toxidrome
Features Drug Toxin Drug Treatment
Slurred speechConfusionStupor ComaApnoea
AnticonvulsantsAntipsychoticsBarbituratesBenzodiazepinesEthanolOpiates
NaloxoneFlumazenilUrinary alkalinization for Phenobarbital
14
Narcotic ToxidromeNarcotic Toxidrome
Features Drug Toxin Drug Treatment
Altered Mental StatusSlow shallow breathsMiosisBradycardiaHypotesionHypothermiaDecreased Bowel Sounds
DextromethorphanOpiatesPentazocinePropoxyphene
Naloxone
15
Extrapyramidal ToxidromeExtrapyramidal Toxidrome
Features Drug Toxin Drug Treatment
RigidityTremorOpisthotonusTrimusHyperreflexiaChoreoathetosis
HaloperidolPhenothiazinesRisperidoneOlanzapine
DiphenhydramineBenztropine
16
Serotonin ToxidromeSerotonin Toxidrome
Features Drug Toxin Drug Treatment
IrritabilityHyperreflexiaFlushing DiarrheaDiaphoresisFeverTrismusTremorMyclonus
FluoxetineParoxetineSertralineTrazodoneClomipramine
BenzodiazepinesWithdrawal of drugCyprohepatidine (?)
17
Solvent ToxidromeSolvent Toxidrome
Features Drug Toxin Drug TreatmentLethargyConfusionHeadacheRestlessnessIncoordinationDepersonalization
HydrocarbonsTolueneAcetoneNaphthaleneChlorinatedHydrocarbons
Withdrawal of toxinAvoid catecholamines
18
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
19
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.
20
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.
21
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.
22
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
23
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
24
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)
25
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.
26
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
27
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
28
Nicotinic (sympathetic)
Tachycardia
Mydriasis
Hypertension
Sweating
Nicotinic (N-M Jn) Muscular weakness
Paralysis
Fasciculation
29
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
30
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
31
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
33
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
34
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
35
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
36
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
37
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
39
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
40
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
42
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
43
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
44
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
45
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
46
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
48
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
50
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
51
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
52
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
53
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
54
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
55
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.
56
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.
57
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
58
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
59
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
60
61
62
Endoscopy
63
Treatment of Corrosive Poisoning
64
65
When to start feeding ?
66
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.
67
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.
68
Acute Methemoglobinemia
69
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
70
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
71
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
72
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)
73
Thankyou !Thankyou !
74
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
75
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
76
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.
77
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
78
79
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
80
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
81
82
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
83
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
84
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,,
85
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
86
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
87
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
88
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
89
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
91
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