Treatment of Organophosphorus (OP) Poisoning

Background: Mechanism of Toxicity

Clinical Features (Reminder)

Treatment

1. General/Supportive Measures

• Remove the patient from the source of exposure
• Remove contaminated clothing and wash skin thoroughly with soap and water
• If ingested: gastric lavage (with water or dilute sodium bicarbonate solution)
• Maintain airway - suction secretions, administer oxygen
• Treat seizures with diazepam
• Avoid succinylcholine (prolonged neuromuscular blockade due to ChE inhibition), ester-type anesthetics, and morphine

2. Specific Antidotes

A. Atropine (Muscarinic Antagonist)

• Mechanism: Competitively blocks muscarinic receptors - counters excessive ACh at parasympathetic sites
• Dose:
  • Initial dose: 2-4 mg IV (adults), repeated every 5-10 minutes
  • In severe cases: up to 10-20 mg or more may be needed in the first hours
  • Continue until signs of atropinization appear:
    • Dry mouth and skin
    • Pupil dilation (mydriasis)
    • Tachycardia (pulse >70/min)
    • Flushing of skin
• Endpoint of atropinization: Drying of bronchial secretions (the most important endpoint). Pupil size and heart rate are poor indicators of adequate atropinization.
• Diagnosis test: Giving 2 mg atropine - in a normal person it causes marked atropinization; in OP poisoning, symptoms are relieved without signs of atropinization, confirming poisoning.
• Important: Cyanosis is NOT a contraindication to atropine; once adequate atropinization appears, the dose is adjusted to maintain it for at least 24 hours
• Atropine does NOT counteract nicotinic effects (muscle weakness, fasciculations)

B. Oximes - Pralidoxime (2-PAM, PAM-2)

• Mechanism: Reactivates phosphorylated acetylcholinesterase by breaking the OP-enzyme bond - restoring enzyme activity. It accelerates reactivation of the enzyme.
• Must be given EARLY - before "aging" (irreversible phosphorylation) occurs; aging happens within 24-48 hours (varies by compound)
• Dose: 1-2 g IV (adults), given as slow infusion; can repeat in 1-2 hours if needed, then 6-12 hourly for 24-48 hours
• Effective against both muscarinic and nicotinic effects (unlike atropine which only covers muscarinic)
• Ineffective in: Intermediate syndrome (does not respond to oximes or atropine)
• Contra-indicated in carbamate poisoning (may worsen it)

C. Benzodiazepines

• Diazepam IV for seizures and to reduce CNS excitability

3. Intermediate Syndrome

• Occurs 1-4 days after poisoning
• Features: Weakness of neck flexors, proximal limb muscles, cranial nerve palsies, acute respiratory paresis
• Due to prolonged cholinesterase inhibition and muscle necrosis
• Does NOT respond to oximes or atropine - supportive/ventilatory care only

4. Delayed Peripheral Neuropathy

• Occurs 1-5 weeks after exposure (especially parathion, malathion, trichlorfon)
• Paresthesia, pain, cramps in calves → ataxia, weakness, toe drop → ascending flaccid paresis (similar to Guillain-Barre syndrome)
• Reflexes diminished; may progress for 2-3 months with muscle wasting

Summary: Antidote Dosing at a Glance

Fatal Dose & Period (Reddy)

• Parathion: 80 mg IM or 175 mg orally
• Malathion/Diazinon: ~1 g orally
• Fatal period: Usually within 24 hours (untreated); up to 10 days in unsuccessfully treated cases
• Recovery: Complete recovery in ~10 days if treated early, unless hypoxic encephalopathy supervenes

Treatment of Opium (Opioid) Poisoning

Background

• Phenanthrene group: Morphine, Codeine, Thebaine (these are toxic)
• Benzyl-isoquinolines: Narcotine, Papaverine (non-narcotic)

• Natural: Morphine, Codeine
• Semisynthetic: Heroin, Pholcodeine, Hydrocodone, Hydromorphone, Oxymorphone
• Synthetic: Fentanyl, Methadone, Pethidine, Tramadol, Dextropropoxyphene, Diphenoxylate

Mechanism of Action

• Mu (μ) receptor: Supraspinal analgesia, euphoria, prolactin release; spinal analgesia, respiratory depression, dependence, GI dysmotility, miosis
• Kappa (κ) receptor: K1 - spinal analgesia and miosis; K2 - psychotomimesis and dysphoria; K3 - supraspinal analgesia

Clinical Features (Stages of Opium Poisoning)

Stage 1 - Excitement (usually brief/may be absent with large doses)

• Euphoria: elated mood, increased sense of wellbeing, talkativeness, freedom from anxiety
• Flushed face, restlessness, manic signs, hallucinations
• Seizures (especially in neonates and children)
• Rhabdomyolysis, hyperkalemia, acute respiratory failure (in severe cases)

Stage 2 - Stupor

• Giddiness, drowsiness, headache, nausea, vomiting
• Itching all over the body (due to histamine release)
• Pupils contracted (miosis)
• Conjunctival congestion, cyanosed face and lips
• Pulse and BP initially normal
• Uncontrolled desire to sleep

Stage 3 - Narcosis/Coma

• Unresponsiveness
• Decreased BP, feeble pulse
• Pin-point pupils (hallmark)
• Facial pallor, cold clammy skin, flaccid muscles
• Terminal: facial flush, gradual hypotension
• Death by respiratory failure

Classic Triad of Opium Poisoning: Pin-point pupils + Coma + Respiratory depression

Differential Diagnosis (Reddy)

Fatal Dose and Period

• Fatal dose: Morphine - 0.2 g (200 mg) orally in a non-tolerant adult; much lower in children
• Fatal period: Usually 6-12 hours; death occurs from respiratory failure

Treatment of Opium Poisoning (Reddy)

1. General/Supportive Measures

• Airway, Breathing, Circulation (ABC) - immediate priority
• Assisted ventilation/mechanical ventilator - respiratory depression is the main killer
• Maintain warm body temperature (patient is hypothermic)
• Gastric lavage with water (if ingested orally and patient is conscious or airway is protected)
• Activated charcoal - adsorbs remaining drug in GI tract

2. Specific Antidotes

A. Naloxone Hydrochloride (Opioid Antagonist) - DRUG OF CHOICE

• Mechanism: Competitive antagonist at all opioid receptors (mu, kappa, delta) - rapidly reverses respiratory depression, sedation, and miosis
• Route: Parenteral (IV preferred; IM/SC also used)
• Dose:
  • Adults: 0.4-1.2 mg IV, repeated as required
  • Children: 0.4 mg (or 0.01 mg/kg)
  • Total dose should not exceed 75 mg in adults
• Key points:
  • Short half-life (~30-90 min) - shorter than most opioids, so repeated doses or infusion may be needed
  • Patient must be monitored for re-narcotization after each dose
  • Precipitates acute withdrawal in opioid-dependent patients (not life-threatening)

B. Naltrexone (Oral Opioid Antagonist)

• Dose: 50 mg orally, repeated as required
• Longer-acting than naloxone; used in less acute settings or for maintenance

C. Physostigmine (Cholinesterase Inhibitor)

• Dose: 0.04 mg/kg IV route
• Used as adjunct; helps counteract CNS depression

3. Forced Diuresis

• Indicated in cases of rhabdomyolysis (especially after seizures or prolonged immobility)
• Alkalinize urine to prevent myoglobin precipitation in renal tubules

4. Treatment of Complications

Chronic Opium Poisoning

1. Restlessness, irritability, emaciation, disturbed sleep
2. Contracted pupils (sluggish reactive)
3. Marked constipation, nausea, anorexia
4. Decreased immune response (decreased immune cell counts, decreased macrophage proliferative capacity)
5. CNS: Dementia and/or mania, intellectual and moral deterioration
6. Memory loss, neurasthenia
7. Temporary impotence
8. Pigmentation around mouth and nostrils

Medicolegal Importance (Reddy)

1. Suicide - death is painless; hence considered an "ideal suicidal poison"
2. Homicide - uncommon (opioids are bitter in taste)
3. Euthanasia - morphine is the most commonly favored drug for causing painless death
4. Accidental poisoning - rare; mainly in children
5. Doping - used in racehorses
6. Addictive foods: Kasoomba (tea from poppy seeds), Bhujri (decoction of green poppy fruits), Halwa (sweet with poppy fruit juice)

Autopsy Findings

1. Deep cyanosis of nails, lips, palms, and soles
2. Intense congestion of all internal organs
3. Froth at mouth and nostrils

Treatment of Strychnine Poisoning

Source Plant: Strychnos Nux Vomica

• Toxic material: Leaves, fruit, and seeds contain active principles in increasing order (seeds most toxic)
• Active principles: Strychnine and Brucine

Mechanism of Action

Routes of Absorption

Signs and Symptoms of Poisoning

1. Muscle spasms and twitching, progressing to full convulsions
2. Opisthotonus - powerful extensor muscle spasm; hyperextension of head, trunk, and lower limbs (classic arched posture)
3. Trismus - lockjaw; also called Risus sardonicus (sardonic smile) due to facial muscle spasm
4. Mydriasis (dilated pupils), proptosis, blurred or diminished vision
5. Patient remains fully conscious between episodes of convulsions - a hallmark distinguishing strychnine from tetanus
6. Death due to respiratory failure (during a convulsive episode)

Key distinguishing feature: The patient is conscious and lucid between convulsive attacks - unlike tetanus, where there is no such lucid interval.

Differential Diagnosis (Reddy)

• Natural diseases: Tetanus, Rabies, Meningitis
• Poisons: Cocaine, Phencyclidine (PCP), Chlorinated hydrocarbons
• Others: Hysteria

Fatal Dose and Period

• Fatal dose: 50-100 mg strychnine orally; 1-3 g of Strychnos seeds
• Fatal period: Death typically occurs during a convulsive episode from respiratory failure, usually within a few hours

Treatment

1. Gastric Decontamination (with caution)

• Stomach wash (gastric lavage): Only in the absence of convulsions - do NOT attempt during a convulsive episode (risk of triggering a seizure by stimulation)
• Activated charcoal: If the patient presents within approximately 1 hour of consumption

2. Enhance Elimination

• Forced diuresis - to promote renal excretion of strychnine

3. Critical Nursing Measure - Minimize Stimulation

• Isolate patient in a dark, silent room - any sensory stimulus (sound, light, touch) can trigger a convulsion; this is a cornerstone of management

4. Aggressive Control of Convulsions (Most Important)

5. Airway and Ventilation

• Intubation and mechanical ventilation if necessary - especially if convulsions are prolonged or respiratory muscles are compromised

6. Metabolic Complications

• IV Sodium Bicarbonate if metabolic acidosis develops (from prolonged convulsions/lactic acidosis)

7. Management of Hyperthermia

• Try conventional cooling measures first
• If these fail: Muscle paralysis (reduces heat production) - succinylcholine initially, then aggressive benzodiazepine infusion for sedation
• Cold fluid lavage
• Dantrolene (reduces muscle contractility) if hyperthermia persists

Summary: Treatment Priorities at a Glance

Forensic Significance (Reddy)

• Homicide: Strychnine is the "choice of poison for homicide" though it does not fulfil all requirements of an ideal homicidal poison (violent convulsions are witnessed)
• Suicide: Consumption of rodenticide containing strychnine
• Some Ayurvedic formulations contain traces of strychnine or brucine

Treatment of Strychnine Poisoning

Mechanism (Quick Recap)

Treatment (in order of priority)

1. Dark, Quiet Room - Minimize All Stimulation

• Any light, sound, or touch can trigger a convulsion
• This is a cornerstone of management

2. Gastric Decontamination (only if convulsion-free)

• Gastric lavage - with caution, only in absence of convulsions
• Activated charcoal - if within ~1 hour of ingestion

3. Forced Diuresis

• Enhances renal elimination of strychnine

4. Aggressive Control of Convulsions (most important)

5. Airway & Ventilation

• Intubation + mechanical ventilation if prolonged convulsions or respiratory compromise

6. Metabolic Complications

• IV Sodium Bicarbonate for metabolic acidosis (lactic acidosis from convulsions)

7. Hyperthermia Management

• Conventional cooling first
• If refractory: muscle paralysis (succinylcholine) → aggressive benzodiazepine infusion
• Cold fluid lavage
• Dantrolene if hyperthermia persists

Key Clinical Feature

Treatment of Sulphuric Acid Poisoning

Sulphuric Acid (H₂SO₄) - Key Facts

• Also called Oil of Vitriol
• Pure form: heavy, odourless, colourless, non-fuming, oily, hygroscopic liquid with tendency to carbonize organic substances
• Commercial form: brown or dark in colour
• Causes superficial burns after just 1 second of contact; full-thickness burns after 30 seconds

Mechanism of Action

• Systemic acidosis
• Haemolysis
• Decreased cardiac output

Signs and Symptoms

Fatal Dose and Period

• Fatal dose: ~5 mL of concentrated sulphuric acid
• Fatal period: 12-24 hours in severe cases; some survive longer with complications

Treatment

⚠️ CONTRAINDICATIONS - NEVER DO THESE:

1. Do NOT induce vomiting - vomiting re-exposes oesophagus and mouth to acid; risk of aspiration and perforation
2. Do NOT perform gastric lavage - risk of perforation of the already-damaged stomach
3. Do NOT give sodium bicarbonate - the CO₂ produced by neutralization causes sudden gastric distension and may precipitate perforation

1. Dilution and Neutralization

• Give large quantities of water or milk immediately to dilute the acid
• Demulcents to coat and soothe the burnt mucosa:
  • Milk
  • Egg white (albumen)
  • Olive oil / coconut oil
  • Gruel (rice water)
• Alkalis to neutralize acid:
  • Milk of magnesia (magnesium hydroxide) - preferred
  • Chalk water (calcium carbonate suspension)
  • Soap water (sodium stearate)
  • Aluminium hydroxide gel
  • Lime water (dilute calcium hydroxide)
  • Avoid sodium bicarbonate (produces CO₂ gas → gastric distension → perforation risk)

2. Pain Relief

• Strong analgesics - morphine or pethidine IV for severe pain
• Appropriate sedation to reduce anxiety and distress

3. Treatment of Shock

• IV fluids - crystalloids/colloids to restore circulating volume
• Vasopressors if required
• Blood transfusion if haemolysis is significant

4. Airway Management

• Oxygen inhalation
• Watch for laryngeal/glottic oedema - may require urgent tracheostomy or endotracheal intubation
• Treat bronchospasm if inhaled fumes were involved

5. Treat Systemic Acidosis

• IV Sodium Bicarbonate (systemic, not oral) to correct metabolic acidosis
• Monitor blood gas and electrolytes

6. Antibiotics

• To prevent secondary infection of burnt and necrotic mucosa
• Cover for sepsis if perforation is suspected

7. Surgical Management

• Exploratory laparotomy if gastric perforation is suspected or confirmed
• Later: management of oesophageal strictures (a common late complication) by dilatation or reconstructive surgery

8. Specific Complications and Their Management

External (Skin/Eye) Exposure

• Skin: Immediately wash with large amounts of water for at least 15-20 minutes; remove contaminated clothing; apply magnesium oxide paste
• Eyes: Copious irrigation with water or saline for at least 15-20 minutes; urgent ophthalmology referral

Autopsy Findings

1. Brown/black corrosion burns on lips, chin, and neck (acid trail)
2. Mucous membranes of mouth, throat, oesophagus, and stomach charred and ulcerated
3. Stomach may show perforation and sloughing of wall
4. Viscera smell acidic
5. Teeth show chalky-white discolouration

Medicolegal Significance

• Commonly used in acid attacks (assault - disfigurement)
• Suicide by ingestion
• Homicide - rarely
• Acid-bath murder - used to destroy a body (famous cases in forensic history)

Treatment of Vitriolage (Acid Attack / Vitriol Throwing)

Definition

• Sulphuric acid (H₂SO₄ - Oil of Vitriol) - most common
• Nitric acid (HNO₃)
• Carbolic acid (phenol)
• Corrosive alkalis
• Juice of marking nut (Semecarpus anacardium)
• Juice of calotropis

Note: Sometimes old electric bulbs filled with acid are used as projectiles.

Pathology of Burns

• Burns are initially painless (nerve endings destroyed by acid)
• They are penetrating - acid devitalizes tissues and predisposes to infection
• Repair is slow; results in permanent scar tissue and contracture
• Coagulation necrosis occurs (crust formation)

Local Effects

1. Severe burning pain and corrosion of tissues with formation of brownish-black burned areas → permanent scarring
2. Blindness may result if eyes are involved
3. Extensive disfiguring injuries of the face
4. Death may occur from shock, toxaemia, or infection if an extensive area is involved
5. Slow repair and scar tissue formation with contracture

Treatment

1. Immediate Decontamination - FIRST AND MOST CRITICAL STEP

• Wash the affected parts immediately with large amounts of water - copious, continuous flushing for at least 15-20 minutes
• Then wash with soap solution or sodium/potassium carbonate solution - to help neutralize residual acid
• Remove all contaminated clothing while washing

2. Neutralization of Residual Acid

• Apply a thick paste of magnesium oxide or magnesium carbonate to the burnt skin surface - neutralizes remaining acid and soothes the wound

3. Wound Dressing

• Cover the raw surface with:
  • Tannic acid jelly, OR
  • Soframycin dressing, OR
  • Penicillin tulle gauze dressing
• These provide antimicrobial protection and promote healing

4. Eye Treatment (if eyes are involved)

• Wash eyes immediately with large amounts of water
• Irrigate with dilute sodium bicarbonate solution (5 g in 30 mL / 1 ounce of water) to neutralize acid
• Instil a few drops of castor oil or olive oil into the eye (demulcent, soothing)
• Treat corneal ulcers with:
  • Atropine ointment (cycloplegia - reduces pain from ciliary spasm)
  • Hydrocortisone (reduces inflammation)
  • Antibiotics (prevent secondary infection)
• Urgent ophthalmology referral

5. General/Supportive Treatment

• IV fluids - treat hypovolaemic shock from fluid loss through burns
• Strong analgesics (morphine/pethidine IV) for pain control
• Antibiotics systemically - to prevent sepsis from infected burn wounds
• Tetanus prophylaxis
• Nutritional support

6. Airway Management

• If acid fumes are inhaled - oxygen, bronchodilators
• Watch for laryngeal oedema - may need intubation or tracheostomy

7. Long-term / Reconstructive Management

• Skin grafting for extensive burns
• Scar revision surgery and plastic surgery for contractures and disfigurement
• Corneal transplant / keratoplasty if corneal damage leads to blindness
• Physiotherapy to prevent contracture deformity
• Psychological rehabilitation

Medicolegal Aspects (Reddy - BNS Sections)

• Blindness caused = grievous hurt under IPC/BNS
• Scar tissue formation = grievous hurt
• Vitriolage itself amounts to dangerous injury