Descriptive epidemiology of infant ingestion calls to a Regional Poison Control Center.

Objective: This study was designed to describe the epidemiology of ingestions in infants 6 months of age or younger.

Methods: A retrospective chart review from a convenience sample of poison center cases in infants younger than 6 months of age from December 28, 2002, to December 28, 2003, was reviewed.

Results: A total of 358 cases were reviewed. Incorrectly measured dose, repeated dosing by different caregivers, incorrect dosing interval, and incorrect route accounted for 41% [95% CI, (36%, 46%)] of caregiver dosing misadventures. Ten cases (3%) were due to pharmacy error, and the wrong medication was given in 32 (9%) cases. The total therapeutic misadventure proportion was 53%. Eight percent were 10-fold dosing errors. Thirty-nine (11%) infants were evaluated in an emergency department and 9 (3%) infants were admitted to a health care facility.

Conclusions: Therapeutic misadventures caused by dosing errors in infants younger than 6 months of age were prevalent. Most errors occurred with inaccurate measurement of the medication, repeated dosing by caregivers, incorrect dosing interval, and incorrect route. Healthcare providers could increase prevention of therapeutic misadventures by educating caregivers on proper administration of medications and by demonstrating the use of appropriate measuring devices.

Key Words: infant, ingestion, poisoning, therapeutic misadventure

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Pediatric poisonings are one of the most frequent presentations evaluated in the emergency department. According to the American Association of Poison Control Centers, approximately 1.2 million ingestions were reported in the United States in 2003 in children younger than 6 years of age. (1) Ingestion of a harmful substance is among the most common cause of injury to children in this age group. The majority of pediatric ingestions have minimal clinical effects and can be managed with supportive treatment. However, certain harmful substances can be life threatening. (2) There has been a dramatic decrease over the last 50 years in the death rates of children attributable to unintentional ingestions, mainly as the result of child-resistant closures and safer medications. (3) Many other prevention interventions implemented by the American Academy of Pediatrics have contributed to the reductions in pediatric ingestions. One of these interventions is the development of systems to identify and learn from medication errors. Children are at a higher risk for dosing errors because of their various weights, body surface area calculations, and small measurements of doses. (4)

Childhood poisonings can be unintentional or intentional. Among children younger than 6 years of age, unintentional ingestions are primarily caused by self-administration or iatrogenic error from a caregiver. School-aged children and adolescents are more likely to present with intentional overdose by suicidal intent or illegal use. (5) Unintentional ingestions comprise approximately 80% of all reported poisonings. In the younger age group, unintentional ingestions are related to their exploratory developmental stage. (6) However, infants who are younger than 6 months of age and nonambulatory are provided medications by a caregiver.

Although much is known concerning the epidemiology of ingestions in children and adolescents, there is a paucity of data in the literature examining infants younger than 6 months of age. The primary purpose of this project was to describe the epidemiology of unintentional ingestions and therapeutic misadventures in infants younger than 6 months of age. The secondary goals were to determine the percentage of ingestions that were over the range of toxicity and the magnitude of the error. We also wanted to examine the most common medications involved in the therapeutic misadventures and identify potential risk factors.

Materials and Methods

This was a descriptive case series analysis of all phone calls made to the Regional Poison Control Center (RPCC) of Birmingham, Alabama. A retrospective chart review of cases from phone calls concerning infants 6 months of age or younger were investigated between December 28, 2002, and December 28, 2003. Cases were documented in a computerized database (Toxicall, version 4.5.15, Computer Automation System, Inc, Aurora, CO). Pertinent data were collected and entered into a computer database using True Epistat Version 5.1 (Epistat Services, Richardson, TX). Data collected from the phone calls were the age of infant, caller to the RPCC, misadventure that was described, medication or substance involved, range of toxicity, symptoms, magnitude of dosing error, and disposition of the infant. Institutional review board approval was obtained from the University of Alabama at Birmingham.

Therapeutic misadventures are defined as any incorrect action occurring in the administration of a medication and include errors in prescribing, errors in dispensing the product to the consumer, dosing errors made by caregivers, and idiosyncratic responses to medications. (7) The type of misadventure was documented from the description by the caller in to the RPCC. The individual cases were classified as a dosing error, plant exposure, incorrect medication dispensed, unintentional ingestion, toxic exposure, pharmacy error, or appropriate dose with parental concern. The dosing errors included incorrect amount dispensed, repeated dosing by two caregivers, incorrect interval between doses, and incorrect route of administration. Plant exposures were identified as oral ingestions of any part from a plant. Therapeutic misadventures defined as ingestions were accidental oral exposures to a substance. Toxic exposures were classified as unintentional or intentional dermal or ocular exposures to a potentially harmful product. Pharmacy error included any incorrect process that occurred within the pharmacy that completed the prescription. The range of toxicity was determined from the RPCC database of triage protocols. A nontoxic substance was defined as any product that did not have potentially harmful effects.

Statistical analysis included the z test to compare the difference in the observed proportion of dosing misadventures versus an expected proportion of 25%, which assumes a uniform distribution of four types of ingestion reported in this age group. A 95% confidence interval (CI) was also calculated for the observed proportion of therapeutic misadventures. According to the Medication Errors Reporting Program operated by the United States Pharmacopeia, improper dose or quantity (47%) was the most frequently reported type of pediatric error in their database. (8)

Results

There were a total of 358 phone calls regarding human infants 6 months of age or younger that were reported during the time period to the RPCC in Birmingham, Alabama. This number accounted for 1.6% of all calls reported during the study period. Seventy-five percent of the callers to the RPCC were from mothers of the infants. Only 8% of callers were from fathers. The mean age of the infants was 4 months (SD: 1.72 months). Total therapeutic misadventures accounted for 53% of the calls in infants 6 months of age or younger, which included dosing errors, pharmacy errors, and incorrect medication dispensed (Table 1.) Fifty-nine percent of the substances reported were medications. The most frequently reported medications were ranitidine (11%), metoclopramide (9%), acetaminophen (8%), and Dimetapp Infant Drops (4%) (Table 2). Thirty-two (9%) infants were dispensed the wrong medication recommended or prescribed to that particular individual (Table 3). Pharmacy dispensing errors to the caregiver occurred in 10 cases (3%). Toxic exposures, which included natural gas, a sibling spraying Windex Concentrate on the face of the infant, or boiling Pine-Sol Lemon Cleaner from Clorox on the stove accounted for 16% of the calls. Thirty-five cases (10%) were due to the oral ingestion of part of a plant. The most common plant involved was the Peace Lily (Spathiphyllum spp). There were 63 (18%) reported unintentional ingestions. Some examples of these types of ingestions included topical creams such as Desitin Diaper Rash Ointment, which the infant placed on their hand topically and then placed orally, diaper gel that was orally ingested, or sun accelerator lotion that was ingested during breast-feeding. There were 13 cases in which the substance given was the appropriate amount and medication; however, there was parental concern about adverse side effects. In none of these cases were the symptoms reported thought to be adverse reactions to the medication.

Therapeutic misadventures in dosing errors accounted for 41% [95% CI (36%, 46%)] of the cases in this age group. Of the 358 calls, 102 (28%) involved dosing errors in the amount of substance dispensed to the infant. Thirty-two cases (9%) reported repeated dosing by one caregiver giving the medication, then a second caregiver giving a second dose soon after the first dose. There were 9 (3%) calls that involved the caregiver giving the medication in the incorrect time interval between doses. Six infants received medication by the incorrect route either by oral, otic, or ocular.

The majority of infants (80%) were treated at home with the guidance of the RPCC (Table 4). Six percent did not follow the recommendations of the RPCC, to proceed to a health care facility as determined by follow-up calls. Eleven percent were evaluated in an emergency department and 3% were admitted to a health care facility. Most of the medication misadventures were under the range of toxicity; however, 12% were over the range of toxicity. Fourteen percent were symptomatic, including lethargy (4%), local reaction (4%), vomiting (4%), and hyperactivity (2%) (Table 5). Thirty percent of the medications reported in this age group were commonly used for upper respiratory infections and 27% for gastroesophageal reflux. Approximately 10% of the medications involved were antibiotics.

Discussion

Medication errors are defined as mistakes in the delivery of a product by the wrong amount given, frequency of dose, incorrect route, or inappropriate drug. (9) In the pediatric population, caregivers are an additional link between the prescribing physician, pharmacist, and patient. One prospective study of children younger than 16 years of age from poison control centers in France reported that 87% of medication errors were committed by a family member of the patient. In the same study, incorrect execution of the prescription occurred in 30% of the patients and wrong dose in 31.5%. (9) In our study, the observed proportion of dosing misadventures in infants 6 months of age or younger was 41%, which was significantly greater than the estimated 25% (z = 4.47, P < 0.001). Research such as this study acknowledges that childhood poisoning is an important area of research.

Therapeutic misadventures accounted for 53% of the cases from the RPCC in infants younger than 6 months of age. The majority of substances involved in the cases were medications. This represents a large number of possible medication errors that could be avoided. Over-the-counter cough and cold preparations comprised a large proportion of these medications, even though the American Academy of Pediatrics has reported that studies have failed to demonstrate any benefit of these medications for young children. (10) Because of the low weight of this age group, most medications are prescribed in extremely small doses. This places the infant at an increased risk of receiving an incorrect dose. According to Li et al, infants younger than 1 year of age were more likely to receive an incorrect dose of medication (RR, 1.40; P < 0.04; 95% CI = 1.06 to 1.86) than children older than 1 year of age. In the same study, approximately half of the caregivers surveyed gave an inaccurate dose of acetaminophen or ibuprofen. (11) We found that errors in the amount of dose dispensed occurred in 28% of the cases in infants younger than 6 months of age.

Pharmacy dispensing errors occurred in only 10 cases for this age group. In a retrospective chart review of drug exposures reported to an American Association of Poison Control Centers, labeling errors were more likely to occur in liquid medications prescribed to children. (12) Pharmacists may have to compound a particular medication into a specific formulation, which can lead to an increased frequency of mistakes. According to a study from New Zealand, 49% of parents surveyed did not recall being given instructions from the pharmacist about medication prescribed for their children. Some parents recalled being given instructions on the dosage (9%), frequency of administration (13%), or directed to take as on the bottle (12%). Only 37% of parents thought they were given enough information from the doctor. (13)

Most of the medications given to infants are in a liquid form, which presents an increased vulnerability to measuring mistakes. One study reported that 73% of study participants used a household teaspoon to dispense medication. (14) Household teaspoons are highly inaccurate in measuring doses because of the wide range of volume dispensed. The oral dosing syringe is recommended as the best device for the delivery of liquid medication. (14) Unfortunately, there is no standard measuring device dispensed with medications. Physicians, pharmacists, and nurses should be encouraged to provide detailed information about the prescription and its execution. (13) Health care providers should be aware of the consequences of dispensing a 5 mL syringe for a 0.5 mL dose. Most prescribers of medications do not know what device is being dispensed along with the medication. Physicians, pharmacists, and other health care providers who dispense medications to infants and children should include appropriate dosing syringes and provide detailed instructions on proper dosing to the caregiver.

Because of the very small doses for infants, 10-fold dosing errors are not uncommon. Twenty-eight cases from our study involved 10-fold dosing errors. Most of these errors occurred as the result of misreading decimal points, for example, 1 mL dispensed instead of 0.1 mL. When a medication is formulated into a concentrated amount within a small volume, these types of 10-fold dosing errors can be extremely harmful, for example, the case sited by Batts and Munter (15) of a 6-month-old who presented with a dystonic reaction after an accidental metoclopramide 10-fold dosing error (8 mL instead of 0.8 mL) by a caregiver.

Other dosing errors reported were the repeated dosing by multiple caregivers, incorrect interval between doses, and incorrect route of administration. One potential solution could be a documentation chart dispensed with the medications so that a caregiver may mark the date and time a medication is administered. Therefore, other caregivers may see when a prior dose was dispensed and prevent overdosing.

Ranitidine and metoclopramide were the two most common medications involved with the therapeutic misadventures. We decided to examine these two medications more closely and compare the results. Ranitidine and metoclopramide are widely used in the treatment for gastroesophageal reflux in the pediatric population. Ranitidine is a histamine-2 antagonist that is formulated into a syrup with a concentration of 15 mg per 1 mL. The recommended dose for pediatrics is 4 to 5 mg per kilogram in 24 hours, divided into 8- or 12-hour intervals. (16) Metoclopromide is a chlorobenzamide dispensed in a syrup form concentrated in a 1 mg per 1 mL solution. The recommended dose for gastroesophageal reflux is 0.1 to 0.15 mg per kg per dose, dispensed four times a day. (16) Ranitidine has a larger amount of medication concentrated into a very small volume. However, metoclopramide has an extremely small recommended dosage. For these reasons, these two medications have an increased risk for therapeutic misadventures. There were 24 cases reported involving ranitidine and 18 cases involving metoclopramide. Both of these medications had more than 80% of their total cases caused by dosing errors reported to the RPCC. More than 40% of the misadventures involving either of these medications was over a 10-fold dosing error. Of the 28 cases of 10-fold dosing errors, there were 11 (40%) cases of ranitidine and 8 (29%) cases of metoclopramide. Sixty-one percent of cases involving metoclopramide were over the range of toxicity in which four were evaluated in an emergency department and two were admitted to a healthcare facility. Fifty-four percent of cases involving ranitidine were over the range of toxicity, in which four were evaluated in an emergency department and one was admitted to a healthcare facility. If the formulations of these two medications were less concentrated, a larger volume could be dispensed that could lead to less dispensing errors. Although making liquid preparations less concentrated might improve accuracy of dosing, the resulting increase in volume may make it more difficult for infants to tolerate. Also, marked dosing syringes would provide the caregiver with a precise measurement to draw up. By examining which medications are at an increased risk of therapeutic misadventures in this age group, we may be able to design risk-reducing strategies.

The limitations of this study include the sample population, which only reflects the specific population of caregivers that called in to the RPCC in Birmingham, Alabama. Thus, this sample does not reflect the population of caregivers for this age group that may or may not have informed their primary care provider of any therapeutic misadventure.

Conclusion

Pediatric medication errors have been extensively examined in the literature and represent a frequent occurrence. However, there are few data in the area of therapeutic misadventures in infants younger than 6 months of age. In our study, dosing therapeutic misadventures accounted for 41% of cases reported to the RPCC in infants 6 months or younger. The observed proportion was significantly greater than the 25% hypothesized. The majority of therapeutic misadventures in this age group are due to either incorrect dose dispensed, repeat dosing by caregivers, incorrect dosing interval, or incorrect route. Most of the errors occurred with inaccurate measurement of the medication. Health care providers might increase prevention of therapeutic misadventures by educating caregivers on the administration of medications and demonstrating the use of appropriate measuring devices. Pharmaceutical companies can contribute to the effort of prevention by creating less-concentrated formulations or including user-friendly dosing devices for common pediatric medications. Pharmacists can be an additional advocate against medication errors in the pediatric population by dispensing marked dosing syringes with medications and demonstrating the appropriate amount. Public education to caregivers may provide information to facilitate questions to healthcare providers about dispensing medications.

References

1. Watson WA, Litovitz TL, Klein-Schwartz W, et al 2003 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2004;22:335-404.

2. Shannon M. Ingestion of toxic substances by children. N Engl J Med 2000;342:186-191.

3. Committee on Injury, Violence, and Poison Prevention. Poison treatment in the home. Pediatrics 2003;112:1182-1185.

4. Committee on Drugs and Committee on Hospital Care. Prevention of medication errors in the pediatric inpatient setting. Pediatrics 2003;112:431-436.

5. Tibballs J, McArdle EJ, Brown TC. Drug overdose in children. Aust Paediatr J 1985;21:7-12.

6. Osterhoudt KC, Shannon M, Henretig FM. Toxicologic Emergencies. In: Feisher GR, Ludwig S (eds). Pediatric Emergency Medicine. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2000:887-942.

7. Understanding and preventing drug misadventures. Proceedings of a multidisciplinary invitational conference sponsored by the ASHP research and education foundation in cooperation with the American Medical Association, the American Nurses Association, and the American Society of Hospital Pharmacists; 1994 Oct 21-23; Chantilly, Virginia. Am J Health-Syst Pharm 1995;52:369-416.

8. Santell JP, Cousins D. Medication errors: documenting and reducing medication errors. US Pharmacist 2003 July [cited 2003 July 15]; 28(7). Available from: URL: http//uspharmacist.com/index.asp?show=article&page=8_1120.htm

9. Jonville AP, Autret E, Bavoux F, Characteristics of medication errors in pediatrics. Ann Pharmacother 1991;25:1113-1117.

10. Gunn VL, Taha SH, Leibelt EL. et al Toxicity of over-the-counter cough and cold medications. Pediatrics 2001;108:e52.

11. Li SF, Lacher B, Crain EF. Acetaminophen and ibuprofen dosing by parents. Pediatr Emerg Care 2002;16:394-397.

12. Seifert SA, Jacobitz K. Pharmacy prescription dispensing errors reported to a regional poison control center. J Toxicol 2002;40:919-923.

13. Counsell AM, Geddis DC, Smith AR. Parental perceptions of information about medication prescribed for their children. N Z Med J 1993;956:205-206.

14. Madlon-Kay DJ, Mosch FS. Liquid medication dosing errors. J Fam Tract 2000;49:741-744.

15. Batts KF, Munter DW. Metoclopramide toxicity in an infant. Pediatr Emerg Care 1998;14:39-41.

16. Hirshfeld AB, Getachew A, Sessions J. Drug Doses. In: Siberry GK, Iannone R (eds). The Harriet Lane Handbook. 15th ed. St Louis, MO: Mosby, Inc; 2000: 771-837.

War is a series of catastrophes that results in a victory.
--Georges Clemenceau

Teresa J. Coco, MD, William D. King, RPH, MPH, DRPH, and Ann P. Slattery, MPH, DABAT 

From the Department of Pediatrics, Division of Pediatric Emergency Medicine, and the Department of Child Safety, Children's Health System, University of Alabama at Birmingham, Birmingham, AL. Email: [e-mail]

Reprint requests to Teresa J. Coco, MD, Department of Pediatrics, University of Alabama in Birmingham, 1600 7th Avenue South, Midtown Suite 205, Birmingham, AL 35233.

Accepted February 15, 2005.

RELATED ARTICLE: Key Points

* Infants are at a higher risk for dosing misadventures because of the smaller amounts of medication prescribed, the dependence on a caregiver to deliver the medication, and a nonuniform protocol for dispensing devices given with certain medications.

* Physicians, pharmacists, and other health care providers who dispense medications to infants and children should include appropriate dosing syringes and provide detailed instructions on proper dosing to the caregiver.

* More research is needed for the creation of innovative preventive strategies to reduce therapeutic misadventures in infants and children.

Table 1. Classification of cases from phone calls in infants six months
of age or younger reported to the RPCC of Birmingham, Alabama (n =
358) (a)

Therapeutic misadventures  191  (53%)
Unintentional ingestions    63  (18%)
Toxic exposures             56  (16%)
Plant exposures             35  (10%)
Other (parental concern)    13   (3%)

(a) RPCC, Regional Poison Control Center.

Table 2. Number of cases of the ten most common medications involved in
therapeutic misadventures in infants six months of age or younger
reported to the RPCC (a)

Ranitidine              24
Metoclopramide          18
Acetaminophen           17
Dimetapp Infant Drops    9
Hyoscyamine sulfate      8
Amoxicillin              7
Simethicone              7
Desitin Diaper Cream     7
Ibuprofen                6
PediaCare Infant Drops   6

(a) RPCC, Regional Poison Control Center.

Table 3. Number of cases and percentage of total cases of each
characterization of therapeutic misadventure in infants six months of
age or younger (n = 358)

Incorrect dose        102  (28%)
Repeated dose          32   (9%)
Incorrect medication   32   (9%)
Pharmacy error         10   (3%)
Incorrect interval      9   (2%)
Incorrect route         6   (2%)

Table 4. Disposition of infants younger than six months of age from
cases reported to the regional poison control center (n = 358) (a)

Observed at home with guidance of RPCC  289  (80%)
Treated in an emergency department       39  (11%)
Did not follow RPCC recommendations      21   (6%)
Admitted to a healthcare facility         9   (3%)

(a) RPCC, Regional Poison Control Center.

Table 5. Primary symptoms that occurred from therapeutic misadventures
in infants younger than six months of age (n = 358)

Asymptomatic    309  (86%)
Local reaction   16   (4%)
Lethargic        13   (4%)
Vomiting         12   (4%)
Hyperactivity     8   (2%)