Critical Care Medicine

Toxic exposures: general pediatric approach

Toxic Exposures: General Approach to the Pediatric Patient

1. Description of the problem

Young children explore their worlds in different ways. Some do so by tasting substances, some by handling them, and some by looking at them. Those who taste materials or handle them may come into contact with potentially large amounts of the product, compared to the weight of the child. At some times, the child mimics adult behavior by consuming many pills, or consumes many pills in the mistaken belief that they are candy or food.

When these large amounts of material are ingested, potentially life-threatening complications may ensue.

What every clinician needs to know

Symptoms of poisoning in a child or adolescent are highly variable. Depending on the substance or substances ingested and the quantity of each, symptoms may range from none to critical illness.

Most pharmaceutical agents produce their usual pharmaceutical action in an exaggerated manner when taken in overdose, though some also may have other effects as well. In order to produce a clinical response, the substance must become bioavailable, or, in the case of locally acting agents, must have dermal or mucous membrane contact.

Because of the smaller body size of young children, a single pill of adult strength of some medications may result in potentially life-threatening toxicity.

In general, care for the poisoned child who is seriously ill calls for meticulous supportive care to reestablish an equilibrium between the effects of the toxins and the drugs being administered therapeutically. Benzodiazepines are the usual first choice for control of seizures or agitation, and dopamine or norepinephrine usually the preferred pressors to treat hypotension unresponsive to crystalloid infusion. Cardiac dysrhythmias should be managed according to the usual PALS algorithms.

The few antidotes available are

naloxone (for opioid poisoning)

flumazenil (for poisoning caused by benzodiazepines in the absence of other toxins)

n-acetylcysteine (for acetaminophen poisoning)

oxygen(for carbon monoxide, methemoglobin inducers, cyanide)

methylene blue (for reversing methemoglobinemia in patients who are not G6PD deficient)

fomepizole(for inhibiting alcohol dehydrogenase activity in methanol or ethylene glycol toxicity)

physostigmine(for reversing anticholinergic toxicity)

In addition, there are chelating agents available to reduce the toxicity of specific heavy metals, each with its own profile of efficacy (succimer [DMSA], dimercaprol [BAL], disodium dicalcium EDTA, penicillamine, deferoxamine).

Key Management Points

1. HISTORY is the most essential key to making a correct diagnosis. Knowing which medications or other substances were readily available to the child makes the likelihood of a prompt correct diagnosis much higher. The historical information is much quicker and more likely to specifically identify the substance(s) involved than any laboratory studies.

2. DOSE controls the severity of illness after exposure more than any other single parameter.

3. DECONTAMINATION may be helpful in reducing the amount absorbed, if performed early. The currently preferred strategy for decontamination is the use of activated charcoal for substances that adsorb to it. Gastric lavage or suction have a limited role. Whole bowel irrigation is generally recommended only for large ingestions of sustained release products, or substances not adsorbed to activated charcoal, when it can be started within several hours after ingestion.

4. LABORATORY: Drug screens for drugs of abuse rarely provide new clinically significant information. Quantitation of acetaminophen and salicylates generally should be performed in settings of unknown substances.

5. THERAPY: Supportive. Antidotes should be used when appropriate.

2. Emergency Management

Emergency management steps

1. DECONTAMINATE the patient, if the patient has external contamination with chemicals that may pose a risk to staff, other patients, and/or the facility. This is usually achieved with cleansing with soap and water for 5 minutes or longer, and should be performed in an outdoor setting or a setting that exhausts air that is not recirculated into the remainder of the facility.

While performing decontamination, staff should use appropriate respiratory and dermal protection, generally using at least a powered air-purifying respirator (PAPR) and chemically resistant clothing covering the entire body, as governed by the institution's guidelines for handling chemically contaminated patients.

2. Stabilize the patient: AIRWAY, BREATHING, CIRCULATION.

3. Check for hypoglycemia using a point-of-care test in obtunded patients or where indicated by the adverse effects of substances involved.

4. If the situation seems unusual, consider where social service support is needed for investigation of possible abuse or neglect.

Management points not to be missed

1. In intentional ingestion situations, it is generally prudent to quantitate acetaminophen and salicylate levels.

2. If dermal exposure has occurred and prior decontamination has not been done, rinse the affected area until reasonably clean. If the substance involved was an acid or base, continue rinsing the skin until pH has returned to between 7 and 8. If the area involved was the eye, rinse until pH has returned to 7.3 to 7.5.

Drugs and dosages

Naloxone (for opioid poisoning). Usual dose 0.1 mg/kg every 3 to 5 minutes until desired effect achieved. Some opioids require larger doses than others. If no effect is achieved after a total of 0.3 mg/kg in 10 minutes, the use of further naloxone is unlikely to produce any therapeutic benefit. (In this setting, alternative explanations for the patient's condition should be excluded.)

Once the desired effect is achieved, it is likely that further repeat dosing will be required, as naloxone's half-life is short. Subsequent dosing should be dictated by the clinical response; however, a good starting point is to administer 2/3 of the successful total dose per hour as a continuous infusion.

Flumazenil (for poisoning caused by benzodiazepines in the absence of other toxins). Usual dose 0.01 mg/kg, max 0.2 mg per dose, every 1 to 2 minutes until desired effect achieved. If no effect achieved after a total of 0.5 mg, the use of further flumazenil is unlikely to produce any therapeutic benefit. CAUTION: flumazenil serves as a benzodiazepine antagonist, and in some settings may increase the risk of seizures and increase the difficulty of achieving control of those seizures.

n-acetylcysteine (NAC; (for acetaminophen poisoning). Can be given either orally/ nasogastrically or intravenously. The intravenous route is often preferable, as it bypasses difficulties due to emesis of doses and has a shorter standard course of therapy, but has a higher drug cost than the oral route. IV dosing: 150 mg/kg IV loading dose over 60 minutes, followed by 50 mg/kg IV total over the next 4 hours, followed by 100 mg/kg IV total over the next 16 hours (ie, total of 300 mg/kg over a total of 21 hours).

PO/NG dosing: dilute NAC to 5% concentration, then administer 140 mg/kg PO/NG first dose, followed by 17 subsequent doses of 70 mg/kg each PO/NG spaced every 4 hours. It may be appropriate to continue NAC longer than these durations, depending on the clinical picture. Consultation with a medical toxicologist or poison center for further advice is recommended.

Oxygen (for carbon monoxide, methemoglobin inducers, cyanide). Usually recommended as high-flow oxygen delivered via a non-rebreathing circuit. Hyperbaric oxygen for the treatment of carbon monoxide poisoning is controversial.

Methylene blue (for reversing methemoglobinemia in patients who are not G6PD deficient). Usual dose 1 mg/kg IV; may repeat once in 10 minutes for insufficient clinical response. May exacerbate clinical condition in patients who are G6PD deficient.

Fomepizole (for inhibiting alcohol dehydrogenase activity in methanol or ethylene glycol toxicity). Usual dose 15 mg/kg IV x1, then 10 mg/kg/dose IV every 12 hours for 4 doses. If patient receives hemodialysis, administration of another 10 mg/kg dose should immediately follow the completion of hemodialysis. Consultation should be sought with a medical toxicologist or poison center for more assistance.

Physostigmine (for reversing anticholinergic toxicity).

3. Diagnosis

Diagnostic approach

HISTORY is the key to efficient case management. Lab studies rarely establish a diagnosis that is not already suspected based on the history. However, once a substance is suspected based on history, confirmation may be obtained by qualitative or quantitative tests.

Establishing the diagnosis

History should focus on

WHAT: substances available to the child,

WHEN: time range during which the exposure might have occurred,

WHERE: circumstances and location,

HOW: route(s) of exposure,

WHY: does the possibility of intentional exposure indicate a need for psychiatric assessment?

Lab studies use various techniques to establish the presence of substances and, when appropriate, to quantify them. The clinician should remember that tests often fail to distinguish between structurally similar compounds, unless high-specificity methods such as GC-MS (gas chromatography-mass spectroscopy) are utilized. In particular, immunoassay methodologies are particularly prone to interaction and false-positive results.

Intentional or non-intentional

It is unusual for developmentally normal children over the age of 6 years to accidentally ingest medications as a means of exploring their environment. Therefore, when such ingestions occur, the possibility of intentional ingestion should be considered, perhaps with a desire to cause self-harm or with suicidal ideation.

Potentially toxic substances

Substances often reported as potentially posing life-threatening toxicity to a young child after ingestion of a single pill (approximately 10 kg body weight) include

- Camphor

- Chloroquine / Hydroxychloroquine

- Clonidine

- Diphenoxylate-Atropine

- Eucalyptus Oil

- Hydrofluoric Acid / Bifluorides

- Imidazoline Decongestants

- Methyl Salicylate/Oil of Wintergreen

- Pennyroyal Oil

- Selenious Acid

- Sulfonylureas

Epidemiology

Unsupervised unintentional childhood ingestions continue to be common events. Some data suggest that such events are increasingly frequent, possibly related to an increase over the past 10 years in the number of medications present in the typical home.

Substantial reduction in unintentional exposures has occurred since the adoption of the Poison Prevention Packaging Act of 1972 that mandated the use of child-resistant-closures (CRCs) on most prescription and nonprescription substances with a potential to cause serious injury. Nonetheless, in some cases, these products are removed from their child-safe packaging, and in other cases, the products may be found by the child while the container is open and in use.

New strategies currently being explored include flow-restriction devices that limit the rate at which the liquid contents of a bottle can be removed, expansion of unit-dose packaging, and educational efforts to encourage keeping medications and potentially harmful substances "up and away" out of the reach of children.

What's the evidence?

Epidemiology

US Centers for Disease Control and Prevention (CDC) data. http://www.cdc.gov/safechild/Child_Injury_Data.html..

(Specific data on unintentional childhood poisoning.)

http://www.cdc.gov/safechild/images/CDC-ChildhoodInjury.pdf..

(Data on all childhood injury, with several pages of excellent data on childhood poisoning.)

Bronstein, AC. "2009 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 27th Annual Report". Clin Toxicol. vol. 48. 2010. pp. 979-1178.

(The latest report of poison center data, with case reports of many of the fatalities.)

Management

Yarema, MC. "The poisoned child in the pediatric intensive care unit". Ann Emerg Med. vol. 54. 2009. pp. 606-14.

(Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning.)

Hanhan, UA. "Pediatric toxicology". Ped Clin North Am. vol. 55. 2008. pp. 669-86.

(Overview of management principles for ingestions.)

Michael, JB, Sztajnkrycer, MD. "Drug dosing data verified with Epocrates.com, accessed October 26, 2011". Emerg Med Clin North Am. vol. 22. 2004. pp. 1019-50.

(General reference update.)

Eldridge, DL, Van Eyk, J, Kornegay, C. "Deadly pediatric poisons: nine common agents that kill at low doses". Emerg Med Clin North Am. vol. 25. 2007. pp. 283-308.

(Review of medications with low therapeutic/toxic ratios)
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