A primer of paediatric toxic syndromes or ‘toxidromes’

Paediatric poisoning is often challenging due to the fact that the offending agent(s) may not be known during the acute and potentially critical phase of the exposure. For example, this may be the case in adolescent suicide on the one end and in neonatal withdrawal on the other end of the paediatric age spectrum. In such cases, laboratory support in identifying the offending agent is not available or is very slow to arrive.

Hence, a reasonable clinical diagnostic approach that has been developed by clinical toxicologists is the identification of ‘toxidromes’. A toxidrome is a syndrome made of symptoms and signs consistent with specific groups of drugs and chemicals. Identification of a toxidrome allows the clinician to narrow down the range and number of potential chemicals involved.

It goes without saying that unless it is shown that the child has ingested a chemical, the clinician must cast a wide net of differential diagnosis. Yet every so often, other diagnoses are considered while poisoning is left as the last option after other diagnoses have been ruled out, thus losing critical time. The present primer is purposefully simple, but hopefully not simplistic, to give the reader the main points to be considered.

HYPOXIC CHILD

Toxic causes: Carbon monoxide, methemoglobinemia (eg, favism and local anesthetics) and cyanide.

Clinical tip: Management should start with supportive care no matter what the offending cause. The discrepancy between the severity of hypoxia and the lack of pulmonary or cardiac symptoms may be an important clue for toxicity.

Pulmonary edema: Cocaine, amphetamines, metal fumes, nitrogen dioxide, opioids, salicylates and smoke inhalation.

Clinical tip: Management should start with supportive care no matter what the offender.

WHEEZING CHILD

Toxic causes: Beta-blockers, irritant gases (eg, chlorine), hydrocarbons, isocyanates, organophosphates, carbamates, smoke inhalation and food-borne sulfites.

Clinical tip: It is critical that parents of a child with reactive airway disease do not smoke in the home or around the child.

CHILD WITH INCREASED OSMOLAR GAP

Toxic causes: Acetone, ethanol, ethyl ether, ethylene glycol, isopropyl alcohol, mannitol, methanol, renal failure and ketoacidosis (diabetic and alcoholic).

Clinical tip: Osmolar gap = measured osmolality –calculated osmolality (normal 0 mOsm/kg ± 5 mOsm/kg).

Calculated osmolality: 2×(Na⁺ [mEq/L]) + glucose (mg/dL)/18 + blood urea nitrogen (mg/dL)/2.8 = ±290 mOsm/kg.

CHILD WITH INCREASED ANION GAP ACIDOSIS

Toxic causes: High acetaminophen, beta-adrenergic agents, carbon monoxide, cyanine, iron, isoniazid, salicylates, theophylline, toxic alcohols and valproic acid.

Clinical tip: Anion gap = Na⁺ – ([Cl^–]+[HCO₃^–]) (normal 8 meq/L to 12 meq/L).

CHILD WITH ACUTE MOVEMENT DISORDER

Dystonia: Antipsychotics and metoclopramide.

Dyskinesia: Amphetamines, anticholinergics, antihistamines, cocaine, gamma-hydroxybutyrate, selective serotonin reuptake inhibitors and tricyclic antidepressants.

Rigidity: Malignant hyperthermia, neuroleptic malignant syndrome and phencyclidine.

Clinical tip: It is worth remembering that metoclopramide is commonly used for acute gastroenteritis in children and can cause dystonia.

HOT, CONFUSED CHILD (SEROTONINERGIC SYNDROME)

Clinical presentation: Confusion, hypomania, restlessness, myoclonus, hyperflexia, sweating, shivering, tremor, incoordination and hyperthermia.

Course: Up to several days to weeks after discontinuing treatment.

Differential diagnosis: May resemble anticholinergic syndrome.

Management: Supportive.

Clinical tip: This clinical picture may resemble an acute infection and, therefore, may be easily overlooked.

CHILD WITH DIFFICULT BREATHING

Neuromuscular blockade: Botulism, neuromuscular blockers, organophosphates, carbamates, strychnine and tetanus.

Central nervous system depression: Opioids, alcohols, sedative hypnotics and tricyclic antidepressants.

Clinical tip: A child with impaired breathing due to lung disease (eg, acute asthma) is much more sensitive to these effects and may progress more easily to respiratory failure.

CHILD WITH HEPATIC FAILURE

Toxic causes: Acetaminophen, Amanita phalloides and similar species, carbon tetrachloride, other chlorinated hydrocarbons, halothane, phenol, phosphorus and valproic acid.

Clinical tip: It is important to include a thorough investigation of the child's exposure to chemicals.

EDGY BABY

Clinical presentation: Onset usually within 72 h of birth, inability to sleep, hypertonia, hyper-reflexia, lacrimation, respiratory distress, fever, sweating, diarrhea and seizures.

Main causes: Withdrawal from opioids, ethanol, benzodiazepines, barbiturates and selective serotonin reuptake inhibitors. In utero toxicity to cocaine and amphetamines.

Treatment: Except for opioids, where specific therapy includes replacement with another opioid (morphine and methadone) with slow tapering-off, for all other causes –supportive care, sedation and comfort, most commonly with phenobarbital.

Clinical tip: This presentation can be due to in utero toxicity of cocaine or amphetamines, or giving naloxone to a baby exposed to opioid.

CHILD WITH VENTRICULAR DYSRHYTHMIAS

Tachyarrhythmia: Amphetamines, cocaine, caffeine, chloral hydrate, aromatic hydrocarbons, anticholinergics and theophylline.

QT prolongation: Amiodarone, arsenic, chloroquine, quinine, quinidine, organophosphates and tricyclic antidepressants.

Clinical tip: More and more medications have been shown to prolong QT. Keep yourself updated.

SLEEPY CHILD

Toxic causes: Antihistamines, any sedative hypnotic, alcohols, gamma-hydroxybutyrate, tricyclic antidepressants, opioids, carbon monoxide, cyanide and hypoglycemic agents.

Clinical tip: Naloxone, glucose or flumazenil may be diagnostic for reversing sedativeness and coma by opioids, hypoglycemia or benzodiazepines, respectively.

SEIZING YOUNGSTER

Toxic causes: Amphetamines, cocaine, caffeine, theophylline, tricyclic antidepressants, venlafaxine, phenothiazines and butyrophenones, camphor, organophosphates, carbamates, ethylene glycol, isoniazid, meperidine, methanol, salicylates and any withdrawal from psychoactive drug.

Clinical tip: The treatment of seizures is not specific in most cases (except maybe for vitamin B₆ deficiency due to isoniazid).

CHILD WITH TACHYCARDIA

Toxic causes: Amphetamines, caffeine, cocaine, theophylline, carbon monoxide, cyanide, hydrogen sulfide, anticholinergics (antihistamines, phenothiazines, tricyclics and atropine), ethanol, withdrawal from any psychoactive drug and thyroid hormone.

Exposure to anticholinergics, antihistamines, antipsychotic antidepressants, atropine, benztropine, scopolamine and ipratropium bromide.

OPIOID TOXIDROME

Clinical presentation: Central nervous system depression, (sedation and lethargy to coma), respiratory depression, hypoxia and miosis.

Differential diagnosis: Other sedative hypnotics typically do not cause miosis.

Management: Supportive.

Specific antidote: Naloxone.

Clinical tip: Young kids may be overdosed with opioids accidentally or nonaccidentally.

NEUROLEPTIC MALIGNANT SYNDROME

Clinical presentation: Hyperthermia, muscle rigidity, metabolic acidosis and confusion.

Toxic causes: Use of antipsychotic agents.

Management: Supportive, decreased temperature and specific antidote – bromocriptine.

Clinical tip: Bear in mind that this presentation may resemble the serotoninergic syndrome.

ANTICHOLINERGIC TOXIDROME

Clinical presentation: Dry flushed skin, dry mouth, mydriosis, delirium, hallucinations, tachycardia, ileus, urinary retention, hyperthermia, coma and respiratory arrest.

Specific antidote: Physiostigmine.

Clinical tip: The syndrome may be overlooked due its resemblance to fever and infection. It may also resemble sympathomimetic overdose.

CHILD WITH SLOW HEART RATE

Toxic causes: Digoxin, organophosphates, carbamates, physiostigmine, beta-blockers, clonidine, opioids, calcium channel blockers and lithium.

Clinical tip: Bradycardia is very rarely encountered in intercurrent paediatric infection in which tachycardia is common place. Take bradycardia very seriously.

CHOLINERGIC TOXIDROME

Toxic causes: Organophosphates and carbamate chemicals. Vomiting, diarrhea, abdominal cramping, bronchospasm, bradycardia, miosis, salivation respiratory hypersecretion and diaphoresis. Tremor, muscle weakness, agitation, seizures and coma.

Differential diagnosis: Opioids.

Management: Supportive.

Specific antidotes: Atropine and pralidoxime.

Clinical tip: The syndrome may be diagnosed by the specific response to antidotes, and by lower levels of the cholinesterase enzyme.

STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS

Toxic causes: Sulfonamides, aromatic antiepileptics, lamotrigine, penicillins, doxycycline and nevirapine.

Clinical tip: You must rule out infections as potential causes of the syndrome (eg, mycoplasma and herpes).