Angelman syndrome

Despite advances such as childproof caps on medications, childproof packaging, increased educational efforts, and increased awareness of commonly ingested substances, deaths due to unintentional poisonings still occur. Unintentional poisonings are an unfortunate and usually preventable cause of death and disability in infants and children. According to Litovitz et al, (1) in the 2001 annual report of the American Association of Poison Control Centers, children aged 12 years and younger accounted for 58.5% of persons poisoned and accounted for 3.5% (38) of all the deaths due to poisoning reported that year. Many categories or classifications of potentially toxic substances can be found within a child's environment. The most common categories of agents ingested by children younger than 6 years old during 2001 are listed in Table 1. Table 2 lists the primary agents involved in fatal poisonings in children up to 12 years old during 2001.

Many descriptive terms are used in the literature on the phenomenon of children and poisoning. Terms used include accidental ingestions, accidental poisoning, accidental overdose, accidental exposures, therapeutic errors, and therapeutic overdosage. Depending on the situation, any one or all of the descriptors could be accurate. However, most recently. Osterhoudt (2) suggested that the term "unintentional poisoning" might be the most appropriate term to use. For the purpose of this article, we use the terms unintentional poisonings and therapeutic errors.

The 2001 data for the Toxic Exposure Surveillance System (TESS) are compiled from 64 cooperating poison control centers across the United States. (1) The TESS database has various classifications for ingestions, but most cases in infants and children are classified as unintentional and include exposures classified as general, environmental, occupational, therapeutic error, unintentional misuse, bites/stings, food poisoning, and unintentional unknown. The American Association of Poison Control Centers (1) defines therapeutic error as "an unintentional deviation from a proper therapeutic regimen that results in the wrong dose, incorrect route of administration, administration to the wrong person, or administration of the wrong substance." Therapeutic errors include errors made both in the natural environment of a child and in healthcare settings. The number of unintentional poisonings of children continues to warrant an increased awareness among healthcare providers. Parents and healthcare providers must have a high index of suspicion when children have signs or symptoms indicative of ingestion of toxic substances. In this article, we present an overview of unintentional poisonings, the influence of growth and development, therapeutic errors, commonly ingested substances (medicinal and household products), and the role of healthcare providers.

Unintentional Poisonings

The very nature of a young child predisposes the child to explore the surrounding environment. As children grow and learn to become independent, they are compelled to investigate new and interesting items, places, and objects. The influence of growth and development upon unintentional poisonings becomes especially important during the toddler and preschool age years. During the toddler years, children are refining gross and fine motor skills. Additionally, they are testing their behavior against the reactions of adults in control. Toward the end of the toddler period, children are using experimentation, accompanied by previously learned skills, as a way of dealing with new situations. This experimentation, a part of normal growth and development, can cause serious consequences if the dangerous behaviors go unnoticed by adults. Toddlers' sense of taste is not well defined, so they may ingest larger quantities of what adults would consider unpalatable products. (3)

As children move into the preschool age years, curiosity about the environment increases. The preschool period is a stage of active learning: however, the cognitive ability to understand words lags behind the ability to use words. Although a child may be able to say the word poison, the ability to reason what the term means is lacking. At this age, children often may mimic the actions of others, such as taking medications. The substances found commonly around the home are often in colors or containers that are familiar to a child. Medications for children are generally formulated with flavors to improve compliance. Once a child's taste is more defined, these flavors may lead to an increase in unintentional poisonings. Cognitive abilities of children at this stage make them unable to discriminate medications from food or candy, and harmful substances can be mistakenly ingested. (4)

Children with cognitive impairments present a similar challenge. Developmentally, children with cognitive impairment, despite their chronological age, may not understand the dangers inherent in ingesting poisons or may still be in a stage of mouthing objects. However, physically, such children may be taller and have the fine and gross motor skills that allow them easier access to poisons. For example, in the summary of fatal exposures reported to TESS in 2001, a 5-year-old with Angelman syndrome, a genetic disorder with cognitive impairment, ingested an air freshener containing propylene glycol and ethoxylate and subsequently died of the ingestion. (1)

Commonly Ingested Pharmaceutical Substances

By and large, the most common category of unintentional poisonings related to pharmaceutical substances in children occurs with analgesics, specifically antipyretic analgesics such as acetaminophen. Other commonly ingested medications include ibuprofen, methadone, oxycodone, salicylates, and morphine. The 2001 TESS statistics report 9 deaths involving single-agent analgesics (2 acetaminophen, 3 aspirin, 1 methadone, 1 morphine, and 2 oxycodone; Table 2). (1)

Acetaminophen can be given safely in therapeutic doses of 10 to 15 mg/kg every 4 hours. Most of the medication is conjugated in the liver; a small amount is excreted in the urine. Liver damage can occur when children ingest 150 mg/kg or more in a single dose. (5,6) Early signs and symptoms (within the first 24 hours) of acetaminophen poisoning are nonspecific and include decreased appetite, nausea, and vomiting or general malaise. After 24 hours, signs of poor hepatic function (elevated liver enzyme levels) begin to emerge. After 48 hours, pain develops in the right upper quadrant, along with alterations in mental status, jaundice, marked elevations of liver enzyme levels, and signs and symptoms of renal failure. Death can occur within 7 days. Children have less liver damage than adults do. (7,8)

Treatment for acetaminophen overdose includes gastrointestinal decontamination with activated charcoal and N-acetylcysteine, the antidote for acetaminophen overdose. N-acetylcysteine is administered in a regimen of 140 mg/kg as a loading dose (orally) and then 70 mg/kg every 4 hours for 17 total doses, and for maximal efficacy, it must be given within 8 hours of the overdose. (5-7,9) Activated charcoal is rarely useful because of the rapid gastrointestinal absorption of acetaminophen and the availability of N-acetylcysteine. (7) Chronic toxic effects may occur when children receive 60 to 150 mg/kg daily of acetaminophen for 2 to 8 days. (8)

Other commonly used pain medications such as nonsteroidal anti-inflammatory drugs, other than aspirin, are generally of low toxicity. If nonsteroidal anti-inflammatory drugs are consumed in toxic quantities, signs and symptoms produced include acute renal failure, gastrointestinal upset, headache, dizziness and/or tinnitus, and vision disturbances. More serious effects can include hypotension, tachycardia, hypothermia, bradycardia, hepatic dysfunction, electrolyte imbalance, metabolic acidosis, central nervous system depression, and respiratory depression. Infants and children with suspected or known ingestion of toxic quantities of these drugs should be observed for 4 to 6 hours for progression of toxic effects and can be discharged if no toxic effects occur. Hospitalization is required for symptomatic children. (9,10)

Several other categories of medications commonly related to unintentional poisonings in children include cough medications, antihistamines, and antidepressants. Most cough medications include more than a single ingredient. Ingredients such as acetaminophen, dextromethorphan, codeine, guaifenesin, and sympathomimetics are present to various degrees and in small amounts. Therefore, because of the small amounts ingested, toxic effects are usually minimal. However, signs and symptoms such as hypertension, bradycardia, arrhythmias, seizures, and gastrointestinal upset can occur. Most often, the treatment for over-doses of these drugs is supportive. Symptomatic children should be hospitalized, observed, and treated if necessary. (11) Table 3 lists commonly ingested pharmaceutical substances, clinical signs and symptoms, and management.

Commonly Ingested Household Product and Plants

Increased attention in the media and lay magazines during the past decade has increased awareness of ingestions of household products and plants. Most parents and caregivers are aware of these dangers and attempt to make homes safe by keeping these substances out of the reach of children. Despite these efforts, a significant number of ingestions of common household products still occur.

The components of the various products ingested vary. Most, however, have an unpleasant taste and therefore are consumed only in small amounts. Effects of unintentional poisonings are typically dose dependent; therefore, as children get older and their sense of taste becomes more defined, the risk of large-dose unintentional poisonings decreases because they are better able to discriminate the unpleasant taste.

With substances such as bleach, the main concerns are oropharyngeal damage and the risk of aspiration pneumonia. (13) Children should be monitored for drooling, difficulty swallowing, noisy respirations, or any indications of respiratory distress. Any suggestion of aspiration requires monitoring in a hospital setting. Some household products may contain an acid or alkaline component. Because of the small percentage of poison present, the most common indication that requires monitoring is related to local oral damage. Additionally, these products may cause some gastrointestinal upset. (13)

Household products such as alcohol, many food flavorings, colognes, perfumes, and mouthwash contain ethanol. Some products contain small amounts of ethanol; however, mouthwashes may contain up to 75% ethanol in the most concentrated form (generally they contain 10%-25% ethanol), and colognes usually are composed of 40% to 60% ethanol. (7-9) Although the concentration of the ethanol varies, the greatest danger lies in the amount consumed. Because mouthwashes often have a palatable taste, they may be consumed in large amounts. The major complication to be monitored is depression of the central nervous system, which can lead to respiratory compromise. The other major complication is related to the competition of ethanol for glucose stores, so children must be monitored closely for hypoglycemia. (14)

Rat and mouse poisons are also unintentional causes of poisoning in children. The active ingredient in most of these products is a warfarinlike long-acting anticoagulant (superwarfarin). (8) Unlike in the past when warfarin was used in rodenticides, these superwarfarins are very potent and have anticoagulant effects for up to 7 weeks even after a small ingestion. (7-9) Although most rodenticides have enough superwarfarin to poison a child, most children do not ingest enough of the rodenticide to cause significant toxic effects. (9) Symptomatic children should be evaluated and should have prothrombin times monitored at 24 and 48 hours. Treatment for children who are symptomatic includes administration of vitamin K. (7-9)

Another common household danger that is often overlooked in children is household plants. Most parents are unaware of poisons within plants. According to data in the 2001 TESS report, (1) among infants and children, plants accounted for 73 287 exposures to toxic substances, which was about 6.3% of all exposures to toxic agents. One of the difficulties in dealing with toxic plants is the variety of possible effects. Many plants have poisonous and nonpoisonous parts. It is also difficult to determine the amount of plant consumed, and whether that amount will produce any signs and symptoms or toxic effects. According to the 2001 TESS report, (1) the top 6 plants that most commonly are the source of exposure to toxic substances are the pepper plant, peace lily, philodendron, holly, poinsettia, and pokeweed (inkberry). Signs and symptoms of ingestion include burning and irritation of oral mucosa, nausea, vomiting, gastric irritation, jitteriness, breathing difficulties, and change in level of consciousness. Any child with suspected ingestion of a poisonous plant substance should be evaluated and treated according to an established management protocol for that substance. (15) Table 4 lists the most commonly ingested household plants and products and common signs and symptoms after ingestion.

Role of Healthcare Providers in Unintentional Poisonings

It is incumbent on healthcare providers to approach any child who has ingested a toxic agent in a quick and accurate manner to reduce fatality and long-term consequences. Such a child may enter the healthcare system either after the child's parent or guardian knows or suspects that the child has ingested a poison or with clinical manifestations that may indicate a poisoning has occurred, but with no documented poisoning.

After ensuring that the child has a stable airway with adequate oxygenation, and that the child's condition is stabilized, the next steps are to determine what substance was ingested and to try to rid the body of the toxic substance. Signs and symptoms should also be treated during this time. Healthcare providers must ask probing questions of the family member seeking care either by telephone or personal contact. Fortunately, many of the commonly ingested substances in a child's environment have low toxicity. Thus, children who ingest toxic substances often may require several hours of observation rather than hospitalization. However, for those substances that can yield long-term effects or cause death, hospitalization is required and at times intensive care monitoring may be necessary.

Once it is determined that a poisoning has occurred, analysis of a urine or blood sample may supply an indication of what antidote and treatment may be required. However, most toxic substances are not detectable on common toxicology screenings, and such screenings rarely add information that has not already emerged from the history and clinical manifestations. (9) On the contrary, if the specific toxic substance is known, serum concentrations of that substance are useful in management of the patient. (8,9) Traditionally, the most common approach has been gastric decontamination, which involves the use of substances to prevent absorption, enhance gastric emptying, and promote catharsis. (17) In the past, the most common interventions used to treat ingestions included syrup of ipecac to induce emesis and activated charcoal to absorb the toxic agent.

According to the 1997 position statement of the American Academy of Clinical Toxicology, (18) however, the use of ipecac syrup and activated charcoal as routine interventions should be limited. The scientific evidence of the efficacy of syrup of ipecac is considered questionable. Studies reviewed indicated too much variability in the amount of toxic substance removed. Likewise, the evidence was inconclusive on general administration of activated charcoal and improvement of patients' outcomes. The position statement did recommend that activated charcoal be used when the substance ingested is known to be affected by activated charcoal and the charcoal can be administered within 1 hour of the ingestion. (18)

Common substances that are not affected by activated charcoal include those represented by the acronym PHAILS: some pesticides, hydrocarbons, alcohols, acids or alkali, iron preparations, lithium, and solvents. (14,15,17) Repeated doses of activated charcoal powder may be useful for ingestions of carbamazepine, barbiturates, dapsone, quinine, theophylline, salicylates, slow-release preparations, digoxin and digitoxin, phenylbutazone, phenytoin, sotalol, piroxicam, and Amanita phalloides (death cap mushroom). (14)

The recommended dosage of activated charcoal is 1 g/kg in children up to 1 year old and 25 to 50 g per dose in children 1 to 12 years old, given either by mouth or by nasogastric tube. (15) The powder of activated charcoal should be mixed with water, which will produce a gritty preparation that should be well shaken. Activated charcoal should not be given with ice cream, milk, or sherbet because these additives decrease its absorptive properties. (19) Potential complications of the use of activated charcoal include aspiration and vomiting. (11) Gastric lavage is contraindicated in patients who are not intubated and in those who have lost the gag reflex. (15)

The American Academy of Clinical Toxicology (18) does not recommend the routine use of a cathartic in conjunction with activated charcoal. If a cathartic is used, it should be limited to a single dose to minimize complications of dehydration, hypernatremia, or hypermagnesemia. The recommended dose for sorbitol is 1 to 2 g/kg (4.3 mL/kg of a 35% solution) for children more than 1 year old. The recommended dose for magnesium citrate in children is 4 mL/kg of a 10% solution. (15,18)

For a few substances, specific antidotes are necessary or beneficial. The antidote may decrease the potential for morbidity or mortality associated with ingestion. Table 5 lists the most common toxic agents and antidotes.

Therapeutic Errors

The smaller physical size of infants and children, as compared with adults, increases the risk for unintentional poisonings and therapeutic errors. All medications for infants and children are individualized, with the dose calculated on the basis of body weight or body surface area. Therefore, all these medications involve the calculation of dosage with the resultant increased potential for errors in the computation of a dose. In addition, because of the small size and body surface area of infants and children, small errors in calculation can make a huge difference in morbidity and mortality. For example, a miscalculation of digoxin that results in 5 [micro]g instead of 0.5 [micro]g or 5 mL instead of 0.5 mL can potentially be fatal.

The most common agents involved in therapeutic errors are single-agent analgesics such as acetaminophen, aspirin, methadone, morphine, and oxycodone. Litovitz et al (1) stated that therapeutic errors made up 7.4% of the total exposures to poisonous substances in all age groups reported to TESS in 2001. Another 3.7% of exposures were due to unintentional misuse of nonpharmaceutical products. Of the 38 deaths in children aged 12 years and younger that were reported in 2001, 9 (24%) of the deaths were due to therapeutic errors. All but 1 of the deaths due to therapeutic errors occurred in children younger than 6 years old. (1)

In the 2001 TESS data for exposures of children aged 12 years and younger, the majority of therapeutic errors made by healthcare professionals were the result of using an incorrect formulation or concentration, dispensing-cup errors, or 10-fold dosing errors. (1) More specifically, therapeutic errors made by healthcare professionals that resulted in death in children aged 12 years and younger included 10-fold errors in morphine sulfate and fosphenytoin dosing; unintentional administrations of an excessive dose of intravenous digoxin; and an inadvertent dosage of 6.5 times the usual dosage of sodium phenylbutyrate solution. (1)

Although therapeutic errors in children are underreported in the literature, we are aware of numerous cases in which parents, caregivers, or siblings unintentionally gave infants and children overdoses of prescription or over-the-counter medications. These errors are a result of misunderstanding of teaching or lack of teaching on dosing and correct formulation. Tenfold errors can also occur when parents or caregivers are withdrawing medications from a container to dispense. According to Lesar, (20) 10-fold or decimal point errors may result in 10-, 100-, or 1000-fold errors in medication dosing. This type of error may result in either overdoses or underdoses. Tenfold errors are potentially devastating, and without proper attention they are relatively easy errors to make, especially in infants and children.

In the study to identify and quantify the characteristics of 10-fold dosing errors, Lesar (20) concluded that such errors are common and are associated with identifiable risk factors. In the study, done in a 631-bed tertiary care teaching hospital (120 beds were pediatric/neonatal), 200 consecutively detected 10-fold medication errors were evaluated. The errors were evaluated on the basis of the potential for the error to be carried out and on the pharmacological potential for adverse effects. All errors classified as potentially severe, serious, or significant were included in the study. Dosing errors in medications for infants and children accounted for 19.5% of all errors. Of note, errors in these patients were detected at a rate of 0.98 per 1000 total patient days as compared with a rate of 0.77 per 1000 total patient days in adults. Contributing to the 10-fold errors in the dosages for infants and children were the dosage calculation used (92.3%), multiple zeroes (38.5%), dose less than 1 (28.2%), and expression or conversion of units of measure (10.2%). Error mechanisms included adding a zero (23.1%), omitting a zero (25.6%), and misplacing decimal points (51.3%).

Another interesting factor evaluated was what Lesar (20) labeled error enablers. These were described as risk factors that would enable an error, such as an injectable dose form, an oral liquid dosage form, and solid oral dose forms such as capsules and tablets. In cases of dosing errors in medications for infants and children, a wide dose range was considered an enabler for all errors. Additionally, injectable and oral liquid medications were enablers. Antimicrobials were the most frequent medication for infants and children ordered in dosages with 10-fold errors (38.5%). However, more severe/serious 10-fold dosing errors were in doses of morphine.

Role of Healthcare Providers in Therapeutic Errors

Errors made in a child's natural environment may be prevented by diligent education of everyone involved in administration of medications, particularly in education on correct formulation and dosage. Anyone who administers the medications must be educated, including parents, relatives, and daycare workers.

Most, if not all, errors made by healthcare professionals could be avoided if attention were paid to the 6 rights of medication administration: right client, right drug, right dose, right route, right time, and right concentration. Particular attention should be given to rules on the use of zeroes and decimal points. Additionally, staff members should be made more aware of the potential for 10-fold errors and how to avoid them.

Part of the responsibility in administering medications is knowledge of safe dosages and expected therapeutic and side effects. Educating parents about the use of prescribed medications is a large responsibility for nurses as well. As nurses, we must be sure that parents understand the directions for administering medications and help the parents understand when it becomes necessary to contact a healthcare provider.

Conclusion

Unintentional poisonings and therapeutic overdoses are real dangers to infants and children. Increased awareness and constant reinforcement are needed not only in the lay community but also in the nursing community. The responsibility for prevention lies within the nursing community to educate itself and others within the community who care for infants and children. Nurses must be aware of the potential dangers associated with commonly used medications. When administering medications to infants and children, and when teaching parents to administer medications, nurses must be absolutely sure of correct dosages.

When parents are being taught, anticipatory guidance includes how to prevent ingestions, the number for the nationwide poison control center (1-800-222-1222), early recognition of common signs and symptoms of poisoning, and the importance of never giving remedies before the poison control center is contacted. Additionally, parents should be instructed on various formulations of acetaminophen and ibuprofen and should be told that the dosages for the various formulations are not interchangeable. Supplying written instructions as well as verbal instructions would be helpful. Written instructions provide parents and caregivers with a reference in case they have a question. It is also important to discuss with parents and caregivers the importance of storing these medications out of the reach of infants and children, using safety locks on cabinets, and keeping purses (or any other places of storage of these medications) out of the reach of infants and children who are at risk for unintentional poisoning. When parents are provided anticipatory guidance, particular emphasis must be placed on the prevention of unintentional poisonings. Guidance should be given on the basis of developmental age rather than chronological age.

As nurses, part of our role is that of education. Talking with parents outside the healthcare arena would be a great start. Girl Scout meetings, meetings of parent-teacher associations, church gatherings, daycare centers, and other community-based activities can provide a forum for teaching and learning, and such training sessions could also provide an opportunity for questions to be answered.

When infants and children are admitted to healthcare facilities after possible exposure to toxic substances, nurses must be gentle in their approach. Nurses should impart information without adding guilt to parents who are already stressed.

Because of the large number of exposures that are "therapeutic," it behooves nurses to be more aware of the importance of knowing the 6 rights of medication administration. Nurses are liable if they give a wrong medication, even if it was ordered. Any nurse who is not familiar with dosages for infants and children should always double-check with another colleague or the pharmacist and should be aware of the potential for 10-fold errors. In intensive care units, medications given to infants and children are almost exclusively injectable or oral liquids. In these units especially, nurses must take special care to eliminate therapeutic errors.

In caring for a child who has been exposed to a toxic substance, all the resources at hand, including the poison control system in a local area, should be used. The overall goal for infants and children is to prevent exposure. However, if an unintentional poisoning or therapeutic error occurs, the goals are to stabilize and prevent complications related to the exposure, return the child to optimal health, and minimize future exposures. With increased awareness and dedication, members of the healthcare profession and the general community can continue to reduce the incidence of exposures of infants and children to toxic substances.

References

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17. DeBoer SL. Ipecac syrup or activated charcoal? When treating a poisoning, know what never PHAILS. Am J Nurs. April 2001;101:75.

18. American Academy of Clinical Toxicology. Position statements. Available at: http://www.clintox.org/Pos_Statements/Intro.html. Accessed May 23, 2005.

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20. Lesar T. Tenfold medication dose prescribing errors. Ann Pharmacother. 2002;36:1833-1839.

Robin Wilkerson, RN, PhD, BC

LaDonna Northington, RN, DNS, BC, CCRN

Wanda Fisher, RN, MSN

Online

Continuing Education

To receive CE credit for this article, visit the American Association of Critical-Care Nurses' (AACN) Web site at http://www.aacn.org, click on "Education" and select "Continuing Education," or call AACN's Fax On Demand at (800) 222-6329 and request item No. 1115.

Authors

Robin Wilkerson and LaDonna Northington are associate professors of nursing and Wanda Fisher is an assistant professor of nursing at the University of Mississippi Medical Center School of Nursing, Jackson, Miss.

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