COMMON SPECIFIC POISONINGS

Some common poisonings in Indian children are as follows:

Hydrocarbon (Kerosene) poisoning: Hydrocarbon poisoning is the commonest cause of accidental poison­ing and poison-related deaths in pre-school Indian children.

Mechanism: Risk as well as manifestations of hydrocarbon poisoning depends on their volatility and viscosity. For toxicity considerations, hydrocarbons may be broadly divided into two groups:

a. Low viscosity-high volatile Aliphatic compounds, e.g. Kerosene and other petroleum distillates, turpentine, lubricants, etc., which carry high risk of aspiration;

b. High viscosity-less volatile Aromatic compounds, e.g. organic solvents, paints/paints remover, nail polish removers, etc., which are predominantly neurotoxic or hepatotoxic.

Some hydrocarbons, used as vehicle for pesticides or insecticides, have additional risks due to additives, e.g. organophosphorus compounds.

Kerosene, the commonest hydrocarbon associated with poisoning in India has been discussed in Ch 16.9.2. Corrosive poisoning due to ingestion of household items containing acids or alkali, e.g. soaps and toilet cleaners are common in toddlers due to their inquisitive and exploratory nature.

Mechanism: Corrosives cause tissue injury on contact by a chemical reaction. Factors that determine the extent of injury include pH of the agent, quantity ingested and duration of contact with tissues, apart from other factors.

After exposure, corrosives initiate immediate inflam­matory reactions at the site of contact, followed by tissue necrosis, leading to ulceration, sloughing and sometimes perforation, usually within 24-48 hours. While alkali ingestion leads to liquefaction necrosis, acids cause coagulation necrosis. In survivors, lesions heal over 2-3 weeks by fibrosis, leading to cicatrization and stricture formation.

Clinically, these cases present in three stages:

a. Immediate burning pain and swelling of the perioral region and oral cavity with drooling of saliva, dys­phagia and epigastric pain, followed by,

b. Secondary complication due to internal tissue damage, e.g. hematemesis, esophagitis, mediastinitis or gut perforation.

c. After few weeks, child may present with dysphagia due to secondary strictures.

Immediate perioral reactions are more prominent in acid ingestion due to highly irritant nature of these chemicals. External lesions are usually mild in caustic or alkali poisoning, but often associated with more severe internal lesions and complications due to liquefaction necrosis.

Evaluation depends on the severity of disease and aims to detect internal complications. A baseline chest X-ray, including lateral film, is indicated in all cases, with neck and abdominal radiographs in selected cases. All cases with ingestion of large volume or concentrated products must undergo flexible endoscopy after 6-12 hours to detect internal lesions. Endoscopy is not needed in asymptomatic or mild cases and contraindicated in those with suspected perforation.

Management rests on the severity of event, time- lapsed since exposure and possibility of complications. Asymptomatic patient with history of minimal ingestion and no oropharyngeal burns may be discharged after few hours of observation.

Symptomatic cases with large volume ingestion require hospitalization, local decontamination by mouth wash, etc. and endoscopic examination at 12-24 hours to detect internal injury. Seriously sick cases may need intensive care.

Important steps in management include: (a) removal of residual chemical by generous wash, (b) protection of airway, including urgent endotracheal intubation in cases with respiratory and airway edema, (c) hemodynamic correction, and (d) supportive therapy for pain, nutrition, etc.

Attempts to dilute the ingested corrosive by encour­aging oral water/milk intake are futile and use of emetics, neutralizing agents (acid for alkali poisoning and vice versa).

except after ingestion of chemicals with systemic toxicity, e.g. zinc chloride, or mixture with other poisonous substance, e.g. organophosphorus compounds.

Role of steroids to decrease airway edema or prevent stricture formation is controversial. Surgical gastrostomy may be required in cases with severe internal burns on endoscopy.

All cases with severe poisoning need repeat bron­choscopy after 3-4 weeks to detect the stricture formation and dilation if required.

Organophosphorus (OP) poisoning: OP poisoning is a major cause of intentional poisoning in adolescents, though most cases are accidental. OP compounds are ingredients of various insecticides/pesticides for domestic/agricultural use. and poisoning may develop after ingestion, inhalation or even contact with skin/ mucus membranes, e.g. eyes.

Mechanism is the irreversible inhibition of enzyme cholinesterase - responsible for degradation of acetyl­choline at post-synaptic sites, which leads to accumulation of acetylcholine and parasympathetic hyperactivity.

Clinical presentation depends on the type of individual OP compound as well as dose and route of exposure. Most cases manifest within few hours of ingestion with headache, weakness, blurred vision, giddiness and vomiting; followed by development of three well-defined symptom complexes with variable severity:

a. CNS effects, e.g. headache, giddiness, restlessness, ataxia, confusion, seizures, coma, etc.

b. Nicotinic effects, e.g. muscular fasciculations and weakness and even respiratory paralysis.

c. Muscarinic effects, e.g. Diaphoresis, Urinary inconti­nence, Miosis, Bradycardia/hypotension, Broncho­spasm with/without pulmonary edema, Emesis, Eacrimation and Salivation (Pnemonics - DUMBBELS). While muscarinic effects are prominent in early

stages and with low-dose exposure, high-dose exposure predominantly presents with neurological and nicotinic effects. Hyperglycemia without ketoacidosis is common.

Diagnosis is largely based on history and clinical presentation with cholinergic toxidrome. It may be confirmed by low plasma pseudocholinesterase and/or RBC acetylcholinesterase enzyme levels, but severity of poisoning may not correlates with these levels.

Management: All patients with suspected OP exposure, even if asymptomatic, should be hospitalized as manifestations may develop even after 24-48 hours. Important steps in management include:

a. Immediate gastric lavage and skin/eye decontami­nation by irrigation with copious amount of water;

b. Appropriate resuscitative and supportive measures. Sedation, Tranquilizers and Theophylline should not be used in OP poisoning.

c. Specific antidotes, e.g. atropine and PAM, only in symptomatic cases.

Atropine is a physiological antidote for muscarinic effects of OP compounds with little effect on neural/ nicotinic effects and should be started as soon as possible with a dose of IV 0.05-0.1 mg/kg, repeated every 10 minutes till full dilatation of pupils.

PAM (Pralidoxime) is the chemical antidote that dephosphorylates OP-cholinesterase complex to free some enzyme, provided given within 24-48 hours of exposure as IV 25-50 mg/kg over 10 minutes, followed by 5-10 mg 12-hourly (or 5 mg/kg/hour infusion). All patients should be observed for 48-72 hours after apparent recovery, as recurrence of respiratory or pro­ximal muscular weakness is common. Some cases may develop OP-induced late peripheral neuropathy with predominantly distal muscle weakness for many months.

Opioids (Narcotics) poisoning: Opioids are natural or synthetic compounds with morphine-like activity, commonly used as pain-relievers in terminally sick persons or as drug abuse. Some common opioids include morphine, pethidine, codeine, heroin, pentazocine, etc. Mechanism: On exposure via oral or IV route, these compounds interact with specific opiate receptors distributed throughout the body (specially brain), to produce central as well autonomic nervous system effects.

Clinically, Opioid toxicity presents with a characteristic triad of—(a) CNS depression, (b) respiratory depression, and (c) severe miosis, i.e. Pin-point pupils; along with other features, e.g. hypotension/bradycardia, constipation/ paralytic ileus, vomiting, urinary retention and pruritis/ bronchospasm due to histamine release. Aspiration, due to impaired gag reflex is common. Infants may present with seizures before development of CNS depression.

Management depends on severity and includes—

(a) gut decontamination with gastric lavage and acti­vated charcoal, (b) supportive care, and (c) specific antidote-IV Naloxone 0.01-0.1 mg/kg, which may be repeated as required or given as continuous infusion.

Opioid withdrawal, seen in chronic opioid dependence is uncommon in children and characterized by rest- lessness/insomnia, muscular twitching/seizures, excessive rhinorrhea/lacrimation/sweating and pupillary dilatation. Severe withdrawal may necessitate administration of a less potent opioid, e.g. methadone, followed by gradual tapering over 5-10 days.

Dhatura (Belladonna) poisoning: Accidental ingestion of the Dhatura seeds (Jimson weed) is not uncommon in Indian villages, though some cases may occur due to intentional ingestion or inhalation of Dhatura-smoke for hallucinogenic effect in adolescents.

Mechanism: Dhatura plant contains many belladonna alkaloids, e.g. atropine, scopolamine, hyoscyamine, etc.,

all strong anticholinergic agents with pronounced action of muscarinic receptors. Nicotinic receptors are less affected. Some of these alkaloids cross blood-brain barrier to cause neurological effects. Lethal dose for these alkaloids is ~4 mg.

Clinically, belladonna poisoning manifests within 30 minutes of exposure with:

a. Peripheral anti-muscarinic effects, e.g. excessive thirst ( salivation), dry-red eyes (^lacrimation), and dry/ flushed skin (^sweating). Severe cases may develop hyperpyrexia due to diminished sweating, diplopia due to symmetrical mydriasis, urinary retention, paralytic ileus and tachycardia/arrhythmia with mild hypertension.

b. Central anti-muscarinic effects begin with neuroexcitatory features, e.g. agitation, hallucinations, delirium, ataxia, tremors and seizures, followed by neurodepression after 1-2 hours, e.g. drowsiness or coma.

A case of Dhatura poisoning is often described as - hot as a hare, blind as a bat, dry as a bone, red as a beet and mad as a hen.

Management of Dhatura poisoning includes:

• Immediate gut decontamination by gastric lavage and activated charcoal,

• Supportive therapy for hyperpyrexia, dehydration, urinary retention, ileus, seizures, etc.,

• Specific antidote - Physostigmine (0.02 mg/kg IV over 5-10 min), which needs to be repeated every 20 minutes. Antidote therapy is indicated only in severe neurological or cardiovascular toxicity.

Forced diuresis, urinary pH manipulation or dialysis have no role in belladonna poisoning.

Barbiturate poisoning: Phenobarbitone poisoning is more likely in epileptic children or those with other epileptic family member, due to easy availability of drug in the household.

Mechanism: Barbiturates act on Gamma aminobutyric acid (GABA) receptors to: (a) to reduce neuronal excitability, (b) block Na+/K⁺ channels, and (c) inhibit release of Calcium-dependent neurotransmitters. Serum phenobarbitone levels gt; 10 mg/dl are potentially lethal. Clinically, these cases presents with dose-dependent severity of—(a) CNS depression, e.g. drowsiness or coma, (b) respiratory depression, and (c) hypotension and shock with/without renal failure. Bullous skin lesions, mimicking Steven-Johnson syndrome are seen in some cases.

Treatment is supportive with no specific antidote. Important measures include:

• Immediate gut decontamination by gastric lavage and activated charcoal;

• Forced alkaline diuresis with mannitol and NaHCO₃.

• Treatment of shock, ventilatory assistance and other supportive measures.

• Refractory cases may benefit from peritoneal/hemo- dialysis or hemoperfusion.

Naphthalene poisoning: Naphthalene balls are commonly used as moth-repellents and accidental ingestion is common in children. However, severe and even fatal toxicity has been reported in infants following prolonged dermal contact or inhalation exposure. Each ball usually weighs ~0.5-3.5 gm, while a dose as less as 0.25 gm may be fatal in infants/toddlers.

Mechanism: Naphthalene itself is an inert substance and toxic effects are caused by its body metabolite -naphthol, which leads to acute hemolysis and methemoglobinemia, specially in children with G6PD deficiency. Fatty meals before or after naphthalene ingestion increase severity of poisoning.

Clinically, most cases are asymptomatic, except GIT upsets, e.g. vomiting, abdominal pain and diarrhea for few days. However, heavy ingestion or co-existing G6PD deficiency may lead to acute hemolytic reaction after 24-48 hours with a triad of—(a) progressive anemia,

(b) jaundice, and (c) dark-color urine; sometimes leading to acute renal failure.

Management: While gastric lavage is enough in most cases, large-quantity ingestion requires:

a. Immediate gastric lavage followed by active charcoal with cathartic administration,

b. Close monitoring for signs of hemolysis,

c. Treatment of severe hemolysis with plain/exchange blood transfusions and forced alkaline diuresis to prevent precipitation of hemoglobin in renal tubules.

d. IV methylene blue therapy (1-2 mg/kg slow infusion) in cases with persistent hypoxemia or methemoglobin levels gt;30%.

e. Exchange transfusion must be considered in cases with severe toxicity or those not responding to methylene blue therapy.

Phenothiazine poisoning: Phenothiazine poisoning, once very common, is rare at present due to declining use of these drugs as antiemetics. However, use of these agents, e.g. chlorpromazine, prochlorperazine or trifluoperazine in adult psychiatric disorders may cause accidental ingestion by household children.

Clinically, Phenothiazine toxicity may be dose-inde­pendent (idiosyncratic) or dose-dependent. Idiosyncratic reactions may develop even after therapeutic dose, pre­senting with extrapyramidal toxidrome, e.g. torticollis, oculogyric crisis, rigid twisting of body and speech/ swallowing difficulties.

Although frightening in appearance, these cases respond dramatically to a single dose of IV/PO Diphen­hydramine (1 mg/kg) or sedative, e.g. diazepam/pro- methazine. Dose-dependent toxicity presents with high

fever and neuro-excitation, e.g. agitation/delirium, seizures followed by coma, arrhythmia and shock. Miosis is common.

Some cases may develop Neuroleptic malignant syndrome—a potentially fatal state with hyperpyrexia, coma, extrapyramidal rigidity and circulatory instability. A simple urine test (Add 10 drops of Tinc. FeCl₃ in acidified urine sample gt; reddish-purple color indicates presence of phenothiazines in urine) may be used for bedside diagnosis.

Management of dose-dependent toxicity includes:

(a) gut decontamination with gastric lavage and cathartics, and (b) supportive therapy for arrhythmia, shock, seizures, hyperthermia, etc.

Paracetamol poisoning: Although paracetamol is the safest antipyretic in therapeutic doses, a dose gt;140 mg/ kg is potentially toxic. Young children are relatively more tolerant than adults to paracetamol overdosage.

Mechanism: Paracetamol toxicity is mediated by its intermediate hepatotoxic metabolite - N-acetyl-p-benzo- quinoeimine (NAPQI), which is rapidly deactivated by conjugation with glutathione. Paracetamol overdose leads to excess glutathione utilization and depletion, enabling free metabolite to cause hepatocellular damage. Clinically, hepatotoxicity is the hallmark of paracetamol overdose and untreated course may be broadly divided into four stages:

a. Acute stage (1-24 hours) with nausea/vomiting, malaise, pallor and diaphoresis.

b. Silent stage (24-48 hours) with apparent recovery except mild tender hepatomegaly, abnormal liver function tests and oliguria.

c. Stage of maximum liver damage (48-96 hours) with reappearance of vomiting, progressive jaundice and peak liver function abnormalities. However, fulminant hepatic failure and death is rare in children (lt;1%). Some cases may develop acute renal failure.

d. Stage of resolution (4-14 days) with progressive and usually complete resolution of liver pathology in survivors.

Paracetamol toxicity is severe, if—(a) Plasma drug levels exceed 200, 100, 50 mg/dl at 4, 8 and 12 hours respectively,(b) Serum bilirubin or aspartate transaminase levels exceed 4 mg/dl or 1000 IU respectively, and (c) Prolonged prothrombin time at any stage.

Management includes:

a. Immediate gastric lavage followed by activated charcoal administration, and

b. N-acetylcysteine (NAC)—a precursor for glutathione synthesis, is the specific antidote for paracetamol poisoning that prevents hepatotoxicity by replenishing glutathione stores to inactivate NAPQI. It should be given as IV infusion 200 mg/kg (in 200-500 ml DW 5%) over 4 hours, followed by 100 mg/kg over next 16 hours. Maintenance dose of 100-200 mg/kg over another 16 hours may be repeated once again, if required.

Oral NAC, though not as effective may be used if IV preparation is not available, given as 140 mg/kg loading dose gt; 70 mg/kg 4 hourly ? 17 doses as 5% solution with soda or fruit juice). Since oral NAC is absorbed by activated charcoal, concurrent administration of both agents should be avoided.

c. Methionine (PO 2.5 gm 4 hourly ? 4 doses) to replenish cellular glutathione, may be used as adjuvant in severe paracetamol toxicity.

Iron poisoning: Accidental ingestion of the large number of iron tablets is a common cause of drug-related poisoning in childhood. An elemental iron dose of ~60 mg/kg presents with serious toxicity, while a dose gt;300 mg/kg is potentially lethal.

Mechanism are—(a) direct corrosive effect on gut mucosa,

(b) accumulation of free iron around mitochondria, leading to anaerobic metabolism and metabolic acidosis,

(c) excessive production of free radicals, and (d) impaired coagulation.

Clinically, iron poisoning may present with five sequen­tial stages with considerable overlapping:

a. Acute stage (frac12;-2 hour), with vomiting, abdominal pain, GIT bleeding, and systemic manifestations, e.g. drowsiness, hyperventilation and hypotension.

b. Stage of apparent recovery (1-2 days),

c. Stage of circulatory failure with metabolic acidosis, coagulopathy and oliguria/anuria,

d. Stage of hepatic failure, usually a terminal event (2-4 days), and

e. Stage of gastric scarring (2-4 weeks) in survivors, which may present as chronic intestinal obstruction.

Management depends on expected dose of ingestion, assessed by history or free serum iron levels (gt; 50 #956;g/ dl: possible, gt; 350 pg/dl: definite). Important steps in management include:

a. Gastric lavage with large-volume saline; 50-100 ml of NaHCO₃ solution must be left in the stomach after lavage to bind unabsorbed iron. Activated charcoal is of no value in iron poisoning while whole bowel irrigation is indicated only if large numbers of tablets are visible on skiagram.

b. Supportive therapy for acidosis, shock, etc.

c. Chelation therapy with IV Desferrioxamine (5-15 mg/ kg/hour) is indicated only if serum iron levels gt;300 #956;g/dl and should be continued till the child continues to pass vinrose-color urine (due to iron- desferrioxamine complex).

d. Exchange transfusion is indicated only in refractory cases with serum iron gt;1000 #956;g/dl. Hemo/peritoneal dialysis has no role in iron poisoning.

Salicylate poisoning: While oral salicylates are rarely used in children at present, accidental ingestion or skin absorption from salicylate-containing rubefacient preparations is not uncommon.

Mechanism: Salicylates act as gastric irritant, inhibit many metabolic reactions, e.g. phosphorylation, Kreb cycle, aminoacid synthesis and decrease platelet adhesiveness. Potentially toxic dose is gt;150 mg/kg.

Clinically, these cases present with three stages:

a. Hyperventilation with respiratory alkalosis due to stimulation of respiratory centers, for ~6-12 hours;

b. Hypokalemia with paradoxical aciduria despite respiratory alkalosis due to compensatory loss of K⁺ and H⁺ ions in urine, lasting for 12-24 hours;

c. Progressive metabolic acidosis due to accumulation of lactic acid with dehydration and hypokalemia, after 12-24 hours.

First two stages may not be obvious in young infants or chronic salicylate poisoning.

Other common manifestations include vomiting/ hematemesis, hypo/hyperglycemia and most cases die due to cerebral or pulmonary edema, hemorrhage, severe dyselectrolytemia or shock.

Serum salicylate levels after 6 hours of exposure (peak levels) are reliable indicators of severity - gt;50 mg/dl indicating toxicity and gt;90 mg/dl indicating severe toxicity. However, these levels are unreliable in chronic salicylate poisoning.

Management includes:

a. Immediate gastric lavage,

b. Supportive care with fluid/electrolyte and acid-base correction,

c. Urinary alkalinization with IV sodium bicarbonate (1-2 mEq/kg at 30 minutes interval for 4-6 hours).

d. Hemodialysis or hemoperfusion in severe cases with levels gt; 800 mg/dl.

Lead poisoning: Lead, a non-essential metal with no known physiological value, is ubiquitously present in human body due to environmental exposure. However, blood lead levels gt;10 pg/dl are potentially toxic.

Sources: Major source of lead-exposure in Indian children are—(a) inhalation of lead-containing vehi­cular/industrial emissions, (b) ingestion of lead- containing wall/toy paints usually as pica, or (c) water contamination due to use of old lead-coated pipes/ containers. Industrial and vehicular pollution control measures have substantially reduced incidence of lead poisoning in recent years.

Mechanism: Primary toxicity of lead is due to its affinity for sulphydryl (SH) group of proteins, present in metabolic enzymes - specially those required for heme synthesis. Irreversible binding of lead to this group leads to impaired heme synthesis as well as accumulation of proximal metabolites, responsible for toxic effects.

Clinically, lead poisoning may be acute or chronic, though acute lead poisoning is rare at present.

Acute lead poisoning presents with—(a) acute abdo­minal colic mimicking surgical emergencies, (b) acute encephalopathy with seizures and coma, (c) severe anemia, and (d) peripheral neuropathy, over a period of few days.

Chronic lead poisoning is related to blood lead levels and may be subclinical at lower levels. Important manifestations of chronic lead poisoning include:

• Recurrent abdominal pain with constipation, anorexia and metallic taste in mouth;

• Microcytic hypochromic anemia, with basophilic stippling of RBCs;

• Progressive lead encephalopathy with headache, irritability and impaired cognitive functions, followed by ataxia, seizures and coma in severe cases;

• Other manifestations, e.g. blue lines over gums, renal rickets due to Fanconi-like syndrome or peripheral neuropathy.

Management depends on presence of symptoms and blood lead levels (BLL) and includes: (a) elimination of the potential source of exposure, (b) supportive therapy for encephalopathy, etc. and (c) chelation therapy as follows:

• BLL lt;45 #956;g#8725;dl: No chelation therapy is required irrespective of age, though attempt should be made to identify and remove the source of exposure, followed by revaluation after 2-4 weeks in borderline cases.

• BLL 45-69 #956;g#8725;dl: Oral chelation therapy is indicated in: (a) all children lt;10 years, (b) all girls gt;10 years, and

(c) symptomatic boys gt;10 years, preferably using Succimer or DMSA (PO 350 mg/m²/dose 8-hourly for 5 days, then 12 hourly for next 14 days). Penicillamine may also be used to treat these cases (25-30 mg/kg/ day for 10-14 days), but with higher risk of side­effects.

• BLL gt;70 #956;g#8725;dl: Oral or parenteral chelation therapy is recommended in all cases irrespective of age or symptoms. Parenteral chelation therapy with urgent hospitalization is essential in all cases with severe neurological symptoms or encephalopathy with Dimercapol (IV 75 mg/m²/dose 4-hourly till BLL drops lt; 60 mg/dl) or Calcium disodium edentate or EDTA (IV 1000 mg/m²/day for 5 days).

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