2. PARACETAMOL POISONING
Most common OD in the west
overdose of acetaminophen has been recognized since
1966 to cause fatal and nonfatal hepatic necrosis
acetaminophen remains a major cause of overdose and
overdose-related liver failure and death in the United
States and many other countries
3. Acetaminophen is available in both immediate-release and sustained-release formulations
The therapeutic dose is 10 to 15 mg/kg per dose in children and 325 to 1000 mg per dose in adults, given every four to six hours.
maximum recommended daily dose of 80 mg/kg in children or 4 g in adults.
The toxic dose may vary among individuals according to baseline glutathione levels and other factors :
1)Toxicity is unlikely to result from a single dose of less than 150 mg/kg in a child or 7.5 to 10 g for an adult .
2)Toxicity is likely to occur with single ingestions greater than 250 mg/kg or those greater than 12 g over a 24-hour period.
3)Virtually all patients who ingest doses in excess of 350 mg/kg develop severe liver toxicity (defined as peak aspartate
aminotransferase [AST] or alanine aminotransferase [ALT] levels greater than 1000 IU/L) unless appropriately treated.
rapidly and completely absorbed from the gastrointestinal tract (duodenum)
Serum concentrations peak between one-half and two hours after an oral therapeutic dose
Peak serum concentrations are generally reached within four hours following overdose of immediate-release preparations
but may be delayed beyond four hours when drugs that delay gastric emptying (eg, opiates,
anticholinergic agents) .
Therapeutic serum concentrations range from 10 to 20 mcg/mL (65 to 130 micromol/L).
Elimination half-lives range from two to four hours for all acetaminophen preparations (delayed in extended release)
Half-lives greater than four hours have been noted in patients who develop hepatotoxicity
At therapeutic doses, 90 percent of acetaminophen is metabolized in the liver to sulfate and glucuronide conjugates via sulfotransferase (SULT)
and UDP-glucuronosyl transferases (UGT)
Conjugated metabolites are then excreted in the urine
2 percent is excreted in the urine unchanged.
The remaining acetaminophen is metabolized via oxidation by the hepatic cytochrome P450 (CYP2E1, CYP1A2, CYP3A4 subfamilies) mixed-
function oxidase pathway into a toxic, highly reactive, electrophilic intermediate N-acetyl-p-benzoquinoneimine (NAPQI)
NAPQI is rapidly conjugated with hepatic glutathione (GSH), forming nontoxic cysteine and mercaptate compounds that are excreted in the
At toxic doses the sulfation and glucuronidation pathways become saturated, and more acetaminophen is shunted to the cytochrome P450
enzymes and metabolized to NAPQI .
Following overdose glucuronidation and sulphation pathways are rapidly saturated -> increased metabolism to NAPQI (N-acetyl-P-
Glutathione is required to inactivate NAPQI and when levels depleted -> hepatocellular death takes place
NAPQI arylates and binds covalently to the cysteine groups on hepatic macromolecules, particularly mitochondrial proteins, forming NAPQI-
protein adducts. This process is irreversible.
7. MECHANISMS OF HEPATOCYTE INJURY
The formation of these adducts leads to oxidative hepatocyte injury, alteration of the mitochondrial ATP-synthase alpha-subunit,
and hepatocellular centrilobular necrosis
Toxic free radicals (eg, peroxynitrite) form nitrotyrosine adducts within the mitochondria .
Injury to the mitochondrial DNA and ATP-synthase causes cessation of ATP synthesis. Lipid peroxidation and membrane injury
may play a role in the progression of hepatocellular injury .
In addition, release of cytokines, apoptosis-inducing factor (AIF), endonuclease G (EndoG), and reactive nitrogen and oxygen
species from damaged mitochondria play a role in the spread of hepatic injury
Damage-associated molecular pattern (DAMP) products (eg, nuclear fragments, mitochondrial DNA) recruit inflammatory cells
via the innate immune system . This secondary injury occurs during stage II of clinical toxicity.
The centrilobular region (zone III) is preferentially involved because it is the area of greatest concentration of CYP2E1 and
therefore the site of maximal production of NAPQI
the role of chemokines (in particular C-C chemokine receptor type 2 [CCR ]-positive monocytes)
the activation of the inflammasome
the contribution of hepatic stellate cells and liver repair .
New models for studying the drug's toxicity include organoids and ex-vivo perfused human liver
8. CLINICAL FEATURES
overdose of > 10g or > 200mg/kg
doses of > 250mg/kg associated with massive hepatic necrosis and liver faillure
be aware of the late presenters (> 8 hours since OD and start NAC empirically)
Stage 1 (0-24hrs)
asymptomatic or GI upset only
Stage 2 (24-72 hrs)
resolution or nausea and vomiting
RUQ pain and tenderness
progressive elevation of transaminases, bilirubin, PT
Stage 3 (72-96 hrs)
hepatic failure (jaundice, coagulopathy, encephalopathy)
Stage 4 (4 days to 2 weeks)
death from hepatic failure
normalisation of LFT’s and complete resolution of hepatic architecture by 3 months
9. Underlying hepatic impairment
alcoholic liver disease
Microsomal enzyme induction
trimethoprim-sulfamethoxazole, opioids, and
zidovudine may potentiate
acetaminophen hepatotoxicity by competing for
chronic alcohol ingestion (CYP2E1)
Acute glutathione depletion states
acute illness with decreased nutrient intake
RISK FACTORS FOR TOXICITY
CLINICAL FACTORS THAT MAY INFLUENCE TOXICITY
Excessive intake of acetaminophen (most important)
Delay between acetaminophen ingestion and N-acetylcysteine (NAC) therapy
Excessive cytochrome P450 activity
Decreased capacity for glucuronidation or sulfation
Depletion of glutathione stores
CLD- not risk factor
Low cyt P450 activity
Elimination t1/2 is prolonged by 2-
LFTs / coags / lactate/ BSL
Signs of severe hepatotoxicity include plasma ALT and AST levels that often exceed 10,000
IU/Lprolongation of the PT/INR, hypoglycemia, lactic acidosis, and a total bilirubin concentration
above 4.0 mg/dL or 68 micromol/L .
Paractamol/ acetaminophen level
10-20 mcg/mL Therapeutic levels
Less than 150
mcg/mL 4 hours
Low risk of liver
Greater than 200
mcg/mL 4 hours
after ingestion Or
Greater than 50
mcg/mL 12 hours
toxicity and liver
paracetamol (APAP) levels:
-> compare to Australasian nomogram (modified version of Rumack-Matthews nomogram) –
to determine need for NAC rx
-> no role in chronic toxicity
-> treat if above threshold @ 4 hrs
-> a level of > 153mg/L is above treatment threshold regardless of time of ingestion
-> NAC must be given within 8 hours of OD (if level going to take longer
than 8 hours start NAC empirically)
transaminases: peak @ 72 hrs
PT: if >180 seconds on day 4 will need transplantation
renal failure (less than 2% population- hepatorenal synd)
metabolic acidosis = poor prognostic marker
A: may require intubation and intubation if polypharmacy overdose and unrousable
B: lung protective ventilation
C: volume resuscitation
D: dextrose for hypoglycaemia
fuliminant hepatic failure signs
signs of other drug toxicity
decrease absorption: activated charcoal if presented within 4 hours
(controversial as if NAC given then this is a benign OD)
N-acetyl cystine in D5W
(based on 4 hour level or empirically if > 8 hours since OD):
-> 150mg/kg LD
-> 50mg/kg over 4 hours
-> 100mg/kg over 16 hours
can be administered at any time of presentation (up to 72 hours post ingestion with some improvement in outcome)
can be administered orally but efficacy reduced by 40% if given with activated charcoal
provides a substrate of glutathione and acts as an alternative substrate for NAPQI metabolism via the cytochrome P450
watch for adverse effects: rash, bronchospasm, hypotension, angioedema (antihistamines helpful and also slowing of
14. Liver failure management
don’t correct coagulopathy unless bleeding (vitamin K IV, blood products)
arterial ammonia (aids in prognostication: absolute level and failure to fall)
reverse jugular venous saturation monitoring
ICP monitoring (controversial)
ventilate to normocapnia
thiopentone and indomethacin infusions (consult with liver unit)
renal failure management
MARS therapy: some benefit shown in paracetamol OD as a bridge to transplantation
15. Patients are at increased risk for developing acetaminophen-induced hepatotoxicity if they have any of the following
Ingestion of greater than 7.5 to 10 g of acetaminophen over 24 hours, or ingestion ofgreater than 4 g over 24 hours and an
increased susceptibility to hepatotoxicity (eg, chronic alcohol use, fasting, use of P450-inducing drugs
Abdominal pain or liver tenderness, nausea, vomiting, jaundice, or are ill appearing.
Supratherapeutic serum acetaminophen concentrations (greater than 20 mcg/mL, or 130 micromol/L) with or without ALT
Elevated ALT or AST concentration (≥50 U/L) on presentation. Patients with a history of RSTI of acetaminophen should be
considered to have acetaminophen-induced hepatotoxicity when aminotransferases are elevated, regardless of the measured
serum acetaminophen concentration.
Elevated acetaminophen-aminotransferase multiplication product on presentation. An elevated product predicts significant
hepatotoxicity independent of the time of ingestion.
Suspect hepatic failure
discuss early with transplantation team (develop liver
failure within 48 hours)
admit to medical/gastro unless requires ICU
will require psychiatric assessment if was an intentional overdose
Prognostication — can use the O’Grady criteria:
acidaemia (pH < 7.3)
renal impairment (creatinine > 300micromoles/L)
hepatic encephalopathy (grade III or IV)
PT > 100 seconds (INR > 6.5)
factor V level < 10%
MECHANISM OF ACTION
? protects the liver by maintaining and restoring glutathione levels or by acting as an alternate substrate for conjugation with -> detoxification of reactive metabolites.
IV or oral formulation
compatible with 5% dextrose
prevention of contrast nephropathy: 1200mg by slow push prior to scan and 48 hrs post investigation
o 150mg/kg in 200mL of D5W over 15 min
o 50mg/kg in 500mL of D5W over 4 hrs
o 100mg/kg in 1000mL of D5W over 16 hrs
21. These rat poisons have recently become a common means of self poisoning in Northern India ,
with a mortality rate of 60%.
National Poison Center data – in India, zinc phosphide, barium carbonate, and aluminum
phosphide remain the most common cause of household and agricultural rodenticide poisoning
Poisoning may be:
Modes of poisoning:
22. The most clinically helpful categorization of rodenticides utilizes the amount of poison that causes death in
50percent of patients following exposure (lethal doseor LD) and a corresponding "signal word"
Highly toxic – LD50: 0 to 50 mg/kg, signal word "Danger"
Toxic – LD50: 50 to 500 mg/kg, signal word "Warning"
Less toxic – LD: 500 to 5000 mg/kg, signal word "Caution“
The clinician is encouraged to contact a regional poison control
center to assist with identification and interpretation of rodenticide labeling.
24. When the poison is not known, clinical features can help with identification and guide treatment as follows :
●Cardiac arrhythmias, refractory shock, or cardiac arrest – Cardiovascular toxicity suggests the followingrodenticides
which can be further classified by when signs appear after exposure:
•Early: Zinc or aluminum phosphide, white (yellow) phosphorus, or barium carbonate
•Late: Arsenic, thallium, sodium monofluoroacetate (SMFA), or fluoroacetamide
●Seizures – SMFA, fluoroacetamide, tetramine, or arsenic
●Muscle rigidity, opisthotonus, trismus, and facial grimacing (risus sardonicus) – Strychnine
●Cranial neuropathy, lethargy, or coma – Thallium, arsenic, alpha-chloralose, bromethalin, Vacor (pyriminil,N-3-pyridylmethyl-N-p-nitrophenylurea,
Bruising or bleeding – Anticoagulants (warfarin, superwarfarin compounds)
Asymptomatic patients — Asymptomatic patients may still develop serious toxicity. The clinician should beespecially cautious when managing patients
with intentional ingestions.
Known poison — Management depends upon the agent as follows:
25. ANTI COAGULANTS:
-After ingestion of lethal dose , it effectively blocks the vit-k cycle , resulting in inability to produce
essential blood clotting factors mainly factors II and VII.
massive toxic doses of 4-hydroxycoumarin cause damage to tiny blood vessels , increasing their
permeability , causing diffuse Internal Bleeding.
-These effects are gradual , developing over several days.
-This is the preferred type of rat bait , as the antidote is available i.e, Vit-K.
26. Do not have onset symptoms , which might manifest days later.
Low Blood pressure
Confusion , Lethargy , Altered mental status
With Warfarin: Pin point Purplish red spots
29. If no coagulopathy is found in the setting of an anti- coagulant exposure ,prophylactic treatment with
Vit-K is absolutely contraindicated.
If a coagulopathy is documented , Vit-K therapy is suggested.
Patients who present with life threatening haemorrhage , in addition to Vit-K, Prothrombin complex
conc. and/or fresh frozen plasma may be needed to reverse anti coagulation.
On ingestion in toxic doses these affect calcium and
phosphate homeostasis causing hypercalcemia.
On accumulation in stomach , kidney , lungs , blood vessels and heart
are all calcified/mineralised.
-It has a synergistic effect with anticoagulant , thereby increasing the
chances of death and decrease in the time involved.
Nausea , Vomiting , Anorexia , Fatigue , Itching and Weakness.
Acute Intoxication: Polyneuropathy.
Chronic Intoxication: Extreme depression , Apathy ,
Confusion , Fatigue.
31. CLINICAL SIGNS
Develop within 18 – 36 hr of ingestion.
Depression & anorexia.
Passing large amounts of urine & excessive thirst.
GI smooth M excitability decrease results into constipation.
• Gastric evacuation followed by administration of activated charcoal@ 2-8 g/kg in water slurry.
• Prednisolone@ 1-2 mg /kg.
• Fluid therapy with NSS.
• Furosemide@5mg/kg i/v followed by 3mg/kg tid.
• Calcitonin@4-10 IU/kg s/c to reduce serum calcium levels.
33. WITH BARIUM: Nausea , Weakness , Abdominal pain.
WITH THALLIUM: Acute GI distress , Anorexia , Myalgias , Painful neuropathy and hair loss.
WITH STRYCHNINE: Anxiety , Generalized seizure like appearance without loss of consciousness ,
Muscle twitching , Facial grimacing.
WITH ARSENIC: Nausea , Vomiting , Bloody diarrhoea and garlic taste in mouth.
34. Pertinent ancillary testing eg,
continuous electrocardiogram monitoring for barium carbonate, phosphide compounds, and phosphorus compounds;
serum lactate and blood gas analysis for SMFA/ fluoroacetamide;
serum calcium in patients possibly exposed to elemental phosphorus;
Serum potassium following barium carbonate exposure or phosphide compound ingestion;
Glucose monitoring after Vacor ingestion).
Observation for a minimum of six hours after exposure
If the patient has any symptoms of poisoning orabnormal findings on ancillary testing, then hospitalization is warranted.
35. All asymptomatic patients with exposure to an unknown rodenticide warrant the following
●12-lead ECG and continuous monitoring
●Plain radiographs of the chest and abdomen
●Complete blood count
●Prothrombin time and international normalized ratio (PT and INR) and partial thromboplastin
●Venous or arterial blood gas
●Serum calcium and phosphorus
●Blood urea nitrogen (BUN) and serum creatinine
● Liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and
36. ●QTc prolongation on ECG – Arsenic, white (yellow) phosphorus, sodium monofluoroacetate (SMFA), orfluoroacetamide
●Hypocalcemia – White (yellow) phosphorus, SMFA, or fluoroacetamide
●Lactic acidosis – SMFA or fluoroacetamide
●Hyperphosphatemia – White (yellow) phosphorus
●Hypokalemia – Zinc or aluminum phosphide or barium carbonate
●Radiopaque substance on abdominal radiograph – Arsenic, thallium, or barium carbonate
●Elevated liver enzymes, BUN, or creatinine – Thallium, white (yellow) phosphorus, arsenic, or zinc oraluminum phosphide
●Hyperglycemia with ketoacidosis – Vacor
● Elevated PT and INR – Anticoagulant
What to expect??
37. asymptomatic patients
- within one hour of ingestion should undergo gastric lavage followed by
administration of activated charcoal with appropriate precautions to protect the
airway and prevent aspiration as needed.
- ACTIVATED CHARCOAL is used as soon as possible to prevent further systemic absorption
of ingested toxin.
- Gastric lavage should not be performed inpatients who have already vomited
Symptomatic and unstable
Secure airway and place IV lines in Haemodynamically unstable patients.
Inducing Vomiting is likely only with in 1-2hrs after ingestion.
39. Commonly found in powder, pellet, or tablet form, the metallic phosphides,zinc and
aluminum phosphide, are both low-cost and highly toxic rodenticides
Common means of self poisoning in northern India.
Inhalation of phosphine gas, produced when aluminum or zinc phosphide is exposed to
moisture in stored grain represents the most common form of exposure.
Oral exposures from deliberate suicidal ingestions with aluminum phosphide are common in
northern India .
Mortality rate of
Direct ingestion of ≥500 mg of phosphides usuallyresults in death.
MECHANISM OF ACTION: • Both the compounds react with gastric acid to form
phosphine, a potent pulmonary and GIT toxicant.
ALUMINIUM & ZINC PHOSPHIDE
40. Zinc phosphide:
- It is a single dose fast acting rodenticide.
-Death occurs with in 1-3days after ingestion.
Acid in the stomach reacts with the phosphide to yield toxic phosphine gas which is a potent pulmonary
WITH ZINC PHOSPHIDE:
-Via Inhalation : Cough, Nausea ,Vomiting,Headache Fatigue.
-Via Ingestion: Abdominal pain , Cough , Diarrhoea , Dizziness , Shortness of breath , Unconsciousness ,
Nausea , Vomiting Uncoordinated movements.
41. Clinical manifestations and diagnosis – Phosphide toxicity occurs rapidly, typically within 30 minutes of exposure.
Clinical findings of zinc phosphide ingestion consist of the following :
•Gastrointestinal (GI) irritation marked by nausea, vomiting, hematemesis, and retrosternal chest and abdominal
•Shock with refractory hypotension caused by direct cardiac toxicity
•Cardiac arrhythmias, including bradycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter and
•Hemorrhagic pulmonary edema with tachypnea, cough, acute respiratory distress syndrome, and respiratory
Less common features include hepatotoxicity, intravascular hemolysis with methemoglobinemia and/or renal
42. • For phosphide ingestion, supportive care is the mainstay of treatment and consists of the following
•Provide supplemental oxygen and ventilation as needed and dictated by the degree of respiratory compromise. Tracheal
intubation may be performed in standard fashion.
•Provide fluid resuscitation with rapid infusions of isotonic normal saline to replace obvious fluid lossesand to treat
•Treat hypoglycemia and correct hypokalemia and hypomagnesemia as indicated.
•Treat cardiogenic shock with vasoactive medications as needed in patients unresponsive to isotonic fluid resuscitation.
Manage atrial and ventricular arrhythmias according to Advanced Cardiac Life Support and Pediatric Life Support guidelines
Other therapies – Individual case reports describe the use of N-acetylcysteine (NAC) as an antioxidantand the antianginal
agent trimetazidine to maintain oxidative phosphorylation
Detection of phosphine in the exhaled air/stomach aspirate.
Using a silver nitrate impregnated strip or a specific phosphine detector tube is diagnostic.
Gas chromatography is most sensitive indicator.
Directed at correcting electrolyte abnormalities & treating complications.
No specific antidote.
Ca gluconate & Na bicarbonate to neutralize stomach acidity.
Early gastric lavage, often with vegetable oil to reduce the release of phosphine.
44. ZINC PHOSPHIDE:
-Supportive therapy remains the only available form as there is no specific antidote.
-Gastric lavage with vegetable oil to reduce the release of toxic phosphine.
-Patients with severe respiratory compromise require endotracheal intubation for ventilatory support.
-Severe haemolysis from phosphine gas may require exchange transfusion of RBCs.
47. Source & characteristics
Greyish green tablet, metallic taste, garlicky odour
Solid fumigant pesticide, insecticide and rodenticide
Widely used as grain preservative (phosphite & hypophosphite of aluminium are non-
toxic residues left in the grains)
Celphos, Alphos, Quickphos, Phostoxin, Phosphotex
Each tablet is 3g, can liberate 1g of phosphine (PH3) when come in contact with moisture
HCl in stomach accelerate the convertion
48. Mode of poisoning & fatal dose
Fatal dose: 0.5 g (1-3 tablets)
Fatal period: 1-4 hours. Majority die within 24 hours
Fatal dose: inhale phosphine 400-600 ppm
Fatal period: 1-4 hours.
Majority die within 24 hours
49. Absorption & Excretion Ingest
Absorbed from GI tract by simple diffusion
Then, some ALP metabolised in liver & phosphine is slowly released
Phosphine is oxidised slowly to oxyacids
Excreted in urine as hypophosphine Inhale
Rapidly absorbed from the lungs
Excreted unchanged form through lungs
55. Postmortem appearances
Garlic-like odour at the mouth & nostrils & gastric content
Blood-stained froth in the mouth & nostrils
Mucous membrane of the lower part of esophagus, stomach & duodenum are
Decreasing congestion of GI in small intestine
Lungs, liver, spleen, kidneys & brain are congested
Centrizonal haemorrhagic necrosis of the liver may be seen
Stomach: congestion, edema, leucocytic infiltration, sloughing of gastric mucosa
Lung: congestion, edema, desquamation of respiratory epithelium, thickened alveoli,
Kidneys: congestion, necrosis, tubular degeneration and regeneration
Adrenals: congestion, haemorrhage, necrosis, area of lipid depletion in cortex
Heart: congestion, edema, fragmentation of fibres, focal necrosis, leucocytic infiltration
Brain: congestion, edema
57. Medicolegal importance
Suicidal in rural area of india
Accidental poisoning by farmer who sleep near godown; leaking phosphine
from godown is possible
Accidental poisoning by children which mistakenly ingest the tablets
58. Chemical tests
5 ml of gastric aspirate + 15 ml of water are put in a flask and the mouth
is covered with a filter paper impregnated with 0.1 N silver nitrate. Flask is
heated at 50C for 15-20 minutes. Filter paper turns black if phosphine
A piece of filter paper impregnated with 0.1 N silver nitrate solution is
used in the form of mask through which the patient breathes for 5-10
minutes. Filter paper turns black if phosphine present. (POSITIVE only
when >6 g is ingested)
No specific antidote
Primarily supportive care
Early arrival, resuscitation, diagnosis, intensive monitoring and supportive treatment
Gastric lavage with potassium permanganate (1:10000)
No activated charcoal
Sorbitol solution1-2 ml/kg may be used as cathartic
In vitro trials of vegetable oils and liquid paraffin prevents conversion to phosphine
Critical care support – haemodynamic instability, airway mx, inotrope support, invasive lines,
60. MgSO4 as anti-peroxidant effect has been used (dec effects of phosphine)
Hyperglycemia on admission is a significant poor prognostic indicator
Acidosis (target pH >7.1 and HCO3 18-20 mmol/lt) – soda bicarb
Refractory acidosis - continuous veno venous hemofiltration
Role of NAC (conflicting studies)
GIK drip (restore Ca influx and inc myocardial contractility)
Hco3 <18 mmol/lt
Sbp < 90 mmHg
Altered mental status
Role of insulin euglycemia in outcome of AlP
Role of ECMO in ALP poisoning patients
Organophosphate (OP) compounds are a diverse group of chemicals used in
bothdomestic and industrial settings. Many phosphates are potent nerve agents,
functioning by inhibiting the action of acetylcholinesterase(AChE) in nerve cells. They
are one of the most common cause of poisoning worldwide , and frequently
intentionally used in suicides in agricultural areas.
68. Mechanism of action
Op inhibit acetylcholine esterase
enzyme at nerve endings by
That results in increase in
acetylcholine at receptor sites.
69. Clinical features in poisoning
Muscarinic features Nicotinic features CNS features
D iarrhoea Muscle weakness Fatigue
U rination Muscle fasciculation confusion
M iosis Muscle fasciculation unconsciousness
E mesis Hypertension Ataxia
L acrimation Tachycardia Resp. depression
H/o Ingestion of poison
Characteristic clinical features
petroleum or garlic like odour
If doubt exists a trial of atropine (0.01 to 0.02 mg/kg) may be employed
The absence of signs abd symptoms of anticholinergic effects following atropine
challenge strongly supports the diagnosis.
1 . Butyrylcholinesterase activity in plasma
2 . Acetylcholinesterase in whole blood
I . CXR – Evaluate pulmonary oedema
II. ECG – Cardiac arrhythmias
III. ABG & Electrolytes
75. Different phases of toxicity
1. Acute cholinergic crisis
2. Intermediate syndrome –
major cause of morbidity
3. Delayed neuropathy
77. Mechanism of IMS
Excess acetylcholine at NMJ
causes downregulation of
nicotinic receptors – muscle
Inadequate oxime therapy
Respiratory failure without
Failure of postsynaptic
acetylcholine release , and
oxidative stress-related myopathy
79. Monitoring for IMS
C/F typically occur within 24 to 96 hours and persists for 4
to 18 days
Affecting conscious patients without cholinergic signs, and
Involve the muscles of respiration, proximal limb muscles,
neck flexors and muscles innervated by motor cranial nerves
Assess flexor neck strength regularly (head lift and hold
Weakness is sign of peripheral respiratory failure
80. Delayed neuropathy
Organophosphate induced delayed neuropathy (OPIDN)
1. 2-3 weeks after large dose
2. Peripheral/ distal neuropathy (proximal sparing)
3. Due to inhibition of neuropathy target esterases (NTE)
4. Recovery can take upto 12 months
Chronic organophosphate induced neuropsychiatric disorder
82. Management of organophosphate
1. Check airway , breathing , circulation
2. Monitor vitals and cardiac rhythm
3. Look for signs and symptoms
4. Obtain IV access
5. Remove contaminated clothes & wash the skin thoroughly
with soap & water.
83. 6. Atropine intravenously as soon as possible for symptomatic
7. Pralidoxime (Reactivator)
8. Gastric lavage once the patient is stabilized & within 2 hours of
ingestion with activated charcoal (50 g in 200 ml )
9. Maintenance atropine infusion
Start with 1.8 – 3.0 mg stat iv bolus
After 3 – 5 min check
1. Bronchorrea & bronchospasm
2. Bradycardia ( < 60)
4. Excessive sweating
If not corrected double the dose of atropine every 5 min until signs of atropinisation.
85. Signs of Atropinization
1. Clear chest on auscultation with no wheeze
2. Heart rate > 80 beats/min
3. Pupils no longer pinpoint
4. Dry axillae
5. Systolic blood pressure > 80 mmHg
86. Maintenance infusion
D5 + 10-20 % of the total initial dose of atropine on an
hourly basis. (after stabilization)
Stop atropine infusion if features of toxicity
loading dose @ 30 mg/kg IV over 10 – 20 mins
Followed by continuous infusion of 8-10 mg/kg/hr.
continue oxime infusion until atropine has not been needed
for 12-24 h and patient extubated.